{
"uniprot_canonical_ac": "O43323-1",
"uniprot_ac": "O43323",
"uniprot_id": "DHH_HUMAN",
"mass": {
"chemical_mass": 43577.0,
"monoisotopic_mass": 43577.0
},
"refseq": {
"ac": "NP_066382",
"name": "desert hedgehog protein preproprotein",
"summary": "This gene encodes a member of the hedgehog family. The hedgehog gene family encodes signaling molecules that play an important role in regulating morphogenesis. This protein is predicted to be made as a precursor that is autocatalytically cleaved; the N-terminal portion is soluble and contains the signalling activity while the C-terminal portion is involved in precursor processing. More importantly, the C-terminal product covalently attaches a cholesterol moiety to the N-terminal product, restricting the N-terminal product to the cell surface and preventing it from freely diffusing throughout the organism. Defects in this protein have been associated with partial gonadal dysgenesis (PGD) accompanied by minifascicular polyneuropathy. This protein may be involved in both male gonadal differentiation and perineurial development. [provided by RefSeq, May 2010].",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_066382"
},
"gene_names": [
{
"name": "DHH",
"resource": "UniProtKB",
"type": "recommended",
"url": "https://www.uniprot.org/uniprot/O43323",
"id": "O43323"
},
{
"name": "DHH",
"resource": "RefSeq",
"type": "synonym",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_066382",
"id": "NP_066382"
},
{
"name": "GDMN; GDXYM; HHG-3; SRXY7",
"resource": "RefSeq",
"type": "synonym",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_066382",
"id": "NP_066382"
}
],
"protein_names": [
{
"name": "Desert hedgehog protein",
"resource": "UniProtKB",
"type": "recommended",
"url": "",
"id": "O43323"
},
{
"name": "3.1.-.-",
"resource": "UniProtKB",
"type": "synonym",
"url": "",
"id": "O43323"
},
{
"name": "DHH",
"resource": "UniProtKB",
"type": "synonym",
"url": "",
"id": "O43323"
},
{
"name": "HHG-3",
"resource": "UniProtKB",
"type": "synonym",
"url": "",
"id": "O43323"
},
{
"name": "desert hedgehog protein preproprotein",
"resource": "RefSeq",
"type": "synonym",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_066382",
"id": "NP_066382"
},
{
"name": "desert hedgehog protein",
"resource": "RefSeq",
"type": "synonym",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_066382",
"id": "NP_066382"
}
],
"function": [
{
"annotation": "DHH pathogenic variants involved in 46,XY disorders of sex development differentially impact protein self-cleavage and structural conformation.",
"evidence": [
{
"database": "RefSeq",
"id": "NP_066382",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_066382"
},
{
"database": "PubMed",
"id": "32504121",
"url": "https://glygen.org/publication/PubMed/32504121"
}
]
},
{
"annotation": "Distinctive functioning of STARD1 in the fetal Leydig cells compared to adult Leydig and adrenal cells. Impact of Hedgehog signaling via the primary cilium.",
"evidence": [
{
"database": "RefSeq",
"id": "NP_066382",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_066382"
},
{
"database": "PubMed",
"id": "33864885",
"url": "https://glygen.org/publication/PubMed/33864885"
}
]
},
{
"annotation": "Mutations in the desert hedgehog (DHH) gene in the disorders of sexual differentiation and male infertility.",
"evidence": [
{
"database": "RefSeq",
"id": "NP_066382",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_066382"
},
{
"database": "PubMed",
"id": "33712994",
"url": "https://glygen.org/publication/PubMed/33712994"
}
]
},
{
"annotation": "PKNOX1 acts as a transcription factor of DHH and promotes the progression of stomach adenocarcinoma by regulating the Hedgehog signalling pathway.",
"evidence": [
{
"database": "RefSeq",
"id": "NP_066382",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_066382"
},
{
"database": "PubMed",
"id": "37864517",
"url": "https://glygen.org/publication/PubMed/37864517"
}
]
},
{
"annotation": "The C-terminal part of the desert hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein into two parts (N-product and C-product) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-product (By similarity). Both activities occur in the reticulum endoplasmic (By similarity). Functions in cell-cell mediated juxtacrine signaling (PubMed:24342078). Promotes endothelium integrity (PubMed:33063110). Binds to PTCH1 receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes in endothelial cells (PubMed:33063110). In Schwann cells, controls the development of the peripheral nerve sheath and the transition of mesenchymal cells to form the epithelium-like structure of the perineurial tube (By similarity).",
"evidence": [
{
"database": "UniProtKB",
"id": "O43323",
"url": "https://www.uniprot.org/uniprot/O43323#function"
},
{
"database": "PubMed",
"id": "24342078",
"url": "https://glygen.org/publication/PubMed/24342078"
},
{
"database": "UniProtKB",
"id": "Q62226",
"url": "https://www.uniprot.org/uniprot/Q62226#function"
},
{
"database": "PubMed",
"id": "33063110",
"url": "https://glygen.org/publication/PubMed/33063110"
},
{
"database": "UniProtKB",
"id": "Q61488",
"url": "https://www.uniprot.org/uniprot/Q61488#function"
}
]
},
{
"annotation": "The dually lipidated desert hedgehog protein N-product is essential for a variety of patterning events during development (By similarity). Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes (PubMed:11472839, PubMed:33063110). Required for normal testis development and spermatogenesis, namely for the formation of adult-type Leydig cells and normal development of peritubular cells and seminiferous tubules (By similarity). Activates primary cilia signaling on neighboring valve interstitial cells through a paracrine mechanism (By similarity). May induce motor neurons in lateral neural tube and may have a polarizing activity (PubMed:11472839). Prevents the desert hedgehog protein precursor binding to PTCH1 (PubMed:33063110).",
"evidence": [
{
"database": "UniProtKB",
"id": "O43323",
"url": "https://www.uniprot.org/uniprot/O43323#function"
},
{
"database": "UniProtKB",
"id": "Q15465",
"url": "https://www.uniprot.org/uniprot/Q15465#function"
},
{
"database": "UniProtKB",
"id": "Q62226",
"url": "https://www.uniprot.org/uniprot/Q62226#function"
},
{
"database": "PubMed",
"id": "33063110",
"url": "https://glygen.org/publication/PubMed/33063110"
},
{
"database": "UniProtKB",
"id": "Q61488",
"url": "https://www.uniprot.org/uniprot/Q61488#function"
},
{
"database": "PubMed",
"id": "11472839",
"url": "https://glygen.org/publication/PubMed/11472839"
}
]
},
{
"annotation": "These data demonstrate that DHH is a key molecule in both male gonadal differentiation and perineurial formation in peripheral nerves Review article",
"evidence": [
{
"database": "RefSeq",
"id": "NP_066382",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_066382"
},
{
"database": "PubMed",
"id": "11990454",
"url": "https://glygen.org/publication/PubMed/11990454"
}
]
},
{
"annotation": "This gene encodes a member of the hedgehog family. The hedgehog gene family encodes signaling molecules that play an important role in regulating morphogenesis. This protein is predicted to be made as a precursor that is autocatalytically cleaved; the N-terminal portion is soluble and contains the signalling activity while the C-terminal portion is involved in precursor processing. More importantly, the C-terminal product covalently attaches a cholesterol moiety to the N-terminal product, restricting the N-terminal product to the cell surface and preventing it from freely diffusing throughout the organism. Defects in this protein have been associated with partial gonadal dysgenesis (PGD) accompanied by minifascicular polyneuropathy. This protein may be involved in both male gonadal differentiation and perineurial development. [provided by RefSeq, May 2010].",
"evidence": [
{
"database": "RefSeq",
"id": "NP_066382",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_066382"
}
]
}
],
"disease": [
{
"disease_id": "DOID:0111774",
"recommended_name": {
"id": "DOID:0111774",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:0111774",
"name": "46,XY sex reversal 7",
"description": "A 46 XY sex reversal characterized by an XY karyotype, phenotypically female genitalia and failure to develop secondary sexual characteristics at puberty including menstruation that has_material_basis_in homozygous or compound heterozygous mutation in DHH on chromosome 12q13.12."
},
"synonyms": [
{
"id": "DOID:0111774",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:0111774",
"name": "46,XY gonadal dysgenesis, partial or complete, DHH-related",
"description": ""
},
{
"id": "DOID:0111774",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:0111774",
"name": "GDXYM",
"description": ""
},
{
"id": "DOID:0111774",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:0111774",
"name": "46,XY sex reversal, partial or complete, DHH-related",
"description": ""
},
{
"id": "DOID:0111774",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:0111774",
"name": "SRXY7",
"description": ""
},
{
"id": "DOID:0111774",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:0111774",
"name": "gonadal dysgenesis, XY, male limited",
"description": ""
},
{
"id": "MONDO:0009301",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0009301",
"name": "46,XY sex reversal 7",
"description": ""
},
{
"id": "MONDO:0009301",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0009301",
"name": "46,XY Sex reversal type 7",
"description": ""
},
{
"id": "MONDO:0009301",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0009301",
"name": "46,XY sex reversal 7",
"description": ""
},
{
"id": "MONDO:0009301",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0009301",
"name": "46XY sex reversal 7",
"description": ""
},
{
"id": "MONDO:0009301",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0009301",
"name": "46,XY SEX reversal 7",
"description": ""
},
{
"id": "MONDO:0009301",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0009301",
"name": "46,XY Sex reversal, partial or complete, Dhh-related",
"description": ""
},
{
"id": "MONDO:0009301",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0009301",
"name": "46,XY gonadal dysgenesis, partial or complete, Dhh-related",
"description": ""
},
{
"id": "MONDO:0009301",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0009301",
"name": "SRXY7",
"description": ""
},
{
"id": "MONDO:0009301",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0009301",
"name": "gonadal dysgenesis, XY, Male-limited",
"description": ""
},
{
"id": "MIM:233420",
"resource": "MIM",
"url": "https://www.omim.org/entry/233420",
"name": "46,XY sex reversal 7",
"description": "46,XY sex reversal 7"
}
],
"evidence": [
{
"id": "233420",
"database": "MIM",
"url": "https://www.omim.org/entry/233420"
}
]
},
{
"disease_id": "DOID:14448",
"recommended_name": {
"id": "DOID:14448",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:14448",
"name": "46,XY sex reversal",
"description": "A gonadal dysgenesis that is characterized by a normal 46,XY karyotype along with a progressive loss of germ cells on the developing gonads of an embryo."
},
"synonyms": [
{
"id": "DOID:14448",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:14448",
"name": "46 XY gonadal dysgenesis",
"description": ""
},
{
"id": "DOID:14448",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:14448",
"name": "Pure gonadal dysgenesis 46,XY",
"description": ""
},
{
"id": "DOID:14448",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:14448",
"name": "Swyer syndrome",
"description": ""
},
{
"id": "MONDO:0020712",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0020712",
"name": "46,XY sex reversal 1",
"description": ""
},
{
"id": "MONDO:0020712",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0020712",
"name": "46,XY gonadal dysgenesis, complete, SRY-related",
"description": ""
},
{
"id": "MONDO:0020712",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0020712",
"name": "46,XY sex reversal 1",
"description": ""
},
{
"id": "MONDO:0020712",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0020712",
"name": "46,XY sex reversal type 1",
"description": ""
},
{
"id": "MONDO:0020712",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0020712",
"name": "46,XY sex reversal, SRY-related",
"description": ""
},
{
"id": "MONDO:0020712",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0020712",
"name": "46,XY true hermaphroditism, SRY-related",
"description": ""
},
{
"id": "MONDO:0020712",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0020712",
"name": "46XY sex reversal 1, Y-linked",
"description": ""
},
{
"id": "MONDO:0020712",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0020712",
"name": "SRXY1",
"description": ""
},
{
"id": "MONDO:0011766",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011766",
"name": "46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome",
"description": ""
},
{
"id": "MONDO:0011766",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011766",
"name": "46XY gonadal dysgenesis with minifascicular neuropathy",
"description": ""
},
{
"id": "MONDO:0011766",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011766",
"name": "46,XY gonadal dysgenesis, partial, with MINIFASCICULAR neuropathy",
"description": ""
},
{
"id": "MIM:400044",
"resource": "MIM",
"url": "https://www.omim.org/entry/400044",
"name": "46,XY sex reversal 1",
"description": "46,XY sex reversal 1"
},
{
"id": "MIM:607080",
"resource": "MIM",
"url": "https://www.omim.org/entry/607080",
"name": "46,XY gonadal dysgenesis with minifascicular neuropathy",
"description": "46,XY gonadal dysgenesis with minifascicular neuropathy"
}
],
"evidence": [
{
"id": "607080",
"database": "MIM",
"url": "https://www.omim.org/entry/607080"
}
]
}
],
"snv": [],
"mutagenesis": [
{
"start_pos": 23,
"end_pos": 23,
"sequence_org": "C",
"sequence_mut": "A",
"comment": "Loss of palmitoylation.",
"evidence": [
{
"database": "UniProtKB",
"id": "O43323",
"url": "https://www.uniprot.org/uniprot/O43323"
},
{
"database": "PubMed",
"id": "24784881",
"url": "https://glygen.org/publication/PubMed/24784881"
}
]
}
],
"expression_tissue": [
{
"tissue": {
"name": "Adult mammalian kidney",
"namespace": "UBERON",
"id": "0000082",
"url": "http://purl.obolibrary.org/obo/UBERON_0000082"
},
"score": "46.66",
"present": "MEDIUM",
"evidence": [
{
"database": "Bgee",
"id": "ENSG00000139549",
"url": "https://bgee.org/?page=gene&gene_id=ENSG00000139549"
}
]
},
{
"tissue": {
"name": "Oral cavity",
"namespace": "UBERON",
"id": "0000167",
"url": "http://purl.obolibrary.org/obo/UBERON_0000167"
},
"score": "41.27",
"present": "ABSENT",
"evidence": [
{
"database": "Bgee",
"id": "ENSG00000139549",
"url": "https://bgee.org/?page=gene&gene_id=ENSG00000139549"
}
]
},
{
"tissue": {
"name": "Stomach",
"namespace": "UBERON",
"id": "0000945",
"url": "http://purl.obolibrary.org/obo/UBERON_0000945"
},
"score": "16.41",
"present": "LOW",
"evidence": [
{
"database": "Bgee",
"id": "ENSG00000139549",
"url": "https://bgee.org/?page=gene&gene_id=ENSG00000139549"
}
]
},
{
"tissue": {
"name": "Esophagus",
"namespace": "UBERON",
"id": "0001043",
"url": "http://purl.obolibrary.org/obo/UBERON_0001043"
},
"score": "61.02",
"present": "MEDIUM",
"evidence": [
{
"database": "Bgee",
"id": "ENSG00000139549",
"url": "https://bgee.org/?page=gene&gene_id=ENSG00000139549"
}
]
},
{
"tissue": {
"name": "Rectum",
"namespace": "UBERON",
"id": "0001052",
"url": "http://purl.obolibrary.org/obo/UBERON_0001052"
},
"score": "46.72",
"present": "ABSENT",
"evidence": [
{
"database": "Bgee",
"id": "ENSG00000139549",
"url": "https://bgee.org/?page=gene&gene_id=ENSG00000139549"
}
]
},
{
"tissue": {
"name": "Urinary bladder",
"namespace": "UBERON",
"id": "0001255",
"url": "http://purl.obolibrary.org/obo/UBERON_0001255"
},
"score": "50.19",
"present": "MEDIUM",
"evidence": [
{
"database": "Bgee",
"id": "ENSG00000139549",
"url": "https://bgee.org/?page=gene&gene_id=ENSG00000139549"
}
]
},
{
"tissue": {
"name": "Thyroid gland",
"namespace": "UBERON",
"id": "0002046",
"url": "http://purl.obolibrary.org/obo/UBERON_0002046"
},
"score": "52.67",
"present": "MEDIUM",
"evidence": [
{
"database": "Bgee",
"id": "ENSG00000139549",
"url": "https://bgee.org/?page=gene&gene_id=ENSG00000139549"
}
]
},
{
"tissue": {
"name": "Liver",
"namespace": "UBERON",
"id": "0002107",
"url": "http://purl.obolibrary.org/obo/UBERON_0002107"
},
"score": "34.15",
"present": "ABSENT",
"evidence": [
{
"database": "Bgee",
"id": "ENSG00000139549",
"url": "https://bgee.org/?page=gene&gene_id=ENSG00000139549"
}
]
},
{
"tissue": {
"name": "Prostate gland",
"namespace": "UBERON",
"id": "0002367",
"url": "http://purl.obolibrary.org/obo/UBERON_0002367"
},
"score": "52.28",
"present": "MEDIUM",
"evidence": [
{
"database": "Bgee",
"id": "ENSG00000139549",
"url": "https://bgee.org/?page=gene&gene_id=ENSG00000139549"
}
]
},
{
"tissue": {
"name": "Thoracic mammary gland",
"namespace": "UBERON",
"id": "0005200",
"url": "http://purl.obolibrary.org/obo/UBERON_0005200"
},
"score": "53.27",
"present": "MEDIUM",
"evidence": [
{
"database": "Bgee",
"id": "ENSG00000139549",
"url": "https://bgee.org/?page=gene&gene_id=ENSG00000139549"
}
]
}
],
"expression_disease": [
{
"significant": "No",
"trend": "down",
"name": "Prostate cancer [DO disease name]",
"url": "http://disease-ontology.org/term/DOID:10283",
"evidence": [
{
"database": "BioXpress",
"id": "O43323",
"url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/O43323"
}
],
"disease": [
{
"disease_id": "DOID:10283",
"recommended_name": {
"id": "DOID:10283",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:10283",
"name": "prostate cancer",
"description": "A male reproductive organ cancer that is located_in the prostate."
},
"synonyms": [
{
"id": "DOID:10283",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:10283",
"name": "NGP - new growth of prostate",
"description": ""
},
{
"id": "DOID:10283",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:10283",
"name": "hereditary prostate cancer",
"description": ""
},
{
"id": "DOID:10283",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:10283",
"name": "malignant tumor of the prostate",
"description": ""
},
{
"id": "DOID:10283",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:10283",
"name": "prostate cancer, familial",
"description": ""
},
{
"id": "DOID:10283",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:10283",
"name": "prostate neoplasm",
"description": ""
},
{
"id": "DOID:10283",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:10283",
"name": "prostatic cancer",
"description": ""
},
{
"id": "DOID:10283",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:10283",
"name": "prostatic neoplasm",
"description": ""
},
{
"id": "DOID:10283",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:10283",
"name": "tumor of the prostate",
"description": ""
},
{
"id": "MONDO:0012597",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012597",
"name": "prostate cancer, hereditary, 9",
"description": ""
},
{
"id": "MONDO:0012597",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012597",
"name": "prostate cancer, hereditary, 9",
"description": ""
},
{
"id": "MONDO:0012597",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012597",
"name": "prostate cancer, hereditary, type 9",
"description": ""
},
{
"id": "MONDO:0012597",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012597",
"name": "HPC9",
"description": ""
},
{
"id": "MONDO:0012741",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012741",
"name": "prostate cancer, hereditary, 12",
"description": "Any familial prostate cancer in which the cause of the disease is a mutation in the EHBP1 gene."
},
{
"id": "MONDO:0012741",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012741",
"name": "EHBP1 familial prostate cancer",
"description": ""
},
{
"id": "MONDO:0012741",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012741",
"name": "familial prostate cancer caused by mutation in EHBP1",
"description": ""
},
{
"id": "MONDO:0012741",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012741",
"name": "prostate cancer, hereditary, 12",
"description": ""
},
{
"id": "MONDO:0012741",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012741",
"name": "prostate cancer, hereditary, type 12",
"description": ""
},
{
"id": "MONDO:0012741",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012741",
"name": "HPC12",
"description": ""
},
{
"id": "MONDO:0012244",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012244",
"name": "prostate cancer, hereditary, 5",
"description": ""
},
{
"id": "MONDO:0012244",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012244",
"name": "prostate cancer, hereditary, 5",
"description": ""
},
{
"id": "MONDO:0012244",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012244",
"name": "prostate cancer, hereditary, type 5",
"description": ""
},
{
"id": "MONDO:0012244",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012244",
"name": "HPC5",
"description": ""
},
{
"id": "MONDO:0012093",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012093",
"name": "prostate cancer, hereditary, 3",
"description": ""
},
{
"id": "MONDO:0012093",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012093",
"name": "prostate cancer, hereditary, 3",
"description": ""
},
{
"id": "MONDO:0012093",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012093",
"name": "prostate cancer, hereditary, type 3",
"description": ""
},
{
"id": "MONDO:0012093",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012093",
"name": "prostate cancer, susceptibility to, 3",
"description": ""
},
{
"id": "MONDO:0012093",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012093",
"name": "HPC3",
"description": ""
},
{
"id": "MONDO:0012094",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012094",
"name": "prostate cancer, hereditary, 4",
"description": ""
},
{
"id": "MONDO:0012094",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012094",
"name": "prostate cancer, hereditary, 4",
"description": ""
},
{
"id": "MONDO:0012094",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012094",
"name": "prostate cancer, hereditary, type 4",
"description": ""
},
{
"id": "MONDO:0012094",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012094",
"name": "prostate cancer, susceptibility to, 4",
"description": ""
},
{
"id": "MONDO:0012094",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012094",
"name": "HPC4",
"description": ""
},
{
"id": "MONDO:0012094",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012094",
"name": "prostate cancer, hereditary, on chromosome 7",
"description": ""
},
{
"id": "MONDO:0012758",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012758",
"name": "prostate cancer, hereditary, 13",
"description": "Any familial prostate cancer in which the cause of the disease is a mutation in the MSMB gene."
},
{
"id": "MONDO:0012758",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012758",
"name": "MSMB familial prostate cancer",
"description": ""
},
{
"id": "MONDO:0012758",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012758",
"name": "familial prostate cancer caused by mutation in MSMB",
"description": ""
},
{
"id": "MONDO:0012758",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012758",
"name": "prostate cancer, hereditary, 13",
"description": ""
},
{
"id": "MONDO:0012758",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012758",
"name": "prostate cancer, hereditary, type 13",
"description": ""
},
{
"id": "MONDO:0012758",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012758",
"name": "HPC13",
"description": ""
},
{
"id": "MONDO:0011270",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011270",
"name": "prostate cancer, hereditary, 8",
"description": ""
},
{
"id": "MONDO:0011270",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011270",
"name": "prostate cancer, hereditary, 8",
"description": ""
},
{
"id": "MONDO:0011270",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011270",
"name": "prostate cancer, hereditary, type 8",
"description": ""
},
{
"id": "MONDO:0011270",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011270",
"name": "HPC8",
"description": ""
},
{
"id": "MONDO:0011270",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011270",
"name": "predisposing for prostate cancer",
"description": ""
},
{
"id": "MONDO:0011270",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011270",
"name": "prostate cancer, susceptibility to",
"description": ""
},
{
"id": "MONDO:0012300",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012300",
"name": "prostate cancer, hereditary, 6",
"description": ""
},
{
"id": "MONDO:0012300",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012300",
"name": "prostate cancer, hereditary, 6",
"description": ""
},
{
"id": "MONDO:0012300",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012300",
"name": "prostate cancer, hereditary, type 6",
"description": ""
},
{
"id": "MONDO:0012300",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012300",
"name": "HPC6",
"description": ""
},
{
"id": "MONDO:0012300",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012300",
"name": "prostate cancer, susceptibility to",
"description": ""
},
{
"id": "MONDO:0012620",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012620",
"name": "prostate cancer, hereditary, 10",
"description": ""
},
{
"id": "MONDO:0012620",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012620",
"name": "HPC10",
"description": ""
},
{
"id": "MONDO:0012620",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012620",
"name": "prostate cancer, hereditary, 10",
"description": ""
},
{
"id": "MONDO:0023122",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0023122",
"name": "familial prostate carcinoma",
"description": "Prostate carcinoma that has developed in relatives of patients with a history of prostate carcinoma."
},
{
"id": "MONDO:0023122",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0023122",
"name": "familial prostate cancer",
"description": ""
},
{
"id": "MONDO:0023122",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0023122",
"name": "hereditary prostate cancer",
"description": ""
},
{
"id": "MONDO:0023122",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0023122",
"name": "hereditary prostate carcinoma",
"description": ""
},
{
"id": "MONDO:0023122",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0023122",
"name": "prostate cancer, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0023122",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0023122",
"name": "prostate cancer, familial, susceptibility to, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0023122",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0023122",
"name": "prostate cancer, somatic",
"description": ""
},
{
"id": "MONDO:0023122",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0023122",
"name": "prostate cancer, susceptibility to, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0023122",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0023122",
"name": "prostate cancer, familial",
"description": ""
},
{
"id": "MONDO:0023122",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0023122",
"name": "prostate cancer, hereditary",
"description": ""
},
{
"id": "MONDO:0012470",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012470",
"name": "prostate cancer, hereditary, 7",
"description": ""
},
{
"id": "MONDO:0012470",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012470",
"name": "HPC7",
"description": ""
},
{
"id": "MONDO:0012470",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012470",
"name": "prostate cancer, hereditary, 7",
"description": ""
},
{
"id": "MONDO:0012470",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012470",
"name": "prostate cancer aggressiveness",
"description": ""
},
{
"id": "MONDO:0011098",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011098",
"name": "prostate cancer, hereditary, 1",
"description": "Any familial prostate cancer in which the cause of the disease is a mutation in the RNASEL gene."
},
{
"id": "MONDO:0011098",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011098",
"name": "RNASEL familial prostate cancer",
"description": ""
},
{
"id": "MONDO:0011098",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011098",
"name": "familial prostate cancer caused by mutation in RNASEL",
"description": ""
},
{
"id": "MONDO:0011098",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011098",
"name": "prostate cancer 1",
"description": ""
},
{
"id": "MONDO:0011098",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011098",
"name": "prostate cancer, hereditary, 1",
"description": ""
},
{
"id": "MONDO:0011098",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011098",
"name": "prostate cancer, hereditary, type 1",
"description": ""
},
{
"id": "MONDO:0011098",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011098",
"name": "HPC1",
"description": ""
},
{
"id": "MONDO:0011098",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011098",
"name": "Prca1",
"description": ""
},
{
"id": "MONDO:0012768",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012768",
"name": "prostate cancer, hereditary, 11",
"description": ""
},
{
"id": "MONDO:0012768",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012768",
"name": "HPC11",
"description": ""
},
{
"id": "MONDO:0012768",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012768",
"name": "prostate cancer, hereditary, 11",
"description": ""
},
{
"id": "MONDO:0012769",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012769",
"name": "prostate cancer, hereditary, 14",
"description": ""
},
{
"id": "MONDO:0012769",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012769",
"name": "HPC14",
"description": ""
},
{
"id": "MONDO:0012769",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012769",
"name": "prostate cancer, hereditary, 14",
"description": ""
},
{
"id": "MONDO:0012770",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012770",
"name": "prostate cancer, hereditary, 15",
"description": ""
},
{
"id": "MONDO:0012770",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012770",
"name": "HPC15",
"description": ""
},
{
"id": "MONDO:0012770",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012770",
"name": "prostate cancer, hereditary, 15",
"description": ""
},
{
"id": "MONDO:0010257",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0010257",
"name": "prostate cancer, hereditary, X-linked 1",
"description": ""
},
{
"id": "MONDO:0010257",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0010257",
"name": "HPCX1",
"description": ""
},
{
"id": "MONDO:0010257",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0010257",
"name": "prostate cancer, hereditary, X-linked 1",
"description": ""
},
{
"id": "MONDO:0010257",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0010257",
"name": "prostate cancer susceptibility, X-linked",
"description": ""
},
{
"id": "MONDO:0010405",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0010405",
"name": "prostate cancer, hereditary, X-linked 2",
"description": ""
},
{
"id": "MONDO:0010405",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0010405",
"name": "HPCX2",
"description": ""
},
{
"id": "MONDO:0010405",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0010405",
"name": "prostate cancer, hereditary, X-linked 2",
"description": ""
},
{
"id": "MIM:611868",
"resource": "MIM",
"url": "https://www.omim.org/entry/611868",
"name": "Prostate cancer, hereditary, 12",
"description": "Prostate cancer, hereditary, 12"
},
{
"id": "MIM:611928",
"resource": "MIM",
"url": "https://www.omim.org/entry/611928",
"name": "Prostate cancer, hereditary, 13",
"description": "Prostate cancer, hereditary, 13"
},
{
"id": "MIM:176807",
"resource": "MIM",
"url": "https://www.omim.org/entry/176807",
"name": "Prostate cancer",
"description": "Prostate cancer"
},
{
"id": "MIM:601518",
"resource": "MIM",
"url": "https://www.omim.org/entry/601518",
"name": "Prostate cancer, hereditary, 1",
"description": "Prostate cancer, hereditary, 1"
},
{
"id": "MIM:611955",
"resource": "MIM",
"url": "https://www.omim.org/entry/611955",
"name": "Prostate cancer, hereditary, 11",
"description": "Prostate cancer, hereditary, 11"
}
]
}
]
},
{
"significant": "No",
"trend": "down",
"name": "Stomach cancer [DO disease name]",
"url": "http://disease-ontology.org/term/DOID:10534",
"evidence": [
{
"database": "BioXpress",
"id": "O43323",
"url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/O43323"
}
],
"disease": [
{
"disease_id": "DOID:10534",
"recommended_name": {
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"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:10534",
"name": "stomach cancer",
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},
"synonyms": [
{
"id": "DOID:10534",
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"url": "http://disease-ontology.org/term/DOID:10534",
"name": "gastric cancer",
"description": ""
},
{
"id": "DOID:10534",
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"url": "http://disease-ontology.org/term/DOID:10534",
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"description": ""
},
{
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"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "gastric cancer",
"description": "A primary or metastatic malignant neoplasm involving the stomach."
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "gastric neoplasm",
"description": ""
},
{
"id": "MONDO:0001056",
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"name": "Ca lesser curvature - stomach",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "cancer of stomach",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "gastric cancer",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "gastric cancer risk after h. pylori infection",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "gastric cancer, somatic",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "malignant gastric neoplasm",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "malignant gastric tumor",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "malignant gastric tumour",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "malignant neoplasm of lesser curve of stomach",
"description": ""
},
{
"id": "MONDO:0001056",
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"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "malignant neoplasm of stomach",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "malignant neoplasm of the stomach",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "malignant stomach neoplasm",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "malignant tumor of body of stomach",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "malignant tumor of greater curve of stomach",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "malignant tumor of lesser curve of stomach",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "malignant tumor of stomach",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "malignant tumor of the stomach",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "malignant tumour of body of stomach",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "malignant tumour of greater curve of stomach",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "malignant tumour of lesser curve of stomach",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "malignant tumour of stomach",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "malignant tumour of the stomach",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "stomach cancer",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "Ca body - stomach",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "ca greater curvature of stomach",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "malignant neoplasm of body of stomach",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "gastric cancer, intestinal",
"description": ""
},
{
"id": "MIM:613659",
"resource": "MIM",
"url": "https://www.omim.org/entry/613659",
"name": "Gastric cancer",
"description": "Gastric cancer"
}
]
}
]
},
{
"significant": "Yes",
"trend": "down",
"name": "Urinary bladder cancer [DO disease name]",
"url": "http://disease-ontology.org/term/DOID:11054",
"evidence": [
{
"database": "BioXpress",
"id": "O43323",
"url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/O43323"
}
],
"disease": [
{
"disease_id": "DOID:11054",
"recommended_name": {
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"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:11054",
"name": "urinary bladder cancer",
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},
"synonyms": [
{
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"resource": "Disease Ontology",
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},
{
"id": "DOID:11054",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:11054",
"name": "tumor of the bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "urinary bladder cancer",
"description": "A primary or metastatic malignant neoplasm involving the bladder."
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "tumor of the bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "tumour of the bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "bladder cancer, somatic",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "cancer of urinary bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant bladder neoplasm",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant bladder tumor",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant bladder tumour",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant neoplasm of bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant neoplasm of the bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant neoplasm of the urinary bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant neoplasm of urinary bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant neoplasm, bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant neoplasm, urinary bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant tumor of bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant tumor of the bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant tumor of the urinary bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant tumor of urinary bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant tumor, urinary bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant tumour of bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant tumour of the bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant tumour of the urinary bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant tumour of urinary bladder",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant urinary bladder neoplasm",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant urinary bladder tumor",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "malignant urinary bladder tumour",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "urinary bladder cancer",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "urinary bladder malignant neoplasm",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "urinary bladder malignant tumor",
"description": ""
},
{
"id": "MONDO:0001187",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001187",
"name": "urinary bladder malignant tumour",
"description": ""
},
{
"id": "MIM:109800",
"resource": "MIM",
"url": "https://www.omim.org/entry/109800",
"name": "Bladder cancer",
"description": "Bladder cancer"
}
]
}
]
},
{
"significant": "Yes",
"trend": "down",
"name": "Head and neck cancer [DO disease name]",
"url": "http://disease-ontology.org/term/DOID:11934",
"evidence": [
{
"database": "BioXpress",
"id": "O43323",
"url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/O43323"
}
],
"disease": [
{
"disease_id": "DOID:11934",
"recommended_name": {
"id": "DOID:11934",
"resource": "Disease Ontology",
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"name": "head and neck cancer",
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},
"synonyms": [
{
"id": "DOID:11934",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:11934",
"name": "head and neck neoplasm",
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},
{
"id": "DOID:11934",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:11934",
"name": "head and neck tumours",
"description": ""
},
{
"id": "DOID:11934",
"resource": "Disease Ontology",
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"name": "head/neck neoplasm",
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},
{
"id": "DOID:11934",
"resource": "Disease Ontology",
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}
]
}
]
},
{
"significant": "Yes",
"trend": "down",
"name": "Lung cancer [DO disease name]",
"url": "http://disease-ontology.org/term/DOID:1324",
"evidence": [
{
"database": "BioXpress",
"id": "O43323",
"url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/O43323"
}
],
"disease": [
{
"disease_id": "DOID:1324",
"recommended_name": {
"id": "DOID:1324",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:1324",
"name": "lung cancer",
"description": "A respiratory system cancer that is located_in the lung."
},
"synonyms": [
{
"id": "MONDO:0012159",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012159",
"name": "lung cancer susceptibility 1",
"description": ""
},
{
"id": "MONDO:0012159",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012159",
"name": "LNCR1",
"description": ""
},
{
"id": "MONDO:0012159",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012159",
"name": "lung cancer susceptibility",
"description": ""
},
{
"id": "MONDO:0012159",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012159",
"name": "lung cancer susceptibility 1",
"description": ""
},
{
"id": "MONDO:0012942",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012942",
"name": "lung cancer susceptibility 3",
"description": ""
},
{
"id": "MONDO:0012942",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012942",
"name": "LNCR3",
"description": ""
},
{
"id": "MONDO:0012942",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012942",
"name": "lung cancer susceptibility 3",
"description": ""
},
{
"id": "MONDO:0012942",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012942",
"name": "adenocarcinoma of lung, susceptibility to",
"description": ""
},
{
"id": "MONDO:0012955",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012955",
"name": "lung cancer susceptibility 4",
"description": ""
},
{
"id": "MONDO:0012955",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012955",
"name": "LNCR4",
"description": ""
},
{
"id": "MONDO:0012955",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012955",
"name": "lung cancer susceptibility 4",
"description": ""
},
{
"id": "MONDO:0013631",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0013631",
"name": "lung cancer susceptibility 5",
"description": ""
},
{
"id": "MONDO:0013631",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0013631",
"name": "LNCR5",
"description": ""
},
{
"id": "MONDO:0013631",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0013631",
"name": "lung cancer susceptibility 5",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "lung cancer",
"description": "A malignant neoplasm involving the lung."
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "adenocarcinoma of lung, response to tyrosine kinase inhibitor in, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "adenocarcinoma of lung, somatic",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "cancer of lung",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "lung cancer",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "lung cancer, protection against, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "lung cancer, resistance to, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "lung cancer, somatic",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "lung cancer, susceptibility to, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "malignant lung neoplasm",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "malignant lung tumor",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "malignant lung tumour",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "malignant neoplasm of lung",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "malignant neoplasm of the lung",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "malignant tumor of lung",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "malignant tumor of the lung",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "malignant tumour of lung",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "malignant tumour of the lung",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "nonsmall cell lung cancer, response to tyrosine kinase inhibitor in, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "nonsmall cell lung cancer, somatic",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "nonsmall cell lung cancer, susceptibility to, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "Nonsmall cell lung cancer",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "alveolar cell carcinoma",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "lung cancer, protection against",
"description": ""
},
{
"id": "MONDO:0008903",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0008903",
"name": "lung neoplasm",
"description": ""
},
{
"id": "MIM:211980",
"resource": "MIM",
"url": "https://www.omim.org/entry/211980",
"name": "Lung cancer",
"description": "Lung cancer"
}
]
}
]
},
{
"significant": "Yes",
"trend": "down",
"name": "Breast cancer [DO disease name]",
"url": "http://disease-ontology.org/term/DOID:1612",
"evidence": [
{
"database": "BioXpress",
"id": "O43323",
"url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/O43323"
}
],
"disease": [
{
"disease_id": "DOID:1612",
"recommended_name": {
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"url": "http://disease-ontology.org/term/DOID:1612",
"name": "breast cancer",
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},
"synonyms": [
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"id": "DOID:1612",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:1612",
"name": "breast tumor",
"description": ""
},
{
"id": "DOID:1612",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:1612",
"name": "malignant neoplasm of breast",
"description": ""
},
{
"id": "DOID:1612",
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"url": "http://disease-ontology.org/term/DOID:1612",
"name": "malignant tumor of the breast",
"description": ""
},
{
"id": "DOID:1612",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:1612",
"name": "mammary cancer",
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},
{
"id": "DOID:1612",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:1612",
"name": "mammary tumor",
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},
{
"id": "DOID:1612",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:1612",
"name": "primary breast cancer",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "hereditary breast carcinoma",
"description": "Breast carcinoma that has developed in relatives of patients with history of breast carcinoma."
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "breast cancer susceptibility, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "breast cancer, early-onset, susceptibility to, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "breast cancer, invasive ductal, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "breast cancer, lobular, somatic",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "breast cancer, male, susceptibility to, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "breast cancer, protection against, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "breast cancer, somatic",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "breast cancer, susceptibility to, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "familial breast cancer",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "familial breast carcinoma",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "familial cancer of breast",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "familial cancer of the breast",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "hereditary breast cancer",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "hereditary breast carcinoma",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "breast cancer, familial",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "breast cancer, familial Male",
"description": ""
},
{
"id": "MIM:114480",
"resource": "MIM",
"url": "https://www.omim.org/entry/114480",
"name": "Breast cancer",
"description": "Breast cancer"
}
]
}
]
},
{
"significant": "Yes",
"trend": "up",
"name": "Thyroid cancer [DO disease name]",
"url": "http://disease-ontology.org/term/DOID:1781",
"evidence": [
{
"database": "BioXpress",
"id": "O43323",
"url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/O43323"
}
],
"disease": [
{
"disease_id": "DOID:1781",
"recommended_name": {
"id": "DOID:1781",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:1781",
"name": "thyroid cancer",
"description": "An endocrine gland cancer located in the thryoid gland located in the neck below the thyroid cartilage."
},
"synonyms": [
{
"id": "DOID:1781",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:1781",
"name": "thyroid gland cancer",
"description": ""
},
{
"id": "DOID:1781",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:1781",
"name": "Thyroid gland neoplasm",
"description": ""
},
{
"id": "DOID:1781",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:1781",
"name": "malignant neoplasm of thyroid gland",
"description": ""
},
{
"id": "DOID:1781",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:1781",
"name": "malignant tumour of thyroid gland",
"description": ""
},
{
"id": "DOID:1781",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:1781",
"name": "neoplasm of thyroid gland",
"description": ""
},
{
"id": "DOID:1781",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:1781",
"name": "thyroid neoplasm",
"description": ""
}
]
}
]
},
{
"significant": "Yes",
"trend": "down",
"name": "Kidney cancer [DO disease name]",
"url": "http://disease-ontology.org/term/DOID:263",
"evidence": [
{
"database": "BioXpress",
"id": "O43323",
"url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/O43323"
}
],
"disease": [
{
"disease_id": "DOID:263",
"recommended_name": {
"id": "DOID:263",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:263",
"name": "kidney cancer",
"description": "A urinary system cancer that is located_in the kidney."
},
"synonyms": [
{
"id": "DOID:263",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:263",
"name": "malignant neoplasm of kidney except pelvis",
"description": ""
},
{
"id": "DOID:263",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:263",
"name": "malignant tumour of kidney",
"description": ""
},
{
"id": "DOID:263",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:263",
"name": "renal cancer",
"description": ""
}
]
}
]
},
{
"significant": "No",
"trend": "up",
"name": "Liver cancer [DO disease name]",
"url": "http://disease-ontology.org/term/DOID:3571",
"evidence": [
{
"database": "BioXpress",
"id": "O43323",
"url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/O43323"
}
],
"disease": [
{
"disease_id": "DOID:3571",
"recommended_name": {
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:3571",
"name": "liver cancer",
"description": "A hepatobiliary system cancer that is located_in the liver."
},
"synonyms": [
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:3571",
"name": "Ca liver - primary",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:3571",
"name": "Resectable malignant neoplasm of Liver",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:3571",
"name": "hepatic cancer",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:3571",
"name": "hepatic neoplasm",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:3571",
"name": "malignant hepato-biliary neoplasm",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:3571",
"name": "malignant neoplasm of liver",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:3571",
"name": "malignant neoplasm of liver, primary",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:3571",
"name": "malignant tumor of liver",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:3571",
"name": "neoplasm of liver",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:3571",
"name": "non-resectable primary hepatic malignant neoplasm",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:3571",
"name": "primary liver cancer",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:3571",
"name": "primary malignant neoplasm of liver",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:3571",
"name": "resectable malignant neoplasm of the liver",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:3571",
"name": "malignant neoplasm of liver, not specified as primary or secondary",
"description": ""
}
]
}
]
},
{
"significant": "Yes",
"trend": "down",
"name": "Uterine cancer [DO disease name]",
"url": "http://disease-ontology.org/term/DOID:363",
"evidence": [
{
"database": "BioXpress",
"id": "O43323",
"url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/O43323"
}
],
"disease": [
{
"disease_id": "DOID:363",
"recommended_name": {
"id": "DOID:363",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:363",
"name": "uterine cancer",
"description": "A female reproductive organ cancer that is located_in the uterus."
},
"synonyms": [
{
"id": "DOID:363",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:363",
"name": "CA - cancer of uterus",
"description": ""
},
{
"id": "DOID:363",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:363",
"name": "Tumour of uterus",
"description": ""
},
{
"id": "DOID:363",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:363",
"name": "malignant neoplasm of uterus",
"description": ""
},
{
"id": "DOID:363",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:363",
"name": "malignant uterine tumor",
"description": ""
},
{
"id": "DOID:363",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:363",
"name": "neoplasm of uterus",
"description": ""
},
{
"id": "DOID:363",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:363",
"name": "uterine tumor",
"description": ""
},
{
"id": "DOID:363",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:363",
"name": "uterus neoplasm",
"description": ""
}
]
}
]
},
{
"significant": "No",
"trend": "down",
"name": "Esophageal cancer [DO disease name]",
"url": "http://disease-ontology.org/term/DOID:5041",
"evidence": [
{
"database": "BioXpress",
"id": "O43323",
"url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/O43323"
}
],
"disease": [
{
"disease_id": "DOID:5041",
"recommended_name": {
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:5041",
"name": "esophageal cancer",
"description": "A gastrointestinal system cancer that is located_in the esophagus."
},
"synonyms": [
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:5041",
"name": "Ca lower third oesophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:5041",
"name": "Ca middle third oesophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:5041",
"name": "esophagus cancer",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:5041",
"name": "malignant neoplasm of distal third of esophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:5041",
"name": "malignant neoplasm of lower third of oesophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:5041",
"name": "malignant neoplasm of middle third of oesophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:5041",
"name": "malignant neoplasm of proximal third of esophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:5041",
"name": "malignant neoplasm of upper third esophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:5041",
"name": "malignant tumor of Distal Third of esophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:5041",
"name": "malignant tumor of Proximal Third of esophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:5041",
"name": "malignant tumor of abdominal esophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "http://disease-ontology.org/term/DOID:5041",
"name": "malignant tumor of the middle Third of the esophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "esophageal cancer",
"description": "A primary or metastatic malignant neoplasm involving the esophagus."
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "cancer of esophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "cancer of oesophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "esophageal cancer",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "esophageal cancer, somatic",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "esophageal carcinoma, somatic",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "esophageal squamous cell carcinoma, somatic",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "esophagus cancer",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant esophageal neoplasm",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant esophageal tumor",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant esophageal tumour",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant esophagus neoplasm",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant esophagus tumor",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant neoplasm of esophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant neoplasm of oesophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant neoplasm of the esophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant neoplasm of the oesophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant oesophagus neoplasm",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant oesophagus tumour",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant tumor of esophagus",
"description": ""
},
{
"id": "MONDO:0007576",
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"name": "malignant tumor of the esophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant tumour of oesophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant tumour of the oesophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "oesophagus cancer",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "Ca lower third esophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "Ca lower third oesophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "Ca middle third esophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "Ca middle third oesophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant neoplasm of distal third of esophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant neoplasm of distal third of oesophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant neoplasm of lower third of esophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant neoplasm of lower third of oesophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant neoplasm of middle third of esophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant neoplasm of middle third of oesophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant neoplasm of proximal third of esophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant neoplasm of proximal third of oesophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant neoplasm of upper third esophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant neoplasm of upper third oesophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant tumor of abdominal esophagus",
"description": ""
},
{
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"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0000139",
"evidence": [
{
"database": "UniProtKB",
"id": "O43323",
"url": "https://www.uniprot.org/uniprot/O43323"
}
],
"pmid": ""
},
{
"name": "extracellular space",
"id": "GO:0005615",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0005615",
"evidence": [
{
"database": "UniProtKB",
"id": "O43323",
"url": "https://www.uniprot.org/uniprot/O43323"
}
],
"pmid": ""
},
{
"name": "plasma membrane",
"id": "GO:0005886",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0005886",
"evidence": [
{
"database": "UniProtKB",
"id": "O43323",
"url": "https://www.uniprot.org/uniprot/O43323"
}
],
"pmid": ""
},
{
"name": "endoplasmic reticulum membrane",
"id": "GO:0005789",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0005789",
"evidence": [
{
"database": "UniProtKB",
"id": "O43323",
"url": "https://www.uniprot.org/uniprot/O43323"
}
],
"pmid": ""
}
]
},
{
"name": "Molecular Function",
"total": 5,
"go_terms": [
{
"name": "zinc ion binding",
"id": "GO:0008270",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0008270",
"evidence": [
{
"database": "UniProtKB",
"id": "O43323",
"url": "https://www.uniprot.org/uniprot/O43323"
}
],
"pmid": ""
},
{
"name": "calcium ion binding",
"id": "GO:0005509",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0005509",
"evidence": [
{
"database": "UniProtKB",
"id": "O43323",
"url": "https://www.uniprot.org/uniprot/O43323"
}
],
"pmid": ""
},
{
"name": "peptidase activity",
"id": "GO:0008233",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0008233",
"evidence": [
{
"database": "UniProtKB",
"id": "O43323",
"url": "https://www.uniprot.org/uniprot/O43323"
}
],
"pmid": ""
},
{
"name": "patched binding",
"id": "GO:0005113",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0005113",
"evidence": [
{
"database": "UniProtKB",
"id": "O43323",
"url": "https://www.uniprot.org/uniprot/O43323"
}
],
"pmid": ""
},
{
"name": "cholesterol-protein transferase activity",
"id": "GO:0140853",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0140853",
"evidence": [
{
"database": "UniProtKB",
"id": "O43323",
"url": "https://www.uniprot.org/uniprot/O43323"
}
],
"pmid": ""
}
]
}
]
},
"pro_annotation": [],
"site_annotation": [
{
"start_pos": 203,
"end_pos": 205,
"annotation": "n_glycosylation_sequon"
}
],
"ptm_annotation": [
{
"annotation": "Partially autoproteolyzed (PubMed:30298535, PubMed:24342078). The C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein and covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-terminal fragment (DhhN) (By similarity).",
"evidence": [
{
"database": "UniProtKB",
"id": "O43323",
"url": "https://www.uniprot.org/uniprot/O43323"
},
{
"database": "PubMed",
"id": "30298535",
"url": "https://glygen.org/publication/PubMed/30298535"
},
{
"database": "PubMed",
"id": "24342078",
"url": "https://glygen.org/publication/PubMed/24342078"
}
]
}
],
"interactions": [],
"reactions": [
{
"id": "59504",
"name": "",
"equation": "cholesterol + glycyl-L-cysteinyl-[protein] + H(+) = [protein]-C-terminal glycyl cholesterol ester + N-terminal L-cysteinyl-[protein]",
"summary": "",
"cellular_location": "",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q63673-1",
"O43323-1",
"Q14623-1",
"Q15465-1",
"Q61488-1",
"P97812-1",
"Q62226-1",
"Q02936-1"
],
"evidence": [
{
"id": "59504",
"database": "Rhea",
"url": "https://www.rhea-db.org/rhea/59504"
}
]
},
{
"id": "R-HSA-445124",
"name": "Patched binds Smoothened",
"equation": "",
"summary": "Smoothened (Smo) is usually classified with family B GPCRs based on homology. There are indications that it can signal via G-proteins Gi and G12/13 (Ruiz-Gomez, 2007) but this role is poorly understood. It's better characterised physiological role is as the transducer of hedgehog (HH) signaling. In this capacity Smo is not acting as a receptor, but as part of a signaling cascade.;
;
; The Hedgehog(HH)/Smo signalling pathway was identified as a key component of Drosophila development and subsequently found to be conserved in all meatazoans. Most of the functions attributed to Smo are associated with development such as digit patterning in the chick limb bud and left\u2013right asymmetry of vertebrate embryos. In addition, Smo appears to be involved in homeostasis; deregulated Smo signaling is implicated in tumorogenesis (Ruiz-Gomez, 2007).;
;
; The ligand of the 12 transmembrane-domain receptor Patched (Ptc) is Hedgehog(HH) but in the absence of HH, Ptc binds Smo (Stone et al. 1996) which consequently becomes internalised into endosomes, where it associates with Costal-2 (Cos2), and lysosomes, where it is degraded. This 'inactivates' Smo by preventing the formation of an active Smo signaling complex at the plasma membrane. Internalised Smo:Cos2 forms a complex with protein kinase A (PKA), casein kinase I (CKI) glycogen synthase kinase-3 (GSK3) and Cucurbitus interruptus (Ci), a transcriptional regulator, enabling phosphorylation of Ci and subsequent processing to a transcriptional repressor form (CiR). When HH binds to Ptc, it does not bind Smo, allowing Smo to undergo a conformational change, exposing a new surface in its cytoplasmic tail. This causes PKA, CKI and GSK3 to dissociate from Smo:Cos2 complexes, so that Ci is no longer phosphorylated or processed to CiR. Accumulating Smo is phosphorylated instead and assumes a third conformational state. Phosphorylated Smo trafficks to the plasma membrane (Denef et al. 2000) and assembles into a signalling complex that promotes the phosphorylation of Fused (Fu) and Cos2. Phosphorylated Cos2 dissociates from membranes and recruits Fu to Sufu (Suppressor of Fused), which produces the activated form of Ci (CiA), probably through phosphorylation of Sufu (Hooper & Scott, 2005).",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"Q15465-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-445124",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-445124"
}
]
},
{
"id": "R-HSA-445448",
"name": "HHIP binds Hedgehog",
"equation": "",
"summary": "HHIP is a Hh-binding transmembrane protein that antagonizes Hh signaling by sequestering the ligand away from PTCH. HHIP is also a downstream target gene of Hh signaling, establishing a negative feedback loop that limits the extent of signaling (Chuang et al, 1999; Chuang et al, 2003; Bosanac et al, 2009; Bishop et al, 2009: Holtz et al, 2013). HHIP binds to all three Hh ligands, and also exists in a secreted form, which also sequesters ligand (Chuang et al, 1999; Coulombe et al, 2004). HHIP expression is altered in some cancers that show upregulated Hh signaling (Olsen et al, 2004; Tada et al, 2008; Tojo et al, 2002).",
"cellular_location": "extracellular region, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"Q15465-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-445448",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-445448"
}
]
},
{
"id": "R-HSA-5358336",
"name": "P4HB forms mixed disulphides with Hh precursors",
"equation": "",
"summary": "Hh ligands undergo a autoproteolytic cleavage mediated by a conserved residue in the C-terminal region to yield an N-terminal fragment destined for further modification and secretion, and a C-terminal fragment that is subsequently degraded by ERAD (reviewed in Gallet, 2011). Recent work has shown that autoproteolytic cleavage of Hh ligands depends on prior formation of an intramolecular disulphide bond between the catalytic cysteine residue and another conserved cysteine residue in the C-terminal region of the precursor (Chen et al, 2011). Mutation of either of these cysteine residues abolishes cleavage, suggesting that the intramolecular disulphide bond is required to establish a catalytically active conformation of the precursor (Chen et al, 2011).
Prior to the autoproteolytic cleavage reaction, the protein disulphide isomerase P4HB is required to reduce the intramolecular disulphide, freeing the catalytic cysteine side chain for nucleophilic attack. Mutational analysis and co-immunoprecipitation studies support a model where the N-terminal CXXC motif of P4HB forms a mixed disulphide with the non-catalytic cysteine residue of the Hh precursor (Chen et al, 2011.",
"cellular_location": "endoplasmic reticulum lumen",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"P07237-1",
"Q15465-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5358336",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5358336"
}
]
},
{
"id": "R-HSA-5358340",
"name": "Autoproteolytic cleavage of Hh precursors",
"equation": "",
"summary": "Autoproteolytic processing of the Hh precursor is essential for the production of active secreted Hh ligand and mutants that disrupt this processing have been identified in the congenital nervous system disorder holoprosencephaly (Traiffort et al, 2004; Maity et al, 2005; Roessler et al, 2009; reviewed in Jiang et al, 2008). Cleavage of Hh occurs through two nucleophilic substitutions. The first step is mediated by the catalytic cysteine residue, which is found in a conserved G-C-F motif. The cysteine side chain attacks the carbonyl carbon of the main peptide chain between the glycine and cysteine residues, replacing the amino group in the peptide backbone with a thioester linkage (Lee et al, 1994; Porter et al, 1995; Porter et al, 1996a, b; Chen et al, 2011). The second step involves nucleophilic attack of the same carbonyl group by cholesterol. This step displaces the C-terminal fragment (Hh-C) of the Hh precursor and results in the formation of the N-terminal fragment (Hh-Np) modified at its C-terminus by an ester linkage with cholesterol (Porter et al, 1996a, b; Chen et al, 2011). Cholesterol modification appears to contribute to further processing and trafficking of the Hh ligand, as engineered forms of vertebrate and fly Hh that lack cholesterol are not efficiently palmitoylated (Pepinsky et al, 1998). Cholesterol also restricts the diffusion of the secreted ligand by interacting with the lipid bilayer of the secreting cell. Consistent with this, aberrant activation of Hh target genes is seen in the absence of cholesterol modification (Peters et al, 2004; Guerrero et al, 2007; Li et al, 2006; Huang et al, 2007).
",
"cellular_location": "endoplasmic reticulum lumen",
"input_participant_list": [
"R-ALL-174672"
],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"P07237-1",
"Q15465-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5358340",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5358340"
}
]
},
{
"id": "R-HSA-5358343",
"name": "HHAT palmitoylates Hh N-terminal fragment",
"equation": "",
"summary": "In addition to being modified by cholesterol at its C-terminal end, the N-terminal fragment of Hh (Hh-Np) is also palmitoylated by the O-acyltransferase HHAT (Pepinsky et al, 1998; Charmoun et al 2001; Chen et al, 2004; Hardy and Resh, 2007). HHAT-mediated palmitoylation of Hh can be recapitulated in vitro and in vivo, and the cholesterol- and palmitoyl-modified N-terminal fragment represents the predominant secreted form of Hh in vivo (Buglino and Resh, 2008; Buglino and Resh, 2010; Taipale et al, 2000). Mutation or depletion of the HHAT enzyme and mutation of the palmitoyl acceptor cysteine in Hh itself abrogates palmitoylation of the ligand and reduces Hh signaling (Chen et al, 2004; Chamoun et al, 2001; Pepinsky et al, 1998; Callier et al, 2014).",
"cellular_location": "endoplasmic reticulum lumen",
"input_participant_list": [
"R-ALL-5358339"
],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"Q15465-1",
"Q5VTY9-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5358343",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5358343"
}
]
},
{
"id": "R-HSA-5362386",
"name": "Glycosylation of Hh",
"equation": "",
"summary": "Proteomic studies show that the C-termini of SHH and IHH are N-glycosylated (Liu et al, 2005). A N278A mutant of SHH does not undergo cholesterol-mediated autoproteolysis suggesting that glycosylation is a prerequisite for this processing step (Huang et al, 2013).",
"cellular_location": "endoplasmic reticulum lumen",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"Q15465-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5362386",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5362386"
}
]
},
{
"id": "R-HSA-5362412",
"name": "SYVN1 ubiquitinates Hh C-terminal fragments",
"equation": "",
"summary": "SYVN1 ubiquitinates Hh-C as part of the retrotranslocon that targets these Hh fragments for degradation through the ERAD pathway. Both depletion of SYVN1 by siRNA and expression of a catalytically inactive form of the enzyme strongly inhibits Hh-C degradation. Consistent with this, a dominant negative version of SYVN1 abrogates the polyubiquitination of Hh-C as assessed by IP-Western from HEK293 cells (Chen et al, 2011).",
"cellular_location": "endoplasmic reticulum membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"Q86TM6-1",
"Q15465-1",
"P55072-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5362412",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5362412"
}
]
},
{
"id": "R-HSA-5362422",
"name": "Hh-Np binds to DISP2",
"equation": "",
"summary": "Long range signaling of Hh depends on a number of additional factors that promote the release and spread of Hh-Np ligand. Dispatched2 (DISP2) is a 12-pass transmembrane protein that was identified as being required for release and long-range signaling by Hh-Np (Burke et al, 1999; Ma et al, 2002; Nakano et al, 2004). In mammals, DISP2 has been shown to bind directly to the cholesterol moiety of Hh-Np through its first extracellular region, and this interaction is required for secretion and long-range signaling. Mutants of DISP2 that are inactive in promoting Hh long-range signaling show tighter binding to Hh-Np, suggesting that these mutants interfere with the release of Hh ligand from the plasma membrane (Tukachinsky et al, 2012). Although this pathway shows DISP2 and Hh-Np interacting at the plasma membrane, it is possible that the interaction occurs earlier in the secretory pathway and that DISP2 escorts Hh-Np to the cell surface.
In addition to binding to DISP2, the cholesterol moiety of Hh-Np is also bound by the secreted protein SCUBE2 (Tukachinsky et al, 2012; Creanga et al, 2012). Like DISP2, SCUBE2 is required for long-range signaling by Hh-Np (Johnson et al, 2012; Tukachinsky et al, 2012; Creanga et al, 2012). DISP2 and SCUBE2 recognize distinct portions of the cholesterol group on Hh-Np, suggesting a possible hand-off mechanism at the plasma membrane that allows the release of Hh from the secreting cell (Tukachinsky et al, 2012; Creanga et al, 2012).
",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"Q15465-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5362422",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5362422"
}
]
},
{
"id": "R-HSA-5362427",
"name": "Hh-Np binds GPC5",
"equation": "",
"summary": "The establishment of a signaling gradient of Hh-Np is modulated in part by the interaction of the ligand with heparin sulphate proteoglycans (HSPGs) in the extracellular matrix (ECM) of the secreting cell. Interactions with HSPGs can influence Hh oligomerization and also impact the lateral and long-range spread of Hh ligand (reviewed in Gallet, 2011; Briscoe and Therond, 2013). Interactions with HSPGs can stimulate or restrict Hh signaling depending on the context and the particular proteoglycans involved (see for instance Witt et al, 2013; Li et al, 2011; Capurro et al, 2005; Capurro et al, 2012; reviewed in Gallet, 2011).
In vertebrate cells, the GPI-anchored HSPG glypican 5 (GPC5) has been shown to stimulate Hh signaling by promoting the interaction between SHH ligand and the PTCH1 receptor (Li et al, 2011; Witt et al, 2013). SHH and PTCH1 binding depends on the GAG chains of GPC5, as versions lacking the GAG insertion sites are compromised for both ligand and receptor binding, and these proteins do not stimulate Hh signaling (Li et al, 2011). Amplification of GPC5 has been observed in 20% of rhabdomyosarcomas (Williamson et al, 2007), and aberrant activation of Hh signaling in these cells promotes cellular proliferation (Li et al, 2011).",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"Q15465-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5362427",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5362427"
}
]
},
{
"id": "R-HSA-5362437",
"name": "C-terminal Hh fragments are bound by lectins",
"equation": "",
"summary": "Promotion of the cholesterol-mediated autocleavage reaction is the only well documented role for the C-terminal region of intact Hh (reviewed in Briscoe and Therond, 2013), and recent in vitro studies suggest that the Hh-C fragment generated by autocleavage is subsequently targeted to the endoplasmic reticulum-associated degradation (ERAD) pathway (Chen et al, 2011; Huang et al, 2013). This pathway delivers N-glycosylated ER-resident substrates to a retrotranslocation channel, where they are ubiquitinated and translocated to the cytosol for proteasome-mediated degradation in an ATP-ase dependent fashion (reviewed in Vembar and Brodsky, 2008). Recognition and targettng of ER proteins for the ERAD pathway depends at least in part on modification and binding of the glycosyl groups. Consistent with this, depletion of the lectins OS9 and ERLEC1 abrogates degradation of the Hh-C fragments (Chen et al, 2011). OS9 and ERLEC1 may target Hh-C to the retrotranslocation channel by virtue of their interaction with SEL1, an ER membrane protein with established roles in the ERAD pathway (Christianson et al, 2008; Mueller et al, 2008; Hosokawa et al, 2008; Hosokawa et al, 2009).",
"cellular_location": "endoplasmic reticulum membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"Q15465-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5362437",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5362437"
}
]
},
{
"id": "R-HSA-5362441",
"name": "C-terminal Hh fragments are recruited to SEL1:SYVN1 at the ER membrane",
"equation": "",
"summary": "After binding to OS9/ERLEC1, the Hh C-terminal fragments are recruited to the ER membrane through a lectin-SEL1 interaction. SEL1 is a component of a multiprotein retrotranslocation complex in the ER membrane that also includes the E3 ubiquitin ligase SYVN1 (also known as HRD1; present as a dimer), DERL2 and the hexameric ATPase VCP (Christianson et al, 2008; Hosokawa et al, 2008; Mueller et al, 2008; Chen et al, 2011; Huang et al, 2013; reviewed in Vembar and Brodsky, 2008). Depletion of SEL1, SYVN1, VCP or DERL2 results in the accumulation of the Hh-C in the ER lumen (Chen et al, 2011; Huang et al, 2013).",
"cellular_location": "endoplasmic reticulum membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"Q86TM6-1",
"Q15465-1",
"P55072-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5362441",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5362441"
}
]
},
{
"id": "R-HSA-5362448",
"name": "Hh C-terminal fragments are degraded by the proteasome",
"equation": "",
"summary": "After retrotranslocation to the cytosol, Hh-C is degraded by the proteasome (Chen et al, 2011; Huang et al, 2013).",
"cellular_location": "cytosol",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"A5LHX3-1",
"O00487-1",
"O43323-1",
"Q15465-1",
"P28074-1",
"Q99436-1",
"P28072-1",
"P40306-1",
"P28065-1",
"Q14623-1",
"P28062-1"
],
"evidence": [
{
"id": "R-HSA-5362448",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5362448"
}
]
},
{
"id": "R-HSA-5362459",
"name": "VCP-catalyzed ATP hydrolysis promotes the translocation of Hh-C into the cytosol",
"equation": "",
"summary": "The ATPase activity of VCP is required for the retrotranslocation of Hh-C across the ER membrane (Chen et al, 2011). Although in this pathway, the VCP hexamer is shown as part of the SEL1:SYVN1:DERL2 retrotranslocon, the details, order of events and even the full complement of protein players in this process are not known. In yeast, the VCP homologue Cdc48 is associated with two additional proteins Ufd1 and Npl4 -both of which are also conserved in mammals- and this complex interacts with several ER components including derlins and the yeast SYVN1 homologue, Hrd1 (reviewed in Vembar and Brodsky, 2009). Consistent with the yeast data, VCP interacts with DERL2 by co-immunoprecipitation in HEK293 cells (Huang et al, 2013).",
"cellular_location": "cytosol",
"input_participant_list": [],
"output_participant_list": [
"R-ALL-1132287"
],
"enzyme_list": [
"O43323-1",
"Q86TM6-1",
"Q15465-1",
"P55072-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5362459",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5362459"
}
]
},
{
"id": "R-HSA-5362549",
"name": "Hh-Np traffics to the plasma membrane",
"equation": "",
"summary": "Hh-Np traffics to the plasma membrane where it may cluster in lipid rafts. Cholesterol modification is thought to contribute to this transit and targeting, possibly by promoting interaction with the lipid raft components caveolin and flotillin2, although this has not been demonstrated in mammalian cells (reviewed in Gallet, 2011). Cholesterol and lipid modification also impact the effective signaling range of the secreted ligand: due to the hydrophobic nature of these modifications, Hh-Np remains closely associated with the plasma membrane of the secreting cell, where it is competent for short-range signaling to adjacent cells. Long-range signaling depends on a number of possible mechanisms to extract the ligand from the secreting cell, including oligomerization of ligand into micelle-like structures, cleavage of the C-terminal cholesterol moiety by metalloproteases, or interaction with additional factors that help promote release from the plasma membrane (reviewed in Gallet, 2011; Briscoe and Therond, 2013).",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"Q15465-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5362549",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5362549"
}
]
},
{
"id": "R-HSA-5362551",
"name": "Hh-Np binds SCUBE2 in the extracellular region to promote long-range signalling",
"equation": "",
"summary": "SCUBE2 is a member of a family of secreted proteins that is required for long-range signaling Hh signaling (Johnson et al, 2012; Tukachinsky et al, 2012; Creanga et al, 2013). Like DISP2, SCUBE2 binds to the cholesterol moiety of the Hh ligand, although the structural elements recognized by the two proteins are distinct. This suggests a model where Hh is released from the plasma membrane to the extracellular region via a DISP2 to SCUBE hand-off (Tukachinsky et al, 2012; Creanga et al, 2013).",
"cellular_location": "extracellular region",
"input_participant_list": [
"R-HSA-5362373"
],
"output_participant_list": [
"R-HSA-445456"
],
"enzyme_list": [
"O43323-1",
"Q15465-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5362551",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5362551"
}
]
},
{
"id": "R-HSA-5362553",
"name": "NOTUM releases Hh-Np:GPC5 from the plasma membrane",
"equation": "",
"summary": "Notum is a secreted protein with phospholipase C activity that has been implicated in promoting long range Hh signaling in Drosophila (Ayers et al, 2010; Eugster et al, 2007; Takeo et al, 2005; Han et al, 2005; Giraldez et al, 2002). Notum is thought to cleave the GPI-anchor from Dally, a Drosophila glypican, to release Hh-Dally complexes from the plasma membrane of the Hh-secreting cell (Ayers et al, 2010; Han et al, 2005), although this cleavage has not been directly demonstrated. In cultured mammalian cells, NOTUM has been shown to cleave the GPI anchor of a number of glypicans to promote their release from the plasma membrane (Traister et al, 2008).",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q6P988-1",
"O43323-1",
"Q15465-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5362553",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5362553"
}
]
},
{
"id": "R-HSA-5362793",
"name": "Hh-Np is cleaved by ADAM17 to promote ligand shedding",
"equation": "",
"summary": "Hh-Np can be untethered from the plasma membrane of the secreting cell by ADAM17-mediated cleavage of the lipidated N- and C-termini (Dierker et al, 2009; Ohlig et al, 2011; Ohlig et al, 2012). Shedding of SHH Np from the plasma membrane is abrogated by siRNA depletion of ADAM17, as well as in the presence of metalloprotease inhibitors or mutation of the ADAM17 catalytic E406 residue (Dierker et al, 2009). ADAM17-mediated cleavage is stimulated by heparin sulphate and likely occurs in the context of a HSPG-SHH complex although specific HSPGs have not been identified (Dierker et al, 2009). Cleavage of the cholesterol- and palmitoyl-modified termini is suggested to promote a SHH conformation that is competent to bind to the Patched receptor (Ohlig et al, 2011).",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"Q15465-1",
"P78536-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5362793",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5362793"
}
]
},
{
"id": "R-HSA-5483229",
"name": "HHAT G287V doesn't palmitoylate Hh-Np",
"equation": "",
"summary": "A G287V loss-of-function mutation in HHAT was identified in a rare case of Syndromic 46, XY Disorder of Sex Development, which results in testis dysgenesis. The mutation does not affect the stability, localization or expression level of the HHAT when expressed from a plasmid in COS-1 cells, but the mutant protein is unable to palmitoylate SHH or DHH in an in vitro assay and expression of the HHAT loss-of-function gene in mice recapitulates the phenotypes seen in the human patient (Callier et al, 2014). These findings support a role for DHH signaling in testis development, consistent with earlier reports (Umehara et al, 2000; Canto et al, 2004; Canto et al, 2005; Das et al, 2011).",
"cellular_location": "endoplasmic reticulum membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"Q15465-1",
"Q5VTY9-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5483229",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5483229"
}
]
},
{
"id": "R-HSA-5632646",
"name": "SMURF1/2 bind PTCH1",
"equation": "",
"summary": "Hh stimulation promotes PTCH1 clearance from the primary cilium to endocytic compartments (Rohatgi et al, 2007; reviewed in Nowaza et al, 2013). Receptor internalization is required for pathway activation, and additionally limits the duration and range of Hh signaling by sequestering the ligand inside the cell (Rohatgi et al, 2007; Incardona et al, 2000; Incardona et al, 2002; Denef et al, 2000; Huang et al, 2013; Yue et al, 2014). Upon Hh pathway activation, the E3 ligases SMURF1 and SMURF2 bind to two PPXY motifs in the C-terminal tail of PTCH1 to promote its ubiquination, endocytosis and degradation. In Drosophila, SMURF-mediated ubiquitination of PTCH is depends on an interaction between SMURF and activated SMO, but this does not appear to be true in vertebrates where PTCH1 turnover is SMO-independent (Yue et al, 2014; Huang et al, 2013; Lu et al, 2006). In flies, SMURF-dependent ubiquitination preferentially downregulates ligand-unbound receptor and is thus believed to regulate downstream signaling by altering the ratio of bound to unbound receptor on the cell surface; this aspect of PTCH1 downregulation has not been examined in detail in vertebrate cells (Huang et al, 2013; Casali and Struhl, 2004; Yue et al, 2014).",
"cellular_location": "ciliary membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"Q15465-1",
"Q9HAU4-1",
"Q9HCE7-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5632646",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5632646"
}
]
},
{
"id": "R-HSA-5632649",
"name": "Hh-Npp binds GAS1 and PTCH",
"equation": "",
"summary": "GAS1 is a vertebrate-specific Hh coreceptor that binds directly to Hh ligand to promote signaling (Martinelli and Fan, 2007; McLellan et al, 2008; Izzi et al, 2011; Pineda-Alvarez et al, 2012). GAS1 interacts directly with PTCH as well as BOC and CDON and contributes in an unclearly defined manner to Hh signal transduction (Martinelli and Fan, 2007; Allen et al, 2007; Izzi et al, 2011; Allen et al, 2011; reviewed in Sanchez-Arrones et al, 2012).",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"Q15465-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5632649",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5632649"
}
]
},
{
"id": "R-HSA-5632652",
"name": "Hh-Npp binds CDON and PTCH",
"equation": "",
"summary": "CDON is a transmembrane glycoprotein that binds directly to Hh ligand and is required in conjunction with PTCH, BOC and GAS1 to promote Hh signaling (Tenzen et al, 2006; McLellan et al, 2008; Kavran et al, 2010; Bae et al, 2011; reviewed in Beachy et al, 2010; Sanchez-Arrones et al, 2012). Conserved fibronectin type III repeats in the extracellular region of CDON and BOC are required for interaction with both Hh ligand and the PTCH receptor and also for interactions between BOC, CDON and GAS1 (Okada et al, 2006; Izzi et al, 2011; Bae et al, 2011). The manner in which each of these co-receptors interact and contribute to Hh signaling is not fully elucidated, but knockout of all three is required to abrogate Hh signaling in mice (Allen et al, 2007; Allen et al, 2011; Izzi et al, 2011; reviewed in Sanchez-Arrones et al, 2012).",
"cellular_location": "ciliary membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"Q15465-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5632652",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5632652"
}
]
},
{
"id": "R-HSA-5632653",
"name": "Hh-Npp binds BOC:PTCH1",
"equation": "",
"summary": "Hh pathway activation depends upon the binding of Hh ligand to the PTCH transmembrane receptor (Chen and Struhl, 1996; Marigo et al, 1996; Stone et al, 1996). Ligand binding relieves the PTCH-dependent inhibition of SMO, allowing SMO to concentrate in the primary cilium and promoting the accumulation of the full-length form of the GLI transcriptional proteins (reviewed in Briscoe and Therond, 2013). PTCH also binds constitutively to the transmembrane protein BOC (brother of CDO), one of three vertebrate co-receptors required for Hh signaling in mice (Izzi et al, 2011; Allen et al, 2011; reviewed in Sanchez-Arrones et al, 2012). BOC interacts with PTCH through the first and second of the BOC fibronectin type 3 (FNIII) repeats, and with SHH through the third FNIII repeat, suggesting the formation of a ternary complex in the presence of ligand (Okada et al, 2006; Izzi et al, 2011). Although GAS1 similarly binds to both PTCH and Hh, it is not co-immunoprecipitated with BOC, suggesting the formation of separate receptor:co-receptor complexes (Izzi et al, 2011; Allen et al, 2011; reviewed in Briscoe and Therond, 2013).",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"Q15465-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5632653",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5632653"
}
]
},
{
"id": "R-HSA-5632668",
"name": "SMO translocates to the cilium",
"equation": "",
"summary": "Binding of ligand to the PTCH receptor activates the Hh signaling pathway and results in the accumulation of SMO in the primary cilium (Denef et al, 2000; Corbit et al, 2005; Rohatgi et al, 2007; Milenkovic et al, 2009; Wang et al, 2009; Wilson et al, 2009; reviewed in Briscoe and Therond, 2013). Neither the mechanism for how PTCH represses SMO in the absence of ligand nor how this relief is lifted upon pathway activation are fully understood, however SMO translocation to the cilium appears to depend upon complex formation with beta-arrestin proteins and the anterograde motor protein KIF3A (Chen et al, 2004; Kovacs et al, 2008). GAS8, a SMO- and microtubule-binding protein, is also required for the ciliary localization of SMO, although the mechanism is not clear (Evron et al, 2011; reviewed in Evron et al, 2012). In response to pathway activation, SMO is phosphorylated in a CKI- and ADRBK1/GRK2-dependent fashion and undergoes a conformational change, both of which are required for downstream pathway activation; accumulation of SMO in the cilium is in itself not sufficient (Chen et al, 2011; Zhao et al, 2007; Chen et al, 2010; Rohatgi et al, 2009). In the primary cilium, SMO interacts with the Ellis-van Creveld syndrome proteins 1 and 2 (EVC1 and 2) in a SMO phosphorylation-dependent manner, and the interaction with EVC1 and 2 is required for downstream signal propagation (Yang et al, 2012; Dorn et al, 2012; Capparos-Martin et al, 2013; Pusapati et al, 2014; Yang et al, 2012). SMO activation results in the concentration of SUFU and the GLI proteins in the cilium, the dissociation of the SUFU:GLI complex and the nuclear accumulation of the full length activator form of the GLI proteins (reviewed in Briscoe and Therond, 2013).",
"cellular_location": "ciliary membrane, endocytic vesicle membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"O43323-1",
"Q15465-1",
"Q14623-1"
],
"evidence": [
{
"id": "R-HSA-5632668",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-5632668"
}
]
},
{
"id": "R-HSA-9692146",
"name": "Expression of DHH in testis differentiation",
"equation": "",
"summary": "The DHH gene is transcribed to yield mRNA and the mRNA is translated to yield DHH protein (Rahmoun et al. 2017 and inferred from mouse homologs). Transcription of DHH is directly activated by SOX9 (inferred from mouse homologs). DHH is secreted from pre-Sertoli cells (Rahmoun et al. 2017 and inferred from mouse homologs) and acts via the PTCH1 receptor to regulate testis development.",
"cellular_location": "extracellular region, nucleoplasm",
"input_participant_list": [
"R-HSA-9692094"
],
"output_participant_list": [
"R-HSA-5362781"
],
"enzyme_list": [
"O43323-1"
],
"evidence": [
{
"id": "R-HSA-9692146",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9692146"
}
]
}
],
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"participant_name": "Palmitoyl-CoA [endoplasmic reticulum lumen]",
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{
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"id": "A7MBM2",
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"participant_id": "R-HSA-5362373",
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