{"count":1,"next":null,"previous":null,"results":[{"gene_data":{"alias":["bA51G5.2"],"biotype":"protein_coding","hgnc_id":"HGNC:21232","gene_name":"melanocortin 2 receptor accessory protein 2","omim_gene":["615410"],"alias_name":null,"gene_symbol":"MRAP2","hgnc_symbol":"MRAP2","hgnc_release":"2017-11-03T00:00:00","ensembl_genes":{"GRch37":{"82":{"location":"6:84743475-84800600","ensembl_id":"ENSG00000135324"}},"GRch38":{"90":{"location":"6:84033756-84090881","ensembl_id":"ENSG00000135324"}}},"hgnc_date_symbol_changed":"2008-07-16"},"entity_type":"gene","entity_name":"MRAP2","confidence_level":"1","penetrance":"Complete","mode_of_pathogenicity":"","publications":["23869016 - sequenced the coding region and intron/exon boundaries of MRAP2 in obese and control individuals from the Genetics of Obesity Study (GOOS) cohort and the Swedish obese children’s cohort. They describe identifying 4 heterozygous variants in 4 individuals with severe obesity, of which only one was predicted to be damaging (E24X)","27474872 - screened the entire coding region of MRAP2 for mutations in 184 children and adolescents with extreme obesity and 184 healthy lean controls. Nonsynonymous variants were then genotyped in a larger, independent study group of 300 children and adolescents with extreme obesity and 436 controls. Detected variants were also analyzed in vitro to determine their effects on MC4R signaling: p.Gln174Arg was the only variant to show an effect by reducing MC4R signalling function. Heterozygous variants were described in 4 individuals. For only two (p.Ala137Thr and p.Arg125His) were relatives also available, and the mothers of the probands were also heterozygous and had not/did not display an obesity phenotype. \"In sum, our family-based genetic data do not support the relevance of the two presumably benign MRAP2 mutations for the development of obesity, they might even have no influence on body weight regulation...additional functional analyses could well reveal a functional effect of all nonsynonymous MRAP2 mutations.\" \"We detected association of nonsynonymous MRAP2 mutations to obesity (eight carriers of nonsynonymous mutations in 1,334 individuals with obesity vs. zero carriers of nonsynonymous mutations in 1,108 controls, nominal Fisher’ exact two-sided P<0.005) in a crude meta-analysis on all currently available data.\"","26795956 - a rare nonsynonymous variant, p.A40S, was detected in the MRAP2 gene in a 10-year old boy with overall obesity in combination with intellectual disability in a screen of Prader-Willi syndrome (PWS) patients. The clinically diagnosed PWS could not be confirmed molecularly with MS-MLPA and CNV analysis of the 6q14.1–q16.3 region also showed no deletions in this patient. No further family data were available to determine whether the variant segregates with obesity in this family. It was shown to be (probably) damaging by in silico analysis and found in only one European (non-Finnish) individual in the ExAC database (since this database cannot release phenotype information about the screened individuals, no conclusions regarding causality of this variant can be drawn)."],"evidence":["Expert list","Expert Review Red","Expert Review"],"phenotypes":["obesity","{?Obesity, susceptibility to, BMIQ18}","Prader-Willi syndrome"],"mode_of_inheritance":"MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","tags":[],"panel":{"id":130,"hash_id":"55d2fc2d22c1fc2cc6635960","name":"Severe early-onset obesity","disease_group":"Endocrine disorders","disease_sub_group":"Obesity syndromes","status":"public","version":"2.0","version_created":"2019-09-23T12:02:23.516332Z","relevant_disorders":["Significant early-onset obesity with or without other endocrine features and short stature","Significant early-onset obesity +/- other endocrine features and short stature","R149"],"stats":{"number_of_genes":39,"number_of_strs":0,"number_of_regions":3},"types":[{"name":"Rare Disease 100K","slug":"rare-disease-100k","description":"Rare Disease 100K"},{"name":"GMS Rare Disease Virtual","slug":"gms-rare-disease-virtual","description":"This is a panel for the Genomic Medicine Service for an exome/genome/panel based test that requires a virtual gene panel for rare disease in the Test Directory."},{"name":"GMS Rare Disease","slug":"gms-rare-disease","description":"This panel type is used for GMS panels that are not virtual (i.e. could be a wet lab test)"},{"name":"GMS signed-off","slug":"gms-signed-off","description":"This panel has undergone review by a NHSE GMS disease specialist group and processes to be signed-off for use within the GMS."}]}}]}