MRAP2
Chr 6ADmelanocortin 2 receptor accessory protein 2
The protein modulates melanocortin receptor 4 (MC4R) signaling, which controls energy homeostasis and body weight regulation by increasing the receptor's ligand sensitivity and cAMP generation. Mutations cause severe early-onset obesity through disrupted energy balance. The gene shows tolerance to loss-of-function variants (low constraint), and inheritance pattern has not been definitively established in the limited reported cases.
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports dominant-negative. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MRAP2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Intensive Weight Loss Intervention Versus Usual Care for Adults With Obesity
ACTIVE NOT RECRUITINGIntensive Weight Loss Intervention Versus Bariatric Surgery for Adults With Severe and Complex Obesity: the LightBAR Randomised Trial
RECRUITINGIntensive Weight Loss Intervention Versus Usual Care for Adults With Severe and Complex Obesity
RECRUITINGExercise to Fight Obesity
RECRUITINGExternal Resources
Links to major genomics databases and tools