Obesity due to melanocortin 4 receptor deficiency: genes and variants
Obesity due to melanocortin 4 receptor deficiency is linked to 2 analyzed proteins (MC4R and PCSK1). 6 DNA variants are known to cause it; 2 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Obesity due to melanocortin 4 receptor deficiency
MC4R: Melanocortin receptor 4
Its melanocortin signaling in hypothalamic circuits suppresses appetite and helps regulate energy expenditure and body weight. Loss-of-function variants are the most common known cause of monogenic obesity and typically produce early hyperphagia.
6 disease-causing and 2 uncertain variants in MC4R are linked to Obesity due to melanocortin 4 receptor deficiency.
PCSK1: Neuroendocrine convertase 1
It activates numerous peptide hormones and neuropeptides by cleaving their precursor proteins in endocrine and neuroendocrine secretory granules. Biallelic loss-of-function variants can cause severe early-onset obesity, endocrine abnormalities, and malabsorptive diarrhea.
0 disease-causing and 0 uncertain variants in PCSK1 are linked to Obesity due to melanocortin 4 receptor deficiency.
Where Obesity due to melanocortin 4 receptor deficiency variants cluster
- MC4R Cytoplasmic (positions 146–166): 3 of 6 disease-causing changes, 7.9× more than its size predicts.
Known disease-causing variants in Obesity due to melanocortin 4 receptor deficiency
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| MC4R R165Q | 165 | Cytoplasmic | Disease-causing (★★★★) |
| MC4R R165G | 165 | Cytoplasmic | Disease-causing (★★★★) |
| MC4R R165W | 165 | Cytoplasmic | Disease-causing (★★★★) |
| MC4R C271Y | 271 | Extracellular | Disease-causing (★★★★) |
| MC4R I316S | 316 | Cytoplasmic | Disease-causing (★★) |
| MC4R N62S | 62 | Transmembrane | Disease-causing (★) |
Same protein, different disease
- Early onset severe obesity is also caused by MC4R variants; they fall mostly in different places as the Obesity due to melanocortin 4 receptor deficiency variants (9 disease-causing).
- BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 20 is also caused by MC4R variants; they fall mostly in different places as the Obesity due to melanocortin 4 receptor deficiency variants (8 disease-causing).
Diseases related to Obesity due to melanocortin 4 receptor deficiency
- BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 20, also linked to MC4R and PCSK1
- Type 2 diabetes mellitus, also linked to MC4R
- Early onset severe obesity, also linked to MC4R
- Obesity due to prohormone convertase I deficiency, also linked to PCSK1
Frequently asked questions
Which genes are linked to Obesity due to melanocortin 4 receptor deficiency?
In CATVariant, Obesity due to melanocortin 4 receptor deficiency is linked to 2 analyzed proteins: MC4R (Melanocortin receptor 4) and PCSK1 (Neuroendocrine convertase 1).
How many genetic variants are linked to Obesity due to melanocortin 4 receptor deficiency?
46 variants: 6 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 2 are of uncertain significance or have conflicting reports.
Which uncertain variants in Obesity due to melanocortin 4 receptor deficiency look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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