MC2R

Chr 18AR

melanocortin 2 receptor

Also known as: ACTHR

NCBI Gene: 4158ENSG00000185231UniProt: Q01718OMIM: 607397

MC2R encodes one member of the five-member G-protein associated melanocortin receptor family. Melanocortins (melanocyte-stimulating hormones and adrenocorticotropic hormone) are peptides derived from pro-opiomelanocortin (POMC). MC2R is selectively activated by adrenocorticotropic hormone, whereas the other four melanocortin receptors recognize a variety of melanocortin ligands. Mutations in MC2R can result in familial glucocorticoid deficiency. Alternate transcript variants have been found for this gene. [provided by RefSeq, May 2014]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Glucocorticoid deficiency, due to ACTH unresponsivenessMIM #202200
AR

Clinical highlights

Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
41
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
1.85
LOEUF
LOF
Mechanism· G2P
📖
GeneReview available — MC2R
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
1.85LOEUF
pLI 0.000
Z-score -0.16
OE 1.08 (0.55–1.85)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.01Z-score
OE missense 1.00 (0.88–1.13)
174 obs / 174.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?1.08 (0.55–1.85)
0≤0.351.4
Missense OE?1.00 (0.88–1.13)
0≤0.61.4
Synonymous OE?1.15
0≤1.21.6
LoF obs/exp: 5 / 4.6Missense obs/exp: 174 / 174.2Syn Z: -1.04

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

MC2R · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients