MC2R

Chr 18AR

melanocortin 2 receptor

Also known as: ACTHR

The melanocortin 2 receptor (MC2R) is a G protein-coupled receptor that responds specifically to adrenocorticotropic hormone (ACTH) and regulates adrenocortical function by stimulating cortisol and corticosterone release from the adrenal cortex. Mutations cause familial glucocorticoid deficiency due to ACTH unresponsiveness, presenting with adrenal insufficiency that can manifest in the neonatal period since MC2R is required for normal fetal and neonatal adrenal gland development. This condition follows autosomal recessive inheritance.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.851 OMIM phenotype
Clinical SummaryMC2R
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — MC2R
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.85LOEUF
pLI 0.000
Z-score -0.16
OE 1.08 (0.551.85)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.01Z-score
OE missense 1.00 (0.881.13)
174 obs / 174.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.08 (0.551.85)
00.351.4
Missense OE1.00 (0.881.13)
00.61.4
Synonymous OE1.15
01.21.6
LoF obs/exp: 5 / 4.6Missense obs/exp: 174 / 174.2Syn Z: -1.04
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMC2R-related glucocorticoid deficiencyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7325th %ile
GOF
0.77top 25%
LOF
0.2678th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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