Human pigmentation phenotype: a point mutation generates nonfunctional MSH receptor.
Frändberg. P A PA; Doufexis. M M; Kapas. S S; Chhájlani. V V
Key Findings
- The Arg151Cys variant of MC1R was found in a person with red hair and type I skin.
- The mutant receptor binds alpha‑MSH (or its analog) just as well as the normal receptor.
- Despite binding, the Arg151Cys receptor cannot generate cAMP, rendering it completely nonfunctional.
Practical Outcomes
- If you carry the Arg151Cys MC1R mutation, melanotan‑I is unlikely to boost your skin pigmentation. Genetic testing can identify non‑responders before you invest in peptide protocols, saving time and money.
Summary
A single genetic change (Arg151Cys) in the skin’s pigment receptor (MC1R) makes it bind the hormone but unable to signal, causing red hair, very fair skin, and poor tanning. This means that people with this mutation won’t respond to melanotan‑I or similar tanning peptides.
Abstract
alpha-Melanocyte stimulating hormone (alpha-MSH) regulates skin and hair pigmentation by modulating the activity of MSH receptor (MC1R). We have identified Arg151Cys variant of human MC1R in genomic DNA isolated from a person with red hair and light skin of type I. The Arg151Cys variant of MC1R binds to radio-labelled analogue of alpha-MSH with identical affinity as wild type MC1R but can not be stimulated to produce cyclic AMP (cAMP). The mutation Arg151Cys renders human MC1R completely nonfunctional, which explains the red hair, light skin and poor tanning ability (skin type I). This is the first report ever describing a nonfunctional MC1R isolated from a human subject.
Study Information
pubmed
1998
1998-04-17T00:00:00.000Z
10.1006/bbrc.1998.8459