PUBLICATION
Novel MC1R variants cause red hair and lighter skin colour
- Authors
- Kashyap, D.K., Agrawal, S.J., Karthikeyan, M., Biradar, D., Ramesh, E., Subramanian, K., Kumar, L., Chorol, U., Bandopadhyay, A., Vasanthakumar, A., Pasupuleti, N., Jayavelu, T., Mahato, A.K., Govindaraj, P., Chaubey, G., Kahali, B., Natarajan, V.T., Thangaraj, K.
- ID
- ZDB-PUB-260406-2
- Date
- 2026
- Source
- HGG advances : 100603 (Journal)
- Registered Authors
- Natarajan, Vivek T
- Keywords
- none
- MeSH Terms
- none
- PubMed
- 41935955 Full text @ HGG Adv
Citation
Kashyap, D.K., Agrawal, S.J., Karthikeyan, M., Biradar, D., Ramesh, E., Subramanian, K., Kumar, L., Chorol, U., Bandopadhyay, A., Vasanthakumar, A., Pasupuleti, N., Jayavelu, T., Mahato, A.K., Govindaraj, P., Chaubey, G., Kahali, B., Natarajan, V.T., Thangaraj, K. (2026) Novel MC1R variants cause red hair and lighter skin colour. HGG advances. :100603.
Abstract
The melanocortin 1 receptor (MC1R) is one of the fundamental proteins to regulate the skin and hair colour in mammals. In India, the red hair colour (RHC) phenotype is extremely rare. We analysed MC1R and identified an ultra-rare pathogenic variant, p.Ala291Asp, which is responsible for the RHC phenotype in an Indian child. Further, we screened the complete coding region of MC1R in a total of 11,021 individuals, representing 91 distinct Indian populations across India and found a total of 21 novel or ultra-rare variants. In silico, in vitro, and Zebrafish-based functional analysis showed that p.Gly248Cys and p.Ala291Asp variants lead to loss of function (LOF) effects. The distribution of some of these variants differed significantly among Indian populations. One of them is MC1R c.-226 A>T (rs3212363), which is significantly associated with lighter skin pigmentation in the Bodh population inhabited in Ladakh. On average, TT homozygotes were 8.46 melanin units lighter compared with AA homozygotes (95% CI 3.211 to 13.72; adjusted p = 0.0005). Our study identifies and functionally validates ultra-rare MC1R variants as potential causes of RHC phenotype in Indians.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping