rs642742

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This is a intergenic variant variant in the KITLG gene.

Key Literature Trait Associations

Skin Pigmentation

The A allele at rs642742, located ~350 kb upstream of KITLG (KIT ligand/stem cell factor), is strongly associated with lighter skin pigmentation. KITLG encodes a signaling molecule critical for melanocyte development, survival, and migration; reduced regulatory activity at this locus decreases melanin production. This variant was identified by Miller et al. (2007) with independent replication in multiple populations as one of the strongest known pigmentation loci outside of MC1R and SLC24A5.

Sulem P et al. “Genetic determinants of hair, eye and skin pigmentation in Europeans.” Nature Genetics 39(12):1443-1452 (2007)

Allele A

OR —

p —

N 6,918

Preliminary work

European

Kelly CR et al. “Repeated exposure to media violence is associated with diminished response in an inhibitory frontolimbic network.” Plos One 2(12):e1268 (2007)

Allele A

OR —

p 9.0e-15

Large GWAS

Jonnalagadda M et al. “Association of genetic variants with skin pigmentation phenotype among populations of west Maharashtra, India.” American Journal of Human Biology : the Official Journal of the Human Biology Council (2016)

Allele A

OR —

p —

N 533

Preliminary work

South Asian

Liu J et al. “Skin colour: A window into human phenotypic evolution and environmental adaptation.” Molecular Ecology (2024)

Allele A

OR —

p —

Candidate gene study

multi-ancestry

Perez Palomeque G et al. “Prediction of Skin Color Using Forensic DNA Phenotyping in Asian Populations: A Focus on Thailand.” Biomolecules (2025)

Allele A

OR —

p —

Candidate gene study

East Asian

Beleza S et al. “The timing of pigmentation lightening in Europeans.” Molecular Biology and Evolution (2013)

Allele A

OR —

p —

Candidate gene study

multi-ancestry

Hair color

A variant at the KITLG locus on chromosome 12q21 was identified in a genome-wide association study of 2,986 Icelanders as significantly associated with hair color in Europeans. The KITLG regulatory region harbors multiple pigmentation variants; rs12821256 (a distinct SNP 355 kb upstream of KITLG) has been functionally validated as reducing KITLG expression by ~21% and contributing to blond hair in northern Europeans. rs642742 represents a marker of this same pigmentation-relevant locus, and the shared selection sweep at KITLG across European and East Asian populations is consistent with a role in hair as well as skin lightening.

Sulem P et al. “Genetic determinants of hair, eye and skin pigmentation in Europeans.” Nature Genetics 39(12):1443-1452 (2007)

Allele T

OR —

p —

N 6,918

Preliminary work

European

Guenther CA et al. “A molecular basis for classic blond hair color in Europeans.” Nature Genetics 46(7):748-752 (2014)

Allele T

OR —

p 5.0e-9

Large GWAS

European

Height

rs642742-T was identified as one of hundreds of common variants associated with standing height in the largest GWAS of human height to date (n=5,314,291, multi-ancestry). The effect size is very small (beta ≈ 0.006 SD units, approximately 0.04 cm per allele), which is typical for the polygenic architecture of height. While the association is highly statistically significant due to the enormous sample size, the per-variant contribution is clinically negligible.

Yengo L et al. “A saturated map of common genetic variants associated with human height.” Nature 610(7933):704-712 (2022)

Allele T

OR —

β -0.006 ±0.001

p 5.0e-11

N 5,314,291

Large GWAS

multi-ancestry

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GWAS Catalog Trait Associations (1)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

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ClinVar annotation

affects

1 submitter1 publication

SKIN/HAIR/EYE PIGMENTATION 7, DARK/LIGHT SKIN

View on ClinVar →

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Research that mentions this SNP (2)

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Association of TGFβ1 and clinical factors with scar outcome following melanoma excision

AssociationN=202Ward SV et al.(2012)· Archives of Dermatological Research

Genetic association study of 202 melanoma patients examining SNPs in 24 candidate genes related to pigmentation and wound healing in relation to scar outcome. SNP rs8110090 in TGFβ1 was significantly associated with poorer scar outcomes (p=0.0002). Clinical factors including younger age, shorter time since surgery, and presence of infection or eczema were also associated with worse scarring.

Traits studied:Scar heightScar outcome following melanoma excisionScar vascularityWound healing

PubMed DOI Metascience Observatory

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The R402Q tyrosinase variant does not cause autosomal recessive ocular albinism

ReviewOetting WS et al.(2009)· American Journal of Medical Genetics Part A

Genome-wide association studies and comparative genomics have identified major pigmentation loci (SLC24A5, SLC45A2, TYR, OCA2, MC1R, IRF4, TPCN2) showing evidence of strong natural selection in human populations. Light skin variants in Europeans and Asians underwent complete or near-complete selective sweeps, with SLC24A5 rs1426654 and SLC45A2 variants representing independent evolutionary mechanisms. Critical skin-lightening variants arose 11,000-30,000 years ago during human demographic expansion, driven by UV radiation exposure, vitamin D synthesis requirements, and possibly sexual selection.

Traits studied:Basal cell carcinomaCutaneous melanomaEye colorHair colorMelanin contentOculocutaneous albinismPigmentationRed hairSkin color

rs642742

Key Literature Trait Associations

Skin Pigmentation

Hair color

Height

GWAS Catalog Trait Associations (1)

ClinVar annotation

Research that mentions this SNP (2)

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