rs1129038

This is a 3 prime utr variant variant in the HERC2 gene.

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GWAS Catalog Trait Associations (15)

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

eye color

Simcoe M et al. “Genome-wide association study in almost 195,000 individuals identifies 50 previously unidentified genetic loci for eye color.” Science Advances 7(11) (2021)
Allele T
OR 2.61
p —
N 157,485
Large GWAS
multi-ancestry
Farré X et al. “Skin Phototype and Disease: A Comprehensive Genetic Approach to Pigmentary Traits Pleiotropy Using PRS in the GCAT Cohort.” Genes 14(1) (2023)
Allele T
OR 0.98
p —
N 4,987
Large GWAS
European

macular degeneration

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele C
OR 0.17
p 1.0e-52
N 439,724
Major Consortium StudyLarge GWAS
European

hair color

Lona-Durazo F et al. “A large Canadian cohort provides insights into the genetic architecture of human hair colour.” Communications Biology 4(1):1253 (2021)
Allele C
OR 0.89
p 3.0e-52
N 10,990
Large GWAS
European

benign neoplasm of eye

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele C
OR 0.65
p 1.0e-22
N 121,190
Major Consortium StudyLarge GWAS
African American or Afro-Caribbean

Corneal astigmatism

Shah RL et al. “Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci.” Human Genetics 137(11-12):881-896 (2018)
Allele C
OR 0.03
p 1.0e-15
N 86,335
Major Consortium StudyLarge GWAS
European

age-related macular degeneration

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele C
OR 0.13
p 1.0e-14
N 442,030
Major Consortium StudyLarge GWAS
European

cataract

Sakaue S et al. “A cross-population atlas of genetic associations for 220 human phenotypes.” Nature Genetics 53(10):1415-1424 (2021)
Allele T
OR 0.08
p 2.0e-14
N 670,603
Large GWAS
multi-ancestry

conjunctivitis

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele C
OR 0.13
p 5.0e-12
N 437,072
Major Consortium StudyLarge GWAS
European

Uveal Melanoma

Mobuchon L et al. “Different Pigmentation Risk Loci for High-Risk Monosomy 3 and Low-Risk Disomy 3 Uveal Melanomas.” Journal of the National Cancer Institute 114(2):302-309 (2022)
Allele C
OR 0.56
p 6.0e-12
N 2,024
Large GWAS
European
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Research that mentions this SNP (4)

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A global view of the OCA2-HERC2 region and pigmentation
AssociationN=3,432Michael P. Donnelly et al.(2012)· Human Genetics

This global population study of 3,432 individuals from 73 populations examined 21 SNPs in the OCA2-HERC2 region associated with eye and skin pigmentation. Blue-eye associated haplotypes (BEH1, BEH2, BEH3) were found at high frequencies in Europe, with BEH2 showing the strongest signal of selection. The East Asian-specific missense SNP rs1800414 (His615Arg) was associated with lighter skin pigmentation and showed strong evidence of positive selection in East Asian populations.

Traits studied:Eye pigmentation (blue eyes)Eye pigmentation (green/hazel eyes)Skin pigmentation (light skin)
PubMedDOIMetascience Observatory
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Genotyping of five single nucleotide polymorphisms in the OCA2 and HERC2 genes associated with blue‐brown eye color in the Japanese population
AssociationN=523Reiko Iida et al.(2009)· Cell Biochemistry and Function

This study examined genotype and haplotype frequencies of five SNPs in the OCA2 and HERC2 genes (rs7495174, rs4778241, rs4778138, rs12913832, rs1129038) that are associated with blue-brown eye color variation in a Japanese population of 523 brown-eyed individuals. Significant differences in genotype and haplotype distributions were found compared to African and European populations, with the A-GAG haplotype being most frequent in Japanese (0.568) versus low in Europeans (0.167), and rs12913832 and rs1129038 being mono-allelic in the Japanese population.

Traits studied:Blue-brown eye colorBrown eye colorEye color
PubMedDOIMetascience Observatory
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Whole genome survey of coding SNPs reveals a reproducible pathway determinant of Parkinson disease
AssociationN=374Srinivasan BS et al.(2009)· Human Mutation

This whole genome association study of 374 Caucasians identified a reproducibly associated axon guidance pathway for Parkinson disease, with rs3770208 (EPHA4, log OR=0.5, p=0.0002) and rs9867325 (EPHA7, log OR=0.61, p=8.65e-05) showing the strongest SNP-level associations. Pathway-level analysis with controlled multiple testing revealed ubiquitin-mediated proteolysis (AUC=0.66, p=0.01), T-cell receptor signaling (AUC=0.59, p=0.04), and axon guidance (AUC=0.60, p=0.05) pathways predictive of PD susceptibility. The axon guidance pathway replicated in an independent PD study.

Traits studied:Idiopathic Parkinson diseaseParkinson disease
PubMedDOIMetascience Observatory
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Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression.
AssociationN=200Eiberg H et al.(2008)· Human genetics

This study identified a founder mutation in HERC2 intron 86 (rs12913832) that is perfectly associated with blue eye color. Through linkage analysis of a large Danish family and association studies in 155 blue-eyed and 45 brown-eyed individuals, the researchers mapped the blue eye color locus to a 166 Kbp region and demonstrated that rs12913832 (G allele) and rs1129038 (A allele) are perfectly associated with blue eyes (P = 6.12e-46). Functional studies showed this regulatory element significantly reduces OCA2 promoter activity through differential binding of transcription factors.

Traits studied:Blue eye colorBrown eye colorEye color variationHair color
PubMedDOIMetascience Observatory

About HERC2

This gene belongs to the HERC gene family that encodes a group of unusually large proteins, which contain multiple structural domains. All members have at least 1 copy of an N-terminal region showing homology to the cell cycle regulator RCC1 and a C-terminal HECT (homologous to E6-AP C terminus) domain found in a number of E3 ubiquitin protein ligases. Genetic variations in this gene are associated with skin/hair/eye pigmentation variability. Multiple pseudogenes of this gene are located on chromosomes 15 and 16. [provided by RefSeq, Mar 2012]

View all HERC2 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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