ArticleGenome research2012
HERC2 rs12913832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter.
Article in Genome research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers, 7 of them syntheses that pooled it.
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Who cites it
157 citing papers in PubMed, 7 syntheses or guidelines pooled it, 282 citations in OpenAlex.
- GWAS meta-analysis provides new insights into uveal melanoma risk.British journal of cancer · 2026Pooled it
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
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- Meta-analysis of GWA studies provides new insights on the genetic architecture of skin pigmentation in recently admixed populations.BMC genetics · 2019Pooled it
- A Genome-Wide Association Study of Skin and Iris Pigmentation among Individuals of South Asian Ancestry.Genome biology and evolution · 2019Pooled it
- Genetic association and meta-analysis of a schizophrenia GWAS variant rs10489202 in East Asian populations.Translational psychiatry · 2018Pooled it
- Meta-analysis of genome-wide association studies identifies 8 novel loci involved in shape variation of human head hair.Human molecular genetics · 2018Pooled it
- GenoEye: A machine learning-based framework for the prediction of intermediate eye color phenotypes.Journal of forensic sciences · 2026Article
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- Multi-omics analysis of HLTF context-dependent regulation across TCGA cohorts revealed its potential as new biomarker in tumour.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- A regulatory 24-bp insertion at the BCO2 gene region is associated with yellow skin in chickens.Genetics, selection, evolution : GSE · 2026Article
- Evolutionary Origin of Ocular Melanoma: Associations With rs12913832 G Allele Frequency and Latitude.Cancer medicine · 2026Observational
- Haplotype-Based Analysis of OCA2 Variants in Oculocutaneous Albinism.Pigment cell & melanoma research · 2026Article
- A comparative GWAS of eye colour in light and dark eye genetic backgrounds defined by HERC2 rs12913832 polymorphism in a Canadian cohort of European ancestry.Scientific reports · 2026Article
- Genetic Background Predicts Uveal Melanoma Patients' Outcomes.Ophthalmology science · 2026Article
- Review
- Genetics of Skin, Hair, and Eye Color in Human Pigmentation Disorders.Annals of human genetics · 2025Review
- The Genetics and Evolution of Human Pigmentation.Biology · 2025Review
- Reprogramming of endolysosomes for melanogenesis in BLOC-1-deficient melanocytes.Current biology : CB · 2025Article
- Mapping chromatin interactions at melanoma susceptibility loci uncovers distant cis-regulatory gene targets.American journal of human genetics · 2025Article
97 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pigmentation of skin, eye, and hair reflects some of the most evident common phenotypes in humans. Several candidate genes for human pigmentation are identified. The SNP rs12913832 has strong statistical association with human pigmentation. It is located within an intron of the nonpigment gene HERC2, 21 kb upstream of the pigment gene OCA2, and the region surrounding rs12913832 is highly conserved among animal species. However, the exact functional role of HERC2 rs12913832 in human pigmentation is unknown. Here we demonstrate that the HERC2 rs12913832 region functions as an enhancer regulating OCA2 transcription. In darkly pigmented human melanocytes carrying the rs12913832 T-allele, we detected binding of the transcription factors HLTF, LEF1, and MITF to the HERC2 rs12913832 enhancer, and a long-range chromatin loop between this enhancer and the OCA2 promoter that leads to elevated OCA2 expression. In contrast, in lightly pigmented melanocytes carrying the rs12913832 C-allele, chromatin-loop formation, transcription factor recruitment, and OCA2 expression are all reduced. Hence, we demonstrate that allelic variation of a common noncoding SNP located in a distal regulatory element not only disrupts the regulatory potential of this element but also affects its interaction with the relevant promoter. We provide the key mechanistic insight that allele-dependent differences in chromatin-loop formation (i.e., structural differences in the folding of gene loci) result in differences in allelic gene expression that affects common phenotypic traits. This concept is highly relevant for future studies aiming to unveil the functional basis of genetically determined phenotypes, including diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.