Genotype-phenotype associations and human eye color

J Hum Genet. 2011 Jan;56(1):5-7. doi: 10.1038/jhg.2010.126. Epub 2010 Oct 14.


Although eye color is usually modeled as a simple, Mendelian trait, further research and observation has indicated that eye color does not follow the classical paths of inheritance. Eye color phenotypes demonstrate both epistasis and incomplete dominance. Although there are about 16 different genes responsible for eye color, it is mostly attributed to two adjacent genes on chromosome 15, hect domain and RCC1-like domain-containing protein 2 (HERC2) and ocular albinism (that is, oculocutaneous albinism II (OCA2)). An intron in HERC2 contains the promoter region for OCA2, affecting its expression. Therefore, single-nucleotide polymorphisms in either of these two genes have a large role in the eye color of an individual. Furthermore, with all genetic expression, aberration also occurs. Some individuals may express two phenotypes--one in each eye--or a complete lack of pigmentation, ocular albinism. In addition, the evolutionary and population roles of the different expressions are significant.

Publication types

  • Review

MeSH terms

  • Albinism, Oculocutaneous / genetics
  • Eye Color / genetics*
  • Genetic Association Studies*
  • Guanine Nucleotide Exchange Factors / genetics
  • Humans
  • Polymorphism, Single Nucleotide*
  • Ubiquitin-Protein Ligases


  • Guanine Nucleotide Exchange Factors
  • HERC2 protein, human
  • Ubiquitin-Protein Ligases

Supplementary concepts

  • Oculocutaneous albinism type 2