P gene mutations associated with oculocutaneous albinism type II (OCA2)

Hum Mutat. 2005 Mar;25(3):323. doi: 10.1002/humu.9318.


Oculocutaneous albinism type II (OCA2) is the most common form of albinism in humans. OCA2 has been previously associated with mutations of the P gene, the human homologue to the murine pink-eyed dilution gene. The P gene encodes a 110 kDa protein containing 12 potential membrane spanning domains and is associated with melanosomal membranes. The specific function of the P protein is currently unknown but is thought to be involved in tyrosinase processing and transport. We report nine novel mutations in the P gene associated with OCA2. These include two missense mutations, c.1938A>C (p.Ile646Val) and c.1556T>C (p.Val519Ala); one nonsense mutation c.612G>A (p.Trp204X); five frameshift mutations: c.2372_2373delTC, c.1555delG, c.1938_1939insC, c.2050delT, and c.1045_1046delAT; and a splice site mutation c.1951+1G>A. We also report 12 novel polymorphisms including one amino acid substitution, c.2365_2366GC>CA (p.Ala789Glu). At present, there is no functional assay to determine if a mutation is truly pathogenic. The presence of numerous polymorphisms of the P gene in the coding region, several of which result in amino acid substitutions, makes molecular diagnosis problematic. To ensure accurate molecular diagnosis, further mutational analysis will be necessary to produce a comprehensive list of mutations associated with OCA2. This information will also help define the critical functional domains of the P protein. Mutations associated with OCA2 can be found in the Albinism Database (http://albinismdb.med.umn.edu).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Albinism, Oculocutaneous / classification
  • Albinism, Oculocutaneous / diagnosis
  • Albinism, Oculocutaneous / ethnology
  • Albinism, Oculocutaneous / genetics*
  • Amino Acid Substitution
  • Asian People / genetics
  • Child, Preschool
  • Codon, Nonsense
  • DNA Mutational Analysis
  • Europe / ethnology
  • Exons / genetics
  • Eye Color / genetics
  • Female
  • Frameshift Mutation*
  • Genotype
  • Hair Color / genetics
  • Hispanic or Latino / genetics
  • Humans
  • Infant
  • Jews / genetics
  • Male
  • Membrane Transport Proteins / genetics*
  • Mutation, Missense*
  • Philippines / ethnology
  • Point Mutation*
  • Polymorphism, Genetic*
  • RNA Splice Sites / genetics*
  • Sequence Deletion*
  • White People / genetics


  • Codon, Nonsense
  • Membrane Transport Proteins
  • OCA2 protein, human
  • RNA Splice Sites