|Coordinate||56,295,460 bp (GRCm38)|
|Base Change||T ⇒ C (forward strand)|
|Gene Name||oculocutaneous albinism II|
|Synonym(s)||D7H15S12, p, D7H15S12|
|Chromosomal Location||56,239,760-56,536,518 bp (+)|
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the human homolog of the mouse p (pink-eyed dilution) gene. The encoded protein is believed to be an integral membrane protein involved in small molecule transport, specifically tyrosine, which is a precursor to melanin synthesis. It is involved in mammalian pigmentation, where it may control skin color variation and act as a determinant of brown or blue eye color. Mutations in this gene result in type 2 oculocutaneous albinism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
PHENOTYPE: Mutations generally result in varying degrees of coat and eye pigment dilution. Specific alleles produce cleft palate, reproductive, endocrine or neurological disorders, and/or lethality. [provided by MGI curators]
|Amino Acid Change||Valine changed to Alanine|
|Institutional Source||Beutler Lab|
|Gene Model||predicted gene model for protein(s): [ENSMUSP00000032633] [ENSMUSP00000119529] [ENSMUSP00000119099]|
AA Change: V272A
|Predicted Effect||possibly damaging
PolyPhen 2 Score 0.819 (Sensitivity: 0.84; Specificity: 0.93)
|Predicted Effect||probably benign|
AA Change: V272A
|Predicted Effect||probably damaging
PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
|Meta Mutation Damage Score||0.64|
|Is this an essential gene?||Possibly nonessential (E-score: 0.317)|
|Candidate Explorer Status||CE: excellent candidate; human score: 0; ML prob: 0.578|
Linkage Analysis Data
|Alleles Listed at MGI|
All mutations/alleles(90) : Chemically and radiation induced(3) Chemically induced (ENU)(12) Chemically induced (other)(1) Gene trapped(1) Radiation induced(49) Spontaneous(20) Targeted(3) Transgenic(1)
|Mode of Inheritance||Autosomal Recessive|
|Local Stock||Live Mice|
|Last Updated||2018-04-04 5:43 PM by Emre Turer|
|Record Created||2017-04-06 7:23 AM by Carlos Reyna|
The hardy phenotype was identified among N-ethyl-N-nitrosourea (ENU)-induced G3 mice of the pedigree R5430, some of which exhibited a light gray coat (Figure 1). Some mice also showed susceptibility to dextran sulfate sodium (DSS)-induced colitis at day 7 post-DSS treatment (Figure 2).
|Nature of Mutation|
Whole exome HiSeq sequencing of the G1 grandsire identified 54 mutations. Both of the above phenotypes were linked to two mutations on chromosome 7: Syt3 and Oca2. The mutation in Oca2 was presumed causative as the hardy hypopigmentation phenotype mimics other known alleles of Oca2 (see MGI for a list of Oca2 alleles as well as the Beutler Oca2 alleles: quicksilver, faded, charbon, draco1, snowflake, and whitemouse). The Oca2 mutation in hardy is a T to C transition at base pair 56,295,460 (v38) on chromosome 7, or base pair 55,868 in the GenBank genomic region NC_000073 encoding Oca2. The strongest association was found with a recessive model of inheritance to the pigmentation phenotype (P = 1.62 x 10-6), wherein five affected mice were homozygous for the variant allele, and 31 unaffected mice were either heterozygous (N = 14) or homozygous for the reference allele (N = 17) (Figure 3).
The mutation corresponds to residue 945 in the NM_021879 mRNA sequence in exon 8 of 24 total exons.
The mutated nucleotide is indicated in red. The mutation results in a valine to alanine substitution at residue 272 in the OCA2 protein.
OCA2 is a 110-kDa twelve transmembrane-spanning protein that exhibits homology to a number of bacterial transporters (1). The exact function of OCA2 in melanocytes is unknown. The hardy mutation occurs in the loop between the first and second transmembrane domains of the OCA2 protein. Protein expression and localization of OCA2 has not been examined in the draco1 mice.
Please see the record quicksilver for information about Oca2.
Mutations in Oca2 are known to cause a variable reduction of eumelanin (black-brown) pigment and altered morphology of black pigment granules (eumelanosomes), but have little effect on pheomelanin (yellow-red) pigment (2;3). For example, mice with null alleles of Oca2 have very little to no eumelanin in their coat and eyes, resulting in a hypopigmentation phenotype: light grey fur with pink eyes on a nonagouti background (e.g., C57BL/6J), and cream-colored mice on an agouti background (4;5). The null mice have a reduced number of very small eumelanosomes in pigmented tissue with a concomitant decrease in the expression levels of melanosomal proteins (e.g., tyrosinase; see the record for ghost). The light coat color of hardy mice suggests a reduced function of the OCA2 protein in these animals.
hardy(F):5'- ATCAGTTGGCATTCCTCACC -3'
hardy(R):5'- CCGGTGCCAAGATGTTGTTG -3'
hardy_seq(F):5'- CCACAGGTTCTACATTCAAGGATTAG -3'
hardy_seq(R):5'- GTGCTATCAGACTTCTCCAGAAACTG -3'
1. Lee, S. T., Nicholls, R. D., Jong, M. T., Fukai, K., and Spritz, R. A. (1995) Organization and Sequence of the Human P Gene and Identification of a New Family of Transport Proteins. Genomics. 26, 354-363.
2. Rinchik, E. M., Bultman, S. J., Horsthemke, B., Lee, S. T., Strunk, K. M., Spritz, R. A., Avidano, K. M., Jong, M. T., and Nicholls, R. D. (1993) A Gene for the Mouse Pink-Eyed Dilution Locus and for Human Type II Oculocutaneous Albinism. Nature. 361, 72-76.
3. RUSSELL, E. S. (1949) A Quantitative Histological Study of the Pigment found in the Coat-Color Mutants of the House Mouse; the Nature of the Effects of Genic Substitution in Five Major Allelic Series. Genetics. 34, 146-166.
4. Silvers, W. K. (Ed.) (1979) The Coat Colors of Mice: a Model for Mammalian Gene Action and Interaction. Springer-Verlag.
|Science Writers||Anne Murray|
|Illustrators||Diantha La Vine|
|Authors||Carlos Reyna, Jamie Russell, and Bruce Beutler|