Alternative titles; symbols
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 5p13.2 | [Skin/hair/eye pigmentation 5, dark/light eyes] | 227240 | Autosomal recessive | 3 | SLC45A2 | 606202 |
| 5p13.2 | [Skin/hair/eye pigmentation 5, dark/fair skin] | 227240 | Autosomal recessive | 3 | SLC45A2 | 606202 |
| 5p13.2 | [Skin/hair/eye pigmentation 5, black/nonblack hair] | 227240 | Autosomal recessive | 3 | SLC45A2 | 606202 |
A number sign (#) is used with this entry because of evidence that variation in the SLC45A2 gene (606202) influences skin, hair, and eye pigmentation.
For a general phenotypic description and a discussion of genetic heterogeneity of variation in skin, hair, and eye pigmentation, see 227220.
Graf et al. (2005) demonstrated a highly significant association of polymorphisms in the MATP gene (SLC45A2; 606202) with normal variation in human pigmentation. Studying Caucasians, Asians, African Americans, and Australian Aborigines, they found associations particularly with 2 polymorphisms, G272K (606202.0007) and F374L (606202.0008). The 2 alleles, leu374 and lys272, were associated with dark hair, skin, and eye color in Caucasians. The odds ratios of the leu/leu genotype for black hair and olive skin were 25.63 and 28.65, respectively, and for the lys/lys genotype were 43.23 and 8.27, respectively. The odds ratio for eye color was lower at 3.48 for leu/leu and 6.57 for lys/lys genotypes.
Stokowski et al. (2007) demonstrated an association between the SNP {dbSNP 16891982} (F374L; 606202.0008) and skin pigmentation variation in individuals of South Asian descent.
Stacey et al. (2009) confirmed association of the SNP {dbSNP 16891982} (L374F) with fair pigmentation using samples from Iceland, eastern Europe, Spain, and the United States, observing strong association with all traits except red hair and freckles. Stacey et al. (2009) found that this variant was associated with risk of both basal cell carcinoma (BCC; see 605462) and squamous cell carcinoma (odds ratio = 1.97, P = 1.6 x 10(-12) for BCC) in 3,326 basal cell carcinoma cases and 5,493 controls of European ancestry.
Graf et al. (2007) examined the association between normal skin color variation in several populations and 3 different promoter polymorphisms in the MATP gene: -1721C-G (rs13289), -1169G-A (rs6867641), and a 3-bp duplication, -1174dupAAT. In Caucasian samples, -1721C-G and -1174dupAAT were in complete linkage disequilibrium. In Caucasians only, the -1721G, -1169A, and +dup alleles were significantly associated with olive skin color. Functional analysis in melanoma skin cells showed that this promoter haplotype decreased MATP transcription, suggesting a functional significance.
Graf, J., Hodgson, R., van Daal, A. Single nucleotide polymorphisms in the MATP gene are associated with normal human pigmentation variation. Hum. Mutat. 25: 278-284, 2005. [PubMed: 15714523] [Full Text: https://doi.org/10.1002/humu.20143]
Graf, J., Voisey, J., Hughes, I., van Daal, A. Promoter polymorphisms in the MATP (SLC45A2) gene are associated with normal human skin color variation. Hum. Mutat. 28: 710-717, 2007. [PubMed: 17358008] [Full Text: https://doi.org/10.1002/humu.20504]
Stacey, S. N., Sulem, P., Masson, G., Gudjonsson, S. A., Thorleifsson, G., Jakobsdottir, M., Sigurdsson, A., Gudjartsson, D. F., Sigurgeirsson, B., Benediktsdottir, K. R., Thorisdottir, K., Ragnarsson, R., and 52 others. New common variants affecting susceptibility to basal cell carcinoma. Nature Genet. 41: 909-914, 2009. [PubMed: 19578363] [Full Text: https://doi.org/10.1038/ng.412]
Stokowski, R. P., Pant, P. V. K., Dadd, T., Fereday, A., Hinds, D. A., Jarman, C., Filsell, W., Ginger, R. S., Green, M. R., van der Ouderaa, F. J., Cox, D. R. A genomewide association study of skin pigmentation in a South Asian population. Am. J. Hum. Genet. 81: 1119-1132, 2007. [PubMed: 17999355] [Full Text: https://doi.org/10.1086/522235]