SLC45A2 is a transporter protein that mediates melanin synthesis. SLC45A2 is also a melanocyte differentiation antigen that is expressed in a high percentage of melanoma cell lines. A similar sequence gene in medaka fish, 'B,' encodes a transporter that mediates melanin synthesis. Mutations in this gene are a cause of oculocutaneous albinism type 4. Alternative splicing results in multiple transcript variants encoding different isoforms. Protein expression is localized to the melanosome, and analysis of the by knockdown of RNA expression leads to altered melanosome pH potentially altering tyrosinase function by affecting copper binding.
SLC45A2 has been found to play a role in pigmentation in several species. In humans, it has been identified as a factor in the light skin of Europeans and as an ancestry-informative marker (AIM) for distinguishing Sri Lankan from European ancestry. SLC45A2 is the so-called cream gene responsible in horses for buckskin, palomino and cremello coloration, while a mutation in this gene underlies the white tiger variant. In dogs a mutation to this gene causes white fur, pink skin, and blue eyes. SLC45A2 was identified as a melanoma tumor-associated antigen with high tumor specificity and reduced potential for autoimmune toxicity, and is currently in clinical development as a target for T-cell based immunotherapy.
^Nakayama K, Fukamachi S, Kimura H, Koda Y, Soemantri A, Ishida T (Mar 2002). "Distinctive distribution of AIM1 polymorphism among major human populations with different skin color". Journal of Human Genetics. 47 (2): 92–4. doi:10.1007/s100380200007. PMID11916009.
^Du J, Fisher DE (January 2002). "Identification of Aim-1 as the underwhite mouse mutant and its transcriptional regulation by MITF". The Journal of Biological Chemistry. 277 (1): 402–6. doi:10.1074/jbc.M110229200. PMID11700328.
^Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, et al. (December 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID19067971.
^Soejima M, Koda Y (January 2007). "Population differences of two coding SNPs in pigmentation-related genes SLC24A5 and SLC45A2". International Journal of Legal Medicine. 121 (1): 36–9. doi:10.1007/s00414-006-0112-z. PMID16847698.
^Wijesena HR, Schmutz SM (May–June 2015). "A Missense Mutation in SLC45A2 Is Associated with Albinism in Several Small Long Haired Dog Breeds". The Journal of Heredity. 106 (3): 285–8. doi:10.1093/jhered/esv008. PMID25790827.
Fukamachi S, Shimada A, Shima A (August 2001). "Mutations in the gene encoding B, a novel transporter protein, reduce melanin content in medaka". Nature Genetics. 28 (4): 381–5. doi:10.1038/ng584. PMID11479596.
Rundshagen U, Zühlke C, Opitz S, Schwinger E, Käsmann-Kellner B (February 2004). "Mutations in the MATP gene in five German patients affected by oculocutaneous albinism type 4". Human Mutation. 23 (2): 106–10. doi:10.1002/humu.10311. PMID14722913.
Yuasa I, Umetsu K, Watanabe G, Nakamura H, Endoh M, Irizawa Y (December 2004). "MATP polymorphisms in Germans and Japanese: the L374F mutation as a population marker for Caucasoids". International Journal of Legal Medicine. 118 (6): 364–6. doi:10.1007/s00414-004-0490-z. PMID15455243.
Suzuki T, Inagaki K, Fukai K, Obana A, Lee ST, Tomita Y (January 2005). "A Korean case of oculocutaneous albinism type IV caused by a D157N mutation in the MATP gene". The British Journal of Dermatology. 152 (1): 174–5. doi:10.1111/j.1365-2133.2005.06403.x. PMID15656822.
Graf J, Hodgson R, van Daal A (March 2005). "Single nucleotide polymorphisms in the MATP gene are associated with normal human pigmentation variation". Human Mutation. 25 (3): 278–84. doi:10.1002/humu.20143. PMID15714523.
Soejima M, Koda Y (January 2007). "Population differences of two coding SNPs in pigmentation-related genes SLC24A5 and SLC45A2". International Journal of Legal Medicine. 121 (1): 36–9. doi:10.1007/s00414-006-0112-z. PMID16847698.
Lezirovitz K, Nicastro FS, Pardono E, Abreu-Silva RS, Batissoco AC, Neustein I, et al. (2006). "Is autosomal recessive deafness associated with oculocutaneous albinism a "coincidence syndrome"?". Journal of Human Genetics. 51 (8): 716–20. doi:10.1007/s10038-006-0003-7. PMID16868655.
Chi A, Valencia JC, Hu ZZ, Watabe H, Yamaguchi H, Mangini NJ, et al. (November 2006). "Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes". Journal of Proteome Research. 5 (11): 3135–44. doi:10.1021/pr060363j. PMID17081065.
Zühlke C, Criée C, Gemoll T, Schillinger T, Kaesmann-Kellner B (June 2007). "Polymorphisms in the genes for oculocutaneous albinism type 1 and type 4 in the German population". Pigment Cell Research. 20 (3): 225–7. doi:10.1111/j.1600-0749.2007.00377.x. PMID17516931.
Sengupta M, Chaki M, Arti N, Ray K (August 2007). "SLC45A2 variations in Indian oculocutaneous albinism patients". Molecular Vision. 13: 1406–11. PMID17768386.