SLC45A2 (solute carrier family 45 member 2)

2019-01-01   Mainak Sengupta , Tithi Dutta , Kunal Ray 

University of Calcutta, Department of Genetics, 35, Ballygunge Circular Road, Kolkata - 700 019, India.; (MS, TD) ATGC Diagnostics Private Limited, Kolkata, India, (KR)


Atlas Image
SLC45A2 Gene in genomic location: Cytogenetic band: 5p13.2 by Entrez Gene, 5p13.2 by HGNC, 5p13.2. The figure represents the cytogenetic banding of SLC45A2 locus (Ref


SLC45A2 gene, having a chromosomal location 5p13.2, encodes a membrane associated transporter protein (MATP). MATP is a transmembrane protein. It is present in the melanosomal membrane in the melanocytes. It maintains the osmotic potential by regulating the pH of the melanosomal lumen. Defects in the SLC45A2 gene causes oculocutaneous albinism type IV; OCA IV



In Chromosome 5, the 40,529 bases of DNA starts from 33,944,616 and ends at 33,985,144(GRCh38/hg38). Orientation: Minus strand. It contains 7 exons.


The gene after transcription produces 7 different mRNAs, 6 alternatively spliced variants and 1 unspliced form. There are 4 non overlapping alternative last exons (



The human SLC45A2 protein is a 530-amino acid polypeptide that contains 12 putative trans-membrane domains, and is only expressed in the melanosomes in the melanocytes (Newton et al., 2001). The SLC45A2 gene initially identified as AIM1 (absent in melanoma 1) by Newton et al, 2001 encodes a Membrane-Associated Transporter Protein (MATP). It acts as a transporter and regulates the melanosomal pH using a proton gradient.


The MATP protein (58 kDa) is expressed in most melanoma cell lines and melanocytes and sorted into the melanosomal membrane. The highest expression level has been observed in the pigmented layer of retina (


It is a transmembrane protein present in the melanosomal membrane in melanin producing melanocytes.


SLC45A2 (MATP) allows the transport of sugar molecule across the membrane into the cytoplasm and maintains osmotic potential of the melanosomes (Rabea Bartolke, 2014, Reinders et al 2015). It maintains the pH of the melanosome which facilitates the binding of Copper to Tyrosinase resulting in the conversion of Apo-Tyrosinase to Tyrosinase. (Newton et al, 2011).
Atlas Image
The SLC45A2 (MATP) acts as a transporter present on the melanosomal membrane. Under normal condition it controls the pH by using a proton gradient. Thus helps in Copper to bind to Apo-Tyrosinase and convert it to active Tyrosinase. In oculocutaneous albinism type IV (OCA4), any deleterious mutation in melanosomal MATP transporter protein makes the melanosomal lumen acidic. Under this condition, the Cu fails to bind to the Apo-Tyr and Tyrosinase activity is reduced. (Bin et al, 2015).


The human MATP shows syntenic homology with the proximal region of mouse chromosome 15. The human orthologue for the mouse underwhite gene locus (uw gene) is encoded by SLC45A2 gene. The predicted mouse MATP protein is 82% identical and 87% similar to the human MATP protein.
The highest degree of homology was found between MATP and sucrose/proton symporters found in plants. The homologous region of MATP includes the sucrose-transporter signature sequence: R-X-G-R-[K/R], found in between the transmembrane domains 2 and 3 (Meyer H et al, 2011, Newton et al, 2011).
The sucrose transporter Slc45-1 in Drosophila shows significant similarity to mammalian SLC45A2 and plays a role in melanin synthesis.



Homozygous mutation or Compound Heterozygote mutations in SLC45A2 gene has been found responsible for causing Oculocutaneous Albinism Type 4 (OCA4). To date around 80 mutations have been reported in SLC45A2 responsible for OCA4. (Kamaraj et al. 2014, Toth et al. 2017). OCA4 was first observed in Turkish population, it is rare among Caucasians and Africans and in Japan it is diagnosed in one of four persons affected with OCA.

There are several non-pathogenic polymorphisms which result into mild pigmentation.

The haplotypes at SLC45A2 is significantly associated in determination of dark or light pigmentation features in human population. (Fracasso et al.2017)


In an attempt to identify genetic and epigenetic marks involved in population structure, a coding SNP: rs16891982 (p.L374F) of SLC45A2, known to play a role in normal pigmentation variation, was found to positively correlate with the methylation level of PM20D1 gene. The minor allele A was been found to be associated with lower methylation of the target gene. (

Implicated in

Entity name
Oculocutaneous albinism type IV (OCA IV)
OCA IV is an autosomal recessive disorder of melanin biosynthesis that results in congenital hypopigmentation of ocular and cutaneous tissues. Common developmental abnormalities of the eye like decreased visual acuity, macular hypoplasia, optic dysplasia, atypical choroidal vessels, and nystagmus are observed in patient suffering from OCA type IV. The severity of hypopigmentation is correlated with melanosome size, shape, melanin content and maturity of the melanosomal structures demonstrating that the encoded protein is a major determinant of mammalian pigmentation.
Entity name
n 2017, Park et al reported that a few variants present in SLC45A2 gene can be a promising immune therapeutic target for melanoma with high tumor selectivity and reduced potential for autoimmune toxicity. It is associated with an increased risk for melanoma in light-skinned populations, and the encoded protein can elicit immune recognition. The Cancer Genome Atlas Research Network (TCGA) database reported that it is expressed by approximately 80% of cutaneous melanomas. In the same year Hafner et al showed that SLC45A2 (also called AIM1, absent in melanoma 1) function as a key suppressor of invasive phenotypes by working in association with the actin cytoskeleton. SLC45A2 becomes dysregulated and suppresses cytoskeletal remodelling in primary and metastatic prostate cancer and in non-malignant prostate epithelial cells. In 2012, Fernandez et al reported in a family that adult siblings presented with congenital neutropenia which later developed into Crohns Disease. Molecular characterisation revealed homozygous mutations both in G6PC3 and SLC45A2 in the sister and mutation in single allele for both genes in the brother.


Pubmed IDLast YearTitleAuthors
251641492014Proton-associated sucrose transport of mammalian solute carrier family 45: an analysis in Saccharomyces cerevisiae.Bartölke R et al
260578902015Membrane-Associated Transporter Protein (MATP) Regulates Melanosomal pH and Influences Tyrosinase Activity.Bin BH et al
250931882014Mutational analysis of oculocutaneous albinism: a compact review.Kamaraj B et al
163572532005SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans.Lamason RL et al
215866092011Identification of an animal sucrose transporter.Meyer H et al
115749072001Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4.Newton JM et al
257606572015Investigating polymorphisms in membrane-associated transporter protein SLC45A2, using sucrose transporters as a model.Reinders A et al
282981932017Identification of two novel mutations in the SLC45A2 gene in a Hungarian pedigree affected by unusual OCA type 4.Tóth L et al

Other Information

Locus ID:

NCBI: 51151
MIM: 606202
HGNC: 16472
Ensembl: ENSG00000164175


dbSNP: 51151
ClinVar: 51151
TCGA: ENSG00000164175


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Metabolism of amino acids and derivativesREACTOMER-HSA-71291
Melanin biosynthesisREACTOMER-HSA-5662702


Pubmed IDYearTitleCitations
205856272010Web-based, participant-driven studies yield novel genetic associations for common traits.155
179993552007A genomewide association study of skin pigmentation in a South Asian population.90
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
115749072001Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4.78
193849532009Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians.67
193849532009Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians.67
197106842010Multiple pigmentation gene polymorphisms account for a substantial proportion of risk of cutaneous malignant melanoma.66
193400122009Genome-wide association study of tanning phenotype in a population of European ancestry.57
157145232005Single nucleotide polymorphisms in the MATP gene are associated with normal human pigmentation variation.51
157145232005Single nucleotide polymorphisms in the MATP gene are associated with normal human pigmentation variation.51


Mainak Sengupta ; Tithi Dutta ; Kunal Ray

SLC45A2 (solute carrier family 45 member 2)

Atlas Genet Cytogenet Oncol Haematol. 2019-01-01

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