SLC24A5 (solute carrier family 24 (sodium/potassium/calcium exchanger), member 5)
2016-04-01 Kunal Ray , Mainak Sengupta , Sampurna Ghosh AffiliationIdentity
HGNC
LOCATION
15q21.1
IMAGE
LEGEND
Cytogenetic band showing SLC24A5 locus (Ref: http://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC24A5&keywords=SLC24A5)
LOCUSID
ALIAS
Oculocutaneous Albinism 6,Na(+)/K(+)/Ca(2+)-Exchange Protein 5,Solute Carrier Family 24, Member 5,NCKX5,JSX,P,Solute Carrier Family 24 Member 5,Ion Transporter JSX,SHEP4,OCA6
Abstract
SLC24A5 is a member of the potassium-dependent sodium\/calcium exchanger family and encodes an intracellular membrane protein. Sequence variations in this gene have been associated with differences in skin pigmentation, and the defective protein leads to Oculocutaneous albinism type VI, OCA6.
DNA/RNA
Description
In Chromosome 15, the 21,701 bases long gene starts from 48,120,972 bp from pter and ends at 48,142,672 bp from pter; Orientation: Plus strand. It contains 9 exons.
Transcription
This gene has 5 transcripts: 4 splice variants and 1 unspliced form (http://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&c=Gene&l=SLC24A5). The full protein coding transcript is 1617 bp long.
Proteins
Description
The gene encodes a cation exchanger which is 500 amino acids protein of molecular mass 54888 Da; this multi-pass membrane protein is an intracellular potassium-dependent sodium/calcium exchanger with 2 large hydrophilic loops and 2 sets of multiple trans-membrane-spanning segments. The first large hydrophilic loop is located extracellularly at the N-terminus while the other is cytoplasmic and separates the two sets of transmembrane domains. It belongs to sodium/potassium/calcium exchanger family, SLC24A subfamily.
Expression
Due to its localization in the melanosomal membrane, SLC24A5 is thought to be expressed in the melanocytes (Wilson S et al., 2013). Interestingly, the expression of the gene in the following tissue types are evident by its existence in the corresponding cDNA libraries: B-cell, brain, cerebellum, cerebrum, colon, embryonic tissue, fetus, gastrointestinal tract, kidney, liver, lung, lymph node, lymphoreticular, mammary gland, nervous, pancreas, pancreatic islet, placenta, prostate, skin, stem cell, stomach, testis, thymus, uterus and vascular tissue (http://cgap.nci.nih.gov/Genes/GeneInfo?ORG=Hs&CID=710240).
Localisation
SLC24A5 is expressed in the trans-Golgi network of melanocytes (Wilson S et al., 2013).
Function
The precise function of SLC24A5 is not yet known. However, the potential functions include: (a) transporting 1 Ca2+ and 1 K+ to the melanosome in exchange for 4 cytoplasmic Na (Lamason RL et al., 2005); (b) Influencing natural variation in skin pigmentation via an unknown mechanism affecting cellular sterol levels (Wilson S et al., 2013).
Homology
It belongs to Solute Carrier Family 24 (http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=202).
Mutations
Germinal
SLC24A5 mutations are responsible for Oculocutaneous Albinism type 6 (OCA6). Only 9 SLC24A5 mutations have been reported till date - one patient from India, one from China, two from France, three from Portugal, one from Belgium and one from Syria (Mondal et al. 2012; Wei et al., 2013; Fanny et al., 2014). Patients are generally characterized by light hair at birth that darkens with age, white skin, transparent irises, photophobia, nystagmus, foveal hypoplasia and reduced visual acuity. In a man from eastern India who had extreme hypopigmentation resulting in pinkish-white skin, but with dark brown hair and brown irises, was found to have a 4-bp insertion in the SLC24A5 gene as homozygous genotype (Mondal et al, 2012).
Somatic
Somatic variations in SLC24A5 have been identified in cancers (https://dcc.icgc.org/mutations/MU45848787; http://cancer.sanger.ac.uk/cosmic/search?q=SLC24A5), but no causality have been reported.
Implicated in
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 16357253 | 2005 | SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. | Lamason RL et al |
| 23010199 | 2012 | Molecular basis of albinism in India: evaluation of seven potential candidate genes and some new findings. | Mondal M et al |
| 23985994 | 2014 | SLC24A5 mutations are associated with non-syndromic oculocutaneous albinism. | Morice-Picard F et al |
| 23364476 | 2013 | Exome sequencing identifies SLC24A5 as a candidate gene for nonsyndromic oculocutaneous albinism. | Wei AH et al |
| 23224873 | 2013 | NCKX5, a natural regulator of human skin colour variation, regulates the expression of key pigment genes MC1R and alpha-MSH and alters cholesterol homeostasis in normal human melanocytes. | Wilson S et al |
Other Information
Locus ID:
NCBI: 283652
MIM: 609802
HGNC: 20611
Ensembl: ENSG00000188467
Variants:
dbSNP: 283652
ClinVar: 283652
TCGA: ENSG00000188467
COSMIC: SLC24A5
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000188467 | ENST00000341459 | Q71RS6 |
| ENSG00000188467 | ENST00000449382 | Q71RS6 |
| ENSG00000188467 | ENST00000482911 | H0YLZ0 |
Expression (GTEx)
Pathways
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37294081 | 2023 | Native American genetic ancestry and pigmentation allele contributions to skin color in a Caribbean population. | 1 |
| 37294081 | 2023 | Native American genetic ancestry and pigmentation allele contributions to skin color in a Caribbean population. | 1 |
| 32274888 | 2020 | Molecular characterization of SLC24A5 variants and evaluation of Nitisinone treatment efficacy in a zebrafish model of OCA6. | 8 |
| 32274888 | 2020 | Molecular characterization of SLC24A5 variants and evaluation of Nitisinone treatment efficacy in a zebrafish model of OCA6. | 8 |
| 29981211 | 2019 | Cellular localization of the K(+) -dependent Na(+) -Ca(2+) exchanger NCKX5 and the role of the cytoplasmic loop in its distribution in pigmented cells. | 9 |
| 31486119 | 2019 | Identification of two Chinese oculocutaneous albinism type 6 patients and mutation updates of the SLC24A5 gene. | 2 |
| 29981211 | 2019 | Cellular localization of the K(+) -dependent Na(+) -Ca(2+) exchanger NCKX5 and the role of the cytoplasmic loop in its distribution in pigmented cells. | 9 |
| 31486119 | 2019 | Identification of two Chinese oculocutaneous albinism type 6 patients and mutation updates of the SLC24A5 gene. | 2 |
| 30530665 | 2018 | Rapid evolution of a skin-lightening allele in southern African KhoeSan. | 9 |
| 30530665 | 2018 | Rapid evolution of a skin-lightening allele in southern African KhoeSan. | 9 |
| 27866970 | 2017 | Genotype-Phenotype Study of the Middle Gangetic Plain in India Shows Association of rs2470102 with Skin Pigmentation. | 6 |
| 27866970 | 2017 | Genotype-Phenotype Study of the Middle Gangetic Plain in India Shows Association of rs2470102 with Skin Pigmentation. | 6 |
| 26491832 | 2016 | Identification of a homozygous mutation of SLC24A5 (OCA6) in two patients with oculocutaneous albinism from French Guiana. | 7 |
| 26686029 | 2016 | Detection of the first OCA6 Italian patient in a large cohort of albino subjects. | 3 |
| 27129268 | 2016 | A Functional Study of Mutations in K+-dependent Na+-Ca2+ Exchangers Associated with Amelogenesis Imperfecta and Non-syndromic Oculocutaneous Albinism. | 11 |
Citation
Kunal Ray ; Mainak Sengupta ; Sampurna Ghosh
SLC24A5 (solute carrier family 24 (sodium/potassium/calcium exchanger), member 5)
Atlas Genet Cytogenet Oncol Haematol. 2016-04-01
Online version: http://atlasgeneticsoncology.org/gene/73332/slc24a5-(solute-carrier-family-24-(sodium-potassium-calcium-exchanger)-member-5)
