SLC24A5 (solute carrier family 24 (sodium/potassium/calcium exchanger), member 5)

2016-04-01   Kunal Ray , Mainak Sengupta , Sampurna Ghosh 

Identity

HGNC
LOCATION
15q21.1
IMAGE
Atlas 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

Bibliography

Pubmed IDLast YearTitleAuthors
163572532005SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans.Lamason RL et al
230101992012Molecular basis of albinism in India: evaluation of seven potential candidate genes and some new findings.Mondal M et al
239859942014SLC24A5 mutations are associated with non-syndromic oculocutaneous albinism.Morice-Picard F et al
233644762013Exome sequencing identifies SLC24A5 as a candidate gene for nonsyndromic oculocutaneous albinism.Wei AH et al
232248732013NCKX5, 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 IDTranscript IDUniprot
ENSG00000188467ENST00000341459Q71RS6
ENSG00000188467ENST00000449382Q71RS6
ENSG00000188467ENST00000482911H0YLZ0

Expression (GTEx)

0
1

Pathways

PathwaySourceExternal ID
Transmembrane transport of small moleculesREACTOMER-HSA-382551
SLC-mediated transmembrane transportREACTOMER-HSA-425407
Transport of inorganic cations/anions and amino acids/oligopeptidesREACTOMER-HSA-425393
Sodium/Calcium exchangersREACTOMER-HSA-425561

References

Pubmed IDYearTitleCitations
179993552007A genomewide association study of skin pigmentation in a South Asian population.90
193849532009Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians.67
181665282008SLC24A5 encodes a trans-Golgi network protein with potassium-dependent sodium-calcium exchange activity that regulates human epidermal melanogenesis.42
181665282008SLC24A5 encodes a trans-Golgi network protein with potassium-dependent sodium-calcium exchange activity that regulates human epidermal melanogenesis.42
186508492009Analysis of cultured human melanocytes based on polymorphisms within the SLC45A2/MATP, SLC24A5/NCKX5, and OCA2/P loci.39
168476982007Population differences of two coding SNPs in pigmentation-related genes SLC24A5 and SLC45A2.35
199447662010A pilot multivariate parallel ICA study to investigate differential linkage between neural networks and genetic profiles in schizophrenia.26
190602772009Birth prevalence and mutation spectrum in danish patients with autosomal recessive albinism.19
193363702009Determination of genetic predisposition to patent ductus arteriosus in preterm infants.17
206914272010Genetic associations of brain structural networks in schizophrenia: a preliminary study.17

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