Sodium/potassium/calcium exchanger 5
SLC24A5 | |||
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Gene ontology | |||
Molecular function | |||
Cellular component | |||
Biological process |
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Sources:Amigo / QuickGO |
Ensembl | |||||||||
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UniProt | |||||||||
RefSeq (mRNA) | |||||||||
RefSeq (protein) | |||||||||
Location (UCSC) | Chr 15: 48.12 – 48.14 Mb | Chr 2: 124.91 – 124.93 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
Sodium/potassium/calcium exchanger 5 (NCKX5), also known as solute carrier family 24 member 5 (SLC24A5), is a protein that in humans is encoded by the SLC24A5 gene that has a major influence on natural skin colour variation.[5] The NCKX5 protein is a member of the potassium-dependent sodium/calcium exchanger family. Sequence variation in the SLC24A5 gene, particularly a non-synonymous SNP changing the amino acid at position 111 in NCKX5 from alanine to threonine, has been associated with differences in skin pigmentation.[6]
The SLC24A5 gene's derived threonine or Ala111Thr allele (rs1426654
Gene
The SLC24A5 gene, in humans, is located on the long (q) arm of
Protein
NCKX5 is 43 k
Effect on skin color
SLC24A5 appears to have played a key role in the evolution of light skin in humans of European ancestry. The gene's function in pigmentation was discovered in zebrafish as a result of the positional cloning of the gene responsible for the "golden" variety of this common pet store fish. Evidence in the International HapMap Project database of genetic variation in human populations showed that Europeans, represented by the "CEU" population, had two primary alleles differing by only one nucleotide, changing the 111th amino acid from alanine to threonine, abbreviated "A111T".[5][14][15]
The derived threonine allele (Ala111Thr; also known as A111T or Thr111) represented 98.7 to 100% of the alleles in European samples, while the ancestral or alanine form was found in 93 to 100% of samples of Sub-Saharan Africans, East Asians and Indigenous Americans. The variation is a
The SNP rs2470102 independently affects skin pigmentation variation among the South Asian population.[16]
Furthermore, the European mutation is associated with the largest region of diminished genetic variation in the CEU HapMap population, suggesting the possibility that the A111T mutation may be the subject of the single largest degree of selection in human populations of European ancestry.[5] It is hypothesized that selection for the derived allele is based on the need for sunlight to produce the essential nutrient vitamin D. In northerly latitudes, where there is less sun, greater requirement for body coverage due to colder climate, and frequently, diets poor in vitamin D, making lighter skin more suitable for survival.[17]
The earliest known sample of the threonine allele is 13,000 years old from Satsurblia Cave in Georgia.[18] The allele was widespread from Anatolia to Ukraine and Iran at the beginning of the Neolithic.[19][20][21]
This allele forms part of the HIrisplex DNA test system used to estimate pigmentation in forensic investigations.[22][23]
See also
- Human skin color
- SLC45A2
- Tiger eye
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000188467 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000035183 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ S2CID 2245002.
- ^ PMID 18166528.
- ^ Reference SNP(refSNP) Cluster Report: rs1426654 **clinically associated**. Ncbi.nlm.nih.gov (2008-12-30). Retrieved on 2011-02-27.
- PMID 17182896.
- Ann Gibbons (20 April 2007). "European Skin Turned Pale Only Recently, Gene Suggests". Science. 316 (5823): 364. S2CID 43290419.
- Ann Gibbons (20 April 2007). "European Skin Turned Pale Only Recently, Gene Suggests". Science. 316 (5823): 364.
- PMID 24616518.
- PMID 22923467.
- S2CID 11192076.
- PMID 22912732.
- PMID 30530665.
- ^ "Key gene 'controls skin colour'". Health. BBC News. 2005-12-16. Retrieved 2010-10-23.
- ^ "Fish gene sheds light on human skin color variation". Penn State Live. Penn State University. 2005-12-16. Archived from the original on 2010-07-21. Retrieved 2010-10-23.
- ISSN 0971-751X. Retrieved 2017-11-08.
- PMID 10896812. Archived from the original(PDF) on 2012-01-14.
- PMID 26567969.
- PMID 27417496.
- bioRxiv 10.1101/016477.
- PMID 28162894.
- S2CID 21673970.
- "Forensics: New tool predicts eye, hair and skin color from a DNA sample of an unidentified individual". ScienceDaily (Press release). May 14, 2018.
- ^ Pollack A (23 February 2015). "Building a Face, and a Case, on DNA". New York Times. Retrieved 7 April 2019.
Further reading
- Grønskov K, Ek J, Sand A, Scheller R, Bygum A, Brixen K, Brondum-Nielsen K, Rosenberg T (March 2009). "Birth prevalence and mutation spectrum in danish patients with autosomal recessive albinism". Investigative Ophthalmology & Visual Science. 50 (3): 1058–64. PMID 19060277.
- Cook AL, Chen W, Thurber AE, Smit DJ, Smith AG, Bladen TG, et al. (February 2009). "Analysis of cultured human melanocytes based on polymorphisms within the SLC45A2/MATP, SLC24A5/NCKX5, and OCA2/P loci". The Journal of Investigative Dermatology. 129 (2): 392–405. PMID 18650849.
- Nan H, Kraft P, Hunter DJ, Han J (August 2009). "Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians". International Journal of Cancer. 125 (4): 909–17. PMID 19384953.
- Meda SA, Jagannathan K, Gelernter J, Calhoun VD, Liu J, Stevens MC, et al. (November 2010). "A pilot multivariate parallel ICA study to investigate differential linkage between neural networks and genetic profiles in schizophrenia". NeuroImage. 53 (3): 1007–15. PMID 19944766.
- Stokowski RP, Pant PV, Dadd T, Fereday A, Hinds DA, Jarman C, et al. (December 2007). "A genomewide association study of skin pigmentation in a South Asian population". American Journal of Human Genetics. 81 (6): 1119–32. PMID 17999355.
- Dagle JM, Lepp NT, Cooper ME, Schaa KL, Kelsey KJ, Orr KL, et al. (April 2009). "Determination of genetic predisposition to patent ductus arteriosus in preterm infants". Pediatrics. 123 (4): 1116–23. PMID 19336370.
- Sulem P, Gudbjartsson DF, Stacey SN, Helgason A, Rafnar T, Magnusson KP, et al. (December 2007). "Genetic determinants of hair, eye and skin pigmentation in Europeans". Nature Genetics. 39 (12): 1443–52. S2CID 19313549.
- Cai X, Lytton J (February 2004). "Molecular cloning of a sixth member of the K+-dependent Na+/Ca2+ exchanger gene family, NCKX6". The Journal of Biological Chemistry. 279 (7): 5867–76. PMID 14625281.
- Chi A, Valencia JC, Hu ZZ, Watabe H, Yamaguchi H, Mangini NJ, Huang H, Canfield VA, Cheng KC, Yang F, Abe R, Yamagishi S, Shabanowitz J, Hearing VJ, Wu C, Appella E, Hunt DF (November 2006). "Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes". Journal of Proteome Research. 5 (11): 3135–44. PMID 17081065.
- 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. S2CID 11192076.
- Dimisianos G, Stefanaki I, Nicolaou V, Sypsa V, Antoniou C, Poulou M, et al. (February 2009). "A study of a single variant allele (rs1426654) of the pigmentation-related gene SLC24A5 in Greek subjects". Experimental Dermatology. 18 (2): 175–7. S2CID 22110110.
External links
- SLC24A5+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)