Defective SLC24A4 causes hypomineralized amelogenesis imperfecta (AI)

Stable Identifier
R-HSA-5619055
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Pathway
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Homo sapiens
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5/5
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Defective SLC24A4 causes hypomineralized amelogenesis imperfecta (AI)
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The five members of the NCKX (SLC24) family are all able to exchange one Ca2+ and one K+ for four Na+. SLC24A4 encodes an exchanger protein NCKX4 which may play a role in calcium transport during amelogenesis (the process of formation of tooth enamel). SLC24A4 is upregulated in ameloblasts during the maturation stage of amelogenesis (Hu et al. 2012). Defects in SLC24A4 can cause hypomineralised amelogenesis imperfecta (AI), an autosomal recessive disorder in which tooth enamel formation fails. Screening of AI families identified mutations which severely diminish or abolish transport function of SLC24A4 (Parry et al. 2013, Wang et al. 2014).

Genetic variants in SLC24A4 define the skin/hair/eye pigmentation variation locus 6 (SHEP6; MIM:210750). In a genomewide association scan of thousands of Icelanders and Dutch, Sulem et al. found a strong association between the T allele of a SNP in the SLC24A4 gene and blond versus brown hair and blue versus green eyes (Sulem et al. 2007).
Literature References
PubMed ID Title Journal Year
23375655 Identification of mutations in SLC24A4, encoding a potassium-dependent sodium/calcium exchanger, as a cause of amelogenesis imperfecta

Ferguson, CH, Brookes, SJ, Logan, CV, Zhao, H, Parry, DA, Johnson, CA, Inglehearn, CF, Anwari, BM, Jafri, H, Rashid, Y, Mighell, AJ, Poulter, JA

Am. J. Hum. Genet. 2013
17952075 Genetic determinants of hair, eye and skin pigmentation in Europeans

Ragnarsson, R, Jonasson, F, Magnusson, KP, Stacey, SN, Thorsteinsdottir, U, Jakobsdottir, M, Thorleifsson, G, Gudbjartsson, DF, Stefansson, K, Aben, KK, Thorisdottir, K, Steinberg, S, Sigurgeirsson, B, Benediktsdottir, KR, Rafnar, T, Gulcher, J, Kong, A, Olafsson, JH, Pálsson, S, Palsson, A, Karason, A, Helgason, A, Sulem, P, Manolescu, A, Kiemeney, LA

Nat. Genet. 2007
24621671 STIM1 and SLC24A4 Are Critical for Enamel Maturation

Gençay, K, Wang, S, Hu, JC, Tuna, E, Yildirim, M, Seymen, F, Reid, BM, Richardson, AS, Choi, M, Simmer, JP

J. Dent. Res. 2014
22677781 Expression of the sodium/calcium/potassium exchanger, NCKX4, in ameloblasts

Paine, ML, Hu, P, Lacruz, RS, Smith, CE, Kurtz, I, Smith, SM

Cells Tissues Organs (Print) 2012
Participants
Events
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Disease
Name Identifier Synonyms
amelogenesis imperfecta DOID:2187
Cross References
BioModels Database
Authored
Jassal, B  (2014-08-22)
Reviewed
Broer, S  (2015-08-04)
Created
Jassal, B  (2014-08-22)
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