Defective SLC24A4 causes hypomineralized amelogenesis imperfecta (AI)

Stable Identifier
R-HSA-5619055
Type
Pathway
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Homo sapiens
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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
17952075 Genetic determinants of hair, eye and skin pigmentation in Europeans

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

Nat. Genet. 2007
23375655 Identification of mutations in SLC24A4, encoding a potassium-dependent sodium/calcium exchanger, as a cause of amelogenesis imperfecta

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

Am. J. Hum. Genet. 2013
24621671 STIM1 and SLC24A4 Are Critical for Enamel Maturation

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

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

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

Cells Tissues Organs (Print) 2012
Participants
Participant Of
Disease
Name Identifier Synonyms
amelogenesis imperfecta 2187
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