Defective SLC24A4 causes hypomineralized amelogenesis imperfecta (AI)

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).<br><br>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).

NCKX（SLC24）家族的五个成员均能以一分子钙离子（Ca2+）和一分子钾离子（K+）与四分子钠离子（Na+）进行交换。SLC24A4编码的NCKX4交换蛋白可能在成釉过程中（牙齿珐琅质的形成过程）的钙离子运输中发挥作用。SLC24A4在成釉细胞成熟阶段的成釉过程中上调（Hu et al. 2012）。SLC24A4的缺陷可能导致低矿化成釉不全症（AI），这是一种常染色体隐性遗传疾病，其特征为牙齿珐琅质形成失败。对AI家系进行筛查时，Parry et al.（2013）、Wang et al.（2014）等研究者发现了严重降低或消除SLC24A4运输功能的突变。

SLC24A4中的遗传变异定义了皮肤/毛发/眼睛色素沉着变异位点6（SHEP6；MIM:210750）。在针对数千名冰岛人和荷兰人的全基因组关联扫描中，Sulem et al.（2007）发现SLC24A4基因中的一个单核苷酸多态性（SNP）的T等位基因与金发与棕发、蓝眼与绿眼之间的显著关联。