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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC24A4
solute carrier family 24 member 4
Chromosome 14 · 14q32.12
NCBI Gene: 123041Ensembl: ENSG00000140090.18HGNC: HGNC:10978UniProt: Q8NFF2
31PubMed Papers
21Diseases
0Drugs
5Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membraneintracellular calcium ion homeostasiscalcium, potassium:sodium antiporter activitysodium ion transmembrane transportHypomaturation amelogenesis imperfectaamelogenesis imperfectahair colorAlzheimer disease
✦AI Summary

SLC24A4 encodes a calcium/potassium:sodium antiporter that exchanges one intracellular Ca²⁺ and one K⁺ for four extracellular Na⁺ ions 12. The transporter localizes to plasma membranes and regulates intracellular calcium homeostasis 3. SLC24A4 is critical for enamel maturation during amelogenesis, with immunohistochemical evidence showing specific expression in maturation-stage ameloblasts of developing teeth 3. Biallelic loss-of-function mutations in SLC24A4 cause amelogenesis imperfecta, hypomaturation type, characterized by thin, soft, yellow-brown discolored enamel with reduced structural integrity 34. Beyond dental development, SLC24A4 variants associate with eye color determination in individuals carrying specific genotypes 56, contributing to melanin-related pigmentation pathways. Additionally, SLC24A4 has been identified as a genome-wide association study locus nominally associated with Alzheimer's disease risk and cognitive decline in some populations 78, though effect sizes are small (relative risk 1.1-1.3). Recent evidence suggests SLC24A4 may function as a tumor suppressor gene in colorectal cancer, with expression changes affecting cell migration and growth 9. Overall, SLC24A4 represents a multifunctional calcium transporter essential for mineralized tissue development and potentially involved in neurodegeneration and cancer biology.

Sources cited
1
SLC24A4 is a calcium/potassium:sodium antiporter exchanging intracellular Ca²⁺ and K⁺ for extracellular Na⁺
PMID: 12379639
2
Confirms SLC24A4 calcium/potassium:sodium antiporter function and stoichiometry
PMID: 26631410
3
SLC24A4 is critical for enamel maturation; mutations cause hypomaturation amelogenesis imperfecta; expressed in maturation-stage ameloblasts
PMID: 24621671
4
Novel nonsense SLC24A4 variant (c.1192C>T) causes hypomaturation amelogenesis imperfecta with yellow-brown enamel discoloration
PMID: 32380970
5
SLC24A4 variants associate with brown eye color in individuals with specific genotypes; involved in pigmentation
PMID: 32915910
6
SLC24A4 is a candidate gene for pigmentation traits identified in genome-wide association studies
PMID: 19297406
7
SLC24A4-RIN3 locus associated with late-onset Alzheimer's disease with small effect size (relative risk 1.1-1.3)
PMID: 25311924
8
SLC24A4 aggregate SNP associations with cognitive decline in older adults, particularly in male cohorts
PMID: 27005436
9
SLC24A4 functions as tumor suppressor gene in colorectal cancer; affects cell migration and growth
PMID: 39006025
Disease Associationsⓘ21
Hypomaturation amelogenesis imperfectaOpen Targets
0.68Moderate
amelogenesis imperfectaOpen Targets
0.65Moderate
hair colorOpen Targets
0.53Moderate
Alzheimer diseaseOpen Targets
0.47Moderate
eye colorOpen Targets
0.46Moderate
smoking initiationOpen Targets
0.39Weak
hypocalcified amelogenesis imperfectaOpen Targets
0.37Weak
late-onset Alzheimers diseaseOpen Targets
0.35Weak
cutaneous melanomaOpen Targets
0.32Weak
ovarian dysfunctionOpen Targets
0.31Weak
suntanOpen Targets
0.31Weak
squamous cell carcinomaOpen Targets
0.31Weak
spermatoceleOpen Targets
0.29Weak
severe acute respiratory syndromeOpen Targets
0.27Weak
COVID-19Open Targets
0.26Weak
myopathyOpen Targets
0.23Weak
cardiomyopathyOpen Targets
0.22Weak
musculoskeletal system diseaseOpen Targets
0.22Weak
genetic disorderOpen Targets
0.19Weak
liver diseaseOpen Targets
0.15Weak
Amelogenesis imperfecta, hypomaturation type, 2A5UniProt
Pathogenic Variants5
NM_153646.4(SLC24A4):c.1192C>T (p.Gln398Ter)Pathogenic
Amelogenesis imperfecta hypomaturation type 2A5
☆☆☆☆2019→ Residue 398
NM_153646.4(SLC24A4):c.437C>T (p.Ala146Val)Pathogenic
Amelogenesis imperfecta hypomaturation type 2A5
☆☆☆☆2014→ Residue 146
NM_153646.4(SLC24A4):c.1015C>T (p.Arg339Ter)Pathogenic
Amelogenesis imperfecta hypomaturation type 2A5
☆☆☆☆2013→ Residue 339
NM_153646.4(SLC24A4):c.1495A>T (p.Ser499Cys)Pathogenic
Amelogenesis imperfecta hypomaturation type 2A5
☆☆☆☆2013→ Residue 499
NM_153646.4(SLC24A4):c.613C>T (p.Arg205Ter)Pathogenic
Amelogenesis imperfecta
☆☆☆☆→ Residue 205
View on ClinVar ↗
Related Genes
CD2APProtein interaction97%TPCN2Protein interaction92%IRF4Protein interaction86%ABCA7Protein interaction80%RIN3Protein interaction80%ASIPProtein interaction74%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
66%
Lung
20%
Ovary
6%
Liver
6%
Heart
4%
Gene Interaction Network
Click a node to explore
SLC24A4CD2APTPCN2IRF4ABCA7RIN3ASIP
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8NFF2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.86LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.67 [0.52–0.86]
RankingsWhere SLC24A4 stands among ~20K protein-coding genes
  • #11,800of 20,598
    Most Researched31
  • #3,619of 5,498
    Most Pathogenic Variants5
  • #7,560of 17,882
    Most Constrained (LOEUF)0.86
Genes detectedSLC24A4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Genetics of Alzheimer's disease.
PMID: 25311924
Adv Genet · 2014
1.00
2
Association between brown eye colour in rs12913832:GG individuals and SNPs in TYR, TYRP1, and SLC24A4.
PMID: 32915910
PLoS One · 2020
0.90
3
STIM1 and SLC24A4 Are Critical for Enamel Maturation.
PMID: 24621671
J Dent Res · 2014
0.80
4
Molecular genetics of human pigmentation diversity.
PMID: 19297406
Hum Mol Genet · 2009
0.70
5
A novel nonsense variant in SLC24A4 causing a rare form of amelogenesis imperfecta in a Pakistani family.
PMID: 32380970
BMC Med Genet · 2020
0.60