SLC24A4 solute carrier family 24 member 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC24A4provided by HGNC
Official Full Name: solute carrier family 24 member 4provided by HGNC
Primary source: HGNC:HGNC:10978
See related: Ensembl:ENSG00000140090 MIM:609840; AllianceGenome:HGNC:10978
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AI2A5; NCKX4; SHEP6; SLC24A2
Summary: This gene encodes a sodium/potassium/calcium exchange protein. The encoded antiporter transports one calcium and one potassium ion in exchange for four sodium ions and has been implicated in amelogenesis and enamel maturation. Certain variants in this gene have been associated with skin, hair, and eye pigmentation, while other variants have been identified in people with hypomaturation-type amelogenesis imperfecta. [provided by RefSeq, Nov 2023]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 14q32.12

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (92322581..92501481)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (86552327..86731081)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (92788925..92967825)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Calmodulin binds and modulates K(+)-dependent Na(+)/Ca(2+)-exchanger isoform 4, NCKX4.
Title: Calmodulin binds and modulates K(+)-dependent Na(+)/Ca(2+)-exchanger isoform 4, NCKX4.
Association between brown eye colour in rs12913832:GG individuals and SNPs in TYR, TYRP1, and SLC24A4.
Title: Association between brown eye colour in rs12913832:GG individuals and SNPs in TYR, TYRP1, and SLC24A4.
This nonsense sequence variant c.1192C > T (p.Gln398*) is the sixth disease-causing variant in SLC24A4, which extends its mutation spectrum and confirms the role of this gene in the morphogenesis of human tooth enamel. The identified variant highlights the critical role of SLC24A4 in causing a rare Amelogenesis imperfecta (AI) type in humans.
Title: A novel nonsense variant in SLC24A4 causing a rare form of amelogenesis imperfecta in a Pakistani family.
no significant relation was noted between SLC24A4 rs10498633 and late-onset Alzheimer;s disease risk in neither apolipoprotein E (APOE) epsilon4 carriers nor non-carriers after adjusting for age and gender
Title: Lack of Association Between SLC24A4 Polymorphism and Late-onset Alzheimer's Disease in Han Chinese.
pigment cells express robust, functional NCKX4 activity
Title: Identification and Characterization of K(+)-Dependent Na(+)-Ca(2+) Exchange Transport in Pigmented MEB4 Cells Mediated by NCKX4.
mutations in SLC24A4 and SLC24A5 are responsible for the phenotypic defects observed in human amylogenesis imperfecta and non-syndromic oculocutaneous albinism patients.
Title: A Functional Study of Mutations in K+-dependent Na+-Ca2+ Exchangers Associated with Amelogenesis Imperfecta and Non-syndromic Oculocutaneous Albinism.
The expressions of NCX1 and NCKX4 were significantly higher in the patent ductus arteriosus group at both the protein and mRNA levels.
Title: Elevated NCX1 and NCKX4 expression in the patent postnatal ductus arteriosus of ductal-dependent congenital heart disease patients.
enamel maturation is dependent upon STIM1 and SLC24A4 function, and that there are important differences in the Ca(2+) transcellular transport systems used by secretory- and maturation-stage ameloblasts.
Title: STIM1 and SLC24A4 Are Critical for Enamel Maturation.
Brain DNA methylation in sLC24A4 was associated with pathological Alzheimer disease.
Title: Association of Brain DNA methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 with pathological diagnosis of Alzheimer disease.
These findings support a key role for SLC24A4 in calcium transport during enamel formation.
Title: Identification of mutations in SLC24A4, encoding a potassium-dependent sodium/calcium exchanger, as a cause of amelogenesis imperfecta.

Submit: New GeneRIF Correction See all GeneRIFs (18)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Amelogenesis imperfecta hypomaturation type 2A5 MedGen: C4014578 OMIM: 615887 GeneReviews: Not available	Compare labs
SKIN/HAIR/EYE PIGMENTATION 6, BLOND/BROWN HAIR MedGen: C2673866 OMIM: 210750 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic determinants of hair, eye and skin pigmentation in Europeans. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association scan for survival on dialysis in African-Americans with type 2 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association studies identify several new loci associated with pigmentation traits and skin cancer risk in European Americans. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Web-based, participant-driven studies yield novel genetic associations for common traits. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

G35860 (e-PCR)
- UniSTS:53518

PMC156606P1 (e-PCR)
- UniSTS:271408

D14S1050 (e-PCR)
- UniSTS:33608

SHGC-107410 (e-PCR)
- UniSTS:170324

STS-M79260 (e-PCR)
- UniSTS:23166

SHGC-67307 (e-PCR)
- UniSTS:89991

SHGC-31732 (e-PCR)
- UniSTS:53387

SHGC-82207 (e-PCR)
- UniSTS:103104

G35718 (e-PCR)
- UniSTS:11458

D14S1016 (e-PCR)
- UniSTS:22491

FB12B12 (e-PCR)
- UniSTS:13536

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables calcium, potassium:sodium antiporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables calcium, potassium:sodium antiporter activity	IDA Inferred from Direct Assay more info	PubMed
enables calcium, potassium:sodium antiporter activity	TAS Traceable Author Statement more info
enables calcium-dependent protein binding	ISS Inferred from Sequence or Structural Similarity more info
enables calmodulin binding	ISS Inferred from Sequence or Structural Similarity more info
enables symporter activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in amelogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in calcium ion export across plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
involved_in calcium ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in calcium ion import across plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
involved_in calcium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in calcium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to high light intensity	IEA Inferred from Electronic Annotation more info
involved_in cone photoresponse recovery	ISS Inferred from Sequence or Structural Similarity more info
involved_in detection of chemical stimulus involved in sensory perception of smell	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of drinking behavior	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of enamel mineralization	TAS Traceable Author Statement more info	PubMed
involved_in intracellular calcium ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within intracellular calcium ion homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in membrane repolarization	ISS Inferred from Sequence or Structural Similarity more info
involved_in monoatomic ion transport	TAS Traceable Author Statement more info
involved_in negative regulation of calcium-mediated signaling	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of olfactory nerve maturation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of phototransduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in potassium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of regulation of G protein-coupled receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of regulation of eating behavior	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to high light intensity	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of response to melanocyte-stimulating hormone	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to odorant	ISS Inferred from Sequence or Structural Similarity more info
involved_in sensory perception of smell	IBA Inferred from Biological aspect of Ancestor more info
involved_in sensory perception of smell	ISS Inferred from Sequence or Structural Similarity more info
involved_in sodium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
is_active_in apical plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in apical plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in cone photoreceptor outer segment	ISS Inferred from Sequence or Structural Similarity more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in membrane	ISS Inferred from Sequence or Structural Similarity more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	RCA inferred from Reviewed Computational Analysis more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in vesicle	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: sodium/potassium/calcium exchanger 4

Names: Na(+)/K(+)/Ca(2+)-exchange protein 4; Na/Ca-K exchanger 4; solute carrier family 24 (sodium/potassium/calcium exchanger), member 4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_023408.1 RefSeqGene

Range

5585..183901

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001378620.1 → NP_001365549.1 sodium/potassium/calcium exchanger 4 isoform 1 precursor

Status: REVIEWED

Source sequence(s)

AL118559

Consensus CDS

CCDS9903.2

UniProtKB/Swiss-Prot

B4DHE7, B9ZVY2, Q8N8U6, Q8NCX1, Q8NFF0, Q8NFF1, Q8NFF2

Related

ENSP00000502715.1, ENST00000676001.1

Conserved Domains (1) summary

TIGR00927
Location:80 → 606

2A1904; K+-dependent Na+/Ca+ exchanger
NM_001425254.1 → NP_001412183.1 sodium/potassium/calcium exchanger 4 isoform 2

Status: REVIEWED

Source sequence(s)

AL118559
NM_153646.4 → NP_705932.2 sodium/potassium/calcium exchanger 4 isoform 1 precursor

See identical proteins and their annotated locations for NP_705932.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AF520704, AL118559, BC050357

Consensus CDS

CCDS9903.2

UniProtKB/Swiss-Prot

B4DHE7, B9ZVY2, Q8N8U6, Q8NCX1, Q8NFF0, Q8NFF1, Q8NFF2

Related

ENSP00000431840.1, ENST00000532405.6

Conserved Domains (1) summary

TIGR00927
Location:80 → 606

2A1904; K+-dependent Na+/Ca+ exchanger
NM_153647.4 → NP_705933.2 sodium/potassium/calcium exchanger 4 isoform 2

See identical proteins and their annotated locations for NP_705933.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and uses an alternate in-frame splice site in the 3' coding region compared to variant 1. The resulting isoform (2) is shorter compared to isoform 1.

Source sequence(s)

AK295059, AL118559, BC050357

Consensus CDS

CCDS45155.2

UniProtKB/Swiss-Prot

Q8NFF2

Related

ENSP00000433302.1, ENST00000531433.5

Conserved Domains (1) summary

cl27511
Location:80 → 587

Na_Ca_ex; Sodium/calcium exchanger protein
NM_153648.4 → NP_705934.1 sodium/potassium/calcium exchanger 4 isoform 3

See identical proteins and their annotated locations for NP_705934.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at a downstream start codon compared to variant 1. The resulting isoform (3) is shorter at the N-terminus compared to variant 1.

Source sequence(s)

AF520706, AL118559, BC050357

Consensus CDS

CCDS45156.1

UniProtKB/Swiss-Prot

Q8NFF2

Related

ENSP00000376948.2, ENST00000393265.6

Conserved Domains (2) summary

TIGR00367
Location:38 → 534

TIGR00367; K+-dependent Na+/Ca+ exchanger related-protein

pfam01699
Location:388 → 540

Na_Ca_ex; Sodium/calcium exchanger protein

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000014.9 Reference GRCh38.p14 Primary Assembly

Range

92322581..92501481

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011536436.3 → XP_011534738.1 sodium/potassium/calcium exchanger 4 isoform X1

Conserved Domains (2) summary

TIGR00367
Location:149 → 645

TIGR00367; K+-dependent Na+/Ca+ exchanger related-protein

pfam01699
Location:499 → 651

Na_Ca_ex; Sodium/calcium exchanger protein
XM_011536437.3 → XP_011534739.1 sodium/potassium/calcium exchanger 4 isoform X2

Conserved Domains (2) summary

TIGR00367
Location:149 → 626

TIGR00367; K+-dependent Na+/Ca+ exchanger related-protein

pfam01699
Location:480 → 632

Na_Ca_ex; Sodium/calcium exchanger protein
XM_005267342.2 → XP_005267399.1 sodium/potassium/calcium exchanger 4 isoform X5

Conserved Domains (1) summary

pfam01699
Location:1 → 97

Na_Ca_ex; Sodium/calcium exchanger protein
XM_011536440.2 → XP_011534742.1 sodium/potassium/calcium exchanger 4 isoform X4

UniProtKB/TrEMBL

B4DHR5

Conserved Domains (1) summary

pfam01699
Location:202 → 354

Na_Ca_ex; Sodium/calcium exchanger protein