GeneBe

SLC24A4

protein-coding

solute carrier family 24 member 4, the group of Solute carrier family 24

Gene 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]

MANE transcript

NM_153646.4

Inheritance

AR, AD

ClinVar variants

P:5U:104B:37

Top phenotype

Ameliogenesis imperfecta, hypomaturation type, IIA5

gnomAD constraint

pLI —, LoF o/e 0.61

Max pathogenic AF

—

Genomic locus

chr14:92,322,581-92,501,481

External References & Databases

Ensembl (ENSG00000140090)NCBI Gene (123041)OMIM (609840)HGNC:10978GenCCUniProt (Q8NFF2)AlphaFoldClinVar (SLC24A4)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~178.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

amelogenesis imperfecta hypomaturation type 2A5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014385

Submitter: Labcorp Genetics (formerly Invitae)

amelogenesis imperfecta, type 3ASUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007538

Submitter: Orphanet

amelogenesis imperfecta hypomaturation type 2A5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014385

Submitter: PanelApp Australia

amelogenesis imperfecta hypomaturation type 2A5MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014385

Submitter: Ambry Genetics

amelogenesis imperfecta type 2SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0015048

Submitter: Orphanet

amelogenesis imperfecta hypomaturation type 2A5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014385

Submitter: G2P

Clinical Genomic Database (CGD)

Ameliogenesis imperfecta, hypomaturation type, IIA5AR

Manifestation: Dental

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 23375655; 24621671Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC24A4 variants in ClinVar

6 Conditions Cataloged
Inborn genetic diseasesTotal: 100
not providedTotal: 31
SLC24A4-related disorderTotal: 16
Amelogenesis imperfecta hypomaturation type 2A5Total: 5
not specifiedTotal: 2
Amelogenesis imperfectaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153646.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
18
clinvar
7
clinvar
 25
missense
2
clinvar
101
clinvar
8
clinvar
4
clinvar
 115
nonsense
3
clinvar
2
clinvar
 5
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total501042611146

Highest pathogenic variant AF is 0.000005476601

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_153646.4RefSeqNP_705932.217MANE Select
ENST00000532405.6EnsemblENSP00000431840.117MANE Select
NM_001378620.1RefSeqNP_001365549.117Standard
NM_001425254.1RefSeqNP_001412183.117Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Olfactory transduction - Homo sapiens (human)
  • Sodium/Calcium exchangers
  • Transport of inorganic cations/anions and amino acids/oligopeptides
  • SLC-mediated transmembrane transport
  • Transport of small molecules

Biological Process

  • ion transport
  • potassium ion transport
  • cellular calcium ion homeostasis
  • sensory perception of smell
  • sodium ion transmembrane transport

Molecular Function

  • calcium channel activity
  • calcium, potassium:sodium antiporter activity
  • symporter activity

Cellular Component

  • cytoplasm
  • plasma membrane
  • integral component of plasma membrane
  • membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000532405
Coding exons
17
Length
173672
Individuals with no LoFs
125697
Homozygous LoFs
0
Heterozygous LoFs
51
Defined
125748
p
0.000203
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.8053403840.8840.00002294060
Missense (PolyPhen)98135.520.723151460
Synonymous-0.06191651641.010.00001151234
Loss of Function2.192337.50.6140.00000213366

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000250.00025rare
Latino/Admixed American0.000230.00023rare
Ashkenazi Jewish0.0000990.000099rare
East Asian0.000110.00011rare
Finnish0.000140.00014rare
European (Non-Finnish)0.000220.00021rare
South Asian0.000260.00026rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+). Controls the rapid response termination and proper regulation of adaptation in olfactory sensory neurons (OSNs) which subsequently influences how odor information is encoded and perceived. May play a role in calcium transport during amelogenesis (By similarity). {ECO:0000250|UniProtKB:Q8CGQ8}.;
Disease
DISEASE: Amelogenesis imperfecta, hypomaturation type, 2A5 (AI2A5) [MIM:615887]: A defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel. {ECO:0000269|PubMed:23375655, ECO:0000269|PubMed:24621671}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.150

Intolerance Scores

LoFtool
0.871
RVIS EVS
0.32
RVIS percentile EVS
72.8

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.197

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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