SLC9A4
protein-codingsolute carrier family 9 member A4, the group of Solute carrier family 9
Gene summary
Predicted to enable potassium:proton antiporter activity and sodium:proton antiporter activity. Predicted to be involved in monoatomic cation transmembrane transport; regulation of intracellular pH; and transepithelial ammonium transport. Predicted to act upstream of or within epithelial cell development and gastric acid secretion. Predicted to be located in basolateral plasma membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~60.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC9A4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001011552.4. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 1 | 5 | |||
| missense | 136 | 6 | 1 | 143 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 140 | 7 | 1 | 148 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001011552.2 | 12 | MANE Select | |
| Ensembl | ENSP00000295269.4 | 12 | MANE Select | |
| Ensembl | ENSP00000804998.1 | 12 | Standard | |
| RefSeq | XP_011509460.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gastric acid secretion - Homo sapiens (human)
- Beta-agonist/Beta-blocker Pathway, Pharmacodynamics
- Sodium/Proton exchangers
- Transport of inorganic cations/anions and amino acids/oligopeptides
- SLC-mediated transmembrane transport
Biological Process
- gastric acid secretion
- epithelial cell development
- ion transport
- regulation of intracellular pH
- potassium ion transmembrane transport
Molecular Function
- sodium:proton antiporter activity
- potassium:proton antiporter activity
Cellular Component
- plasma membrane
- integral component of membrane
- basolateral plasma membrane
- apical plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000295269
- Coding exons
- 12
- Length
- 60670
- Individuals with no LoFs
- 125619
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 128
- Defined
- 125748
- p
- 0.000513
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.611 | 492 | 455 | 1.08 | 0.0000250 | 5245 |
| Missense (PolyPhen) | 192 | 185.54 | 1.0348 | 2206 | ||
| Synonymous | -0.667 | 191 | 180 | 1.06 | 0.0000110 | 1559 |
| Loss of Function | 1.12 | 24 | 30.7 | 0.782 | 0.00000155 | 360 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0035 | 0.0035 | notable |
| Latino/Admixed American | 0.00035 | 0.00035 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00065 | 0.00065 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00032 | 0.00031 | rare |
| South Asian | 0.00039 | 0.00033 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction. May play a specialized role in the kidney in rectifying cell volume in response to extreme fluctuations of hyperosmolar-stimulated cell shrinkage. Is relatively amiloride and ethylisopropylamiloride (EIPA) insensitive. Can be activated under conditions of hyperosmolar-induced cell shrinkage in a sustained intracellular acidification-dependence manner. Activated by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) in a sustained intracellular acidification-dependence manner. Affects potassium/proton exchange as well as sodium/proton and lithium/proton exchange. In basolateral cell membrane, participates in homeostatic control of intracellular pH, and may play a role in proton extrusion in order to achieve transepithelial HCO3(-) secretion. In apical cell membrane may be involved in mediating sodium absorption. Requires for normal levels of gastric acid secretion, secretory membrane development, parietal cell maturation and/or differentiation and at least secondarily for chief cell differentiation (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.107
Intolerance Scores
- LoFtool
- 0.911
- RVIS EVS
- 0.85
- RVIS percentile EVS
- 88.49
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.818
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |