SLC9A5
protein-codingsolute carrier family 9 member A5, the group of Solute carrier family 9
Gene summary
Enables arrestin family protein binding activity and sodium:proton antiporter activity. Involved in regulation of intracellular pH and sodium ion transmembrane transport. Located in several cellular components, including focal adhesion; neuron spine; and recycling endosome membrane. Implicated in end stage renal disease. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~34.5 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 SLC9A5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004594.3. 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 | 1 | 2 | 3 | |||
| missense | 114 | 3 | 117 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 116 | 5 | 0 | 121 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004585.1 | 16 | MANE Select | |
| Ensembl | ENSP00000299798.11 | 16 | MANE Select | |
| RefSeq | NP_001310900.1 | 13 | Standard | |
| RefSeq | NP_001310901.1 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Beta-agonist/Beta-blocker Pathway, Pharmacodynamics
- Sodium/Proton exchangers
- Transport of inorganic cations/anions and amino acids/oligopeptides
- SLC-mediated transmembrane transport
- Transport of small molecules
Biological Process
- ion transport
- regulation of intracellular pH
- potassium ion transmembrane transport
- sodium ion import across plasma membrane
- proton transmembrane transport
Molecular Function
- sodium:proton antiporter activity
- potassium:proton antiporter activity
Cellular Component
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000299798
- Coding exons
- 16
- Length
- 34508
- Individuals with no LoFs
- 124802
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 74
- Defined
- 124876
- p
- 0.000296
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.94 | 341 | 532 | 0.641 | 0.0000319 | 5743 |
| Missense (PolyPhen) | 107 | 195.4 | 0.54759 | 2154 | ||
| Synonymous | 1.48 | 192 | 220 | 0.873 | 0.0000131 | 1893 |
| Loss of Function | 3.15 | 20 | 42.1 | 0.476 | 0.00000249 | 429 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00019 | rare |
| Latino/Admixed American | 0.00043 | 0.00043 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00028 | 0.00028 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00038 | 0.00038 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.0012 | 0.0012 | notable |
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 (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.126
Intolerance Scores
- LoFtool
- 0.417
- RVIS EVS
- -0.87
- RVIS percentile EVS
- 10.8
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.819
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |