SLC9A4
Sodium/hydrogen exchanger 4
Also known as: NHE4, SL9A4_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q6AI14
- Gene
- SLC9A4
- Ensembl
- ENSG00000180251
- Chromosome
- 2
- Canonical length
- 798 aa
- Protein class
- Metabolic proteins, Predicted membrane proteins, Transporters
- Subcellular location
- Nucleoplasm,Plasma membrane
- Quaternary structure
- Homodimer
OverviewNCBI Gene
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 gastric acid secretion and glandular epithelial cell development. Predicted to be located in basolateral plasma membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]
Canonical amino-acid sequenceUniProt
798 residues, UniProt reviewed canonical sequence.
>Q6AI14|SLC9A4
1 MALQMFVTYS PWNCLLLLVA LECSEASSDL NESANSTAQY ASNAWFAAAS SEPEEGISVF
61 ELDYDYVQIP YEVTLWILLA SLAKIGFHLY HRLPGLMPES CLLILVGALV GGIIFGTDHK
121 SPPVMDSSIY FLYLLPPIVL EGGYFMPTRP FFENIGSILW WAVLGALINA LGIGLSLYLI
181 CQVKAFGLGD VNLLQNLLFG SLISAVDPVA VLAVFEEARV NEQLYMMIFG EALLNDGITV
241 VLYNMLIAFT KMHKFEDIET VDILAGCARF IVVGLGGVLF GIVFGFISAF ITRFTQNISA
301 IEPLIVFMFS YLSYLAAETL YLSGILAITA CAVTMKKYVE ENVSQTSYTT IKYFMKMLSS
361 VSETLIFIFM GVSTVGKNHE WNWAFICFTL AFCQIWRAIS VFALFYISNQ FRTFPFSIKD
421 QCIIFYSGVR GAGSFSLAFL LPLSLFPRKK MFVTATLVVI YFTVFIQGIT VGPLVRYLDV
481 KKTNKKESIN EELHIRLMDH LKAGIEDVCG HWSHYQVRDK FKKFDHRYLR KILIRKNLPK
541 SSIVSLYKKL EMKQAIEMVE TGILSSTAFS IPHQAQRIQG IKRLSPEDVE SIRDILTSNM
601 YQVRQRTLSY NKYNLKPQTS EKQAKEILIR RQNTLRESMR KGHSLPWGKP AGTKNIRYLS
661 YPYGNPQSAG RDTRAAGFSD DDSSDPGSPS ITFSACSRIG SLQKQEAQEI IPMKSLHRGR
721 KAFSFGYQRN TSQEEYLGGV RRVALRPKPL FHAVDEEGES GGESEGKASL VEVRSRWTAD
781 HGHGRDHHRS HSPLLQKKLocalizationUniProt · AlphaFold · HPA
Whether an antibody against SLC9A4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 10
- Mean surface accessibility (rSASA)
- 0.42
- Highest tissue expression
- 51 nTPM
Expression across tissuesHPA
Tissue
- stomach: 51 nTPM
- kidney: 8 nTPM
- duodenum: 1.8 nTPM
- esophagus: 1.4 nTPM
- salivary gland: 1.3 nTPM
- skeletal muscle: 1.2 nTPM
Single-cell type
- mucous neck cells: 170 nCPM
- gastric chief cells: 134 nCPM
- parietal cells: 99 nCPM
- renal connecting tubule cells: 94 nCPM
- renal collecting duct principal cells: 67 nCPM
- foveolar cells: 58 nCPM
Immune cell
- neutrophil: 0.1 nTPM
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
Brain region
- cerebellum: 3.8 nTPM
- cerebral cortex: 3.4 nTPM
- basal ganglia: 3.1 nTPM
- hippocampal formation: 3 nTPM
- hypothalamus: 3 nTPM
- white matter: 3 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.1
- gnomAD pLI
- 0
- gnomAD missense Z
- -0.61
- DepMap mean gene effect
- -0.05
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- gastric acid secretion
- glandular epithelial cell development
- monoatomic ion transport
- potassium ion transmembrane transport
- regulation of intracellular pH
- sodium ion import across plasma membrane
- transepithelial ammonium transport
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of SLC9A4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads SLC9A4 as an antibody target. Whether an autoantibody or antibody against SLC9A4 could matter depends on whether native SLC9A4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
SLC9A4 is annotated at the cell surface, where native SLC9A4 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label SLC9A4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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