SLC9A3

Protein identityUniProt · HPA

UniProt accession

P48764

Gene

SLC9A3

Ensembl

ENSG00000066230

Chromosome

5

Canonical length

834 aa

Protein class

Disease related genes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted membrane proteins, Transporters

Subcellular location

Plasma membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene is an epithelial brush border Na/H exchanger that uses an inward sodium ion gradient to expel acids from the cell. Defects in this gene are a cause of congenital secretory sodium diarrhea. Pseudogenes of this gene exist on chromosomes 10 and 22. [provided by RefSeq, Mar 2016]

Canonical amino-acid sequenceUniProt

834 residues, UniProt reviewed canonical sequence.

>P48764|SLC9A3
     1  MWGLGARGPD RGLLLALALG GLARAGGVEV EPGGAHGESG GFQVVTFEWA HVQDPYVIAL
    61  WILVASLAKI GFHLSHKVTS VVPESALLIV LGLVLGGIVW AADHIASFTL TPTVFFFYLL
   121  PPIVLDAGYF MPNRLFFGNL GTILLYAVVG TVWNAATTGL SLYGVFLSGL MGDLQIGLLD
   181  FLLFGSLMAA VDPVAVLAVF EEVHVNEVLF IIVFGESLLN DAVTVVLYNV FESFVALGGD
   241  NVTGVDCVKG IVSFFVVSLG GTLVGVVFAF LLSLVTRFTK HVRIIEPGFV FIISYLSYLT
   301  SEMLSLSAIL AITFCGICCQ KYVKANISEQ SATTVRYTMK MLASSAETII FMFLGISAVN
   361  PFIWTWNTAF VLLTLVFISV YRAIGVVLQT WLLNRYRMVQ LEPIDQVVLS YGGLRGAVAF
   421  ALVVLLDGDK VKEKNLFVST TIIVVFFTVI FQGLTIKPLV QWLKVKRSEH REPRLNEKLH
   481  GRAFDHILSA IEDISGQIGH NYLRDKWSHF DRKFLSRVLM RRSAQKSRDR ILNVFHELNL
   541  KDAISYVAEG ERRGSLAFIR SPSTDNVVNV DFTPRSSTVE ASVSYLLREN VSAVCLDMQS
   601  LEQRRRSIRD AEDMVTHHTL QQYLYKPRQE YKHLYSRHEL TPTEDEKQDR EIFHRTMRKR
   661  LESFKSTKLG LNQNKKAAKL YKRERAQKRR NSSIPNGKLP MESPAQNFTI KEKDLELSDT
   721  EEPPNYDEEM SGGIEFLASV TKDTASDSPA GIDNPVFSPD EALDRSLLAR LPPWLSPGET
   781  VVPSQRARTQ IPYSPGTFCR LMPFRLSSKS VDSFLQADGP EERPPAALPE STHM

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SLC9A3 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

13

Mean surface accessibility (rSASA)

0.43

Highest tissue expression

88 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SLC9A3.

Disease | AllUniProt

Conditions SLC9A3 is implicated in, by any mechanism.

• Diarrhea 8, secretory sodium, congenital (DIAR8) MIM:616868

Disease | GeneticClinVar

24 pathogenic / likely-pathogenic of 831 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Congenital secretory sodium diarrhea 8

ReferencesPubMed · IEDB

Publications for SLC9A3 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.31

gnomAD pLI

0.98

gnomAD missense Z

2.49

DepMap mean gene effect

-0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• monoatomic ion transport
• potassium ion transmembrane transport
• regulation of intracellular pH
• sodium ion import across plasma membrane

Molecular functions

• identical protein binding
• PDZ domain binding
• phosphatidylinositol binding
• potassium:proton antiporter activity
• sodium:proton antiporter activity

Cellular components

• apical plasma membrane
• brush border
• brush border membrane
• cell surface
• early endosome
• early endosome membrane
• extracellular exosome
• plasma membrane
• recycling endosome membrane

Protein domainsUniProt · Pfam · InterPro

• Na+/H+ exchanger
• Cation/H+ exchanger, transmembrane domain
• Na+/H+ exchanger, isoforms 3/5
• Cation/H+ exchanger, CPA1 family
• Sodium/hydrogen exchanger, transmembrane

KeywordsUniProt

• Antiport
• Cell membrane
• Endosome
• Glycoprotein
• Ion transport
• Membrane
• Phosphoprotein
• Signal
• Sodium
• Sodium transport
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

Protein binding partners of SLC9A3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• AHCYL1
• CHP1
• CHP2
• EZR
• NHERF4
• PDZK1
• SHANK2
• SNX27