Seroatlas · Human Serome Atlas

SLC4A4

Electrogenic sodium bicarbonate cotransporter 1

Also known as: hhNMC, HNBC1, NBC1, NBC2, pNBC, S4A4_HUMAN, SLC4A5

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
Q9Y6R1
Gene
SLC4A4
Ensembl
ENSG00000080493
Chromosome
4
Canonical length
1079 aa
Protein class
Disease related genes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters
Subcellular location
Plasma membrane,Cytosol
Quaternary structure
Homodimer

OverviewNCBI Gene

This gene encodes a sodium bicarbonate cotransporter (NBC) involved in the regulation of bicarbonate secretion and absorption and intracellular pH. Mutations in this gene are associated with proximal renal tubular acidosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

Canonical amino-acid sequenceUniProt

1079 residues, UniProt reviewed canonical sequence.

>Q9Y6R1|SLC4A4
     1  MEDEAVLDRG ASFLKHVCDE EEVEGHHTIY IGVHVPKSYR RRRRHKRKTG HKEKKEKERI
    61  SENYSDKSDI ENADESSSSI LKPLISPAAE RIRFILGEED DSPAPPQLFT ELDELLAVDG
   121  QEMEWKETAR WIKFEEKVEQ GGERWSKPHV ATLSLHSLFE LRTCMEKGSI MLDREASSLP
   181  QLVEMIVDHQ IETGLLKPEL KDKVTYTLLR KHRHQTKKSN LRSLADIGKT VSSASRMFTN
   241  PDNGSPAMTH RNLTSSSLND ISDKPEKDQL KNKFMKKLPR DAEASNVLVG EVDFLDTPFI
   301  AFVRLQQAVM LGALTEVPVP TRFLFILLGP KGKAKSYHEI GRAIATLMSD EVFHDIAYKA
   361  KDRHDLIAGI DEFLDEVIVL PPGEWDPAIR IEPPKSLPSS DKRKNMYSGG ENVQMNGDTP
   421  HDGGHGGGGH GDCEELQRTG RFCGGLIKDI KRKAPFFASD FYDALNIQAL SAILFIYLAT
   481  VTNAITFGGL LGDATDNMQG VLESFLGTAV SGAIFCLFAG QPLTILSSTG PVLVFERLLF
   541  NFSKDNNFDY LEFRLWIGLW SAFLCLILVA TDASFLVQYF TRFTEEGFSS LISFIFIYDA
   601  FKKMIKLADY YPINSNFKVG YNTLFSCTCV PPDPANISIS NDTTLAPEYL PTMSSTDMYH
   661  NTTFDWAFLS KKECSKYGGN LVGNNCNFVP DITLMSFILF LGTYTSSMAL KKFKTSPYFP
   721  TTARKLISDF AIILSILIFC VIDALVGVDT PKLIVPSEFK PTSPNRGWFV PPFGENPWWV
   781  CLAAAIPALL VTILIFMDQQ ITAVIVNRKE HKLKKGAGYH LDLFWVAILM VICSLMALPW
   841  YVAATVISIA HIDSLKMETE TSAPGEQPKF LGVREQRVTG TLVFILTGLS VFMAPILKFI
   901  PMPVLYGVFL YMGVASLNGV QFMDRLKLLL MPLKHQPDFI YLRHVPLRRV HLFTFLQVLC
   961  LALLWILKST VAAIIFPVMI LALVAVRKGM DYLFSQHDLS FLDDVIPEKD KKKKEDEKKK
  1021  KKKKGSLDSD NDDSDCPYSE KVPSIKIPMD IMEQQPFLSD SKPSDRERSP TFLERHTSC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SLC4A4 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
12
Mean surface accessibility (rSASA)
0.35
Highest tissue expression
245 nTPM

Expression across tissuesHPA

Tissue

  • pancreas: 245 nTPM
  • kidney: 112 nTPM
  • duodenum: 51 nTPM
  • rectum: 39 nTPM
  • colon: 38 nTPM
  • basal ganglia: 34 nTPM

Single-cell type

  • bergmann glia: 4,234 nCPM
  • pancreatic duct cells: 3,795 nCPM
  • astrocytes: 1,379 nCPM
  • pituicytes/fscs: 1,072 nCPM
  • proximal tubule cells: 968 nCPM
  • retinal ganglion cells: 691 nCPM

Immune cell

  • gdT-cell: 0.7 nTPM
  • memory CD8 T-cell: 0.6 nTPM
  • MAIT T-cell: 0.3 nTPM
  • naive CD8 T-cell: 0.2 nTPM
  • memory CD4 T-cell: 0.1 nTPM
  • NK-cell: 0.1 nTPM

Brain region

  • cerebellum: 124 nTPM
  • basal ganglia: 117 nTPM
  • medulla oblongata: 110 nTPM
  • spinal cord: 108 nTPM
  • hypothalamus: 106 nTPM
  • white matter: 95 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SLC4A4.

Disease | AllUniProt

Conditions SLC4A4 is implicated in, by any mechanism.

  • Proximal renal tubular acidosis-ocular anomaly syndrome (PRTAO) MIM:604278

Disease | GeneticClinVar

17 pathogenic / likely-pathogenic of 484 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

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)
0.27
gnomAD pLI
1
gnomAD missense Z
3.14
DepMap mean gene effect
0.09
DepMap dependency class
none

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

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of SLC4A4 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 SLC4A4 as an antibody target. Whether an autoantibody or antibody against SLC4A4 could matter depends on whether native SLC4A4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SLC4A4 is annotated at the cell surface, where native SLC4A4 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 SLC4A4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/SLC4A4. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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