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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC4A7
solute carrier family 4 member 7
Chromosome 3 · 3p24.1
NCBI Gene: 9497Ensembl: ENSG00000033867.18HGNC: HGNC:11033UniProt: B5M450
121PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
purine nucleotide biosynthetic processplasma membranebasolateral plasma membranepyrimidine nucleotide biosynthetic processhypertensionatrial fibrillationessential hypertensionAbnormality of the skeletal system
✦AI Summary

SLC4A7 (NBCn1) is an electroneutral sodium-bicarbonate cotransporter that mediates bicarbonate import into the cytoplasm, playing a critical role in intracellular pH regulation and acid-base homeostasis 1. In normal physiology, SLC4A7 functions across diverse tissues including epithelial, neuronal, cardiac, and vascular tissues to maintain pH balance and support various cellular functions 1. The transporter is regulated by mTORC1 signaling, which selectively enhances SLC4A7 translation to promote bicarbonate import and support de novo nucleotide synthesis during cell growth 2. However, SLC4A7 exhibits context-dependent roles in cancer pathogenesis. In breast cancer, upregulated Na+,HCO3- cotransport via NBCn1/SLC4A7 facilitates net acid extrusion, maintaining permissive intracellular pH for cancer cell proliferation, with knockout mice showing delayed tumor progression 3. Conversely, in lung adenocarcinoma, SLC4A7 suppresses oncogenesis by reducing lactate transport and protein lactylation, inhibiting tumor stemness and metastatic capacity 4. In head and neck squamous cell carcinoma, SLC4A7 promotes epithelial-mesenchymal transition and metastasis through PI3K/AKT/mTOR pathway activation 5. The SLC4A7 variant rs4973768 is associated with increased breast cancer susceptibility 6. These divergent cancer-specific effects suggest SLC4A7's role depends on tumor type and metabolic context, presenting both therapeutic opportunities and challenges.

Sources cited
1
SLC4A7 is the electroneutral Na,HCO3-cotransporter NBCn1, involved in acid-base regulation across multiple tissues
PMID: 25428855
2
mTORC1 stimulates SLC4A7 translation to promote bicarbonate import and de novo nucleotide synthesis
PMID: 35772404
3
SLC4A7/NBCn1 is upregulated in breast cancer and facilitates acid extrusion, supporting tumor progression
PMID: 30715643
4
SLC4A7 suppresses lung adenocarcinoma by reducing lactate transport and protein lactylation
PMID: 40084702
5
SLC4A7 promotes epithelial-mesenchymal transition and metastasis in head and neck squamous cell carcinoma via PI3K/AKT/mTOR pathway
PMID: 36727616
6
SLC4A7 rs4973768 polymorphism is associated with increased breast cancer risk
PMID: 37128157
7
SLC4A7 emerges as a potential effector in immune modulation in KRAS G12C-mutant lung adenocarcinoma
PMID: 40957478
Disease Associationsⓘ20
hypertensionOpen Targets
0.52Moderate
atrial fibrillationOpen Targets
0.48Moderate
essential hypertensionOpen Targets
0.42Moderate
Abnormality of the skeletal systemOpen Targets
0.42Moderate
alcohol drinkingOpen Targets
0.40Weak
placenta praeviaOpen Targets
0.40Weak
heart failureOpen Targets
0.39Weak
cardiovascular diseaseOpen Targets
0.38Weak
breast carcinomaOpen Targets
0.35Weak
Increased blood pressureOpen Targets
0.35Weak
potassium deficiency diseaseOpen Targets
0.35Weak
Uterine leiomyomaOpen Targets
0.33Weak
response to xenobiotic stimulusOpen Targets
0.32Weak
breast cancerOpen Targets
0.31Weak
thoracic aortic aneurysmOpen Targets
0.31Weak
generalized dystoniaOpen Targets
0.27Weak
agingOpen Targets
0.27Weak
uterine fibroidOpen Targets
0.18Weak
Retinal dystrophyOpen Targets
0.16Weak
nerve plexus diseaseOpen Targets
0.10Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ADGRV1Protein interaction99%USH2AProtein interaction85%USH1CProtein interaction85%PPP3CBProtein interaction80%COX11Protein interaction78%LSP1Protein interaction78%
Tissue Expression6 tissues
Ovary
100%
Lung
89%
Heart
74%
Bone Marrow
62%
Brain
39%
Liver
28%
Gene Interaction Network
Click a node to explore
SLC4A7ADGRV1USH2AUSH1CPPP3CBCOX11LSP1
PROTEIN STRUCTURE
Preparing viewer…
PDB9OVR · 3.30 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.56Moderately Constrained
pLIⓘ
0.61Intermediate
Observed/Expected LoF0.39 [0.28–0.56]
RankingsWhere SLC4A7 stands among ~20K protein-coding genes
  • #3,899of 20,598
    Most Researched121 · top quartile
  • #3,621of 17,882
    Most Constrained (LOEUF)0.56 · top quartile
Genes detectedSLC4A7
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study.
PMID: 22135276
J Med Genet · 2012
1.00
2
SLC4A7 suppresses lung adenocarcinoma oncogenesis by reducing lactate transport and protein lactylation.
PMID: 40084702
Int J Oncol · 2025
0.90
3
Cation-coupled bicarbonate transporters.
PMID: 25428855
Compr Physiol · 2014
0.80
4
Update on the relationship between the
PMID: 37128157
J Int Med Res · 2023
0.70
5
Bicarbonate transporter SLC4A7 promotes EMT and metastasis of HNSCC by activating the PI3K/AKT/mTOR signaling pathway.
PMID: 36727616
Mol Carcinog · 2023
0.60