Affinage

SLC4A7

Sodium bicarbonate cotransporter 3 · UniProt Q9Y6M7

Length
1214 aa
Mass
136.0 kDa
Annotated
2026-06-10
33 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC4A7 (NBCn1) is an electroneutral, Na+-dependent, amiloride-insensitive Na+/HCO3- cotransporter that mediates bicarbonate import to maintain intracellular pH across vascular smooth muscle, endothelium, neurons, epithelium, and macrophages (PMID:16439691, PMID:18077606). Its transport activity is shaped by alternative N-termini and optional splice cassettes that independently tune surface abundance versus per-molecule activity (PMID:23959679), and by a C-terminal PDZ-binding domain that recruits scaffold proteins such as syntrophin γ2 to enhance both cotransport and channel-like conductance (PMID:24844638). In arteries, NBCn1-set pHi supports NO production and rho-kinase-dependent Ca2+ sensitization, linking the transporter to blood pressure regulation, and its loss produces mild hypertension (PMID:21947296). NBCn1 is a dominant acid-extrusion mechanism in breast carcinoma, where it is induced downstream of ErbB2/HER2 via PI3K/Akt/ERK/Src and the transcription factor KLF4 to alkalinize the tumor and sustain proliferation; genetic loss delays tumorigenesis and high-affinity blocking antibodies slow patient-derived tumor growth (PMID:24088818, PMID:26212013, PMID:29907770, PMID:38310186). Beyond pH homeostasis, mTORC1 selectively upregulates SLC4A7 translation through S6K-mediated eIF4B phosphorylation to supply bicarbonate for de novo purine and pyrimidine synthesis and cell growth, a function independent of bulk intracellular pH (PMID:35772404), and SLC4A7 supports phagosome acidification and microbicidal activity in macrophages (PMID:29779931). Independently of its transport activity, SLC4A7 is a membrane-binding partner of Rhes that promotes tunneling-nanotube formation and intercellular spread of mutant Huntingtin (PMID:41861004).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2006 High

    Established that NBCn1 is the principal Na+/HCO3- cotransporter setting resting pHi in vascular smooth muscle, answering which molecule performs amiloride-insensitive base influx in arteries.

    Evidence BCECF pH imaging with siRNA knockdown and immunogold EM in intact mouse arteries

    PMID:16439691

    Open questions at the time
    • Did not resolve transport stoichiometry or electrogenicity
    • Tissue scope limited to vascular beds
  2. 2007 High

    Mapped the broad tissue and subcellular distribution of NBCn1 and confirmed its functional dependence on CO2/HCO3-, defining where the transporter operates.

    Evidence LacZ knock-in reporter, RT-PCR, and pH measurement across multiple tissues

    PMID:18077606

    Open questions at the time
    • Reporter localizes expression but not active transport per tissue
    • Functional contribution outside smooth muscle not quantified here
  3. 2008 Medium

    Identified scaffold interactions (PSD-95) and differential trafficking stability that begin to explain how NBCn1 is anchored and regulated at the membrane.

    Evidence GST pulldown and co-IP from rat brain; surface biotinylation/confocal in polarized acinar cells

    PMID:18815229 PMID:20147654

    Open questions at the time
    • No mutagenesis to map the PSD-95 binding interface
    • Functional consequence of PSD-95 binding on transport not measured
  4. 2008 Medium

    Probed NBCn1's role in neuronal injury, showing pH-driven upregulation and a context-dependent contribution to excitotoxicity rather than acid-induced death.

    Evidence siRNA knockdown with LDH cytotoxicity assays in primary hippocampal neurons

    PMID:19170751

    Open questions at the time
    • Mechanism linking Mg2+ depletion to NBCn1-dependent injury unresolved
    • Single-lab phenotype
  5. 2010 Medium

    Linked SLC4A7 to mitochondrial apoptosis suppression in endothelium under ischemia, expanding its role beyond plasma-membrane pH regulation.

    Evidence Subcellular fractionation, siRNA, S0859 inhibitor, and caspase pathway dissection in a simulated ischemia model

    PMID:20962104

    Open questions at the time
    • Mitochondrial localization not reconciled with canonical plasmalemmal role
    • Mechanism connecting transport to Bax/caspase-9 unclear
  6. 2011 High

    Connected NBCn1-set pHi to vascular signaling, establishing a pHi→NO→rho-kinase axis and a blood-pressure phenotype in vivo.

    Evidence NBCn1 knockout mice with myography, NO electrode/radioisotope assays, in vitro rho-kinase assay, and radiotelemetry

    PMID:21947296

    Open questions at the time
    • Relative contributions of endothelial vs. smooth muscle NBCn1 not separated
    • Direct pH-sensitivity mechanism of rho-kinase only shown in vitro
  7. 2012 Medium

    Demonstrated NBCn1 as the dominant acid extruder in human breast carcinoma, positioning it as a candidate driver of tumor pH dysregulation.

    Evidence pH fluorophore transport assays, DIDS inhibition, and IHC/Western on primary human breast tissue

    PMID:22907202

    Open questions at the time
    • Nature of carcinoma-associated post-translational modification unidentified
    • Correlative tissue data without causal manipulation
  8. 2013 High

    Defined the upstream oncogenic control of NBCn1, placing it downstream of ErbB2 via PI3K/Akt/ERK/Src and the transcription factors KLF4 (positive) and Sp1 (negative).

    Evidence Multi-target siRNA, dominant-negative Sp1, promoter luciferase, and acid-extrusion assays in breast cancer cells

    PMID:24088818

    Open questions at the time
    • Did not establish in vivo tumor relevance of each node
    • KLF4/Sp1 binding sites not directly footprinted
  9. 2013 High

    Resolved how alternative N-termini and splice cassettes independently regulate surface abundance versus intrinsic transport, explaining isoform-level tuning of NBCn1.

    Evidence Xenopus oocyte expression with electrophysiology and surface biotinylation of OSE variants

    PMID:23959679

    Open questions at the time
    • Physiological tissues using each variant not mapped
    • Structural basis of cassette effects unknown
  10. 2014 Medium

    Cataloged the PDZ interactome and showed a scaffold (syntrophin γ2) directly enhances transport, clarifying how C-terminal partners regulate activity.

    Evidence PDZ array screen, reciprocal GST pulldowns, and oocyte pHi/electrophysiology

    PMID:24844638

    Open questions at the time
    • Physiological relevance of most of the 13 partners untested
    • Single-lab oocyte system
  11. 2015 High

    Provided causal in vivo proof that NBCn1 promotes breast carcinogenesis through pH/metabolic regulation, beyond correlation.

    Evidence NBCn1 knockout crossed with a tumor model, pHi imaging, microdialysis, and proliferation IHC

    PMID:26212013

    Open questions at the time
    • Mechanistic link between altered glucose/lactate and reduced proliferation incomplete
    • Did not test therapeutic targeting
  12. 2016 Medium

    Identified a regulatory variant mechanism, showing the hypertension-risk allele rs820430 acts as a c-Fos-dependent transcriptional enhancer of SLC4A7.

    Evidence Luciferase reporter, EMSA, ChIP, and genotyping in a human cohort

    PMID:27784683

    Open questions at the time
    • Causal link from enhanced expression to blood pressure not demonstrated in vivo
    • Single locus, single lab
  13. 2017 Medium

    Explained how additional SLC4A7 SNPs reduce functional transporter by driving an N-terminally truncated, poorly trafficked NBCn1ΔN450 isoform.

    Evidence Alternative promoter/TSS analysis, HEK293 expression, Western, and pHi measurement

    PMID:28087757

    Open questions at the time
    • Physiological tissues producing the truncated isoform not identified
    • Phenotypic consequence in carriers untested
  14. 2018 High

    Established a transport-dependent role in innate immunity, showing SLC4A7-mediated bicarbonate import sustains cytoplasmic pH to enable phagosome acidification and microbial killing.

    Evidence Loss-of-function with WT vs. transport-dead/mislocalized rescue and phagosome pH/killing assays in macrophages

    PMID:29779931

    Open questions at the time
    • Coupling between cytoplasmic pH and phagosomal proton pumping mechanistically incomplete
    • Cell-line based
  15. 2018 High

    Confirmed NBCn1's pro-tumor role specifically in ErbB2-driven cancer in vivo and uncovered post-transcriptional (not transcriptional) upregulation of the protein.

    Evidence NBCn1 knockout crossed with ErbB2 tumor model, Western/RT-PCR mismatch, pHi imaging, microdialysis, Ki-67

    PMID:29907770

    Open questions at the time
    • Identity of the post-transcriptional regulatory mechanism not defined here
    • Region-specific proliferation effect mechanism partial
  16. 2022 High

    Revealed a growth-promoting function decoupled from bulk pH: mTORC1 translationally upregulates SLC4A7 to supply bicarbonate for de novo nucleotide synthesis.

    Evidence mTORC1/S6K inhibition, eIF4B knockdown, SLC4A7 loss-of-function, isotope flux of nucleotide synthesis, and xenografts

    PMID:35772404

    Open questions at the time
    • How imported HCO3- is partitioned to carbamoyl-phosphate-dependent steps not directly traced
    • Generality across non-mTORC1-driven tumors unknown
  17. 2024 Medium

    Extended NBCn1 function to epithelial motility, linking it to focal adhesions and migration/proliferation in colonic cells.

    Evidence siRNA and KO enteroids with pH imaging, migration assays, and focal adhesion marker colocalization

    PMID:38646790

    Open questions at the time
    • Direct molecular interaction with adhesion machinery not established
    • Causality between pHi and adhesion not separated from other roles
  18. 2024 High

    Validated NBCn1 as a druggable cancer target with extracellularly-targeted high-affinity blocking antibodies effective in patient-derived models.

    Evidence Anti-NBCn1 antibodies, transport inhibition, primary organoids, patient tissue, PDX growth, cell cycle and apoptosis assays

    PMID:38310186

    Open questions at the time
    • In vivo toxicity/normal-tissue effects of inhibition not detailed
    • Resistance mechanisms unaddressed
  19. 2025 Medium

    Reported a context-dependent tumor-suppressive role in lung adenocarcinoma via reduced lactate and protein lactylation, contrasting with its pro-tumor breast cancer role.

    Evidence Lactylome proteomics with loss/gain-of-function and xenografts in LUAD cells

    PMID:40084702

    Open questions at the time
    • Mechanism reconciling opposite tumor roles across cancers unknown
    • Direct link between transport and lactylome not established
  20. 2026 High

    Uncovered a transport-independent function: SLC4A7 partners with Rhes to drive tunneling-nanotube formation and intercellular mutant Huntingtin spread.

    Evidence Unbiased LC-MS/MS, siRNA/pharmacology, Rhes domain mapping, TNT and mHTT transfer assays, and KO mice in vivo

    PMID:41861004

    Open questions at the time
    • Structural basis of the Rhes–SLC4A7 membrane complex unresolved
    • Relevance to endogenous neuronal physiology beyond mHTT spread unclear
  21. 2026 Medium

    Showed SLC4A7 shapes the tumor microenvironment and antitumor immunity, with knockout alkalinizing the niche, boosting T cell function, and synergizing with checkpoint blockade.

    Evidence siRNA/KO in NSCLC models, pH and glycolysis assays, T cell infiltration, PD-1/PD-L1 combination, RNA-seq+ATAC-seq identifying CTCF

    PMID:42088432

    Open questions at the time
    • CTCF regulation based on integrated genomics without direct validation
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how SLC4A7 produces opposite (pro- vs. anti-tumor) outcomes across cancer types and how its transport-independent scaffolding functions are mechanistically partitioned from its bicarbonate transport role.
  • No unifying model for tissue-specific pro- vs. tumor-suppressive behavior
  • Structural mechanism distinguishing transport vs. scaffold functions undefined
  • No high-resolution structure of the transporter or its complexes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 6 GO:0140104 molecular carrier activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 5 GO:0005739 mitochondrion 1
Pathway
R-HSA-382551 Transport of small molecules 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 2
Partners
ERBINMAGI3NHERF1NHERF2PDZK1PSD-95RHESSNTB2

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 NBCn1 (SLC4A7) mediates Na+-dependent, bicarbonate-dependent intracellular pH recovery in vascular smooth muscle cells of mouse mesenteric, coronary, and cerebral arteries; siRNA knockdown reduced steady-state pHi by 0.21 pH units and decreased net Na+-dependent, amiloride-insensitive base influx by 68%, confirming NBCn1 as the primary Na+-HCO3- cotransporter in these cells. pH-sensitive fluorophore (BCECF), RT-PCR, immunogold electron microscopy, siRNA knockdown in intact arteries, ammonium prepulse assay Circulation research High 16439691
2007 NBCn1 (SLC4A7) is expressed at the sarcolemma of vascular smooth muscle and endothelial cells, kidney thick ascending limb, medullary collecting duct, choroid plexus, hippocampus, retina, atrial cardiomyocytes, and nonvascular smooth muscle; disruption of NBCn1 reduced amiloride-insensitive Na+-dependent HCO3- influx and lowered steady-state pHi in bladder smooth muscle cells in the presence of CO2/HCO3- but not in its nominal absence. Beta-galactosidase reporter (LacZ knock-in), RT-PCR, fluorescence pH measurement in smooth muscle cells American journal of physiology. Cell physiology High 18077606
2008 NBCn1 (SLC4A7) colocalizes with the postsynaptic density protein PSD-95 in hippocampal CA3 neuron dendrites; PSD-95 was pulled down from rat brain lysates with a GST/NBCn1 fusion protein and co-immunoprecipitated with NBCn1, establishing a direct physical interaction. GST pulldown from rat brain lysates, co-immunoprecipitation, double immunofluorescence labeling American journal of physiology. Cell physiology Medium 20147654
2008 NBCn1 (SLC4A7) upregulates expression at low extracellular pH (increases ~5-fold at pHo <6.5) and during Mg2+-free incubation; NBCn1 knockdown did not protect neurons from acid-induced cytotoxicity but progressively attenuated cytotoxicity in Mg2+-free conditions after glutamate exposure, indicating NBCn1 increases excitotoxic injury under Mg2+ depletion. siRNA knockdown, immunochemistry, LDH release cytotoxicity assay, Western blot in primary hippocampal neurons The European journal of neuroscience Medium 19170751
2008 NBCe1 (SLC4A4) undergoes cholinergic/PKC-stimulated endocytosis in parotid acinar cells, whereas NBCn1 (SLC4A7) remains stably at the basolateral membrane under the same conditions, indicating differential trafficking regulation; stable membrane association of NBCn1 supports constitutive HCO3- uptake. Confocal fluorescence microscopy, surface biotinylation, cholinergic/PMA stimulation, PKC inhibition in polarized ParC5 cells American journal of physiology. Cell physiology Medium 18815229
2010 SLC4A7 localizes to mitochondria in rat coronary endothelial cells and suppresses ischemia-induced mitochondrial apoptosis; pharmacological inhibition (S0859) or siRNA knockdown of SLC4A7 increased caspase-3 activity, activated the mitochondrial pathway (caspase-9 cleavage, Bax-mitochondria binding), without activating ER-dependent (caspase-12) or extrinsic (caspase-8) pathways. Subcellular fractionation/immunolocalization, siRNA knockdown, selective inhibitor S0859, caspase activity assays, Western blot in simulated ischemia model Cardiovascular research Medium 20962104
2011 Knockout of NBCn1 (SLC4A7) in mice caused lower steady-state pHi in mesenteric artery smooth muscle and endothelial cells, reduced NO production (measured by electrode and radioisotope conversion), reduced acetylcholine-induced NO-mediated relaxation, and decreased rho-kinase-dependent smooth muscle Ca2+ sensitivity (reduced MYPT1 Thr-850 phosphorylation); rho-kinase activity was reduced at low pH in vitro; NBCn1 KO mice were mildly hypertensive and resistant to angiotensin-II-induced hypertension. Fluorescence microscopy (pHi), myography, NO electrode, radioisotope L-arginine conversion, Western blot, in vitro rho-kinase assay, radiotelemetry blood pressure in knockout mice Circulation High 21947296
2012 Na+,HCO3- cotransport mediated by NBCn1 (SLC4A7) is the predominant mechanism of acid extrusion in human primary breast carcinomas (accounts for >90% of net acid extrusion at pHi >6.6); DIDS inhibits this activity by 34%; NBCn1 plasmalemmal density is 20-30% higher in primary breast carcinomas and metastases vs. matched normal tissue; apparent molecular weight of NBCn1 is increased in carcinomas suggesting post-translational modification. pH-sensitive fluorophores, DIDS inhibition assay, immunohistochemistry/Western blot in human primary breast tissue International journal of cancer Medium 22907202
2013 ErbB2 (HER2) signaling upregulates NBCn1 (SLC4A7) protein expression via PI3K/Akt1, ERK1/2, Src kinases and the transcription factor KLF4 (positive regulator, ~40-50% effect each); Sp1 negatively regulates NBCn1 expression; ErbB receptor stimulation doubles acid extrusion capacity in SKBr3 cells via NBCn1-mediated Na+,HCO3- cotransport. siRNA knockdown of PI3K, Akt1, ERK1/2, Src, KLF4, Sp1; dominant-negative Sp1; promoter luciferase assay; Western blot; pH-based acid extrusion measurement in breast cancer cells FASEB journal High 24088818
2013 Alternative optional structural elements (OSEs) of NBCn1 (SLC4A7) — including the MEAD vs. MERF N-terminus and novel cassette IV — differentially affect surface membrane abundance and intrinsic HCO3- transport activity when expressed in Xenopus oocytes; MEAD increases surface abundance; cassette IV reduces surface abundance but increases intrinsic per-molecule activity; cassettes II and III also increase intrinsic activity. Xenopus oocyte expression, electrophysiology, surface biotinylation The Journal of physiology High 23959679
2014 The C-terminal PDZ-binding domain of NBCn1 (SLC4A7) interacts with 13 PDZ scaffold proteins including MAGI-3, NHERF-1, NHERF-2, PSD-95, ERBIN, syntrophins, and PDZK1; syntrophin γ2 directly binds NBCn1 (reciprocal GST pulldowns) and increases both Na+/HCO3- cotransport-mediated intracellular pH recovery and channel-like ionic conductance of NBCn1 in Xenopus oocytes. PDZ protein array screen, GST pulldown (reciprocal), Xenopus oocyte expression with pHi measurement and electrophysiology Physiological reports Medium 24844638
2015 NBCn1 (SLC4A7) protein expression increases ~2.5-fold during breast carcinogenesis and is responsible for increased net acid extrusion and alkaline intracellular pH in breast cancer compared with normal breast tissue; genetic disruption of NBCn1 delayed tumor latency by ~50%, reduced tumor growth rate by ~65%, altered tumor histopathology to less aggressive types, and lowered cancer cell proliferation (Ki-67/phospho-H3 staining), with higher interstitial glucose and lower lactate in NBCn1 KO tumors. NBCn1 knockout mice crossed with tumor model, pHi fluorescence measurement, microdialysis metabolite analysis, immunohistochemistry (Ki-67, pH3, PARP-1), Western blot Oncogene High 26212013
2016 The hypertension-risk SNP rs820430 T allele functions as a transcriptional enhancer of SLC4A7 by increasing c-Fos transcription factor binding to this locus, leading to higher SLC4A7 mRNA expression. Luciferase reporter assay, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), genotyping in human cohort American journal of hypertension Medium 27784683
2017 SNPs rs3278 and rs3755652 in SLC4A7 stimulate an alternative intronic promoter driving production of NH2-terminally truncated NBCn1ΔN450; this truncated protein reaches the plasma membrane at significantly lower levels than full-length NBCn1 and mediates reduced pH change; the amino acid change E326K caused by rs3755652 has negligible effect on transporter function per se. Luciferase reporter assay, transcription start site analysis, HEK293 cell expression, Western blot, pHi measurement Physiological genomics Medium 28087757
2018 SLC4A7 is strongly induced during macrophage differentiation and is critical for phagosome acidification; loss of SLC4A7 reduces phagosome acidification of beads or bacteria and impairs microbicidal capacity; rescue with wild-type SLC4A7 but not transport-deficient or mislocalized mutants restores phagosome acidification; mechanistically, SLC4A7-mediated bicarbonate import maintains cytoplasmic pH, which is necessary to drive phagosome acidification. Loss-of-function (genetic), rescue with WT and mutant SLC4A7, phagosome pH measurement, intracellular bacterial killing assay in human macrophage cell lines Cell host & microbe High 29779931
2018 NBCn1 (SLC4A7) protein abundance increases ~2-fold in ErbB2-induced breast cancer tissue (despite 4-fold decrease in mRNA, suggesting post-transcriptional regulation); NBCn1 facilitates net acid extrusion and elevates steady-state intracellular pH in ErbB2-driven breast cancer; NBCn1 knockout delayed ErbB2-induced carcinogenesis, reduced tumor growth rate by ~1/3, and inhibited cell proliferation particularly in central (high acid load) tumor areas. Genetically engineered NBCn1 knockout mice crossed with ErbB2 tumor model, Western blot, RT-PCR, pHi fluorescence, microdialysis, Ki-67 immunostaining Oncogene High 29907770
2022 mTORC1 stimulates intracellular HCO3- transport through selective translational upregulation of SLC4A7, dependent on S6K-mediated phosphorylation of translation factor eIF4B; loss of SLC4A7 in mTORC1-driven cells reduces purine and pyrimidine de novo synthesis flux and decreases cell and tumor growth without altering intracellular pH. mTORC1/S6K inhibition, eIF4B knockdown, SLC4A7 knockdown/knockout, isotope flux (nucleotide synthesis), tumor growth assays in human cells and xenografts Molecular cell High 35772404
2024 NBCn1 (SLC4A7) is expressed at the leading edge of migrating colonic epithelial cells (Caco2BBe) and colocalizes with focal adhesion markers vinculin and paxillin; siRNA knockdown of NBCn1 decreases intracellular pH proportional to knockdown degree, impairs cell adhesion, reduces migratory speed, and reduces proliferation; NBCn1-/- murine colonic enteroids show reduced proliferative activity. siRNA knockdown, pH fluorescence, wound healing/migration assay, immunofluorescence colocalization with focal adhesion markers, murine knockout enteroids American journal of physiology. Cell physiology Medium 38646790
2024 Extracellularly-targeted anti-NBCn1 antibodies (KD ~0.14 nM) block human NBCn1-mediated Na+,HCO3- cotransport in cells and primary breast carcinoma organoids, lower net acid extrusion in breast cancer tissue from patients with lymph node metastases, decelerate patient-derived xenograft (triple-negative breast cancer) tumor growth by ~50%, and pH-dependently reduce colony formation, cause G2/M cell cycle arrest, and increase apoptosis in metastatic breast cancer cells. Antibody development, transport inhibition assay, primary human organoids, patient tissue acid extrusion measurement, PDX xenograft tumor growth, cell cycle and apoptosis assays British journal of cancer High 38310186
2025 SLC4A7 suppresses lung adenocarcinoma progression by decreasing intracellular and extracellular lactate accumulation and inhibiting global protein lactylation, including lysine lactylation of HSP90AA1 and focal adhesion pathway proteins; SLC4A7 also reduces tumor stemness. Lactylome analysis, Transwell/wound-healing migration assay, animal xenograft experiments, SLC4A7 knockdown/overexpression in LUAD cells International journal of oncology Medium 40084702
2026 Slc4a7 is a top membrane-binding partner of Rhes (identified by unbiased LC-MS/MS); Rhes directly interacts with Slc4a7 through both amino- and carboxyl-terminal domains; siRNA depletion or pharmacological inhibition of Slc4a7 substantially reduces Rhes-induced tunneling nanotube (TNT) formation and suppresses mutant Huntingtin (mHTT) intercellular transfer; this function does not require Slc4a7 transporter activity but does require Rhes farnesylation for membrane anchoring; Slc4a7 KO mice show reduced mHTT cell-to-cell transmission in the striatum in vivo. LC-MS/MS proteomics of membrane-associated Rhes complexes, siRNA knockdown, pharmacological inhibition, TNT formation assay, mHTT transfer assay, Rhes domain mapping, Slc4a7 knockout mice with in vivo mHTT transmission assay Science advances High 41861004
2026 SLC4A7 knockdown in NSCLC impairs bicarbonate uptake causing intracellular acidification and extracellular alkalinization, suppresses glycolysis, and reduces tumor growth and metastasis; Slc4a7 knockout alkalinizes the tumor microenvironment enhancing cytotoxic T cell infiltration and function; Slc4a7 KO synergizes with PD-1/PD-L1 checkpoint inhibitors; CTCF was identified as a transcription factor regulating SLC4A7 expression by integrated RNA-seq and ATAC-seq analysis. SLC4A7 siRNA knockdown, Slc4a7 knockout mice (in vivo tumor model), pH measurement, glycolysis assay, T cell infiltration/function assay, combination with PD-1/PD-L1 inhibitors, RNA-seq + ATAC-seq International journal of biological sciences Medium 42088432

Source papers

Stage 0 corpus · 33 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Disruption of Na+,HCO₃⁻ cotransporter NBCn1 (slc4a7) inhibits NO-mediated vasorelaxation, smooth muscle Ca²⁺ sensitivity, and hypertension development in mice. Circulation 121 21947296
2012 Contribution of Na+,HCO3(-)-cotransport to cellular pH control in human breast cancer: a role for the breast cancer susceptibility locus NBCn1 (SLC4A7). International journal of cancer 100 22907202
2015 Disrupting Na⁺, HCO₃⁻-cotransporter NBCn1 (Slc4a7) delays murine breast cancer development. Oncogene 78 26212013
2006 NBCn1 (slc4a7) mediates the Na+-dependent bicarbonate transport important for regulation of intracellular pH in mouse vascular smooth muscle cells. Circulation research 75 16439691
2007 Antibody-independent localization of the electroneutral Na+-HCO3- cotransporter NBCn1 (slc4a7) in mice. American journal of physiology. Cell physiology 71 18077606
2018 The Bicarbonate Transporter SLC4A7 Plays a Key Role in Macrophage Phagosome Acidification. Cell host & microbe 66 29779931
2018 Na+,HCO3--cotransporter NBCn1 (Slc4a7) accelerates ErbB2-induced breast cancer development and tumor growth in mice. Oncogene 48 29907770
2010 Neuronal expression of sodium/bicarbonate cotransporter NBCn1 (SLC4A7) and its response to chronic metabolic acidosis. American journal of physiology. Cell physiology 40 20147654
2013 ErbB2 upregulates the Na+,HCO3(-)-cotransporter NBCn1/SLC4A7 in human breast cancer cells via Akt, ERK, Src, and Kruppel-like factor 4. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 38 24088818
2022 The mTORC1-SLC4A7 axis stimulates bicarbonate import to enhance de novo nucleotide synthesis. Molecular cell 33 35772404
2008 Sodium/bicarbonate cotransporter NBCn1/slc4a7 increases cytotoxicity in magnesium depletion in primary cultures of hippocampal neurons. The European journal of neuroscience 28 19170751
2010 SLC4A7 sodium bicarbonate co-transporter controls mitochondrial apoptosis in ischaemic coronary endothelial cells. Cardiovascular research 27 20962104
2007 Chronic continuous hypoxia decreases the expression of SLC4A7 (NBCn1) and SLC4A10 (NCBE) in mouse brain. American journal of physiology. Regulatory, integrative and comparative physiology 24 17928512
2005 Time course of auditory impairment in mice lacking the electroneutral sodium bicarbonate cotransporter NBC3 (slc4a7). Brain research. Developmental brain research 22 16181686
2023 Bicarbonate transporter SLC4A7 promotes EMT and metastasis of HNSCC by activating the PI3K/AKT/mTOR signaling pathway. Molecular carcinogenesis 17 36727616
2013 Effects of optional structural elements, including two alternative amino termini and a new splicing cassette IV, on the function of the sodium-bicarbonate cotransporter NBCn1 (SLC4A7). The Journal of physiology 17 23959679
2008 Electrogenic NBCe1 (SLC4A4), but not electroneutral NBCn1 (SLC4A7), cotransporter undergoes cholinergic-stimulated endocytosis in salivary ParC5 cells. American journal of physiology. Cell physiology 17 18815229
2016 The Hypertension Risk Variant Rs820430 Functions as an Enhancer of SLC4A7. American journal of hypertension 15 27784683
2014 Systematic family-wide analysis of sodium bicarbonate cotransporter NBCn1/SLC4A7 interactions with PDZ scaffold proteins. Physiological reports 14 24844638
2007 Variation in a bicarbonate co-transporter gene family member SLC4A7 is associated with propensity to addictions: a study using fine-mapping and three samples. Addiction (Abingdon, England) 11 17624982
2024 Antibodies toward Na+,HCO3--cotransporter NBCn1/SLC4A7 block net acid extrusion and cause pH-dependent growth inhibition and apoptosis in breast cancer. British journal of cancer 9 38310186
2020 Sodium bicarbonate cotransporter NBCn1/Slc4a7 affects locomotor activity and hearing in mice. Behavioural brain research 9 33321164
2025 SLC4A7 suppresses lung adenocarcinoma oncogenesis by reducing lactate transport and protein lactylation. International journal of oncology 7 40084702
2020 Novel mutation in SLC4A7 gene causing autosomal recessive progressive rod-cone dystrophy. Ophthalmic genetics 7 32594822
2017 Alternative transcription of sodium/bicarbonate transporter SLC4A7 gene enhanced by single nucleotide polymorphisms. Physiological genomics 7 28087757
2024 The electroneutral Na+-HCO3- cotransporter NBCn1 (SLC4A7) modulates colonic enterocyte pHi, proliferation, and migration. American journal of physiology. Cell physiology 6 38646790
2023 Update on the relationship between the SLC4A7 variant rs4973768 and breast cancer risk: a systematic review and meta-analysis. The Journal of international medical research 4 37128157
2022 SLC4A7 and mTORC1 raise nucleotide synthesis with bicarbonate. Molecular cell 4 36055205
2019 The apical Na+ -HCO3 - cotransporter Slc4a7 (NBCn1) does not contribute to bicarbonate transport by mouse salivary gland ducts. Journal of cellular physiology 4 30767201
2024 Slc4a7 Regulates Retina Development in Zebrafish. International journal of molecular sciences 2 39273559
2026 Membrane-associated Rhes-Slc4a7 complex orchestrates tunneling nanotube formation and mutant Huntingtin spread. Science advances 0 41861004
2026 SLC4A7 Drives NSCLC Progression and Immune Evasion via pH Dysregulation: Its Targeting Synergizes with Anti-PD-1/L1 Therapy. International journal of biological sciences 0 42088432
2025 Sulforaphane inhibits gastric cancer progression by regulating the YY1/PSMB8-AS1/miR-888-5p/SLC4A7 axis. Biochemical and biophysical research communications 0 41056875

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