SLC4A8 Gene

HGNC Family	Solute carriers (SLC)
Name	solute carrier family 4, sodium bicarbonate cotransporter, member 8
Description	The protein encoded by this gene is a membrane protein that functions to transport sodium and bicarbonate ions across the cell membrane. The encoded protein is important for pH regulation in neurons. The activity of this protein can be inhibited by 4,4'-Di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC4A8 encodes a Na⁺‐driven Cl⁻/HCO₃⁻ exchanger, also known as NDCBE, that plays a key role in regulating intracellular pH by mediating the coupled transport of sodium, chloride, and bicarbonate. Detailed transcript analyses have revealed multiple isoforms with distinct cytosolic termini; notably, human transcripts include both longer and shorter C-terminal variants, where the presence of a 17–amino acid cassette leads to a reduction in basal functional activity compared with the longer counterpart. These findings highlight the importance of alternative splicing in modulating exchanger function and expression in the brain."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nStructural analysis using cryo–electron microscopy has provided further insights into SLC4A8’s functional architecture. The outward–facing conformation of NDCBE features a well–resolved extracellular loop and a defined substrate–binding pocket containing sodium and carbonate ions, underscoring its role in facilitating the electroneutral exchange of sodium–carbonate for chloride. This overall fold is conserved among SLC4 family members, consistent with their shared roles in ion transport despite differing exchange modes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nComplementary studies focusing on the regulatory N–terminal domain have uncovered a dimerization interface mediated by a highly conserved VTVLP motif—integral for forming the functional dimer observed in similar transporters—as well as a zinc–binding motif situated near a conserved regulatory sequence. The Zn²⁺–dependent modulation of transport activity identified in these analyses suggests that such regulatory domains are critical for fine–tuning the exchanger’s activity, thereby ensuring effective pH homeostasis in neuronal cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mark D Parker, Patrice Bouyer, Christopher M Daly, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cloning and characterization of novel human SLC4A8 gene products encoding Na+-driven Cl-/HCO3(-) exchanger variants NDCBE-A, -C, and -D."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Physiol Genomics (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/physiolgenomics.90259.2008"}], "href": "https://doi.org/10.1152/physiolgenomics.90259.2008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18577713"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18577713"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Weiguang Wang, Kirill Tsirulnikov, Hristina R Zhekova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cryo-EM structure of the sodium-driven chloride/bicarbonate exchanger NDCBE."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-25998-2"}], "href": "https://doi.org/10.1038/s41467-021-25998-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34584093"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34584093"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Carolina M Alvadia, Theis Sommer, Kaare Bjerregaard-Andersen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The crystal structure of the regulatory domain of the human sodium-driven chloride/bicarbonate exchanger."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-12409-0"}], "href": "https://doi.org/10.1038/s41598-017-12409-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28935959"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28935959"}]}]}]}
Synonyms	NDCBE
Proteins	S4A8_HUMAN
NCBI Gene ID	9498
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SLC4A8 has 6,293 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 117 datasets.

Click the + buttons to view associations for SLC4A8 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SLC4A8 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by SLC4A8 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SLC4A8 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of SLC4A8 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of SLC4A8 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of SLC4A8 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of SLC4A8 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SLC4A8 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of SLC4A8 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SLC4A8 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SLC4A8 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of SLC4A8 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SLC4A8 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of SLC4A8 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SLC4A8 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SLC4A8 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SLC4A8 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of SLC4A8 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of SLC4A8 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SLC4A8 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SLC4A8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SLC4A8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SLC4A8 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with SLC4A8 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SLC4A8 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SLC4A8 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with SLC4A8 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SLC4A8 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for SLC4A8 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SLC4A8 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with SLC4A8 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with SLC4A8 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DrugBank Drug Targets	interacting drugs for SLC4A8 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SLC4A8 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SLC4A8 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SLC4A8 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing SLC4A8 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of SLC4A8 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with SLC4A8 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing SLC4A8 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of SLC4A8 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.