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... See more...

Aliases for SLC4A8 Gene

Aliases for SLC4A8 Gene

  • Solute Carrier Family 4 Member 8 2 3 4 5
  • NBC3 2 3 4
  • Solute Carrier Family 4, Sodium Bicarbonate Cotransporter, Member 8 2 3
  • Electroneutral Sodium Bicarbonate Exchanger 1 3 4
  • Electroneutral Na(+)-Driven Cl-HCO3 Exchanger 3 4
  • K-NBC3 3 4
  • KIAA0739 4
  • SLC4A8 5
  • NDCBE1 4
  • NDCBE 3
  • NBC 4

External Ids for SLC4A8 Gene

Previous GeneCards Identifiers for SLC4A8 Gene

  • GC12P051941
  • GC12P051807
  • GC12P051501
  • GC12P050071
  • GC12P048851

Summaries for SLC4A8 Gene

Entrez Gene Summary for SLC4A8 Gene

  • 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]

GeneCards Summary for SLC4A8 Gene

SLC4A8 (Solute Carrier Family 4 Member 8) is a Protein Coding gene. Diseases associated with SLC4A8 include Ring Dermoid Of Cornea and Suppurative Cholangitis. Among its related pathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds. Gene Ontology (GO) annotations related to this gene include transporter activity and anion transmembrane transporter activity. An important paralog of this gene is SLC4A10.

UniProtKB/Swiss-Prot Summary for SLC4A8 Gene

  • Mediates electroneutral sodium- and carbonate-dependent chloride-HCO3(-) exchange with a Na(+):HCO3(-) stoichiometry of 2:1. Plays a major role in pH regulation in neurons. May be involved in cell pH regulation by transporting HCO3(-) from blood to cell. Enhanced expression in severe acid stress could be important for cell survival by mediating the influx of HCO3(-) into the cells. Also mediates lithium-dependent HCO3(-) cotransport. May be regulated by osmolarity.

Gene Wiki entry for SLC4A8 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SLC4A8 Gene

Genomics for SLC4A8 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SLC4A8 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SLC4A8 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SLC4A8

Top Transcription factor binding sites by QIAGEN in the SLC4A8 gene promoter:
  • AML1a
  • AREB6
  • C/EBPbeta
  • E2F
  • E2F-1
  • E47
  • Gfi-1
  • Hand1
  • NF-kappaB1
  • Nkx2-5

Genomic Locations for SLC4A8 Gene

Genomic Locations for SLC4A8 Gene
chr12:51,391,317-51,515,763
(GRCh38/hg38)
Size:
124,447 bases
Orientation:
Plus strand
chr12:51,785,101-51,902,980
(GRCh37/hg19)
Size:
117,880 bases
Orientation:
Plus strand

Genomic View for SLC4A8 Gene

Genes around SLC4A8 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SLC4A8 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SLC4A8 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SLC4A8 Gene

Proteins for SLC4A8 Gene

  • Protein details for SLC4A8 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q2Y0W8-S4A8_HUMAN
    Recommended name:
    Electroneutral sodium bicarbonate exchanger 1
    Protein Accession:
    Q2Y0W8
    Secondary Accessions:
    • A0MMZ1
    • B4DHY0
    • E7EML0
    • F5GZ31
    • F5H7F5
    • O94843
    • O95233
    • Q004B4
    • Q8N3U2
    • Q8TC60
    • Q9UKX8

    Protein attributes for SLC4A8 Gene

    Size:
    1093 amino acids
    Molecular mass:
    122938 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=BAA34459.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAD38576.2; Type=Erroneous initiation; Evidence={ECO:0000305};
    Miscellaneous:
    • [Isoform 3]: May be due to an intron retention.
    • [Isoform 4]: May be due to an intron retention.

    Three dimensional structures from OCA and Proteopedia for SLC4A8 Gene

    Alternative splice isoforms for SLC4A8 Gene

neXtProt entry for SLC4A8 Gene

Post-translational modifications for SLC4A8 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for SLC4A8 Gene

Domains & Families for SLC4A8 Gene

Gene Families for SLC4A8 Gene

Protein Domains for SLC4A8 Gene

InterPro:
Blocks:
  • Na+/HCO3- co-transporter signature
  • HCO3- transporter, cytoplasmic
ProtoNet:

Suggested Antigen Peptide Sequences for SLC4A8 Gene

GenScript: Design optimal peptide antigens:
  • k-NBC3 (S4A8_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q2Y0W8

UniProtKB/Swiss-Prot:

S4A8_HUMAN :
  • Belongs to the anion exchanger (TC 2.A.31) family.
Family:
  • Belongs to the anion exchanger (TC 2.A.31) family.
genes like me logo Genes that share domains with SLC4A8: view

Function for SLC4A8 Gene

Molecular function for SLC4A8 Gene

UniProtKB/Swiss-Prot Function:
Mediates electroneutral sodium- and carbonate-dependent chloride-HCO3(-) exchange with a Na(+):HCO3(-) stoichiometry of 2:1. Plays a major role in pH regulation in neurons. May be involved in cell pH regulation by transporting HCO3(-) from blood to cell. Enhanced expression in severe acid stress could be important for cell survival by mediating the influx of HCO3(-) into the cells. Also mediates lithium-dependent HCO3(-) cotransport. May be regulated by osmolarity.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activity is inhibited by 4,4'-Di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS - an inhibitor of several anion channels and transporters).

Phenotypes From GWAS Catalog for SLC4A8 Gene

Gene Ontology (GO) - Molecular Function for SLC4A8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005452 inorganic anion exchanger activity IEA --
GO:0008509 anion transmembrane transporter activity IEA --
GO:0008510 sodium:bicarbonate symporter activity IBA,IDA 11133997
GO:0015081 sodium ion transmembrane transporter activity IDA 11133997
GO:0015106 bicarbonate transmembrane transporter activity IDA 11133997
genes like me logo Genes that share ontologies with SLC4A8: view
genes like me logo Genes that share phenotypes with SLC4A8: view

Animal Models for SLC4A8 Gene

MGI Knock Outs for SLC4A8:

Animal Model Products

  • Taconic Biosciences Mouse Models for SLC4A8

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SLC4A8

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SLC4A8 Gene

Localization for SLC4A8 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SLC4A8 Gene

Membrane. Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SLC4A8 gene
Compartment Confidence
plasma membrane 5
cytosol 3
extracellular 2
cytoskeleton 2
mitochondrion 2
nucleus 2
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SLC4A8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005623 cell IEA --
GO:0005886 plasma membrane TAS --
GO:0008021 synaptic vesicle ISS --
GO:0016020 membrane ISS --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with SLC4A8: view

Pathways & Interactions for SLC4A8 Gene

genes like me logo Genes that share pathways with SLC4A8: view

Gene Ontology (GO) - Biological Process for SLC4A8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0006814 sodium ion transport IEA --
GO:0006820 anion transport IEA --
GO:0015701 bicarbonate transport IDA,TAS --
GO:0035725 sodium ion transmembrane transport IDA 11133997
genes like me logo Genes that share ontologies with SLC4A8: view

No data available for SIGNOR curated interactions for SLC4A8 Gene

Drugs & Compounds for SLC4A8 Gene

(2) Drugs for SLC4A8 Gene - From: DrugBank and PharmGKB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Sodium bicarbonate Approved Pharma Transporter, substrate 0
Ethanol Approved Pharma 3266

(1) Additional Compounds for SLC4A8 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
sodium
  • Na(+)
  • Na+
  • SODIUM ion
7440-23-5
genes like me logo Genes that share compounds with SLC4A8: view

Transcripts for SLC4A8 Gene

mRNA/cDNA for SLC4A8 Gene

6 REFSEQ mRNAs :
23 NCBI additional mRNA sequence :
18 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SLC4A8

Alternative Splicing Database (ASD) splice patterns (SP) for SLC4A8 Gene

No ASD Table

Relevant External Links for SLC4A8 Gene

GeneLoc Exon Structure for
SLC4A8

Expression for SLC4A8 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SLC4A8 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SLC4A8 Gene

This gene is overexpressed in Pituitary (x6.0).

Protein differential expression in normal tissues from HIPED for SLC4A8 Gene

This gene is overexpressed in Retina (19.3), Heart (17.4), Brain (12.0), Rectum (10.5), and Frontal cortex (9.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SLC4A8 Gene



Protein tissue co-expression partners for SLC4A8 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SLC4A8

SOURCE GeneReport for Unigene cluster for SLC4A8 Gene:

Hs.4749

mRNA Expression by UniProt/SwissProt for SLC4A8 Gene:

Q2Y0W8-S4A8_HUMAN
Tissue specificity: Expressed in the pyramidal cells of the hippocampus (at protein level). Highly expressed in all major regions of the brain, spinal column and in testis, and moderate levels in trachea, thyroid and medulla region of kidney. Low expression levels observed in pancreas and kidney cortex.

Evidence on tissue expression from TISSUES for SLC4A8 Gene

  • Nervous system(4.9)
  • Kidney(2.8)
  • Heart(2.6)
  • Muscle(2.5)
  • Skin(2.4)
  • Pancreas(2.3)
  • Liver(2.2)
  • Eye(2.1)
  • Intestine(2.1)
  • Blood(2)
genes like me logo Genes that share expression patterns with SLC4A8: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for SLC4A8 Gene

Orthologs for SLC4A8 Gene

This gene was present in the common ancestor of animals.

Orthologs for SLC4A8 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia SLC4A8 31
  • 100 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia KNBC3 31
  • 98 (a)
OneToOne
SLC4A8 30
  • 93.69 (n)
Cow
(Bos Taurus)
Mammalia SLC4A8 30 31
  • 92.4 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Slc4a8 30 17 31
  • 87.53 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Slc4a8 30
  • 86.78 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia SLC4A8 31
  • 85 (a)
OneToOne
Chicken
(Gallus gallus)
Aves SLC4A8 31
  • 80 (a)
OneToOne
LOC425441 30
  • 75.26 (n)
Lizard
(Anolis carolinensis)
Reptilia -- 31
  • 70 (a)
OneToMany
-- 31
  • 65 (a)
OneToMany
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia slc4a8 30
  • 76.12 (n)
Zebrafish
(Danio rerio)
Actinopterygii SLC4A8 31
  • 76 (a)
OneToOne
slc4a8 30
  • 70.63 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta Ndae1 31 32
  • 45 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea F52B5.1 32
  • 49 (a)
abts-1 31
  • 41 (a)
OneToMany
R03E9.3 32
  • 24 (a)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 52 (a)
OneToMany
Species where no ortholog for SLC4A8 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for SLC4A8 Gene

ENSEMBL:
Gene Tree for SLC4A8 (if available)
TreeFam:
Gene Tree for SLC4A8 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SLC4A8: view image

Paralogs for SLC4A8 Gene

Paralogs for SLC4A8 Gene

(21) SIMAP similar genes for SLC4A8 Gene using alignment to 3 proteins:

  • S4A8_HUMAN
  • E7EML0_HUMAN
  • F5GZ31_HUMAN
genes like me logo Genes that share paralogs with SLC4A8: view

Variants for SLC4A8 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SLC4A8 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
rs12318785 - p.Ile898Val
rs35966334 - p.Asp312Ala

Additional dbSNP identifiers (rs#s) for SLC4A8 Gene

Structural Variations from Database of Genomic Variants (DGV) for SLC4A8 Gene

Variant ID Type Subtype PubMed ID
dgv83e215 CNV deletion 23714750
esv1019413 CNV insertion 17803354
esv1508794 CNV deletion 17803354
esv1700899 CNV insertion 17803354
esv2745884 CNV deletion 23290073
esv3629502 CNV gain 21293372
nsv1045796 CNV loss 25217958
nsv1119955 CNV deletion 24896259
nsv513361 CNV insertion 21212237
nsv519438 CNV gain 19592680
nsv52505 CNV deletion 16902084
nsv705 CNV insertion 18451855
nsv832408 CNV gain 17160897

Variation tolerance for SLC4A8 Gene

Residual Variation Intolerance Score: 1.66% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.45; 28.43% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SLC4A8 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
SLC4A8

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SLC4A8 Gene

Disorders for SLC4A8 Gene

MalaCards: The human disease database

(6) MalaCards diseases for SLC4A8 Gene - From: DISEASES

- elite association - COSMIC cancer census association via MalaCards
genes like me logo Genes that share disorders with SLC4A8: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SLC4A8 Gene

Publications for SLC4A8 Gene

  1. Cloning, characterization, and chromosomal mapping of a human electroneutral Na(+)-driven Cl-HCO3 exchanger. (PMID: 11133997) Grichtchenko II … Boron WF (The Journal of biological chemistry 2001) 2 3 4 23
  2. Molecular expression of SLC4-derived Na+-dependent anion transporters in selected human tissues. (PMID: 17715183) Damkier HH … Praetorius J (American journal of physiology. Regulatory, integrative and comparative physiology 2007) 3 4 23
  3. Cloning and characterization of novel human SLC4A8 gene products encoding Na+-driven Cl-/HCO3(-) exchanger variants NDCBE-A, -C, and -D. (PMID: 18577713) Parker MD … Boron WF (Physiological genomics 2008) 3 23
  4. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4
  5. Characterization of Na+/HCO-3 cotransporter isoform NBC-3. (PMID: 10362779) Amlal H … Soleimani M (The American journal of physiology 1999) 3 4

Products for SLC4A8 Gene

Sources for SLC4A8 Gene