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SLC4A8 solute carrier family 4 member 8 [ Homo sapiens (human) ]

Gene ID: 9498, updated on 3-Apr-2024

Summary

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Official Symbol
SLC4A8provided by HGNC
Official Full Name
solute carrier family 4 member 8provided by HGNC
Primary source
HGNC:HGNC:11034
See related
Ensembl:ENSG00000050438 MIM:605024; AllianceGenome:HGNC:11034
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
NBC3; NDCBE
Summary
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]
Expression
Biased expression in testis (RPKM 5.0), brain (RPKM 4.6) and 9 other tissues See more
Orthologs
mouse all
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Genomic context

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See SLC4A8 in Genome Data Viewer
Location:
12q13.13
Exon count:
31
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (51391446..51515763)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (51354255..51479285)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (51785230..51909547)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105369767 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6377 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4466 Neighboring gene Sharpr-MPRA regulatory region 12465 Neighboring gene bridging integrator 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6378 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6379 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr12:51765098-51765664 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:51773037-51773538 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:51773539-51774038 Neighboring gene chymotrypsin like elastase 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:51781791-51782290 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6380 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:51784367-51784952 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:51784953-51785537 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6381 Neighboring gene polypeptide N-acetylgalactosaminyltransferase 6 Neighboring gene NANOG hESC enhancer GRCh37_chr12:51813535-51814036 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4468 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4469 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6382 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:51826488-51826988 Neighboring gene SLC4A8 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4470 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:51895635-51896136 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:51896137-51896636 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6383 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6384 Neighboring gene NANOG hESC enhancer GRCh37_chr12:51938922-51939423 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4471 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4472 Neighboring gene sodium voltage-gated channel alpha subunit 8 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:52039206-52040092 Neighboring gene SCN8A eExon liver enhancer Neighboring gene heterogeneous nuclear ribonucleoprotein A3 pseudogene 10 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4473 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:52208409-52208908 Neighboring gene transmembrane and death domain 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The crystal structure of the regulatory domain of the human sodium-driven chloride/bicarbonate exchanger. Alvadia CM, et al. Sci Rep, 2017 Sep 21. PMID 28935959, Free PMC Article
  2. Na+:HCO3- cotransporters (NBC): expression and regulation in the kidney. Soleimani M. J Nephrol, 2002 Mar-Apr. PMID 12027220
  3. Characterization of Na+/HCO-3 cotransporter isoform NBC-3. Amlal H, et al. Am J Physiol, 1999 Jun. PMID 10362779
  4. Cryo-EM structure of the sodium-driven chloride/bicarbonate exchanger NDCBE. Wang W, et al. Nat Commun, 2021 Sep 28. PMID 34584093, Free PMC Article
  5. Cloning and characterization of novel human SLC4A8 gene products encoding Na+-driven Cl-/HCO3(-) exchanger variants NDCBE-A, -C, and -D. Parker MD, et al. Physiol Genomics, 2008 Aug 15. PMID 18577713, Free PMC Article

See all (24) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Cryo-EM structure of the sodium-driven chloride/bicarbonate exchanger NDCBE.
    Title: Cryo-EM structure of the sodium-driven chloride/bicarbonate exchanger NDCBE.
  2. The crystal structure at 2.8 A resolution of the regulatory N-terminal domain of human NDCBE represents the first crystal structure of an electroneutral sodium-bicarbonate cotransporter. The crystal structure forms an equivalent dimeric interface as observed for the cytoplasmic domain of Band 3, and thus establishes that the consensus motif VTVLP is the key minimal dimerization motif.
    Title: The crystal structure of the regulatory domain of the human sodium-driven chloride/bicarbonate exchanger.
  3. This study confirmed the presence in human cDNA of mouse NDCBE-like transcripts (human NDCBE-A) and three novel transcripts NDCBE-C, NDCBE-D, and NDCBE-D'.
    Title: Cloning and characterization of novel human SLC4A8 gene products encoding Na+-driven Cl-/HCO3(-) exchanger variants NDCBE-A, -C, and -D.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study of the rate of cognitive decline in Alzheimer's disease.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ46462, DKFZp761B2318

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables bicarbonate transmembrane transporter activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables chloride transmembrane transporter activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables identical protein binding IEA
Inferred from Electronic Annotation
more info
  
enables sodium ion transmembrane transporter activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables sodium,bicarbonate:chloride antiporter activity IEA
Inferred from Electronic Annotation
more info
  
enables sodium:bicarbonate symporter activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables sodium:bicarbonate symporter activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables solute:inorganic anion antiporter activity TAS
Traceable Author Statement
more info
  
Process Evidence Code Pubs
involved_in basolateral protein secretion IEA
Inferred from Electronic Annotation
more info
  
involved_in bicarbonate transport IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in bicarbonate transport IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in bicarbonate transport TAS
Traceable Author Statement
more info
  
involved_in chloride transmembrane transport IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within modulation of chemical synaptic transmission ISS
Inferred from Sequence or Structural Similarity
more info
  
acts_upstream_of_or_within positive regulation of synaptic vesicle exocytosis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of intracellular pH IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within regulation of intracellular pH IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within regulation of intracellular pH ISS
Inferred from Sequence or Structural Similarity
more info
  
acts_upstream_of_or_within regulation of membrane potential IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in sodium ion transmembrane transport IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in transmembrane transport IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in transport across blood-brain barrier NAS
Non-traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in apical plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in asymmetric synapse ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in axon terminus ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in basolateral plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in dendrite IDA
Inferred from Direct Assay
more info
 PubMed 
located_in glial cell projection ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in glutamatergic synapse ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in hippocampal mossy fiber ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in neuron projection ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in neuronal cell body membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  
located_in presynapse ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in presynaptic membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in symmetric synapse ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in synaptic vesicle ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in synaptic vesicle membrane IEA
Inferred from Electronic Annotation
more info
  
located_in terminal bouton ISS
Inferred from Sequence or Structural Similarity
more info
  

General protein information

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Preferred Names
electroneutral sodium bicarbonate exchanger 1
Names
electroneutral Na(+)-driven Cl-HCO3 exchanger
k-NBC3
solute carrier family 4, sodium bicarbonate cotransporter, member 8

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_032675.2 RefSeqGene

    Range
    38385..129317
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001039960.3 → NP_001035049.1  electroneutral sodium bicarbonate exchanger 1 isoform a

    See identical proteins and their annotated locations for NP_001035049.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
    Source sequence(s)
    AC025097, AW118662, DQ063579
    Consensus CDS
    CCDS44890.1
    UniProtKB/Swiss-Prot
    A0MMZ1, B4DHY0, E7EML0, F5GZ31, F5H7F5, O94843, O95233, Q004B4, Q2Y0W8, Q8N3U2, Q8TC60, Q9UKX8
    Related
    ENSP00000405812.2, ENST00000453097.7
    Conserved Domains (3) summary
    TIGR00834
    Location:117 → 1005
    ae; anion exchange protein
    pfam00955
    Location:445 → 958
    HCO3_cotransp; HCO3- transporter family
    pfam07565
    Location:145 → 404
    Band_3_cyto; Band 3 cytoplasmic domain

  2. NM_001258401.3 → NP_001245330.1  electroneutral sodium bicarbonate exchanger 1 isoform c

    See identical proteins and their annotated locations for NP_001245330.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (c) is shorter at the N-terminus compared to isoform a.
    Source sequence(s)
    AC025097, AK295315, AW118662, DQ975204
    Consensus CDS
    CCDS73470.1
    UniProtKB/Swiss-Prot
    Q2Y0W8
    Related
    ENSP00000351483.4, ENST00000358657.7
    Conserved Domains (3) summary
    TIGR00834
    Location:64 → 952
    ae; anion exchange protein
    pfam00955
    Location:392 → 905
    HCO3_cotransp; HCO3- transporter family
    pfam07565
    Location:92 → 351
    Band_3_cyto; Band 3 cytoplasmic domain

  3. NM_001258402.2 → NP_001245331.1  electroneutral sodium bicarbonate exchanger 1 isoform d

    See identical proteins and their annotated locations for NP_001245331.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 3' UTR and coding sequence compared to variant 1. The resulting isoform (d) has a shorter and distinct C-terminus compared to isoform a.
    Source sequence(s)
    BC025994, DB220099
    UniProtKB/Swiss-Prot
    Q2Y0W8
    Conserved Domains (1) summary
    cl26877
    Location:117 → 623
    Band_3_cyto; Band 3 cytoplasmic domain

  4. NM_001258403.2 → NP_001245332.1  electroneutral sodium bicarbonate exchanger 1 isoform e

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 5' and 3' UTRs and coding sequences compared to variant 1. The resulting isoform (e) is shorter at the N-terminus and has a shorter and distinct C-terminus compared to isoform a.
    Source sequence(s)
    AC107031, AL831915
    Consensus CDS
    CCDS58232.1
    UniProtKB/TrEMBL
    B4DS29
    Related
    ENSP00000442561.2, ENST00000514353.7
    Conserved Domains (3) summary
    pfam07565
    Location:92 → 351
    Band_3_cyto; Band 3 cytoplasmic domain
    pfam13900
    Location:695 → 714
    GVQW; Putative domain of unknown function
    cl23746
    Location:392 → 671
    HCO3_cotransp; HCO3- transporter family

  5. NM_001267615.2 → NP_001254544.1  electroneutral sodium bicarbonate exchanger 1 isoform f

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) has an alternate first exon and differs in the 3' UTR and coding sequence compared to variant 1. The resulting isoform (f) is shorter at the N-terminus and has a shorter and distinct C-terminus compared to isoform a.
    Source sequence(s)
    AK295315, BC025994
    Consensus CDS
    CCDS58233.1
    UniProtKB/Swiss-Prot
    Q2Y0W8
    Related
    ENSP00000441520.1, ENST00000535225.6
    Conserved Domains (2) summary
    pfam07565
    Location:92 → 351
    Band_3_cyto; Band 3 cytoplasmic domain
    cl23746
    Location:392 → 593
    HCO3_cotransp; HCO3- transporter family

  6. NM_001405266.1 → NP_001392195.1  electroneutral sodium bicarbonate exchanger 1 isoform e

    Status: REVIEWED

    Source sequence(s)
    AC046135, AC107031
    Consensus CDS
    CCDS58232.1

  7. NM_001405268.1 → NP_001392197.1  electroneutral sodium bicarbonate exchanger 1 isoform 7

    Status: REVIEWED

    Source sequence(s)
    AC025097, AC107031

  8. NM_001405270.1 → NP_001392199.1  electroneutral sodium bicarbonate exchanger 1 isoform 8

    Status: REVIEWED

    Source sequence(s)
    AC025097, AC046135, AC107031

RNA

  1. NR_047672.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) lacks most of the 3' end and contains an alternate 3' exon compared to variant 1. This variant is not thought to be protein-coding.
    Source sequence(s)
    AI377345, DB220099
    Related
    ENST00000548811.5

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    51391446..51515763
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011539011.2 → XP_011537313.1  electroneutral sodium bicarbonate exchanger 1 isoform X2

    Conserved Domains (1) summary
    cl26877
    Location:64 → 970
    Band_3_cyto; Band 3 cytoplasmic domain

  2. XM_011539010.2 → XP_011537312.1  electroneutral sodium bicarbonate exchanger 1 isoform X1

    Conserved Domains (1) summary
    cl26877
    Location:117 → 1023
    Band_3_cyto; Band 3 cytoplasmic domain

  3. XM_047429911.1 → XP_047285867.1  electroneutral sodium bicarbonate exchanger 1 isoform X3

    Related
    ENST00000319957.10

  4. XM_006719700.2 → XP_006719763.1  electroneutral sodium bicarbonate exchanger 1 isoform X4

    UniProtKB/TrEMBL
    B4DS29
    Conserved Domains (3) summary
    pfam07565
    Location:145 → 404
    Band_3_cyto; Band 3 cytoplasmic domain
    pfam13900
    Location:748 → 767
    GVQW; Putative domain of unknown function
    cl23746
    Location:445 → 724
    HCO3_cotransp; HCO3- transporter family

  5. XM_011539014.4 → XP_011537316.1  electroneutral sodium bicarbonate exchanger 1 isoform X5

    Conserved Domains (1) summary
    pfam00955
    Location:1 → 487
    HCO3_cotransp; HCO3- transporter family

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    51354255..51479285
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054373876.1 → XP_054229851.1  electroneutral sodium bicarbonate exchanger 1 isoform X2

  2. XM_054373875.1 → XP_054229850.1  electroneutral sodium bicarbonate exchanger 1 isoform X1

  3. XM_054373877.1 → XP_054229852.1  electroneutral sodium bicarbonate exchanger 1 isoform X4

  4. XM_054373878.1 → XP_054229853.1  electroneutral sodium bicarbonate exchanger 1 isoform X5

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_004858.2: Suppressed sequence

    Description
    NM_004858.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q2Y0W8.1 GenPept UniProtKB/Swiss-Prot:Q2Y0W8

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