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

    Gene ID: 9498, updated on 28-Oct-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_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (51391446..51515763)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (51354255..51479285)
    RS_2024_09 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 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. Characterization of Na+/HCO-3 cotransporter isoform NBC-3. Amlal H, et al. Am J Physiol, 1999 Jun. PMID 10362779
    2. Na+:HCO3- cotransporters (NBC): expression and regulation in the kidney. Soleimani M. J Nephrol, 2002 Mar-Apr. PMID 12027220
    3. 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
    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, characterization, and chromosomal mapping of a human electroneutral Na(+)-driven Cl-HCO3 exchanger. Grichtchenko II, et al. J Biol Chem, 2001 Mar 16. PMID 11133997

    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 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 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
    		  
    enables zinc ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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 sodium ion transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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_2024_08

    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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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