Human Gene SLC4A8 (ENST00000453097.7) from GENCODE V44
  Description: Homo sapiens solute carrier family 4 member 8 (SLC4A8), transcript variant 1, mRNA. (from RefSeq NM_001039960)
RefSeq Summary (NM_001039960): 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].
Gencode Transcript: ENST00000453097.7
Gencode Gene: ENSG00000050438.17
Transcript (Including UTRs)
   Position: hg38 chr12:51,424,831-51,515,763 Size: 90,933 Total Exon Count: 25 Strand: +
Coding Region
   Position: hg38 chr12:51,424,988-51,507,438 Size: 82,451 Coding Exon Count: 25 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:51,424,831-51,515,763)mRNA (may differ from genome)Protein (1093 aa)
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OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: S4A8_HUMAN
DESCRIPTION: RecName: Full=Electroneutral sodium bicarbonate exchanger 1; AltName: Full=Electroneutral Na(+)-driven Cl-HCO3 exchanger; AltName: Full=Solute carrier family 4 member 8; AltName: Full=k-NBC3;
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.
ENZYME REGULATION: Activity is inhibited by 4,4'-Di- isothiocyanatostilbene-2,2'-disulfonic acid (DIDS - an inhibitor of several anion channels and transporters).
SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
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.
SIMILARITY: Belongs to the anion exchanger (TC 2.A.31) family.
SEQUENCE CAUTION: Sequence=BAA34459.1; Type=Erroneous initiation; Sequence=CAD38576.2; Type=Erroneous initiation;

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: SLC4A8
Diseases sorted by gene-association score: voyeurism (4), transvestism (3), fetishism (3), exhibitionism (2), suppurative cholangitis (1), usher syndrome, type 2c (1), paraphilia disorder (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 7.58 RPKM in Pituitary
Total median expression: 45.82 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -73.70157-0.469 Picture PostScript Text
3' UTR -2886.708325-0.347 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011531 - HCO3_transpt_C
IPR013769 - HCO3_transpt_cyt
IPR003020 - HCO3_transpt_euk
IPR003024 - Na/HCO3_transpt
IPR016152 - PTrfase/Anion_transptr

Pfam Domains:
PF07565 - Band 3 cytoplasmic domain
PF00955 - HCO3- transporter family

ModBase Predicted Comparative 3D Structure on Q2Y0W8
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
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Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005452 inorganic anion exchanger activity
GO:0008509 anion transmembrane transporter activity
GO:0008510 sodium:bicarbonate symporter activity
GO:0015297 antiporter activity
GO:0015301 anion:anion antiporter activity

Biological Process:
GO:0006811 ion transport
GO:0006814 sodium ion transport
GO:0006820 anion transport
GO:0015698 inorganic anion transport
GO:0015701 bicarbonate transport
GO:0051453 regulation of intracellular pH
GO:0055085 transmembrane transport
GO:0098656 anion transmembrane transport

Cellular Component:
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0032809 neuronal cell body membrane
GO:0043005 neuron projection


-  Descriptions from all associated GenBank mRNAs
  EU637925 - Homo sapiens Na+-driven Cl-HCO3 exchanger (SLC4A8) mRNA, 3' UTR.
AK124576 - Homo sapiens cDNA FLJ42585 fis, clone BRACE3009237.
AK295315 - Homo sapiens cDNA FLJ60258 complete cds, highly similar to Homo sapiens solute carrier family 4, sodium bicarbonate cotransporter, member 8, transcript variant 2, mRNA.
AB018282 - Homo sapiens mRNA for KIAA0739 protein, partial cds.
DQ996398 - Homo sapiens tissue-type heart sodium bicarbonate cotransporter (SLC4A8) mRNA, complete cds, alternatively spliced.
DQ996537 - Homo sapiens tissue-type brain sodium bicarbonate cotransporter (SLC4A8) mRNA, complete cds, alternatively spliced.
DQ975204 - Homo sapiens sodium-driven chloride bicarbonate exchanger (SLC4A8) mRNA, complete cds.
AK128321 - Homo sapiens cDNA FLJ46462 fis, clone THYMU3021755.
AB384518 - Synthetic construct DNA, clone: pF1KA0739, Homo sapiens SLC4A8 gene for solute carrier family 4, anion exchanger, member 8, complete cds, without stop codon, in Flexi system.
AK299545 - Homo sapiens cDNA FLJ60342 complete cds, highly similar to Homo sapiens solute carrier family 4, sodium bicarbonate cotransporter, member 8, transcript variant 2, mRNA.
DQ063579 - Homo sapiens Na+-driven Cl-HCO3 exchanger (SLC4A8) mRNA, complete cds.
BC025994 - Homo sapiens solute carrier family 4, sodium bicarbonate cotransporter, member 8, mRNA (cDNA clone MGC:26446 IMAGE:4822306), complete cds.
AF069512 - Homo sapiens sodium bicarbonate cotransporter (NBC) mRNA, complete cds.
AF107099 - Homo sapiens sodium bicarbonate cotransporter isoform 3 (NBC-3) mRNA, partial cds.
CU693092 - Synthetic construct Homo sapiens gateway clone IMAGE:100018418 5' read SLC4A8 mRNA.
KJ901982 - Synthetic construct Homo sapiens clone ccsbBroadEn_11376 SLC4A8 gene, encodes complete protein.
AL831915 - Homo sapiens mRNA; cDNA DKFZp761B2318 (from clone DKFZp761B2318).
DQ595030 - Homo sapiens piRNA piR-61142, complete sequence.
DQ587277 - Homo sapiens piRNA piR-54389, complete sequence.
DQ599838 - Homo sapiens piRNA piR-37904, complete sequence.
DQ586198 - Homo sapiens piRNA piR-53310, complete sequence.
AK310017 - Homo sapiens cDNA, FLJ17059.
AK093357 - Homo sapiens cDNA FLJ36038 fis, clone TESTI2017305.
AX748074 - Sequence 1599 from Patent EP1308459.
AK093005 - Homo sapiens cDNA FLJ35686 fis, clone SPLEN2019323.
AX747851 - Sequence 1376 from Patent EP1308459.
BC036413 - Homo sapiens cDNA clone IMAGE:4793730, **** WARNING: chimeric clone ****.
BC047623 - Homo sapiens hypothetical protein LOC283400, mRNA (cDNA clone IMAGE:4793680), **** WARNING: chimeric clone ****.
JD024892 - Sequence 5916 from Patent EP1572962.
JD449559 - Sequence 430583 from Patent EP1572962.
JD466715 - Sequence 447739 from Patent EP1572962.
JD024824 - Sequence 5848 from Patent EP1572962.
JD031984 - Sequence 13008 from Patent EP1572962.
JD527018 - Sequence 508042 from Patent EP1572962.
JD547738 - Sequence 528762 from Patent EP1572962.
JD171283 - Sequence 152307 from Patent EP1572962.
JD288816 - Sequence 269840 from Patent EP1572962.
JD363576 - Sequence 344600 from Patent EP1572962.
JD259877 - Sequence 240901 from Patent EP1572962.
JD122849 - Sequence 103873 from Patent EP1572962.
JD122584 - Sequence 103608 from Patent EP1572962.
JD323691 - Sequence 304715 from Patent EP1572962.
JD357407 - Sequence 338431 from Patent EP1572962.
JD047040 - Sequence 28064 from Patent EP1572962.
JD101869 - Sequence 82893 from Patent EP1572962.
JD101867 - Sequence 82891 from Patent EP1572962.
JD101868 - Sequence 82892 from Patent EP1572962.
JD481194 - Sequence 462218 from Patent EP1572962.
JD481195 - Sequence 462219 from Patent EP1572962.
JD376345 - Sequence 357369 from Patent EP1572962.
DQ589458 - Homo sapiens piRNA piR-56570, complete sequence.
DQ590240 - Homo sapiens piRNA piR-57352, complete sequence.
JD566812 - Sequence 547836 from Patent EP1572962.
JD506218 - Sequence 487242 from Patent EP1572962.
JD506219 - Sequence 487243 from Patent EP1572962.
JD329987 - Sequence 311011 from Patent EP1572962.
JD058816 - Sequence 39840 from Patent EP1572962.
JD506220 - Sequence 487244 from Patent EP1572962.
AL137310 - Homo sapiens mRNA; cDNA DKFZp761E13121 (from clone DKFZp761E13121).
AK056222 - Homo sapiens cDNA FLJ31660 fis, clone NT2RI2004410.
JD074164 - Sequence 55188 from Patent EP1572962.
JD074163 - Sequence 55187 from Patent EP1572962.
JD488510 - Sequence 469534 from Patent EP1572962.
DQ573361 - Homo sapiens piRNA piR-41473, complete sequence.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q2Y0W8 (Reactome details) participates in the following event(s):

R-HSA-425577 Na+-driven Cl-/HCO3- exchanger transport
R-HSA-425381 Bicarbonate transporters
R-HSA-425393 Metabolism of nitrogenous molecules
R-HSA-425407 SLC-mediated transmembrane transport
R-HSA-382551 Transport of small molecules

-  Other Names for This Gene
  Alternate Gene Symbols: A0MMZ1, ENST00000453097.1, ENST00000453097.2, ENST00000453097.3, ENST00000453097.4, ENST00000453097.5, ENST00000453097.6, KIAA0739, NBC, NBC3, NDCBE1, NM_001039960, O94843, O95233, Q004B4, Q2Y0W8, Q8N3U2, Q8TC60, Q9UKX8, S4A8_HUMAN, uc001rys.1, uc001rys.2, uc001rys.3, uc001rys.4
UCSC ID: ENST00000453097.7
RefSeq Accession: NM_001039960
Protein: Q2Y0W8 (aka S4A8_HUMAN)
CCDS: CCDS73470.1, CCDS44890.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.