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Aliases for SLC4A4 Gene

Aliases for SLC4A4 Gene

  • Solute Carrier Family 4 Member 4 2 3 4 5
  • Solute Carrier Family 4 (Sodium Bicarbonate Cotransporter), Member 4 2 3
  • Na(+)/HCO3(-) Cotransporter 3 4
  • KNBC1 3 4
  • NBC1 3 4
  • Sodium Bicarbonate Cotransporter 1 (Sodium Bicarbonate Cotransporter, Kidney; Sodium Bicarbonate Cotransporter, Pancreas) 3
  • Solute Carrier Family 4, Sodium Bicarbonate Cotransporter, Member 4, Brain Type 3
  • Solute Carrier Family 4, Sodium Bicarbonate Cotransporter, Member 4 2
  • Solute Carrier Family 4, Sodium Bicarbonate Cotransporter, Member 5 3
  • Electrogenic Sodium Bicarbonate Cotransporter 1 3
  • Sodium Bicarbonate Cotransporter 4
  • NBCe1-A 3
  • SLC4A5 3
  • HNBC1 3
  • HhNMC 3
  • NBCE1 4
  • KNBC 3
  • NBC2 3
  • PNBC 3
  • NBC 4

External Ids for SLC4A4 Gene

Previous HGNC Symbols for SLC4A4 Gene

  • SLC4A5

Previous GeneCards Identifiers for SLC4A4 Gene

  • GC04P072017
  • GC04P072293
  • GC04P072453
  • GC04P072568
  • GC04P072418
  • GC04P067858

Summaries for SLC4A4 Gene

Entrez Gene Summary for SLC4A4 Gene

  • This gene encodes a sodium bicarbonate cotransporter (NBC) involved in the regulation of bicarbonate secretion and absorption and intracellular pH. Mutations in this gene are associated with proximal renal tubular acidosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

GeneCards Summary for SLC4A4 Gene

SLC4A4 (Solute Carrier Family 4 Member 4) is a Protein Coding gene. Diseases associated with SLC4A4 include Renal Tubular Acidosis, Proximal, With Ocular Abnormalities and Proximal Renal Tubular Acidosis. Among its related pathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and Glucose / Energy Metabolism. GO annotations related to this gene include transporter activity and anion transmembrane transporter activity. An important paralog of this gene is SLC4A5.

UniProtKB/Swiss-Prot for SLC4A4 Gene

  • Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intracellular pH.

  • Isoform 2: May have a higher activity than isoform 1.

Gene Wiki entry for SLC4A4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SLC4A4 Gene

Genomics for SLC4A4 Gene

Regulatory Elements for SLC4A4 Gene

Enhancers for SLC4A4 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH04F071126 0.8 Ensembl ENCODE 8.7 -59.8 -59795 1.2 JUND STAT1 BHLHE40 FOS BCL6 SLC4A4 DCK GC04M071034
GH04F071229 1.2 FANTOM5 Ensembl ENCODE 3.9 +44.3 44285 3.3 CTCF ZNF654 RAD21 NR2F2 YY1 ZNF121 ATF3 PBX2 SMC3 HNF4G SLC4A4 ENSG00000249170
GH04F071601 0.6 ENCODE 5.9 +415.8 415819 1.4 CTCF ZNF654 PKNOX1 ZMYM3 REST RAD21 PBX2 SMC3 SLC4A4 LOC105377271 GC04M071452
GH04F071059 0.6 Ensembl 4.4 -127.2 -127242 0.6 ZNF316 POLR2A NRF1 NFRKB TRIM24 ZSCAN29 EMSY SUPT5H SLC4A4 DCK GC04M071034
GH04F071107 0.4 ENCODE 6 -78.8 -78777 1.6 YY1 SLC4A4 DCK GC04M071034
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around SLC4A4 on UCSC Golden Path with GeneCards custom track

Promoters for SLC4A4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00001431880 1243 3601 CTCF RAD21 ZNF2 YY1 HIC1 ZFHX2 GATA3 GLIS2 ZBTB48 POLR2A

Genomic Location for SLC4A4 Gene

Chromosome:
4
Start:
71,186,757 bp from pter
End:
71,572,087 bp from pter
Size:
385,331 bases
Orientation:
Plus strand

Genomic View for SLC4A4 Gene

Genes around SLC4A4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SLC4A4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SLC4A4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SLC4A4 Gene

Proteins for SLC4A4 Gene

  • Protein details for SLC4A4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y6R1-S4A4_HUMAN
    Recommended name:
    Electrogenic sodium bicarbonate cotransporter 1
    Protein Accession:
    Q9Y6R1
    Secondary Accessions:
    • C4B714
    • O15153
    • Q8NEJ2
    • Q9H262
    • Q9NRZ1
    • Q9UIC0
    • Q9UIC1
    • Q9UP50

    Protein attributes for SLC4A4 Gene

    Size:
    1079 amino acids
    Molecular mass:
    121461 Da
    Quaternary structure:
    • Interacts with CA2/carbonic anhydrase 2 and CA4/carbonic anhydrase 4 which may regulate transporter activity (PubMed:12411514, PubMed:14567693, PubMed:15218065, PubMed:15563508). Isoform 1 but not isoform 2 interacts with AHCYL1 (via PEST domain when phosphorylated); the interaction increases SLC4A4 isoform 1 activity (PubMed:16769890). Interacts with AHCYL2 (By similarity).

    Alternative splice isoforms for SLC4A4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SLC4A4 Gene

Post-translational modifications for SLC4A4 Gene

  • N-glycosylation is not necessary for the transporter basic functions.
  • Phosphorylation of Ser-1026 by PKA increases the binding of CA2 and changes the Na(+):HCO3(-) stoichiometry of the transporter from 3:1 to 2:1. Phosphorylated in presence of STK39 and dephosphorylated in presence of PP1 phosphatase; phosphorylation seems to inhibit SLC4A4 activity.
  • Glycosylation at Asn 641 and Asn 661
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for SLC4A4 (SLC4A4)

No data available for DME Specific Peptides for SLC4A4 Gene

Domains & Families for SLC4A4 Gene

Gene Families for SLC4A4 Gene

Suggested Antigen Peptide Sequences for SLC4A4 Gene

Graphical View of Domain Structure for InterPro Entry

Q9Y6R1

UniProtKB/Swiss-Prot:

S4A4_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 SLC4A4: view

Function for SLC4A4 Gene

Molecular function for SLC4A4 Gene

GENATLAS Biochemistry:
solute carrier family 4,sodium bicarbonate cotransporter member 4,expressed in the basolateral membrane of renal proximal tubule cells
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by stilbene derivatives and regulated by cyclic AMP.
UniProtKB/Swiss-Prot Function:
Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intracellular pH.
UniProtKB/Swiss-Prot Function:
Isoform 2: May have a higher activity than isoform 1.

Gene Ontology (GO) - Molecular Function for SLC4A4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005452 inorganic anion exchanger activity IEA --
GO:0005515 protein binding IPI 15563508
GO:0008509 anion transmembrane transporter activity IEA --
GO:0008510 sodium:bicarbonate symporter activity TAS --
GO:0015293 symporter activity IEA --
genes like me logo Genes that share ontologies with SLC4A4: view
genes like me logo Genes that share phenotypes with SLC4A4: view

Human Phenotype Ontology for SLC4A4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SLC4A4 Gene

MGI Knock Outs for SLC4A4:

Animal Model Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for SLC4A4 Gene

Localization for SLC4A4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SLC4A4 Gene

Basolateral cell 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 SLC4A4 gene
Compartment Confidence
plasma membrane 5
extracellular 5
cytosol 3
nucleus 2
mitochondrion 1
endosome 1

Gene Ontology (GO) - Cellular Components for SLC4A4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS 9235899
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0016323 basolateral plasma membrane IEA,IDA 17661077
genes like me logo Genes that share ontologies with SLC4A4: view

Pathways & Interactions for SLC4A4 Gene

genes like me logo Genes that share pathways with SLC4A4: view

Gene Ontology (GO) - Biological Process for SLC4A4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006810 transport TAS 9235899
GO:0006811 ion transport IEA --
GO:0006814 sodium ion transport IEA,IDA 16769890
GO:0006820 anion transport IEA --
GO:0015698 inorganic anion transport IEA --
genes like me logo Genes that share ontologies with SLC4A4: view

No data available for SIGNOR curated interactions for SLC4A4 Gene

Drugs & Compounds for SLC4A4 Gene

(9) Drugs for SLC4A4 Gene - From: DrugBank, ApexBio, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Sodium bicarbonate Approved Pharma Transporter, substrate 0
S0859 Pharma NBC inhibitor,potent and selective 0

(8) Additional Compounds for SLC4A4 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
sodium
  • Sodium
  • Sodium ion
7440-23-5
Hydrogen carbonate
  • Bicarbonate
  • Bicarbonate (HCO3-)
  • Bicarbonate anion
  • Bicarbonate ion
  • Bicarbonate ion (HCO31-)
71-52-3

(1) ApexBio Compounds for SLC4A4 Gene

Compound Action Cas Number
S0859 NBC inhibitor,potent and selective 1019331-10-2
genes like me logo Genes that share compounds with SLC4A4: view

Transcripts for SLC4A4 Gene

Unigene Clusters for SLC4A4 Gene

Solute carrier family 4, sodium bicarbonate cotransporter, member 4:
Representative Sequences:

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for SLC4A4 Gene

No ASD Table

Relevant External Links for SLC4A4 Gene

GeneLoc Exon Structure for
SLC4A4
ECgene alternative splicing isoforms for
SLC4A4

Expression for SLC4A4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SLC4A4 Gene

mRNA differential expression in normal tissues according to GTEx for SLC4A4 Gene

This gene is overexpressed in Pancreas (x11.3), Kidney - Cortex (x4.2), and Brain - Nucleus accumbens (basal ganglia) (x4.1).

Protein differential expression in normal tissues from HIPED for SLC4A4 Gene

This gene is overexpressed in Frontal cortex (16.8), Urine (16.1), Spinal cord (13.9), and Kidney (8.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for SLC4A4 Gene



NURSA nuclear receptor signaling pathways regulating expression of SLC4A4 Gene:

SLC4A4

SOURCE GeneReport for Unigene cluster for SLC4A4 Gene:

Hs.5462

mRNA Expression by UniProt/SwissProt for SLC4A4 Gene:

Q9Y6R1-S4A4_HUMAN
Tissue specificity: Isoform 1 is expressed in pancreas and to a lower extent in heart, skeletal muscle, liver, parotid salivary glands, prostate, colon, stomach, thyroid, brain and spinal chord. Corneal endothelium cells express only isoform 1 (at protein level). Isoform 2 is specifically expressed in kidney at the level of proximal tubules.
genes like me logo Genes that share expression patterns with SLC4A4: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Protein tissue co-expression partners for SLC4A4 Gene

Orthologs for SLC4A4 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for SLC4A4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SLC4A4 34 35
  • 99.57 (n)
oppossum
(Monodelphis domestica)
Mammalia SLC4A4 35
  • 94 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SLC4A4 34 35
  • 93.29 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia SLC4A4 35
  • 93 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SLC4A4 34 35
  • 92.83 (n)
rat
(Rattus norvegicus)
Mammalia Slc4a4 34
  • 89.4 (n)
mouse
(Mus musculus)
Mammalia Slc4a4 34 16 35
  • 89.31 (n)
chicken
(Gallus gallus)
Aves SLC4A4 34 35
  • 83.4 (n)
lizard
(Anolis carolinensis)
Reptilia SLC4A4 35
  • 92 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia slc4a4 34
  • 79.49 (n)
zebrafish
(Danio rerio)
Actinopterygii slc4a4b 35
  • 81 (a)
OneToMany
slc4a4a 34 35
  • 75.02 (n)
Dr.2506 34
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.32 34
fruit fly
(Drosophila melanogaster)
Insecta Ndae1 36 35
  • 49 (a)
worm
(Caenorhabditis elegans)
Secernentea F52B5.1 36
  • 46 (a)
abts-1 35
  • 39 (a)
OneToMany
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0C02123g 34
  • 43.21 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes BOR1 34
  • 42.73 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AFR677C 34
  • 40.83 (n)
thale cress
(Arabidopsis thaliana)
eudicotyledons BOR4 34
  • 44.59 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 46 (a)
OneToMany
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes SPBC543.05c 34
  • 42.09 (n)
bread mold
(Neurospora crassa)
Ascomycetes NCU01480 34
  • 42.06 (n)
Species where no ortholog for SLC4A4 was found in the sources mined by GeneCards:
  • 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)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for SLC4A4 Gene

ENSEMBL:
Gene Tree for SLC4A4 (if available)
TreeFam:
Gene Tree for SLC4A4 (if available)

Paralogs for SLC4A4 Gene

Paralogs for SLC4A4 Gene

(11) SIMAP similar genes for SLC4A4 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with SLC4A4: view

Variants for SLC4A4 Gene

Sequence variations from dbSNP and Humsavar for SLC4A4 Gene

SNP ID Clin Chr 04 pos Sequence Context AA Info Type
rs121908856 Renal tubular acidosis, proximal, with ocular abnormalities and mental retardation (pRTA-OA) [MIM:604278], Pathogenic 71,447,706(+) GGCAG(A/C)GCCAT reference, missense
rs121908857 Renal tubular acidosis, proximal, with ocular abnormalities and mental retardation (pRTA-OA) [MIM:604278], Pathogenic 71,472,728(+) GTTTC(A/G)CCTTT reference, missense
VAR_024752 Renal tubular acidosis, proximal, with ocular abnormalities and mental retardation (pRTA-OA) [MIM:604278]
VAR_024753 Renal tubular acidosis, proximal, with ocular abnormalities and mental retardation (pRTA-OA) [MIM:604278]
VAR_024755 Renal tubular acidosis, proximal, with ocular abnormalities and mental retardation (pRTA-OA) [MIM:604278]

Structural Variations from Database of Genomic Variants (DGV) for SLC4A4 Gene

Variant ID Type Subtype PubMed ID
esv1975599 CNV deletion 18987734
esv2476295 CNV deletion 19546169
esv2669073 CNV deletion 23128226
esv2727799 CNV deletion 23290073
esv2763808 CNV gain 21179565
esv3346423 CNV insertion 20981092
esv3354185 CNV insertion 20981092
esv3600949 CNV loss 21293372
nsv1004558 CNV gain 25217958
nsv1136875 CNV deletion 24896259
nsv4382 CNV deletion 18451855
nsv4383 CNV insertion 18451855
nsv4384 CNV deletion 18451855
nsv523289 CNV loss 19592680
nsv950051 CNV deletion 24416366
nsv997788 CNV loss 25217958

Variation tolerance for SLC4A4 Gene

Residual Variation Intolerance Score: 18.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.80; 83.42% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for SLC4A4 Gene

Human Gene Mutation Database (HGMD)
SLC4A4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SLC4A4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SLC4A4 Gene

Disorders for SLC4A4 Gene

MalaCards: The human disease database

(17) MalaCards diseases for SLC4A4 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
renal tubular acidosis, proximal, with ocular abnormalities
  • renal tubular acidosis, proximal, with ocular abnormalities and mental retardation
proximal renal tubular acidosis
  • renal tubular acidosis type 2
renal tubular acidosis
  • acidosis renal tubular
band keratopathy
  • band-shaped keratopathy
voyeurism
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

S4A4_HUMAN
  • Note=Loss of interaction with and stimulation by CA4 is the cause of retinitis pigmentosa type 17 (RP17).
  • Renal tubular acidosis, proximal, with ocular abnormalities and mental retardation (pRTA-OA) [MIM:604278]: An extremely rare autosomal recessive syndrome characterized by short stature, profound proximal renal tubular acidosis, mental retardation, bilateral glaucoma, cataracts and bandkeratopathy. pRTA is due to a failure of the proximal tubular cells to reabsorb filtered bicarbonate from the urine, leading to urinary bicarbonate wasting and subsequent acidemia. {ECO:0000269 PubMed:10545938, ECO:0000269 PubMed:15471865, ECO:0000269 PubMed:15713912, ECO:0000269 PubMed:15930088, ECO:0000269 PubMed:16636648, ECO:0000269 PubMed:17661077}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for SLC4A4

Genetic Association Database (GAD)
SLC4A4
Human Genome Epidemiology (HuGE) Navigator
SLC4A4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
SLC4A4
genes like me logo Genes that share disorders with SLC4A4: view

No data available for Genatlas for SLC4A4 Gene

Publications for SLC4A4 Gene

  1. Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter. (PMID: 9651366) Abuladze N. … Kurtz I. (J. Biol. Chem. 1998) 2 3 4 22 64
  2. Functional analysis of a novel missense NBC1 mutation and of other mutations causing proximal renal tubular acidosis. (PMID: 17661077) Suzuki M. … Fujita T. (Pflugers Arch. 2008) 3 4 22 64
  3. IRBIT, an inositol 1,4,5-trisphosphate receptor-binding protein, specifically binds to and activates pancreas-type Na+/HCO3- cotransporter 1 (pNBC1). (PMID: 16769890) Shirakabe K. … Mikoshiba K. (Proc. Natl. Acad. Sci. U.S.A. 2006) 3 4 22 64
  4. Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration. (PMID: 15563508) Yang Z. … Zhang K. (Hum. Mol. Genet. 2005) 3 4 22 64
  5. Functional analysis of NBC1 mutants associated with proximal renal tubular acidosis and ocular abnormalities. (PMID: 15930088) Horita S. … Fujita T. (J. Am. Soc. Nephrol. 2005) 3 4 22 64

Products for SLC4A4 Gene

Sources for SLC4A4 Gene

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