SLC4A5 solute carrier family 4 member 5 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC4A5provided by HGNC
Official Full Name: solute carrier family 4 member 5provided by HGNC
Primary source: HGNC:HGNC:18168
See related: Ensembl:ENSG00000188687 MIM:606757; AllianceGenome:HGNC:18168
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: NBC4; NBCe2
Summary: This gene encodes a member of the sodium bicarbonate cotransporter (NBC) family, part of the bicarbonate transporter superfamily. Sodium bicarbonate cotransporters are involved in intracellular pH regulation and electroneural or electrogenic sodium bicarbonate transport. This protein is thought to be an integral membrane protein. Multiple transcript variants encoding different isoforms have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]
Expression: Broad expression in thyroid (RPKM 9.5), testis (RPKM 8.1) and 14 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2p13.1

Exon count:: 33

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (74216242..74343416, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (74224993..74351975, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (74443369..74570543, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

NBCe2 activity is stimulated by an increase in intracellular sodium and is hyper-responsive in hRPTCs carrying HV SLC4A5 rs7571842 through an aberrant HNF4A-mediated mechanism
Title: Sodium bicarbonate cotransporter NBCe2 gene variants increase sodium and bicarbonate transport in human renal proximal tubule cells.
NBCe2 could be important in proximal kidney tubule apical sodium and bicarbonate cotransport under high-salt conditions.
Title: The sodium-bicarbonate cotransporter NBCe2 (slc4a5) expressed in human renal proximal tubules shows increased apical expression under high-salt conditions.
we summarize the potential function of NBCe2 in the regulation of blood pressure, acid-base, and K(+) and Ca(2+) transport in the distal nephron--{REVIEW}
Title: Physiological role of NBCe2 in the regulation of electrolyte transport in the distal nephron.
Data indicate that 2 SNPs in SLC4A5 (rs7571842 and rs10177833) showed highly significant results and large effects sizes.
Title: Salt sensitivity of blood pressure is associated with polymorphisms in the sodium-bicarbonate cotransporter.
The additive effect of rs10177833 of SLC4A5 on systolic blood pressure is statistically different between women with dark skin color and women with medium skin color (P = .0153).
Title: Gene-environment effects of SLC4A5 and skin color on blood pressure among African American women.
Summarizing, the observed associations with resting and submaximal-exercise cardiovascular and metabolic traits in the HERITAGE Family Study are likely due to neither variation in the promoter nor known coding SNPs of SLC4A5
Title: Functional identification of the promoter of SLC4A5, a gene associated with cardiovascular and metabolic phenotypes in the HERITAGE Family Study.
Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Genetic and environmental risks for high blood pressure among African American mothers and daughters.
Observational study of gene-disease association. (HuGE Navigator)
Title: Functional identification of the promoter of SLC4A5, a gene associated with cardiovascular and metabolic phenotypes in the HERITAGE Family Study.
Genomic organization of the DCTN1-SLC4A5 locus encoding both NBC4 and p150(Glued).
Title: Genomic organization of the DCTN1-SLC4A5 locus encoding both NBC4 and p150(Glued).
These results additionally confirm the involvement of SLC4A5 with blood pressure control, although the mechanism is still unclear.
Title: Sodium bicarbonate cotransporter polymorphisms are associated with baseline and 10-year follow-up blood pressures.

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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 analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies new susceptibility loci for posttraumatic stress disorder. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH118960 (e-PCR)
- UniSTS:138245

RH123242 (e-PCR)
- UniSTS:138006

WI-17080 (e-PCR)
- UniSTS:29214

D1S1423 (e-PCR)
- UniSTS:149619

AFM326wg9 (e-PCR)
- UniSTS:78770

SHGC-77769 (e-PCR)
- UniSTS:95949

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables monoatomic anion transmembrane transporter 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 sodium:bicarbonate symporter activity	NAS Non-traceable Author Statement more info	PubMed
enables sodium:bicarbonate symporter activity	TAS Traceable Author Statement more info
enables solute:inorganic anion antiporter activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in bicarbonate transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in bicarbonate transport	IEA Inferred from Electronic Annotation more info
involved_in bicarbonate transport	NAS Non-traceable Author Statement more info	PubMed
involved_in bicarbonate transport	TAS Traceable Author Statement more info
involved_in cerebrospinal fluid secretion	IEA Inferred from Electronic Annotation more info
involved_in epithelial cell development	IEA Inferred from Electronic Annotation more info
involved_in inorganic anion transport	IEA Inferred from Electronic Annotation more info
involved_in mitochondrion distribution	IEA Inferred from Electronic Annotation more info
involved_in monoatomic anion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in regulation of intracellular pH	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of systemic arterial blood pressure	IEA Inferred from Electronic Annotation more info
involved_in renal system process	IBA Inferred from Biological aspect of Ancestor more info
involved_in retina development in camera-type eye	IEA Inferred from Electronic Annotation more info
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

Component	Evidence Code	Pubs
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in basolateral plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: electrogenic sodium bicarbonate cotransporter 4

Names: solute carrier family 4 (sodium bicarbonate cotransporter), member 5

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

NG_032663.1 RefSeqGene

Range

4992..132166

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001386136.1 → NP_001373065.1 electrogenic sodium bicarbonate cotransporter 4 isoform e

Status: REVIEWED

Source sequence(s)

AC006030, AC073263, AC103915

Conserved Domains (1) summary

cl26877
Location:7 → 938

Band_3_cyto; Band 3 cytoplasmic domain
NM_021196.3 → NP_067019.3 electrogenic sodium bicarbonate cotransporter 4 isoform a

See identical proteins and their annotated locations for NP_067019.3

Status: REVIEWED

Description

Transcript Variant: This variant (a) encodes the longest isoform (a)

Source sequence(s)

AF243499, AF293337

Consensus CDS

CCDS1936.1

UniProtKB/Swiss-Prot

Q32MA7, Q59EQ9, Q8WXD3, Q8WXD7, Q96DS7, Q96DS8, Q9BY07, Q9HBU5

Related

ENSP00000366861.4, ENST00000377634.8

Conserved Domains (3) summary

TIGR00834
Location:114 → 1070

ae; anion exchange protein

pfam00955
Location:488 → 1023

HCO3_cotransp; HCO3- transporter family

pfam07565
Location:141 → 408

Band_3_cyto; Band 3 cytoplasmic domain
NM_133478.3 → NP_597812.1 electrogenic sodium bicarbonate cotransporter 4 isoform c

See identical proteins and their annotated locations for NP_597812.1

Status: REVIEWED

Description

Transcript Variant: This variant (c) lacks an internal exon in the coding region as compared to variant a. Variant c encodes a protein that lacks a 16 aa internal segment.

Source sequence(s)

AC006030, AF293337, DB455137

Consensus CDS

CCDS1937.1

UniProtKB/Swiss-Prot

Q9BY07

Related

ENSP00000377587.2, ENST00000394019.7

Conserved Domains (3) summary

TIGR00834
Location:114 → 1054

ae; anion exchange protein

pfam00955
Location:488 → 1007

HCO3_cotransp; HCO3- transporter family

pfam07565
Location:141 → 408

Band_3_cyto; Band 3 cytoplasmic domain

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

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

74216242..74343416 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060926.1 Alternate T2T-CHM13v2.0

Range

74224993..74351975 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_033323.2: Suppressed sequence

Description

NM_033323.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
NM_133479.1: Suppressed sequence

Description

NM_133479.1: This RefSeq was permanently suppressed because currently there is not sufficient data to support this transcript.