SLC9A3 solute carrier family 9 member A3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC9A3provided by HGNC
Official Full Name: solute carrier family 9 member A3provided by HGNC
Primary source: HGNC:HGNC:11073
See related: Ensembl:ENSG00000066230 MIM:182307; AllianceGenome:HGNC:11073
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: NHE3; DIAR8; NHE-3
Summary: The protein encoded by this gene is an epithelial brush border Na/H exchanger that uses an inward sodium ion gradient to expel acids from the cell. Defects in this gene are a cause of congenital secretory sodium diarrhea. Pseudogenes of this gene exist on chromosomes 10 and 22. [provided by RefSeq, Mar 2016]
Expression: Biased expression in colon (RPKM 56.4), kidney (RPKM 51.3) and 9 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5p15.33

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (470456..524449, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (465265..518871, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (470571..524564, complement)

Chromosome 5 - NC_000005.10 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?

Revisiting the association of sudden infant death syndrome (SIDS) with polymorphisms of NHE3 and IL13.
Title: Revisiting the association of sudden infant death syndrome (SIDS) with polymorphisms of NHE3 and IL13.
New functions and roles of the Na[+]-H[+]-exchanger NHE3.
Title: New functions and roles of the Na(+)-H(+)-exchanger NHE3.
Regulation of the intestinal Na[+]/H[+] exchanger NHE3 by AMP-activated kinase is dependent on phosphorylation of NHE3 at S555 and S563.
Title: Regulation of the intestinal Na(+)/H(+) exchanger NHE3 by AMP-activated kinase is dependent on phosphorylation of NHE3 at S555 and S563.
Downregulation of NHE-3 (SLC9A3) expression by MicroRNAs in intestinal epithelial cells.
Title: Downregulation of NHE-3 (SLC9A3) expression by MicroRNAs in intestinal epithelial cells.
Intestine-Specific NHE3 Deletion in Adulthood Causes Microbial Dysbiosis.
Title: Intestine-Specific NHE3 Deletion in Adulthood Causes Microbial Dysbiosis.
Nedd4-2-dependent Ubiquitination Potentiates the Inhibition of Human NHE3 by Cholera Toxin and Enteropathogenic Escherichia coli.
Title: Nedd4-2-dependent Ubiquitination Potentiates the Inhibition of Human NHE3 by Cholera Toxin and Enteropathogenic Escherichia coli.
Ubiquitin-specific peptidase 7 (USP7) and USP10 mediate deubiquitination of human NHE3 regulating its expression and activity.
Title: Ubiquitin-specific peptidase 7 (USP7) and USP10 mediate deubiquitination of human NHE3 regulating its expression and activity.
Altered absorptive function in the gall bladder during cholesterol gallstone formation is associated with abnormal NHE3 complex formation.
Title: Altered absorptive function in the gall bladder during cholesterol gallstone formation is associated with abnormal NHE3 complex formation.
Most of Taiwanese congenital bilateral absence of vas deferens (CBAVD) have at least one variant of SLC9A3 deletion and CFTR IVS8-5T, which co-contribute to Taiwanese CBAVD. [review]
Title: The role of SLC9A3 in Taiwanese patients with congenital bilateral absence of vas deferens (CBAVD).
The knowledge of this genetic form of non-syndromic CSD means that it can be detected early during the third trimester of pregnancy by the combined use of US signs, MRI and amniotic fluid digestive enzymes. Its main differential diagnosis is CCD due to mutation of the SLC26A3 gene.
Title: Congenital Sodium Diarrhea by mutation of the SLC9A3 gene.

Submit: New GeneRIF Correction See all GeneRIFs (79)

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

Associated conditions

Description	Tests
Congenital secretory sodium diarrhea 8 MedGen: C5441928 OMIM: 616868 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. 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)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of solute carrier family 9 (sodium/hydrogen exchanger), member 3 (SLC9A3) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	EIPA, a potent and specific inhibitor of Na+/H+ exchanger activity, significantly inhibits the Nef internalization into M2-macrophages, indicating that Nef is imported by Na+/H+ exchanger (solute carrier family 9, subfamily A)	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-36639 (e-PCR)
- UniSTS:62835

STS-Z39377 (e-PCR)
- UniSTS:2984

RH91398 (e-PCR)
- UniSTS:87003

D5S2774 (e-PCR)
- UniSTS:473842

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables PDZ domain binding	ISS Inferred from Sequence or Structural Similarity more info
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol binding	IDA Inferred from Direct Assay more info	PubMed
enables potassium:proton antiporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sodium:proton antiporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables sodium:proton antiporter activity	IDA Inferred from Direct Assay more info	PubMed
enables sodium:proton antiporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables sodium:proton antiporter activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in monoatomic ion transport	TAS Traceable Author Statement more info
involved_in potassium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in proton transmembrane transport	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 intracellular pH	IDA Inferred from Direct Assay more info	PubMed
involved_in sodium ion import across plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in sodium ion import across plasma membrane	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
is_active_in apical plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in apical plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in brush border	ISS Inferred from Sequence or Structural Similarity more info
is_active_in brush border membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in brush border membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in cell surface	ISS Inferred from Sequence or Structural Similarity more info
located_in early endosome	IDA Inferred from Direct Assay more info	PubMed
located_in early endosome membrane	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular exosome	IDA Inferred from Direct Assay more info	PubMed
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
located_in plasma membrane	TAS Traceable Author Statement more info
located_in recycling endosome membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: sodium/hydrogen exchanger 3

Names: Na(+)/H(+) exchanger 3; solute carrier family 9 (sodium/hydrogen exchanger), member 3; solute carrier family 9, subfamily A (NHE3, cation proton antiporter 3), member 3

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_046804.1 RefSeqGene

Range

50980..104973

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001284351.3 → NP_001271280.1 sodium/hydrogen exchanger 3 isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame acceptor splice site in the mid-coding region compared to variant 1. The resulting shorter isoform (2) lacks a 9 aa protein segment compared to isoform 1.

Source sequence(s)

AC010442, AC106772, BC011555, BC101669, BC143328, BP270851

Consensus CDS

CCDS64116.1

UniProtKB/TrEMBL

A0A2R8Y780

Related

ENSP00000422983.1, ENST00000514375.1

Conserved Domains (3) summary

TIGR00840
Location:48 → 637

b_cpa1; sodium/hydrogen exchanger 3

pfam00999
Location:105 → 457

Na_H_Exchanger; Sodium/hydrogen exchanger family

pfam16644
Location:595 → 667

NEXCaM_BD; Regulatory region of Na+/H+ exchanger NHE binds to calmodulin
NM_004174.4 → NP_004165.2 sodium/hydrogen exchanger 3 isoform 1 precursor

See identical proteins and their annotated locations for NP_004165.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC010442, AC106772, BC011555, BC101669, BP270851

Consensus CDS

CCDS3855.1

UniProtKB/Swiss-Prot

B7ZKR2, E9PF67, P48764, Q3MIW3

UniProtKB/TrEMBL

A0A2R8Y780

Related

ENSP00000264938.3, ENST00000264938.8

Conserved Domains (3) summary

TIGR00840
Location:48 → 646

b_cpa1; sodium/hydrogen exchanger 3

pfam00999
Location:105 → 462

Na_H_Exchanger; Sodium/hydrogen exchanger family

pfam16644
Location:604 → 676

NEXCaM_BD; Regulatory region of Na+/H+ exchanger NHE binds to calmodulin