SLC9A8 solute carrier family 9 member A8 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC9A8provided by HGNC
Official Full Name: solute carrier family 9 member A8provided by HGNC
Primary source: HGNC:HGNC:20728
See related: Ensembl:ENSG00000197818 MIM:612730; AllianceGenome:HGNC:20728
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NHE8; NHE-8
Summary: Sodium-hydrogen exchangers (NHEs), such as SLC9A8, are integral transmembrane proteins that exchange extracellular Na+ for intracellular H+. NHEs have multiple functions, including intracellular pH homeostasis, cell volume regulation, and electroneutral NaCl absorption in epithelia (Xu et al., 2008 [PubMed 18209477]).[supplied by OMIM, Apr 2009]
Expression: Ubiquitous expression in bone marrow (RPKM 8.0), testis (RPKM 5.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 20q13.13

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	20	NC_000020.11 (49812828..49892242)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	20	NC_060944.1 (51582354..51661679)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	20	NC_000020.10 (48429365..48508779)

Chromosome 20 - NC_000020.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Downregulation of SLC9A8 Promotes Epithelial-Mesenchymal Transition and Metastasis in Colorectal Cancer Cells via the IL6-JAK1/STAT3 Signaling Pathway.
Title: Downregulation of SLC9A8 Promotes Epithelial-Mesenchymal Transition and Metastasis in Colorectal Cancer Cells via the IL6-JAK1/STAT3 Signaling Pathway.
Functional characterization of the sodium/hydrogen exchanger 8 and its role in proliferation of colonic epithelial cells.
Title: Functional characterization of the sodium/hydrogen exchanger 8 and its role in proliferation of colonic epithelial cells.
work has uncovered a crucial role of NHE8 in acrosome biogenesis and suggests that some forms of human globozoospermia might be caused by a loss of function of this Na(+)/H(+) exchanger.
Title: Loss of the Na(+)/H(+) exchanger NHE8 causes male infertility in mice by disrupting acrosome formation.
NHE8 is expressed in goblet cells, and the inflammatory cytokine TNF-alpha downregulates NHE8 expression by a transcriptional mechanism.
Title: Intestinal NHE8 is highly expressed in goblet cells and its expression is subject to TNF-α regulation.
Exonic mutations in NHE8 cannot account for congenital sodium diarrhea.
Title: Nucleotide sequence of the Na+/H+ exchanger-8 in patients with congenital sodium diarrhea.
This review defines NHE6-9 as organellar NHEs that are fairly dynamic, implying that they are subjected to intracellular trafficking and thus they continuously shuttle between organelles and the plasma membrane.
Title: Organellar Na+/H+ exchangers: novel players in organelle pH regulation and their emerging functions.
These data point to a role for the ion exchange activity of NHE8 being required to maintain endosome morphology.
Title: The sodium/proton exchanger NHE8 regulates late endosomal morphology and function.
EGF inhibits intestinal NHE8 gene expression by reducing its basal transcription.
Title: Epidermal growth factor inhibits intestinal NHE8 expression via reducing its basal transcription.
Tumor necrosis factor-alpha downregulates intestinal NHE8 expression by reducing basal promoter activity.
Title: Tumor necrosis factor-{alpha} downregulates intestinal NHE8 expression by reducing basal promoter activity.
No mutation was found in the coding regions and intron-exon boundaries of the genes for CA II, CA IV, CA XIV, kNCB1, NHE3, NHE8, NHRF1, NHRF2 and SLC26A6 amplified from genomic DNA of family members with pRTA.
Title: Familial pure proximal renal tubular acidosis--a clinical and genetic study.

Submit: New GeneRIF Correction See all GeneRIFs (11)

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 analysis identifies three psoriasis susceptibility loci. 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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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

Z94308 (e-PCR)
- UniSTS:78858

WI-20567 (e-PCR)
- UniSTS:1864

STS-F09734 (e-PCR)
- UniSTS:14927

Z94546 (e-PCR)
- UniSTS:71272

RH70097 (e-PCR)
- UniSTS:86721

G20391 (e-PCR)
- UniSTS:59081

A005P06 (e-PCR)
- UniSTS:59082

AL030965 (e-PCR)
- UniSTS:78554

Clone Names

FLJ42500, KIAA0939, MGC138418, DKFZp686C03237

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables potassium:proton antiporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables potassium:proton antiporter activity	IDA Inferred from Direct Assay more info	PubMed
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	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in acrosome assembly	ISS Inferred from Sequence or Structural Similarity more info
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	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of Golgi lumen acidification	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of intracellular pH	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of intracellular pH	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in sodium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi membrane	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi membrane	TAS Traceable Author Statement more info
located_in acrosomal vesicle	ISS Inferred from Sequence or Structural Similarity more info
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in multivesicular body membrane	IDA Inferred from Direct Assay more info	PubMed
located_in trans-Golgi network membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: sodium/hydrogen exchanger 8

Names: Na(+)/H(+) exchanger 8; solute carrier family 9 (sodium/hydrogen exchanger), member 8; solute carrier family 9, subfamily A (NHE8, cation proton antiporter 8), 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.

mRNA and Protein(s)

NM_001260491.2 → NP_001247420.1 sodium/hydrogen exchanger 8 isoform 1

See identical proteins and their annotated locations for NP_001247420.1

Status: VALIDATED

Description

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

Source sequence(s)

AB023156, AK295822, AK300318, AL049469

Consensus CDS

CCDS58774.1

UniProtKB/Swiss-Prot

Q9Y2E8

UniProtKB/TrEMBL

B4DIX7

Related

ENSP00000416418.1, ENST00000417961.5

Conserved Domains (1) summary

COG0025
Location:60 → 500

NhaP; NhaP-type Na+/H+ or K+/H+ antiporter [Inorganic ion transport and metabolism]
NM_015266.3 → NP_056081.1 sodium/hydrogen exchanger 8 isoform 2

See identical proteins and their annotated locations for NP_056081.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AB023156, AL031685, AL049469, AL162615

Consensus CDS

CCDS13421.1

UniProtKB/Swiss-Prot

B4DTQ8, Q2M1U9, Q68CZ8, Q9BX15, Q9Y2E8, Q9Y507

Related

ENSP00000354966.2, ENST00000361573.3

Conserved Domains (1) summary

cl25615
Location:64 → 542

NhaP2; NhaP-type Na+/H+ and K+/H+ antiporter with C-terminal TrkAC and CorC domains [Energy production and conversion, Inorganic ion transport and metabolism]

RNA

NR_048537.2 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (3) lacks an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AB023156, AK295822, AL049469, AL162615
NR_048538.2 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (4) lacks two internal exons, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AB023156, AK295665, AK295822, AL049469, AL162615
NR_048539.2 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (5) lacks an internal exon and uses an alternate splice site, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AB023156, AK295803, AK295822, AL049469, AL162615
NR_048540.2 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (6) lacks four internal exons, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AB023156, AK308328, AL049469, AL162615

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_000020.11 Reference GRCh38.p14 Primary Assembly

Range

49812828..49892242

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011528736.3 → XP_011527038.1 sodium/hydrogen exchanger 8 isoform X1

Conserved Domains (1) summary

COG0025
Location:60 → 533

NhaP; NhaP-type Na+/H+ or K+/H+ antiporter [Inorganic ion transport and metabolism]
XM_011528738.3 → XP_011527040.1 sodium/hydrogen exchanger 8 isoform X4

Conserved Domains (1) summary

cl01133
Location:60 → 494

Na_H_Exchanger; Sodium/hydrogen exchanger family
XM_011528741.3 → XP_011527043.1 sodium/hydrogen exchanger 8 isoform X8

Conserved Domains (1) summary

COG0025
Location:60 → 461

NhaP; NhaP-type Na+/H+ or K+/H+ antiporter [Inorganic ion transport and metabolism]
XM_006723756.2 → XP_006723819.1 sodium/hydrogen exchanger 8 isoform X2

Conserved Domains (1) summary

COG0025
Location:60 → 517

NhaP; NhaP-type Na+/H+ or K+/H+ antiporter [Inorganic ion transport and metabolism]
XM_047440071.1 → XP_047296027.1 sodium/hydrogen exchanger 8 isoform X10
XM_011528737.2 → XP_011527039.1 sodium/hydrogen exchanger 8 isoform X3

Conserved Domains (1) summary

COG0025
Location:62 → 505

NhaP; NhaP-type Na+/H+ or K+/H+ antiporter [Inorganic ion transport and metabolism]
XM_047440070.1 → XP_047296026.1 sodium/hydrogen exchanger 8 isoform X9
XM_011528740.3 → XP_011527042.1 sodium/hydrogen exchanger 8 isoform X7

Conserved Domains (1) summary

COG0025
Location:60 → 533

NhaP; NhaP-type Na+/H+ or K+/H+ antiporter [Inorganic ion transport and metabolism]
XM_017027754.3 → XP_016883243.1 sodium/hydrogen exchanger 8 isoform X6
XM_047440073.1 → XP_047296029.1 sodium/hydrogen exchanger 8 isoform X13
XM_011528745.3 → XP_011527047.1 sodium/hydrogen exchanger 8 isoform X12

Conserved Domains (1) summary

cl01133
Location:60 → 253

Na_H_Exchanger; Sodium/hydrogen exchanger family
XM_047440069.1 → XP_047296025.1 sodium/hydrogen exchanger 8 isoform X5
XM_047440072.1 → XP_047296028.1 sodium/hydrogen exchanger 8 isoform X11