SLC9A6 solute carrier family 9 member A6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC9A6provided by HGNC
Official Full Name: solute carrier family 9 member A6provided by HGNC
Primary source: HGNC:HGNC:11079
See related: Ensembl:ENSG00000198689 MIM:300231; AllianceGenome:HGNC:11079
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: MRSA; NHE6; MRXSCH
Summary: This gene encodes a sodium-hydrogen exchanger that is amember of the solute carrier family 9. The encoded protein localizes to early and recycling endosomes and may be involved in regulating endosomal pH and volume. Defects in this gene are associated with X-linked syndromic cognitive disability, Christianson type. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]
Expression: Ubiquitous expression in brain (RPKM 26.2), adrenal (RPKM 4.9) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: Xq26.3

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (135973837..136047269)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (134282570..134355980)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (135055996..135129428)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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?

Targeting NHE6 gene expression identifies lysosome and neurodevelopmental mechanisms in a haploid in vitro cell model.
Title: Targeting NHE6 gene expression identifies lysosome and neurodevelopmental mechanisms in a haploid in vitro cell model.
Functional analysis of two SLC9A6 frameshift variants in lymphoblastoid cells from patients with Christianson syndrome.
Title: Functional analysis of two SLC9A6 frameshift variants in lymphoblastoid cells from patients with Christianson syndrome.
Structural and functional implications of SLC13A3 and SLC9A6 mutations: an in silico approach to understanding intellectual disability.
Title: Structural and functional implications of SLC13A3 and SLC9A6 mutations: an in silico approach to understanding intellectual disability.
SCAMP5 plays a critical role in axonal trafficking and synaptic localization of NHE6 to adjust quantal size at glutamatergic synapses.
Title: SCAMP5 plays a critical role in axonal trafficking and synaptic localization of NHE6 to adjust quantal size at glutamatergic synapses.
Assorted dysfunctions of endosomal alkali cation/proton exchanger SLC9A6 variants linked to Christianson syndrome.
Title: Assorted dysfunctions of endosomal alkali cation/proton exchanger SLC9A6 variants linked to Christianson syndrome.
NHE6 role in the neoplasm chemoresistance.NHE6 transport from endosomes to the plasma membrane triggers endosome hyperacidification.
Title: Hypoxia-induced mobilization of NHE6 to the plasma membrane triggers endosome hyperacidification and chemoresistance.
membrane trafficking of the ES mutant in SLC9A6was impaired and elicited marked reductions in total dendritic length, area and arborization, and triggered apoptotic cell death
Title: A Christianson syndrome-linked deletion mutation (∆(287)ES(288)) in SLC9A6 disrupts recycling endosomal function and elicits neurodegeneration and cell death.
by sequencing panels of genes in patients with no precise clinical diagnosis, NGS can broaden the clinical variability associated with a known gene. We also argue that SLC9A6 gene mutations in females could be responsible for a monogenic cause of mild learning disability/constitutive speech disorders.
Title: A new family with an SLC9A6 mutation expanding the phenotypic spectrum of Christianson syndrome.
We describe a large extended family with three affected males, four carrier females, one presumed carrier female and one obligate carrier female with a c.190G>T, p.E64X mutation known to cause a premature stop codon in SLC9A6
Title: The expanding phenotypic spectrum of female SLC9A6 mutation carriers: a case series and review of the literature.
Epileptic encephalopathy related to mutations in the SLC9A6 genes.
Title: Diagnostic yield of genetic testing in epileptic encephalopathy in childhood.

Submit: New GeneRIF Correction See all GeneRIFs (27)

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
Christianson syndrome MedGen: C2678194 OMIM: 300243 GeneReviews: Christianson Syndrome	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2020-12-08) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2020-12-08) ClinGen Genome Curation PagePubMed

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 6 (SLC9A6) by siRNA inhibits HIV-1 replication in HeLa P4/R5 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

G62608 (e-PCR)
- UniSTS:139588

SHGC-31813 (e-PCR)
- UniSTS:55670

DXS548 (e-PCR)
- UniSTS:98971

DXS1009E.1 (e-PCR)
- UniSTS:99233

DXS6845 (e-PCR)
- UniSTS:99000

SLC9A6_3766 (e-PCR)
- UniSTS:462555

DXS424 (e-PCR)
- UniSTS:36070

DXS1009E (e-PCR)
- UniSTS:147434

G09809 (e-PCR)
- UniSTS:10998

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables identical protein 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	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within axon extension	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within dendrite extension	IDA Inferred from Direct Assay more info	PubMed
involved_in establishment of cell polarity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in monoatomic ion transport	TAS Traceable Author Statement more info
acts_upstream_of_or_within neuron projection morphogenesis	IDA Inferred from Direct Assay more info	PubMed
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 regulation of intracellular pH	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in sodium ion import across plasma membrane	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in early endosome membrane	IDA Inferred from Direct Assay more info	PubMed
located_in early endosome membrane	TAS Traceable Author Statement more info
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in late endosome membrane	IEA Inferred from Electronic Annotation more info
NOT located_in mitochondrion	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
is_active_in recycling endosome	IBA Inferred from Biological aspect of Ancestor 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 6

Names: Na(+)/H(+) exchanger 6; solute carrier family 9 (sodium/hydrogen exchanger), member 6; solute carrier family 9, subfamily A (NHE6, cation proton antiporter 6), member 6

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_017160.2 RefSeqGene

Range

16600..78434

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001042537.2 → NP_001036002.1 sodium/hydrogen exchanger 6 isoform a precursor

See identical proteins and their annotated locations for NP_001036002.1

Status: REVIEWED

Description

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

Source sequence(s)

AF030409, BC035029, DB483081, R15803

Consensus CDS

CCDS44003.1

UniProtKB/Swiss-Prot

A6NIQ9, A8K160, B4DU30, B7ZAE0, Q3ZCW7, Q5JPP8, Q5JPP9, Q86VS0, Q8WYK8, Q92581

UniProtKB/TrEMBL

B4DK83

Related

ENSP00000359729.4, ENST00000370695.8

Conserved Domains (1) summary

cl25615
Location:93 → 583

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]
NM_001177651.2 → NP_001171122.1 sodium/hydrogen exchanger 6 isoform c

See identical proteins and their annotated locations for NP_001171122.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (c) has a shorter N-terminus, compared to isoform a.

Source sequence(s)

AK300475, AL732579, R15803

Consensus CDS

CCDS55504.1

UniProtKB/TrEMBL

B4DK83

Related

ENSP00000359735.1, ENST00000370701.6

Conserved Domains (1) summary

pfam00999
Location:124 → 481

Na_H_Exchanger; Sodium/hydrogen exchanger family
NM_001330652.2 → NP_001317581.1 sodium/hydrogen exchanger 6 isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR and 5' coding region, and uses a downstream in-frame start codon, compared to variant 1. The encoded isoform (d) is shorter than isoform a.

Source sequence(s)

AL732579

Consensus CDS

CCDS83492.1

UniProtKB/TrEMBL

A0A1B0GV11, B4DK83

Related

ENSP00000490330.1, ENST00000637195.1

Conserved Domains (1) summary

cl25615
Location:41 → 499

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]
NM_001379110.1 → NP_001366039.1 sodium/hydrogen exchanger 6 isoform 5

Status: REVIEWED

Source sequence(s)

AL732579

Consensus CDS

CCDS94676.1

UniProtKB/TrEMBL

A0A0D9SGH0, B4DK83

Related

ENSP00000487486.2, ENST00000630721.3

Conserved Domains (1) summary

TIGR00840
Location:41 → 487

b_cpa1; sodium/hydrogen exchanger 3
NM_001400909.1 → NP_001387838.1 sodium/hydrogen exchanger 6 isoform c

Status: REVIEWED

Source sequence(s)

AL732579

Consensus CDS

CCDS55504.1

Related

ENSP00000490648.1, ENST00000636347.1
NM_001400910.1 → NP_001387839.1 sodium/hydrogen exchanger 6 isoform c

Status: REVIEWED

Source sequence(s)

AL732579

Consensus CDS

CCDS55504.1

Related

ENSP00000490406.1, ENST00000636092.1
NM_001400911.1 → NP_001387840.1 sodium/hydrogen exchanger 6 isoform c

Status: REVIEWED

Source sequence(s)

AL732579

Consensus CDS

CCDS55504.1

Related

ENSP00000490731.1, ENST00000637581.1
NM_001400912.1 → NP_001387841.1 sodium/hydrogen exchanger 6 isoform c

Status: REVIEWED

Source sequence(s)

AL732579

Consensus CDS

CCDS55504.1
NM_001400913.1 → NP_001387842.1 sodium/hydrogen exchanger 6 isoform d

Status: REVIEWED

Source sequence(s)

AL732579

Consensus CDS

CCDS83492.1

UniProtKB/TrEMBL

A0A1B0GV11
NM_006359.3 → NP_006350.1 sodium/hydrogen exchanger 6 isoform b precursor

See identical proteins and their annotated locations for NP_006350.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform b), compared to isoform a.

Source sequence(s)

AF030409, BC035029, BC049169, DB483081, R15803

Consensus CDS

CCDS14654.1

UniProtKB/TrEMBL

B4DK83

Related

ENSP00000359732.3, ENST00000370698.7

Conserved Domains (1) summary

cl25615
Location:93 → 551

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]