SLC9A6 solute carrier family 9, subfamily A (NHE6, cation proton antiporter 6), member 6 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: SLC9A6provided by HGNC
Official Full Name: solute carrier family 9, subfamily A (NHE6, cation proton antiporter 6), member 6provided by HGNC
Primary source: HGNC:11079
Locus tag: RP11-274K13.1
See related: Ensembl:ENSG00000198689; HPRD:02208; MIM:300231; Vega:OTTHUMG00000022498
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
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 mental retardation, Christianson type. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]

Genomic context

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Location :: Xq26.3

Sequence :: Chromosome: X; NC_000023.10 (135067583..135129428)

See SLC9A6 in Epigenomics, MapViewer

Chromosome X - NC_000023.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

The involvement of SLC9A6 mutations in 22 males initially suspected to have Angelman syndrome (AS) but found on genetic testing not to have AS (AS-like cohort), and 104 male patients with X-linked mental retardation (XMR) (XMR cohort), was investigated.
Title: A loss-of-function mutation in the SLC9A6 gene causes X-linked mental retardation resembling Angelman syndrome.
These observations suggest that NHE6 regulates clathrin-dependent endocytosis of transferrin via pH regulation.
Title: Na+/H+ exchanger isoform 6 (NHE6/SLC9A6) is involved in clathrin-dependent endocytosis of transferrin.
In mineralizing osteoblasts, slightly basic basal intracellular pH is maintained, and external acid load is dissipated, by high-capacity Na(+) /H(+) exchange via NHE1 and NHE6.
Title: High capacity Na+/H+ exchange activity in mineralizing osteoblasts.
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.
NHE6 in the endosomal recycling system is involved in the development of apical bile canalicular surface domains in HepG2 cells
Title: The Na+/H+ exchanger NHE6 in the endosomal recycling system is involved in the development of apical bile canalicular surface domains in HepG2 cells.
NHE6 with alanine substitutions in the membrane-proximal region exhibited no apparent change in localization.
Title: A membrane-proximal region in the C-terminal tail of NHE7 is required for its distribution in the trans-Golgi network, distinct from NHE6 localization at endosomes.
Analysis identified an in-frame 9 base pair deletion in the solute carrier family 9, isoform A6 (SLC9A6 gene), which encodes sodium/hydrogen exchanger-6 localized to endosomal vesicles.
Title: A mutation affecting the sodium/proton exchanger, SLC9A6, causes mental retardation with tau deposition.
NHE6 participates in regulation of endosomal pH and provides a basis for understanding loss of NHE6 function leading to a phenotype resembling Angelman syndrome.
Title: Dual degradation mechanisms ensure disposal of NHE6 mutant protein associated with neurological disease.
Observational study of gene-disease association. (HuGE Navigator)
Title: Mutation in the SLC9A6 gene is not a frequent cause of sporadic Angelman-like syndrome.
Mutations in SLC9A6 cause X-linked mental retardation;males with findings suggestive of unexplained Angelman syndrome should be considered as potential candidates for SLC9A6 mutations.
Title: SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome.

Submit: New GeneRIF Correction See all (12)

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

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
Q92581	P13569	CFTR	HPRD	PubMed
BioGRID:115742	BioGRID:108309	ELAVL1	BioGRID	PubMed	Affinity Capture-RNA
BioGRID:115742	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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Cardiac muscle contraction, organism-specific biosystem (from KEGG)
Cardiac muscle contraction, organism-specific biosystemContraction of the heart is a complex process initiated by the electrical excitation of cardiac myocytes (excitation-contraction coupling, ECC). In cardiac myocytes, Ca2+ influx induced by activation...
Cardiac muscle contraction, conserved biosystem (from KEGG)
Cardiac muscle contraction, conserved biosystemContraction of the heart is a complex process initiated by the electrical excitation of cardiac myocytes (excitation-contraction coupling, ECC). In cardiac myocytes, Ca2+ influx induced by activation...
SLC-mediated transmembrane transport, organism-specific biosystem (from REACTOME)
SLC-mediated transmembrane transport, organism-specific biosystemProteins with transporting functions can be roughly classified into 3 categories: ATP-powered pumps, ion channels, and transporters. Pumps utilize the energy released by ATP hydrolysis to power the m...
Sodium/Proton exchangers, organism-specific biosystem (from REACTOME)
Sodium/Proton exchangers, organism-specific biosystemThe SLC9 gene family encode proteins (sodium/proton exchangers, NHE or NHX) which exchange sodium (influx) for protons (efflux) electroneutrally. This mechanism is important because many metabolic pr...
Transmembrane transport of small molecules, organism-specific biosystem (from REACTOME)
Transmembrane transport of small molecules, organism-specific biosystem
Transmembrane transport of small molecules
Transport of inorganic cations/anions and amino acids/oligopeptides, organism-specific biosystem (from REACTOME)
Transport of inorganic cations/anions and amino acids/oligopeptides, organism-specific biosystemTeleologically, one might argue that inorganic cation and anion transport would be evolutionarily among the oldest transport functions. Eight families comprise the group that transports exclusively i...

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

Homology

Homologs of the SLC9A6 gene: The SLC9A6 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
sodium:hydrogen antiporter activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
ion transport	TAS Traceable Author Statement more info
regulation of pH	IEA Inferred from Electronic Annotation more info
transmembrane transport	TAS Traceable Author Statement more info
transport	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
early endosome membrane	IDA Inferred from Direct Assay more info	PubMed
early endosome membrane	TAS Traceable Author Statement more info
endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
integral to membrane	IEA Inferred from Electronic Annotation more info
NOT mitochondrion	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
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: sodium/hydrogen exchanger 6; Na(+)/H(+) exchanger 6; solute carrier family 9 (sodium/hydrogen exchanger), 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_017160.1 RefSeqGene

Range

4998..66843

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

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

Q92581

Related

ENSP00000359729, OTTHUMP00000024090, ENST00000370695, OTTHUMT00000058451

Conserved Domains (1) summary

TIGR00840
Location:176 – 583
Blast Score: 685

b_cpa1; sodium/hydrogen exchanger 3
NM_001177651.1 → NP_001171122.1 sodium/hydrogen exchanger 6 isoform c

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, DC308430, R15803

Consensus CDS

CCDS55504.1

UniProtKB/Swiss-Prot

Q92581

Related

ENSP00000359735, OTTHUMP00000024091, ENST00000370701, OTTHUMT00000058452

Conserved Domains (1) summary

TIGR00840
Location:124 – 531
Blast Score: 680

b_cpa1; sodium/hydrogen exchanger 3
NM_006359.2 → NP_006350.1 sodium/hydrogen exchanger 6 isoform b precursor

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/Swiss-Prot

Q92581

Related

ENSP00000359732, OTTHUMP00000024089, ENST00000370698, OTTHUMT00000058450

Conserved Domains (1) summary

TIGR00840
Location:93 – 551
Blast Score: 691

b_cpa1; sodium/hydrogen exchanger 3

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 PATCHES

Genomic

NW_004070887.1 Reference GRCh37.p10 PATCHES

Range

916567..978412

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GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000023.10 Reference GRCh37.p10 Primary Assembly

Range

135067583..135129428

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000155.1 Alternate HuRef

Range

124341164..124403216

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018934.1 Alternate CHM1_1.0

Range

135025723..135087542

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01055849.1	None
genomic	ABBA01055850.1	None
genomic	ABBA01055851.1	None
genomic	ABBA01055852.1	None
genomic	ABBA01055853.1	None
genomic	ABBA01055854.1	None
genomic	AL732579.5 (22377..84222)	None
genomic	AMYH01023046.1 (10993..22963)	None
genomic	AMYH01023047.1	None
genomic	CH471150.2	EAW88481.1
		EAW88482.1
mRNA	AB074255.1	BAB72002.1
mRNA	AF030409.1	AAC39643.1
mRNA	AK289775.1	BAF82464.1
mRNA	AK296444.1	BAG59095.1
mRNA	AK297218.1	BAG59701.1
mRNA	AK300475.1	BAG62192.1
mRNA	AK314562.1	None
mRNA	AK316255.1	BAH14626.1
mRNA	BC035029.1	AAH35029.1
mRNA	BC047375.1	None
mRNA	BC049169.1	AAH49169.1
mRNA	D87743.1	BAA13449.1
mRNA	DB483081.1	None
mRNA	DC308430.1	None
mRNA	R15803.1	None