SLC17A8 solute carrier family 17 member 8 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC17A8provided by HGNC
Official Full Name: solute carrier family 17 member 8provided by HGNC
Primary source: HGNC:HGNC:20151
See related: Ensembl:ENSG00000179520 MIM:607557; AllianceGenome:HGNC:20151
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: DFNA25; VGLUT3
Summary: This gene encodes a vesicular glutamate transporter. The encoded protein transports the neurotransmitter glutamate into synaptic vesicles before it is released into the synaptic cleft. Mutations in this gene are the cause of autosomal-dominant nonsyndromic type 25 deafness. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]
Expression: Biased expression in small intestine (RPKM 3.2), brain (RPKM 0.5) and 3 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q23.1

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (100357074..100422055)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (100318500..100383494)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (100750852..100815833)

Chromosome 12 - NC_000012.12 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: 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?

The c.824C>A and c.616dupA mutations in the SLC17a8 gene are associated with auditory neuropathy and lead to defective expression of VGluT3.
Title: The c.824C>A and c.616dupA mutations in the SLC17a8 gene are associated with auditory neuropathy and lead to defective expression of VGluT3.
Targeting Vesicular Glutamate Transporter Machinery: Implications on Metabotropic Glutamate Receptor 5 Signaling and Behavior.
Title: Targeting Vesicular Glutamate Transporter Machinery: Implications on Metabotropic Glutamate Receptor 5 Signaling and Behavior.
Novel pathogenic splicing mutation in SLC17A8 gene identified in a family with hearing loss.
Title: Identification of a novel splicing mutation within SLC17A8 in a Korean family with hearing loss by whole-exome sequencing.
A point mutation in VGLUT3 dramatically reduces its expression in synaptic terminals without altering its function.
Title: Characterization of a Human Point Mutation of VGLUT3 (p.A211V) in the Rodent Brain Suggests a Nonuniform Distribution of the Transporter in Synaptic Vesicles.
The results of this study identify VGLUT3 as an unexpected regulator of drug abuse.
Title: The absence of VGLUT3 predisposes to cocaine abuse by increasing dopamine and glutamate signaling in the nucleus accumbens.
The results from our study suggest that the p.M206Nfs*4 mutation in the SLC17A8 gene is likely a pathogenic mutation that causes autosomal dominant non-syndromic hearing loss.
Title: Screening of the SLC17A8 gene as a causative factor for autosomal dominant non-syndromic hearing loss in Koreans.
The absence of VGLUT3 in transgenic mice leads to an up-regulation of the midbrain dopamine system and ameliorates motor dysfunction in a model of Parkinson's disease.
Title: Loss of VGLUT3 Produces Circadian-Dependent Hyperdopaminergia and Ameliorates Motor Dysfunction and l-Dopa-Mediated Dyskinesias in a Model of Parkinson's Disease.
SLC17A8 encodes vesicular glutamate transporter-3, VGLUT3 and its impairment has a role in nonsyndromic deafness DFNA25 and inner hair cell dysfunction
Title: Impairment of SLC17A8 encoding vesicular glutamate transporter-3, VGLUT3, underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in null mice.
VGLUT3 immunoreactivity covered only a limited portion of the possible Glu-ergic pathways in the human fetal small intestine.
Title: Developmental pattern of three vesicular glutamate transporters in the myenteric plexus of the human fetal small intestine.
Docking and homology modeling explain the inhibition of VGLUT3.
Title: Docking and homology modeling explain inhibition of the human vesicular glutamate transporters.

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

Associated conditions

Description	Tests
Autosomal dominant nonsyndromic hearing loss 25 MedGen: C1854158 OMIM: 605583 GeneReviews: Genetic Hearing Loss Overview	not available

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2022-02-08) ClinGen Genome Curation Page Haploinsufficency Little evidence for dosage pathogenicity (Last evaluated 2022-02-08) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Genome-wide association study identifies a novel susceptibility locus at 12q23.1 for lung squamous cell carcinoma in han chinese. 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

SHGC-145725 (e-PCR)
- UniSTS:182565

D12S1030 (e-PCR), detects polymorphism
- UniSTS:66394

SHGC-110863 (e-PCR)
- UniSTS:168054

G64831 (e-PCR)
- UniSTS:164799

G64829 (e-PCR)
- UniSTS:164818

SLC17A8_1283 (e-PCR)
- UniSTS:277724

G10266 (e-PCR)
- UniSTS:8414

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables L-glutamate transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables L-glutamate transmembrane transporter activity	TAS Traceable Author Statement more info
enables L-glutamate uniporter activity	IDA Inferred from Direct Assay more info	PubMed
enables L-glutamate uniporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables chloride channel activity	ISS Inferred from Sequence or Structural Similarity more info
enables neurotransmitter transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sodium:phosphate symporter activity	IC Inferred by Curator more info	PubMed
enables sodium:phosphate symporter activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in L-glutamate import	ISS Inferred from Sequence or Structural Similarity more info
involved_in L-glutamate transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in chloride transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in cochlea development	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion transport	TAS Traceable Author Statement more info
involved_in neural retina development	IEA Inferred from Electronic Annotation more info
involved_in neurotransmitter loading into synaptic vesicle	IBA Inferred from Biological aspect of Ancestor more info
involved_in neurotransmitter loading into synaptic vesicle	IDA Inferred from Direct Assay more info	PubMed
involved_in neurotransmitter loading into synaptic vesicle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in phosphate ion homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of glutamate uptake involved in transmission of nerve impulse	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of acetylcholine uptake	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of synapse structure or activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in sensory perception of sound	IEA Inferred from Electronic Annotation more info
involved_in sodium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in sodium-dependent phosphate transport	IC Inferred by Curator more info	PubMed
involved_in synaptic transmission, glutamatergic	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in apical dendrite	IEA Inferred from Electronic Annotation more info
located_in axon terminus	IEA Inferred from Electronic Annotation more info
located_in basal dendrite	IEA Inferred from Electronic Annotation more info
part_of chloride channel complex	IEA Inferred from Electronic Annotation more info
is_active_in excitatory synapse	IBA Inferred from Biological aspect of Ancestor more info
located_in glial limiting end-foot	IEA Inferred from Electronic Annotation more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in multivesicular body	IEA Inferred from Electronic Annotation more info
located_in pericellular basket	IEA Inferred from Electronic Annotation more info
located_in perikaryon	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
is_active_in synaptic vesicle membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in synaptic vesicle membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: vesicular glutamate transporter 3

Names: solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 8; solute carrier family 17 (vesicular glutamate transporter), 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.

Genomic

NG_021175.1 RefSeqGene

Range

4996..69977

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001145288.2 → NP_001138760.1 vesicular glutamate transporter 3 isoform 2

See identical proteins and their annotated locations for NP_001138760.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon in the coding region compared to variant 1. The encoded isoform (2) is shorter but has the same N- and C-termini compared to isoform 1.

Source sequence(s)

AC026110, AC126308, AJ459241, AK128319, BC143396

Consensus CDS

CCDS44957.1

UniProtKB/Swiss-Prot

Q8NDX2

Related

ENSP00000376715.3, ENST00000392989.3

Conserved Domains (1) summary

cl27298
Location:75 → 463

UhpC; Sugar phosphate permease [Carbohydrate transport and metabolism]
NM_139319.3 → NP_647480.1 vesicular glutamate transporter 3 isoform 1

See identical proteins and their annotated locations for NP_647480.1

Status: REVIEWED

Description

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

Source sequence(s)

AC026110, AC126308, AJ459241, AK128319

Consensus CDS

CCDS9077.1

UniProtKB/Swiss-Prot

B3KXZ6, B7ZKV4, Q17RQ8, Q8NDX2

Related

ENSP00000316909.4, ENST00000323346.10

Conserved Domains (2) summary

cd06174
Location:80 → 502

MFS; The Major Facilitator Superfamily (MFS) is a large and diverse group of secondary transporters that includes uniporters, symporters, and antiporters. MFS proteins facilitate the transport across cytoplasmic or internal membranes of a variety of ...

TIGR00894
Location:75 → 513

2A0114euk; Na(+)-dependent inorganic phosphate cotransporter