SLC17A8

Summary

SLC17A8 (solute carrier family 17 member 8, HGNC:20151) is a protein-coding gene on chromosome 12q23.1, encoding Vesicular glutamate transporter 3 (Q8NDX2). Multifunctional transporter that transports L-glutamate as well as multiple ions such as chloride, sodium and phosphate.

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.

Source: NCBI Gene 246213 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nonsyndromic genetic hearing loss (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 362 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 4
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_139319

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20151
Approved symbol	SLC17A8
Name	solute carrier family 17 member 8
Location	12q23.1
Locus type	gene with protein product
Status	Approved
Aliases	VGLUT3
Ensembl gene	ENSG00000179520
Ensembl biotype	protein_coding
OMIM	607557
Entrez	246213

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000323346, ENST00000392989, ENST00000547922, ENST00000552697, ENST00000874772

RefSeq mRNA: 2 — MANE Select: NM_139319 NM_001145288, NM_139319

CCDS: CCDS44957, CCDS9077

Canonical transcript exons

ENST00000323346 — 12 exons

Exon	Start	End
ENSE00001244868	100404038	100404170
ENSE00001244876	100402596	100402745
ENSE00001244881	100402340	100402479
ENSE00001244886	100401777	100401863
ENSE00001244900	100393369	100393483
ENSE00001244907	100391001	100391119
ENSE00001244915	100380701	100380953
ENSE00001244923	100419815	100422055
ENSE00001244928	100357074	100357492
ENSE00001632008	100396330	100396417
ENSE00003480039	100412770	100412880
ENSE00003531083	100418029	100418156

Expression profiles

Bgee: expression breadth broad, 81 present calls, max score 76.74.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0693 / max 10.4953, expressed in 43 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127571	0.0544	34
127572	0.0149	8

Top tissues by expression

218 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.74	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.05	silver quality
small intestine Peyer’s patch	UBERON:0003454	68.36	gold quality
oocyte	CL:0000023	65.68	gold quality
small intestine	UBERON:0002108	65.52	gold quality
secondary oocyte	CL:0000655	61.15	silver quality
prefrontal cortex	UBERON:0000451	60.83	gold quality
mucosa of transverse colon	UBERON:0004991	59.67	gold quality
rectum	UBERON:0001052	58.69	gold quality
lower lobe of lung	UBERON:0008949	58.13	silver quality
endothelial cell	CL:0000115	56.73	gold quality
hypothalamus	UBERON:0001898	55.88	gold quality
amygdala	UBERON:0001876	55.29	gold quality
caudate nucleus	UBERON:0001873	55.22	gold quality
ganglionic eminence	UBERON:0004023	54.80	gold quality
ventricular zone	UBERON:0003053	54.26	gold quality
anterior cingulate cortex	UBERON:0009835	53.12	gold quality
putamen	UBERON:0001874	52.90	gold quality
duodenum	UBERON:0002114	51.98	gold quality
Brodmann (1909) area 9	UBERON:0013540	51.40	gold quality
neocortex	UBERON:0001950	51.13	gold quality
frontal cortex	UBERON:0001870	51.08	gold quality
superior vestibular nucleus	UBERON:0007227	50.36	silver quality
Ammon’s horn	UBERON:0001954	49.76	gold quality
transverse colon	UBERON:0001157	49.47	gold quality
cerebral cortex	UBERON:0000956	49.29	gold quality
forebrain	UBERON:0001890	48.69	gold quality
temporal lobe	UBERON:0001871	48.67	gold quality
cortical plate	UBERON:0005343	48.48	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	48.32	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

117 targeting SLC17A8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 11)

• human vesicular glutamate transporter 3 was cloned, shows 72% identity to both hVGLUT1 and hVGLUT2, and its expression in brain overlaps with hVGLUT1 and hVGLUT2 (PMID:12151341)
• Docking and homology modeling explain the inhibition of VGLUT3. (PMID:17660252)
• VGLUT3 immunoreactivity covered only a limited portion of the possible Glu-ergic pathways in the human fetal small intestine. (PMID:18498073)
• SLC17A8 encodes vesicular glutamate transporter-3, VGLUT3 and its impairment has a role in nonsyndromic deafness DFNA25 and inner hair cell dysfunction (PMID:18674745)
• The results of this study identify VGLUT3 as an unexpected regulator of drug abuse. (PMID:26239290)
• 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. (PMID:26558771)
• 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. (PMID:26797701)
• A point mutation in VGLUT3 dramatically reduces its expression in synaptic terminals without altering its function. (PMID:28314816)
• Novel pathogenic splicing mutation in SLC17A8 gene identified in a family with hearing loss. (PMID:28647561)
• Targeting Vesicular Glutamate Transporter Machinery: Implications on Metabotropic Glutamate Receptor 5 Signaling and Behavior. (PMID:32873747)
• The c.824C>A and c.616dupA mutations in the SLC17a8 gene are associated with auditory neuropathy and lead to defective expression of VGluT3. (PMID:34145196)

Cross-species orthologs

51 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc17a8	ENSDARG00000057728
mus_musculus	Slc17a8	ENSMUSG00000019935
rattus_norvegicus	Slc17a8	ENSRNOG00000007581
drosophila_melanogaster	dmGlut	FBGN0010497
drosophila_melanogaster	MFS14	FBGN0010651
drosophila_melanogaster	Picot	FBGN0024315
drosophila_melanogaster	CG9254	FBGN0028513
drosophila_melanogaster	CG6978	FBGN0029727
drosophila_melanogaster	VGlut	FBGN0031424
drosophila_melanogaster	CG7881	FBGN0033048
drosophila_melanogaster	MFS12	FBGN0033234
drosophila_melanogaster	MFS15	FBGN0034392
drosophila_melanogaster	CG15096	FBGN0034394
drosophila_melanogaster	MFS16	FBGN0034611
drosophila_melanogaster	CG12490	FBGN0034782
drosophila_melanogaster	CG9825	FBGN0034783
drosophila_melanogaster	CG9826	FBGN0034784
drosophila_melanogaster	CG3649	FBGN0034785
drosophila_melanogaster	CG2003	FBGN0039886
drosophila_melanogaster	CG30265	FBGN0050265
drosophila_melanogaster	MFS1	FBGN0050272
caenorhabditis_elegans		WBGENE00001135
caenorhabditis_elegans		WBGENE00007669
caenorhabditis_elegans		WBGENE00008000
caenorhabditis_elegans		WBGENE00008677
caenorhabditis_elegans		WBGENE00010755
caenorhabditis_elegans		WBGENE00010931
caenorhabditis_elegans		WBGENE00011185
caenorhabditis_elegans		WBGENE00011556
caenorhabditis_elegans		WBGENE00012443
caenorhabditis_elegans		WBGENE00015271
caenorhabditis_elegans		WBGENE00015272
caenorhabditis_elegans		WBGENE00016003
caenorhabditis_elegans		WBGENE00018429
caenorhabditis_elegans		WBGENE00018918
caenorhabditis_elegans		WBGENE00018920
caenorhabditis_elegans		WBGENE00019187
caenorhabditis_elegans		WBGENE00019655
caenorhabditis_elegans		WBGENE00020583
caenorhabditis_elegans		WBGENE00020584
caenorhabditis_elegans		WBGENE00020697
caenorhabditis_elegans		WBGENE00020698
caenorhabditis_elegans		WBGENE00020699
caenorhabditis_elegans		WBGENE00020700
caenorhabditis_elegans		WBGENE00021157
caenorhabditis_elegans		WBGENE00021158
caenorhabditis_elegans		WBGENE00021219
caenorhabditis_elegans		WBGENE00021220
caenorhabditis_elegans		WBGENE00021223
caenorhabditis_elegans		WBGENE00021226
caenorhabditis_elegans		WBGENE00302978

Paralogs (12): SLC17A6 (ENSG00000091664), SLC17A9 (ENSG00000101194), SLC17A7 (ENSG00000104888), SLC17A2 (ENSG00000112337), SLC17A5 (ENSG00000119899), SLC17A3 (ENSG00000124564), SLC17A1 (ENSG00000124568), SLC37A2 (ENSG00000134955), SLC37A4 (ENSG00000137700), SLC17A4 (ENSG00000146039), SLC37A3 (ENSG00000157800), SLC37A1 (ENSG00000160190)

Protein

Protein identifiers

Vesicular glutamate transporter 3 — Q8NDX2 (reviewed: Q8NDX2)

Alternative names: Solute carrier family 17 member 8

All UniProt accessions (1): Q8NDX2

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional transporter that transports L-glutamate as well as multiple ions such as chloride, sodium and phosphate. At the synaptic vesicle membrane, mainly functions as an uniporter that mediates the uptake of L-glutamate into synaptic vesicles at presynaptic nerve terminals of excitatory neural cells. The L-glutamate uniporter activity is electrogenic and is driven by the proton electrochemical gradient, mainly by the electrical gradient established by the vacuolar H(+)-ATPase across the synaptic vesicle membrane. In addition, functions as a chloride channel that allows a chloride permeation through the synaptic vesicle membrane that affects the proton electrochemical gradient and promotes synaptic vesicles acidification. At the plasma membrane, following exocytosis, functions as a symporter of Na(+) and phosphate from the extracellular space to the cytoplasm allowing synaptic phosphate homeostasis regulation. The symporter activity is electrogenic. Moreover, operates synergistically with SLC18A3/VACHT under a constant H(+) gradient, thereby allowing striatal vesicular acetylcholine uptake.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane. Cell membrane. Synapse. Synaptosome.

Tissue specificity. Expressed in amygdala, cerebellum, hippocampus, medulla, spinal cord and thalamus.

Disease relevance. Deafness, autosomal dominant, 25 (DFNA25) [MIM:605583] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA25 expression is variable in terms of onset and rate of progression, with an age-dependent penetrance resembling an early-onset presbycusis, or senile deafness, a progressive bilateral loss of hearing that occurs in the aged. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The L-glutamate uniporter activity exhibits a biphasic dependence on chloride concentration. Chloride channel activity is allosterically activated by lumenal H(+) and Cl(-) leading to synaptic vesicles acidification. The glutamate transport activity is allosterically activated by lumenal H(+) and Cl(-), preventing non-vesicular L-glutamate release.

Similarity. Belongs to the major facilitator superfamily. Sodium/anion cotransporter family. VGLUT subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NDX2-1	1	yes
Q8NDX2-2	2

RefSeq proteins (2): NP_001138760, NP_647480* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011701	MFS	Family
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily
IPR050382	MFS_Na/Anion_cotransporter	Family

Pfam: PF07690

Catalyzed reactions (Rhea), 3 shown:

• chloride(in) = chloride(out) (RHEA:29823)
• L-glutamate(out) = L-glutamate(in) (RHEA:66336)
• 3 Na(+)(out) + phosphate(out) = 3 Na(+)(in) + phosphate(in) (RHEA:71255)

UniProt features (36 total): topological domain 13, transmembrane region 12, sequence variant 4, region of interest 2, compositionally biased region 2, chain 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NDX2-F1	77.81	0.46

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 106

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-442660	SLC-mediated transport of neurotransmitters
R-HSA-5619076	Defective SLC17A8 causes autosomal dominant deafness 25 (DFNA25)
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea
R-HSA-428643	Organic anion transport by SLC5/17/25 transporters

MSigDB gene sets: 188 (showing top): GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, GOBP_NEUROTRANSMITTER_UPTAKE, MODULE_255, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, MODULE_317, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_NEURAL_RETINA_DEVELOPMENT, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_ACID_TRANSPORT

GO Biological Process (21): neural retina development (GO:0003407), monoatomic ion transport (GO:0006811), sensory perception of sound (GO:0007605), L-glutamate transmembrane transport (GO:0015813), synaptic transmission, glutamatergic (GO:0035249), sodium-dependent phosphate transport (GO:0044341), regulation of synapse structure or activity (GO:0050803), regulation of acetylcholine uptake (GO:0051631), L-glutamate import (GO:0051938), positive regulation of glutamate uptake involved in transmission of nerve impulse (GO:0051951), phosphate ion homeostasis (GO:0055062), cochlea development (GO:0090102), neurotransmitter loading into synaptic vesicle (GO:0098700), sodium ion transport (GO:0006814), phosphate ion transport (GO:0006817), chloride transport (GO:0006821), neurotransmitter transport (GO:0006836), monoatomic ion transmembrane transport (GO:0034220), sodium ion transmembrane transport (GO:0035725), transmembrane transport (GO:0055085), chloride transmembrane transport (GO:1902476)

GO Molecular Function (9): chloride channel activity (GO:0005254), L-glutamate transmembrane transporter activity (GO:0005313), neurotransmitter transmembrane transporter activity (GO:0005326), sodium:phosphate symporter activity (GO:0005436), L-glutamate uniporter activity (GO:0140788), protein binding (GO:0005515), secondary active transmembrane transporter activity (GO:0015291), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857)

GO Cellular Component (19): multivesicular body (GO:0005771), plasma membrane (GO:0005886), synaptic vesicle membrane (GO:0030672), chloride channel complex (GO:0034707), perikaryon (GO:0043204), axon terminus (GO:0043679), excitatory synapse (GO:0060076), apical dendrite (GO:0097440), basal dendrite (GO:0097441), glial limiting end-foot (GO:0097451), glutamatergic synapse (GO:0098978), pericellular basket (GO:1990030), synaptic vesicle (GO:0008021), membrane (GO:0016020), dendrite (GO:0030425), cytoplasmic vesicle (GO:0031410), neuron projection (GO:0043005), neuronal cell body (GO:0043025), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
SLC-mediated transmembrane transport	1
SLC transporter disorders	1
Sensory processing of sound	1
SLC-mediated transport of organic anions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
cellular anatomical structure	3
anatomical structure development	2
neurotransmitter transport	2
inorganic anion transport	2
transmembrane transport	2
presynapse	2
synapse	2
dendrite	2
retina development in camera-type eye	1
sensory perception of mechanical stimulus	1
L-glutamate import	1
L-alpha-amino acid transmembrane transport	1
chemical synaptic transmission	1
phosphate ion transport	1
regulation of biological quality	1
acetylcholine uptake	1
regulation of amine transport	1
dicarboxylic acid transport	1
acidic amino acid transport	1
L-amino acid transport	1
positive regulation of L-glutamate import across plasma membrane	1
positive regulation of neurotransmitter uptake	1
glutamate reuptake	1
regulation of glutamate uptake involved in transmission of nerve impulse	1
inorganic ion homeostasis	1
inner ear development	1
intercellular transport	1
establishment of localization in cell	1
synaptic vesicle cycle	1
metal ion transport	1
monoatomic anion transport	1
monoatomic ion transport	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
cellular process	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
dicarboxylic acid transmembrane transporter activity	1
acidic amino acid transmembrane transporter activity	1

Protein interactions and networks

STRING

1362 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC17A8	SLC32A1	Q9H598	827
SLC17A8	ANO4	Q32M45	779
SLC17A8	SLC18A3	Q16572	775
SLC17A8	OTOF	Q9HC10	691
SLC17A8	PRKCG	P05129	678
SLC17A8	UBE3B	Q7Z3V4	639
SLC17A8	TMC1	Q8TDI8	634
SLC17A8	MYO7A	P78427	622
SLC17A8	GAD1	Q99259	615
SLC17A8	CALB2	P22676	613
SLC17A8	PVALB	P20472	611
SLC17A8	SLC26A5	P58743	610
SLC17A8	CALB1	P05937	605
SLC17A8	KCNQ4	P56696	601
SLC17A8	CHAT	P28329	598

IntAct

4 interactions, top by confidence:

A	B	Type	Score
DNAJC5	SLC17A8	psi-mi:“MI:0915”(physical association)	0.400
SLC17A8	RHBDD1	psi-mi:“MI:0914”(association)	0.350
SLC17A8	PLPP1	psi-mi:“MI:0914”(association)	0.350

BioGRID (33): DNAJC5 (FRET), SLC17A8 (Affinity Capture-Luminescence), YIPF6 (Two-hybrid), CYP4F2 (Two-hybrid), TMEM120B (Two-hybrid), RHBDD1 (Affinity Capture-MS), SARAF (Affinity Capture-MS), SLC17A8 (Positive Genetic), SLC17A8 (Positive Genetic), ATP11C (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A2 (Affinity Capture-MS), ATP6V0C (Affinity Capture-MS), ATP6V0D1 (Affinity Capture-MS), ATP6V1A (Affinity Capture-MS)

ESM2 similar proteins: A4FV52, A6QLI1, O00476, O00624, O61369, O62786, P34272, P34644, P38142, Q03567, Q05B21, Q10046, Q14916, Q1L8X9, Q21455, Q28722, Q2QWW7, Q32LF0, Q3TXX4, Q3UHK1, Q5NCM1, Q5SZA1, Q5W8I7, Q5W8I8, Q61983, Q62634, Q62795, Q66KG0, Q6INC8, Q7TSF2, Q7ZX53, Q8BFU8, Q8BLE7, Q8NDX2, Q921A2, Q95R48, Q961J5, Q96QE2, Q9C757, Q9FKV1

Diamond homologs: A4FV52, A6QLI1, O00476, O00624, O61369, O82390, P34644, Q03567, Q05B21, Q0IZQ3, Q10046, Q14916, Q1L8X9, Q28722, Q2QWW7, Q32LF0, Q3E9A0, Q3TXX4, Q53P54, Q5NCM1, Q5Q0U0, Q5SZA1, Q5W8I7, Q5W8I8, Q61983, Q62634, Q62795, Q652N5, Q66GI9, Q6INC8, Q7TSF2, Q8BFU8, Q8BLE7, Q8BN82, Q8GX78, Q8NDX2, Q9FKV1, Q9JI12, Q9MZD1, Q9NRA2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

362 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	220
Likely benign	80
Benign	38

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1077163	NM_139319.3(SLC17A8):c.616dup (p.Met206fs)	Pathogenic
3250400	NM_139319.3(SLC17A8):c.43A>T (p.Lys15Ter)	Pathogenic
1174525	NM_139319.3(SLC17A8):c.634C>A (p.Pro212Thr)	Likely pathogenic
3066296	NM_139319.3(SLC17A8):c.903+1_903+6del	Likely pathogenic
3109	NM_139319.3(SLC17A8):c.632C>T (p.Ala211Val)	Likely pathogenic

SpliceAI

1631 predictions. Top by Δscore:

Variant	Effect	Δscore
12:100380696:T:G	acceptor_gain	1.0000
12:100380698:TAG:T	acceptor_loss	1.0000
12:100380699:A:AG	acceptor_gain	1.0000
12:100380700:G:GA	acceptor_gain	1.0000
12:100380700:GA:G	acceptor_gain	1.0000
12:100380700:GAA:G	acceptor_gain	1.0000
12:100380700:GAAA:G	acceptor_gain	1.0000
12:100380700:GAAAA:G	acceptor_gain	1.0000
12:100380951:CAG:C	donor_loss	1.0000
12:100380952:AG:A	donor_loss	1.0000
12:100380953:GG:G	donor_loss	1.0000
12:100380954:G:T	donor_loss	1.0000
12:100380955:T:A	donor_loss	1.0000
12:100402475:TAAGT:T	donor_gain	1.0000
12:100402476:AAGT:A	donor_gain	1.0000
12:100402477:AGT:A	donor_gain	1.0000
12:100402478:GT:G	donor_gain	1.0000
12:100402478:GTG:G	donor_gain	1.0000
12:100402479:TGT:T	donor_gain	1.0000
12:100402480:G:GG	donor_gain	1.0000
12:100402481:TA:T	donor_loss	1.0000
12:100402482:AA:A	donor_loss	1.0000
12:100412877:TCAG:T	donor_loss	1.0000
12:100412878:CAGG:C	donor_loss	1.0000
12:100412880:GGTA:G	donor_loss	1.0000
12:100412882:T:A	donor_loss	1.0000
12:100380695:A:AG	acceptor_gain	0.9900
12:100380695:AT:A	acceptor_gain	0.9900
12:100380696:T:TA	acceptor_gain	0.9900
12:100398910:C:A	acceptor_gain	0.9900

AlphaMissense

3882 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:100380853:G:A	G85E	1.000
12:100380867:T:C	F90L	1.000
12:100380869:T:A	F90L	1.000
12:100380869:T:G	F90L	1.000
12:100391016:T:A	W124R	1.000
12:100391016:T:C	W124R	1.000
12:100391018:G:C	W124C	1.000
12:100391018:G:T	W124C	1.000
12:100391052:T:C	F136L	1.000
12:100391054:T:A	F136L	1.000
12:100391054:T:G	F136L	1.000
12:100391061:G:C	G139R	1.000
12:100391062:G:A	G139D	1.000
12:100393472:G:C	G193R	1.000
12:100393473:G:A	G193D	1.000
12:100396330:G:C	G197R	1.000
12:100396360:T:A	W207R	1.000
12:100396360:T:C	W207R	1.000
12:100396369:T:A	W210R	1.000
12:100396369:T:C	W210R	1.000
12:100396370:G:C	W210S	1.000
12:100396371:G:C	W210C	1.000
12:100396371:G:T	W210C	1.000
12:100396390:A:C	S217R	1.000
12:100396392:C:A	S217R	1.000
12:100396392:C:G	S217R	1.000
12:100396397:T:C	L219P	1.000
12:100396400:C:A	A220D	1.000
12:100401777:G:A	G226D	1.000
12:100401788:G:A	G230R	1.000

dbSNP variants (sampled 300 via entrez): RS1000043454 (12:100367468 G>A), RS1000052437 (12:100408735 T>G), RS1000089690 (12:100404912 A>C), RS1000093718 (12:100385953 G>A), RS1000095266 (12:100367136 C>T), RS1000260688 (12:100373877 C>G,T), RS1000323809 (12:100391868 C>T), RS1000331915 (12:100373266 C>G), RS1000397469 (12:100361052 A>C), RS1000505008 (12:100409489 C>T), RS1000567129 (12:100403426 A>C,G,T), RS1000567390 (12:100379617 A>C,G), RS1000658211 (12:100360881 G>A), RS1000679635 (12:100403275 C>T), RS1000733859 (12:100416214 C>T)

Disease associations

OMIM: gene MIM:607557 | disease phenotypes: MIM:605583

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant nonsyndromic hearing loss 25	Strong	Autosomal dominant
autosomal dominant nonsyndromic hearing loss	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Definitive	AD

Mondo (2): autosomal dominant nonsyndromic hearing loss 25 (MONDO:0011568), autosomal dominant nonsyndromic hearing loss (MONDO:0019587)

Orphanet (1): Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000407	Sensorineural hearing impairment
HP:0001751	Abnormal vestibular function
HP:0003581	Adult onset

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001827_1	Squamous cell carcinoma	1.000000e-10
GCST010204_145	Low density lipoprotein cholesterol levels	7.000000e-11
GCST012490_572	Femur bone mineral density x serum urate levels interaction	3.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565319	Deafness, Autosomal Dominant 25 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — Vesicular glutamate transporters (VGLUTs)

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Valproic Acid	increases expression	2
bisphenol A	affects cotreatment, increases methylation	1
perfluorooctanoic acid	affects cotreatment, increases expression	1
perfluorooctane sulfonic acid	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	affects cotreatment, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Lead	affects expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Zidovudine	increases expression	1
Aflatoxin B1	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D4S0	HuH7-SLC17A8-KO-c1	Cancer cell line	Male
CVCL_D4S1	HuH7-SLC17A8-KO-c4	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.