SLC17A8

solute carrier family 17 member 8, the group of Solute carrier family 17

Basic information

Region (hg38): 12:100357074-100422055

Previous symbols: [ "DFNA25" ]

Links

ENSG00000179520 ∙ NCBI:246213 ∙ OMIM:607557 ∙ HGNC:20151 ∙ Uniprot:Q8NDX2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss 25 (Strong), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Limited), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 25 (Limited), mode of inheritance: Unknown
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 25	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic	11115382; 18674745

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC17A8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC17A8 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	21	4	26
missense		2	99	3	1	105
nonsense						0
start loss						0
frameshift		1	3			4
inframe indel						0
splice donor/acceptor (+/-2bp)		1	3		1	5
splice region			8	8	1	17
non coding			34	37	31	102
Total	0	4	140	61	37

Variants in SLC17A8

This is a list of pathogenic ClinVar variants found in the SLC17A8 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-100357081-G-A		Autosomal dominant nonsyndromic hearing loss 25	Uncertain significance (Apr 27, 2017)
12-100357097-C-G		Autosomal dominant nonsyndromic hearing loss 25	Uncertain significance (Jan 13, 2018)
12-100357146-T-C		Autosomal dominant nonsyndromic hearing loss 25	Likely benign (Jan 13, 2018)
12-100357174-T-C		Autosomal dominant nonsyndromic hearing loss 25	Benign (Apr 07, 2019)
12-100357299-A-G		Autosomal dominant nonsyndromic hearing loss 25	Uncertain significance (Jan 13, 2018)
12-100357304-A-C		Autosomal dominant nonsyndromic hearing loss 25	Uncertain significance (Jan 13, 2018)
12-100357320-A-T		Autosomal dominant nonsyndromic hearing loss 25	Uncertain significance (Jan 13, 2018)
12-100357360-T-G		Autosomal dominant nonsyndromic hearing loss 25	Uncertain significance (Jan 12, 2018)
12-100357406-A-G			Benign/Likely benign (Dec 17, 2023)
12-100357408-T-C			Uncertain significance (Jun 08, 2020)
12-100357414-C-T		not specified • Autosomal dominant nonsyndromic hearing loss 25 • SLC17A8-related disorder	Benign (Jan 29, 2024)
12-100357417-TCAAA-T			Likely pathogenic (Aug 02, 2018)
12-100357418-C-T			Likely benign (Nov 10, 2021)
12-100357420-A-G		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
12-100357422-G-GA			Uncertain significance (May 27, 2022)
12-100357434-A-T		Autosomal dominant nonsyndromic hearing loss 25	Pathogenic (Jun 06, 2024)
12-100357445-G-A		not specified • Autosomal dominant nonsyndromic hearing loss 25	Benign (Jan 29, 2024)
12-100357451-A-T			Likely benign (Feb 13, 2023)
12-100357472-T-G		Inborn genetic diseases	Uncertain significance (Dec 07, 2021)
12-100380391-A-G			Benign (Nov 12, 2018)
12-100380677-C-A			Benign (Aug 03, 2020)
12-100380683-A-G			Likely benign (Oct 17, 2022)
12-100380696-T-C			Likely benign (Sep 20, 2023)
12-100380708-G-A		Autosomal dominant nonsyndromic hearing loss 25	Uncertain significance (Nov 11, 2019)
12-100380709-A-G		Autosomal dominant nonsyndromic hearing loss 25	Uncertain significance (Jan 15, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC17A8	protein_coding	protein_coding	ENST00000323346	12	64981

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00132	0.998	125695	0	53	125748	0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.830	279	321	0.870	0.0000168	3868
Missense in Polyphen		132	160.72	0.82131		1892
Synonymous	0.886	103	115	0.895	0.00000686	1124
Loss of Function	3.14	10	27.9	0.358	0.00000129	342

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000575	0.000575
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.000324	0.000323
European (Non-Finnish)	0.000211	0.000211
Middle Eastern	0.000272	0.000272
South Asian	0.000131	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mediates the uptake of glutamate into synaptic vesicles at presynaptic nerve terminals of excitatory neural cells. May also mediate the transport of inorganic phosphate. {ECO:0000269|PubMed:12151341}.
• Pathway: Synaptic vesicle cycle - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);Glutamatergic synapse - Homo sapiens (human);Nicotine addiction - Homo sapiens (human);Synaptic Vesicle Pathway;Organic anion transporters;Amino acid and oligopeptide SLC transporters;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;Histidine metabolism (Consensus)

Recessive Scores

• pRec: 0.142

Intolerance Scores

• loftool: 0.855
• rvis_EVS: -0.96
• rvis_percentile_EVS: 9.17

Haploinsufficiency Scores

• pHI: 0.187
• hipred: N
• hipred_score: 0.466
• ghis: 0.447

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.369

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Slc17a8
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: slc17a8
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: decreased functionality

Gene ontology

• Biological process: neural retina development;ion transport;sodium ion transport;brain development;sensory perception of sound;L-glutamate transmembrane transport;synaptic transmission, glutamatergic;regulation of synapse structure or activity;cochlea development;neurotransmitter loading into synaptic vesicle
• Cellular component: multivesicular body;integral component of membrane;cell junction;integral component of synaptic vesicle membrane;synaptic vesicle membrane;perikaryon;axon terminus;excitatory synapse;apical dendrite;basal dendrite;glial limiting end-foot;pericellular basket
• Molecular function: L-glutamate transmembrane transporter activity;neurotransmitter transporter activity;symporter activity