SLC26A5

solute carrier family 26 member 5, the group of Solute carrier family 26

Basic information

Region (hg38): 7:103352730-103446207

Previous symbols: [ "PRES" ]

Links

ENSG00000170615 ∙ NCBI:375611 ∙ OMIM:604943 ∙ HGNC:9359 ∙ Uniprot:P58743 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 61 (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 61 (Strong), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 61 (Moderate), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 61	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	12719379; 24164807
Heterozygosity has been observed in individuals with hearing loss as well, indicating possible semidominance

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC26A5 gene.

• not provided (8 variants)
• Autosomal recessive nonsyndromic hearing loss 61 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC26A5 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			2	32	1	35
missense		1	62	7	1	71
nonsense	3					3
start loss						0
frameshift	5	1	1			7
inframe indel			1			1
splice donor/acceptor (+/-2bp)		6	1	1		8
splice region			4	4	1	9
non coding			9	37	38	84
Total	8	8	76	77	40

Highest pathogenic variant AF is 0.00000657

Variants in SLC26A5

This is a list of pathogenic ClinVar variants found in the SLC26A5 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-103354878-C-G		not specified	Uncertain significance (Jun 30, 2022)
7-103354913-A-T		not specified	Uncertain significance (Apr 19, 2023)
7-103354946-A-G		not specified	Uncertain significance (Dec 22, 2023)
7-103361968-T-C		not specified	Uncertain significance (Jan 27, 2022)
7-103361991-C-T			Uncertain significance (Apr 04, 2023)
7-103362026-G-GT			Uncertain significance (Feb 01, 2020)
7-103363349-A-G			Likely benign (Dec 01, 2022)
7-103364302-G-T			Uncertain significance (Aug 28, 2020)
7-103367599-G-A		not specified	Uncertain significance (Sep 25, 2023)
7-103367944-A-C			Likely benign (Apr 01, 2022)
7-103367986-G-T		not specified	Uncertain significance (May 01, 2024)
7-103374133-A-G			Benign (Mar 31, 2019)
7-103374180-C-A			Likely benign (Jan 13, 2019)
7-103374371-T-C			Likely benign (Oct 15, 2020)
7-103374397-A-T			Likely benign (Jun 16, 2021)
7-103374409-G-A		Inborn genetic diseases	Uncertain significance (Dec 19, 2022)
7-103374413-T-C		Inborn genetic diseases	Uncertain significance (Feb 10, 2023)
7-103374422-T-A			Uncertain significance (Aug 04, 2023)
7-103374428-T-G			Uncertain significance (Aug 31, 2022)
7-103374450-A-C			Benign/Likely benign (Sep 14, 2023)
7-103374457-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Feb 13, 2024)
7-103374459-C-T			Likely benign (Jul 26, 2018)
7-103374466-T-C		Inborn genetic diseases	Uncertain significance (Oct 05, 2023)
7-103374473-C-T			Uncertain significance (Jun 24, 2022)
7-103374487-CT-C		Autosomal recessive nonsyndromic hearing loss 61	Likely pathogenic (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC26A5	protein_coding	protein_coding	ENST00000306312	18	93448

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.99e-8	0.999	125704	0	44	125748	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.901	355	406	0.874	0.0000210	4821
Missense in Polyphen		188	229.35	0.81971		2750
Synonymous	1.14	138	156	0.884	0.00000901	1508
Loss of Function	2.88	18	36.9	0.488	0.00000191	465

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000485	0.000485
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.000109	0.000109
South Asian	0.000327	0.000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Motor protein that converts auditory stimuli to length changes in outer hair cells and mediates sound amplification in the mammalian hearing organ. Prestin is a bidirectional voltage- to-force converter, it can operate at microsecond rates. It uses cytoplasmic anions as extrinsic voltage sensors, probably chloride and bicarbonate. After binding to a site with millimolar affinity, these anions are translocated across the membrane in response to changes in the transmembrane voltage. They move towards the extracellular surface following hyperpolarization, and towards the cytoplasmic side in response to depolarization. As a consequence, this translocation triggers conformational changes in the protein that ultimately alter its surface area in the plane of the plasma membrane. The area decreases when the anion is near the cytoplasmic face of the membrane (short state), and increases when the ion has crossed the membrane to the outer surface (long state). So, it acts as an incomplete transporter. It swings anions across the membrane, but does not allow these anions to dissociate and escape to the extracellular space. Salicylate, an inhibitor of outer hair cell motility, acts as competitive antagonist at the prestin anion-binding site (By similarity). {ECO:0000250}.
• Disease: DISEASE: Deafness, autosomal recessive, 61 (DFNB61) [MIM:613865]: 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. {ECO:0000269|PubMed:12719379}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.310

Intolerance Scores

• loftool: 0.0406
• rvis_EVS: -0.35
• rvis_percentile_EVS: 29.43

Haploinsufficiency Scores

• pHI: 0.272
• hipred: Y
• hipred_score: 0.523
• ghis: 0.424

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.156

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc26a5
• Phenotype: growth/size/body region phenotype; 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)

Gene ontology

• Biological process: response to ischemia;sensory perception of sound;regulation of cell shape;response to salicylic acid;response to auditory stimulus;bicarbonate transport;fructose transmembrane transport;oxalate transport;negative regulation of ion transmembrane transport;response to potassium ion;positive regulation of cell size;protein tetramerization;cochlea development;response to thyroid hormone;response to salt;sulfate transmembrane transport;chloride transmembrane transport;positive regulation of cell motility
• Cellular component: cytoplasm;integral component of plasma membrane;basolateral plasma membrane;lateral plasma membrane
• Molecular function: transcription factor binding;secondary active sulfate transmembrane transporter activity;bicarbonate transmembrane transporter activity;chloride transmembrane transporter activity;sulfate transmembrane transporter activity;anion:anion antiporter activity;oxalate transmembrane transporter activity;spectrin binding;protein homodimerization activity