SLC26A5

Chr 7AR

solute carrier family 26 member 5

Also known as: DFNB61, PRES

NCBI Gene: 375611ENSG00000170615UniProt: P58743

This gene encodes a member of the SLC26A/SulP transporter family. The protein functions as a molecular motor in motile outer hair cells (OHCs) of the cochlea, inducing changes in cell length that act to amplify sound levels. The transmembrane protein is an incomplete anion transporter, and does not allow anions to cross the cell membrane but instead undergoes a conformational change in response to changes in intracellular Cl- levels that results in a change in cell length. The protein functions at microsecond rates, which is several orders of magnitude faster than conventional molecular motor proteins. Mutations in this gene are potential candidates for causing neurosensory deafness. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2009]

Primary Disease Associations & Inheritance

?Deafness, autosomal recessive 61MIM #613865
AR
340
ClinVar variants
41
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC26A5
🧬
Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
41 Pathogenic / Likely Pathogenic· 148 VUS of 340 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.72LOEUF
pLI 0.000
Z-score 2.88
OE 0.49 (0.34–0.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.90Z-score
OE missense 0.87 (0.80–0.95)
355 obs / 406.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.49 (0.34–0.72)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.80–0.95)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 18 / 36.9Missense obs/exp: 355 / 406.1Syn Z: 1.14

ClinVar Variant Classifications

340 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic10
VUS148
Likely Benign94
Benign44
Conflicting13
31
Pathogenic
10
Likely Pathogenic
148
VUS
94
Likely Benign
44
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
1
22
0
31
Likely Pathogenic
8
1
1
0
10
VUS
3
131
12
2
148
Likely Benign
1
4
48
41
94
Benign
0
1
41
2
44
Conflicting
—13
Total2013812445340

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SLC26A5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Deafness, autosomal recessive 61

MIM #613865

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — SLC26A5
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The pathogenic roles of the p.R130S prestin variant in DFNB61 hearing loss.
Takahashi S et al.·J Physiol
2024
Splice variant IVS2-2A>G in the SLC26A5 (Prestin) gene in five Estonian families with hearing loss.
Teek R et al.·Int J Pediatr Otorhinolaryngol
2009
DNA sequence analysis of SLC26A5, encoding prestin, in a patient-control cohort: identification of fourteen novel DNA sequence variations.
Minor JS et al.·PLoS One
2009Cohort
High frequency of the IVS2-2A>G DNA sequence variation in SLC26A5, encoding the cochlear motor protein prestin, precludes its involvement in hereditary hearing loss.
Tang HY et al.·BMC Med Genet
2005
Functional Studies of Deafness-Associated Pendrin and Prestin Variants.
Takahashi S et al.·Int J Mol Sci
2024Functional
Genetic analysis of presbycusis by arrayed primer extension.
Rodriguez-Paris J et al.·Ann Clin Lab Sci
2008
High-throughput detection of mutations responsible for childhood hearing loss using resequencing microarrays.
Kothiyal P et al.·BMC Biotechnol
2010
The auditory phenotype of children harboring mutations in the prestin gene.
Matsunaga T et al.·Acta Otolaryngol
2016Case report
Hearing impairment in Estonia: an algorithm to investigate genetic causes in pediatric patients.
Teek R et al.·Adv Med Sci
2013Case report
Diverse spectrum of rare deafness genes underlies early-childhood hearing loss in Japanese patients: a cross-sectional, multi-center next-generation sequencing study.
Mutai H et al.·Orphanet J Rare Dis
2013Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools