Autosomal recessive nonsyndromic hearing loss 61

Summary

Autosomal recessive nonsyndromic hearing loss 61 (MONDO:0013471) is a disease caused by SLC26A5 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SLC26A5 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive nonsyndromic hearing loss 61
Mondo ID	MONDO:0013471
OMIM	613865
DOID	DOID:0110513
UMLS	C3151230
MedGen	462580
GARD	0022639
Is cancer (heuristic)	no

Also known as: autosomal recessive deafness 61 · autosomal recessive nonsyndromic deafness 61 · autosomal recessive nonsyndromic deafness caused by mutation in SLC26A5 · autosomal recessive nonsyndromic deafness type 61 · deafness, autosomal recessive 61 · deafness, autosomal recessive type 61 · DFNB61 · SLC26A5 autosomal recessive nonsyndromic deafness

Data availability: 19 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › hearing loss, autosomal recessive › autosomal recessive nonsyndromic hearing loss 61

Related subtypes (101): autosomal recessive nonsyndromic hearing loss 5, autosomal recessive nonsyndromic hearing loss 1A, autosomal recessive nonsyndromic hearing loss 2, autosomal recessive nonsyndromic hearing loss 3, autosomal recessive nonsyndromic hearing loss 4, autosomal recessive nonsyndromic hearing loss 6, autosomal recessive nonsyndromic hearing loss 7, autosomal recessive nonsyndromic hearing loss 9, autosomal recessive nonsyndromic hearing loss 8, autosomal recessive nonsyndromic hearing loss 12, autosomal recessive nonsyndromic hearing loss 15, autosomal recessive nonsyndromic hearing loss 18A, autosomal recessive nonsyndromic hearing loss 17, autosomal recessive nonsyndromic hearing loss 13, autosomal recessive nonsyndromic hearing loss 21, autosomal recessive nonsyndromic hearing loss 14, autosomal recessive nonsyndromic hearing loss 16, autosomal recessive nonsyndromic hearing loss 20, autosomal recessive nonsyndromic hearing loss 26, autosomal recessive nonsyndromic hearing loss 27, autosomal recessive nonsyndromic hearing loss 22, autosomal recessive nonsyndromic hearing loss 31, autosomal recessive nonsyndromic hearing loss 30, autosomal recessive nonsyndromic hearing loss 33, autosomal recessive nonsyndromic hearing loss 37, autosomal recessive nonsyndromic hearing loss 38, autosomal recessive nonsyndromic hearing loss 40, autosomal recessive nonsyndromic hearing loss 39, autosomal recessive nonsyndromic hearing loss 35, autosomal recessive nonsyndromic hearing loss 32, autosomal recessive nonsyndromic hearing loss 36, autosomal recessive nonsyndromic hearing loss 48, autosomal recessive nonsyndromic hearing loss 23, autosomal recessive nonsyndromic hearing loss 42, autosomal recessive nonsyndromic hearing loss 46, autosomal recessive nonsyndromic hearing loss 53, autosomal recessive nonsyndromic hearing loss 28, autosomal recessive nonsyndromic hearing loss 51, autosomal recessive nonsyndromic hearing loss 47, autosomal recessive nonsyndromic hearing loss 55, autosomal recessive nonsyndromic hearing loss 62, autosomal recessive nonsyndromic hearing loss 49, autosomal recessive nonsyndromic hearing loss 44, autosomal recessive nonsyndromic hearing loss 66, autosomal recessive nonsyndromic hearing loss 59, autosomal recessive nonsyndromic hearing loss 65, autosomal recessive nonsyndromic hearing loss 67, autosomal recessive nonsyndromic hearing loss 68, autosomal recessive nonsyndromic hearing loss 24, autosomal recessive nonsyndromic hearing loss 63, autosomal recessive nonsyndromic hearing loss 45, autosomal recessive nonsyndromic hearing loss 1B, autosomal recessive nonsyndromic hearing loss 71, autosomal recessive nonsyndromic hearing loss 77, autosomal recessive nonsyndromic hearing loss 25, autosomal recessive nonsyndromic hearing loss 79, autosomal recessive nonsyndromic hearing loss 84A, autosomal recessive nonsyndromic hearing loss 85, autosomal recessive nonsyndromic hearing loss 91, autosomal recessive nonsyndromic hearing loss 83, autosomal recessive nonsyndromic hearing loss 74, autosomal recessive nonsyndromic hearing loss 89, autosomal recessive nonsyndromic hearing loss 29, autosomal recessive nonsyndromic hearing loss 96, autosomal recessive nonsyndromic hearing loss 86, autosomal recessive nonsyndromic hearing loss 98, autosomal recessive nonsyndromic hearing loss 93, autosomal recessive nonsyndromic hearing loss 70, autosomal recessive nonsyndromic hearing loss 84B, autosomal recessive nonsyndromic hearing loss 18B, autosomal recessive nonsyndromic hearing loss 88, autosomal recessive nonsyndromic hearing loss 76, autosomal recessive nonsyndromic hearing loss 101, autosomal recessive nonsyndromic hearing loss 102, autosomal recessive nonsyndromic hearing loss 103, autosomal recessive nonsyndromic hearing loss 104, autosomal recessive nonsyndromic hearing loss 97, hearing loss, autosomal recessive 111, hearing loss, autosomal recessive 118, with cochlear aplasia, hearing loss, autosomal recessive 119, hearing loss, autosomal recessive 117, hearing loss, autosomal recessive 112, hearing loss, autosomal recessive 113, hearing loss, autosomal recessive 100, hearing loss, autosomal recessive 94, hearing loss, autosomal recessive 114, hearing loss, autosomal recessive 115, hearing loss, autosomal recessive 99, hearing loss, autosomal recessive 106, hearing loss, autosomal recessive 107, hearing loss, autosomal recessive 108, hearing loss, autosomal recessive 57, hearing loss, autosomal recessive 109, hearing loss, autosomal recessive 116, hearing loss, autosomal recessive 110, hearing loss, autosomal recessive 120, hearing loss, autosomal recessive 121, hearing loss, autosomal recessive 122, hearing loss, autosomal recessive 123, autosomal recessive nonsyndromic hearing loss 124, hearing loss, autosomal recessive 125

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

19 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 3 benign, 3 pathogenic, 2 benign/likely benign, 2 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1236171	NM_198999.3(SLC26A5):c.949del (p.Val317fs)	SLC26A5	Pathogenic	criteria provided, multiple submitters, no conflicts
97020	NM_198999.3(SLC26A5):c.390A>C (p.Arg130Ser)	SLC26A5	Pathogenic	no assertion criteria provided
97021	NM_198999.3(SLC26A5):c.209G>A (p.Trp70Ter)	SLC26A5	Pathogenic	no assertion criteria provided
2505543	NM_198999.3(SLC26A5):c.2146del (p.Arg716fs)	SLC26A5	Likely pathogenic	criteria provided, single submitter
2180539	NM_198999.3(SLC26A5):c.646G>A (p.Ala216Thr)	SLC26A5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
358347	NM_198999.3(SLC26A5):c.1699A>G (p.Ile567Val)	SLC26A5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1033673	NM_198999.3(SLC26A5):c.92G>C (p.Arg31Thr)	SLC26A5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1383757	NM_198999.3(SLC26A5):c.1061C>A (p.Thr354Asn)	SLC26A5	Uncertain significance	criteria provided, multiple submitters, no conflicts
2436007	NM_198999.3(SLC26A5):c.1936T>C (p.Phe646Leu)	SLC26A5	Uncertain significance	criteria provided, single submitter
3250440	NM_198999.3(SLC26A5):c.1539G>T (p.Lys513Asn)	SLC26A5	Uncertain significance	criteria provided, multiple submitters, no conflicts
3393303	NM_198999.3(SLC26A5):c.809G>A (p.Gly270Asp)	SLC26A5	Uncertain significance	criteria provided, single submitter
3393406	NM_198999.3(SLC26A5):c.1487T>C (p.Leu496Pro)	SLC26A5	Uncertain significance	criteria provided, single submitter
3393407	NM_198999.3(SLC26A5):c.2125G>C (p.Ala709Pro)	SLC26A5	Uncertain significance	criteria provided, single submitter
358345	NM_198999.3(SLC26A5):c.2066G>A (p.Arg689Gln)	SLC26A5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1235817	NM_198999.3(SLC26A5):c.1986+30T>C	SLC26A5	Benign	criteria provided, multiple submitters, no conflicts
165272	NM_198999.3(SLC26A5):c.137T>C (p.Leu46Pro)	SLC26A5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
48339	NM_198999.3(SLC26A5):c.403+14T>C	SLC26A5	Benign	criteria provided, multiple submitters, no conflicts
48341	NM_198999.3(SLC26A5):c.989A>G (p.Asn330Ser)	SLC26A5	Benign	criteria provided, multiple submitters, no conflicts
5289	NM_198999.3(SLC26A5):c.-53-2A>G	SLC26A5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SLC26A5	Strong	Autosomal recessive	autosomal recessive nonsyndromic hearing loss 61	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC26A5	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC26A5	HGNC:9359	ENSG00000170615	P58743	Prestin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC26A5	Prestin	Voltage-sensitive motor protein that drives outer hair cell (OHC) electromotility (eM) and participates in sound amplification in the hearing organ.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC26A5	Transporter	yes		SLC26A/SulP_fam, STAS_dom, SLC26A/SulP_dom

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar cortex	1
cerebellum	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC26A5	81	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, cerebellar cortex, cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC26A5	1,287

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC26A5	P58743	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Sensory processing of sound	1	308.6×	0.007	SLC26A5
Sensory processing of sound by outer hair cells of the cochlea	1	203.9×	0.007	SLC26A5
Sensory Perception	1	95.2×	0.011	SLC26A5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to salicylic acid	1	16852.0×	0.001	SLC26A5
negative regulation of monoatomic ion transmembrane transport	1	5617.3×	0.001	SLC26A5
oxalate transport	1	2407.4×	0.001	SLC26A5
fructose transmembrane transport	1	2106.5×	0.001	SLC26A5
response to potassium ion	1	2106.5×	0.001	SLC26A5
response to thyroid hormone	1	2106.5×	0.001	SLC26A5
response to salt	1	2106.5×	0.001	SLC26A5
positive regulation of cell size	1	1296.3×	0.002	SLC26A5
sulfate transmembrane transport	1	1203.7×	0.002	SLC26A5
bicarbonate transport	1	802.5×	0.002	SLC26A5
positive regulation of cell motility	1	766.0×	0.002	SLC26A5
response to auditory stimulus	1	732.7×	0.002	SLC26A5
cochlea development	1	468.1×	0.003	SLC26A5
chloride transport	1	455.5×	0.003	SLC26A5
response to ischemia	1	251.5×	0.005	SLC26A5
chloride transmembrane transport	1	237.3×	0.005	SLC26A5
regulation of membrane potential	1	230.8×	0.005	SLC26A5
regulation of cell shape	1	123.0×	0.009	SLC26A5
sensory perception of sound	1	100.9×	0.010	SLC26A5
response to xenobiotic stimulus	1	69.1×	0.014	SLC26A5

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC26A5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	SLC26A5
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC26A5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.