Autosomal recessive nonsyndromic hearing loss 36

Summary

Autosomal recessive nonsyndromic hearing loss 36 (MONDO:0012170) is a disease caused by ESPN (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: ESPN (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 34

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive nonsyndromic hearing loss 36
Mondo ID	MONDO:0012170
MeSH	C563815
OMIM	609006
DOID	DOID:0110494
UMLS	C1837007
MedGen	324662
GARD	0022611
Is cancer (heuristic)	no

Also known as: autosomal recessive deafness 36 · autosomal recessive nonsyndromic deafness 36 · autosomal recessive nonsyndromic deafness caused by mutation in ESPN · autosomal recessive nonsyndromic deafness type 36 · autosomal recessive nonsyndromic hearing loss 36 · deafness, autosomal dominant, without vestibular involvement · deafness, autosomal recessive 36 · deafness, autosomal recessive 36, with or without vestibular involvement · deafness, neurosensory, without vestibular involvement, autosomal dominant · DFNB36 · ESPN autosomal recessive nonsyndromic deafness

Data availability: 34 ClinVar variants · 4 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 36

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 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 61, 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

34 retrieved; paginated sample, class counts are floors:

14 uncertain significance, 9 pathogenic, 5 likely pathogenic, 3 benign/likely benign, 1 conflicting classifications of pathogenicity, 1 likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1299307	NM_031475.3(ESPN):c.2081_2082del (p.Ser694fs)	ESPN	Pathogenic	criteria provided, single submitter
2445633	NM_031475.3(ESPN):c.2496C>G (p.Tyr832Ter)	ESPN	Pathogenic	criteria provided, single submitter
2572469	NM_031475.3(ESPN):c.1649_1665del (p.Arg550fs)	ESPN	Pathogenic	criteria provided, single submitter
3601083	NM_031475.3(ESPN):c.1916-1G>A	ESPN	Pathogenic	criteria provided, single submitter
3601084	NM_031475.3(ESPN):c.1995_2056del (p.Lys666fs)	ESPN	Pathogenic	criteria provided, single submitter
4291998	NM_031475.3(ESPN):c.489-2A>G	ESPN	Pathogenic	criteria provided, single submitter
4418	NM_031475.3(ESPN):c.2470_2473del (p.Ser824fs)	ESPN	Pathogenic	no assertion criteria provided
4419	NM_031475.3(ESPN):c.1988_1991del (p.Lys663fs)	ESPN	Pathogenic	no assertion criteria provided
562076	NM_031475.3(ESPN):c.2496del (p.Gly831_Tyr832insTer)	ESPN	Pathogenic/Likely pathogenic	no assertion criteria provided
984702	NM_031475.3(ESPN):c.1916-1G>C	ESPN	Pathogenic	criteria provided, single submitter
1333558	NM_031475.3(ESPN):c.2524C>T (p.Arg842Ter)	ESPN	Likely pathogenic	criteria provided, single submitter
2445625	NM_031475.3(ESPN):c.1972G>A (p.Glu658Lys)	ESPN	Likely pathogenic	criteria provided, single submitter
4423	NM_031475.3(ESPN):c.2539AAG[1] (p.Lys848del)	ESPN	Likely pathogenic	criteria provided, single submitter
450999	NM_031475.3(ESPN):c.1464+1G>A	ESPN	Likely pathogenic	criteria provided, multiple submitters, no conflicts
623132	NM_031475.3(ESPN):c.2446G>T (p.Glu816Ter)	ESPN	Likely pathogenic	criteria provided, single submitter
1219107	NM_031475.3(ESPN):c.1803GCC[5] (p.Pro605dup)	ESPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028415	NM_031475.3(ESPN):c.1426A>C (p.Lys476Gln)	ESPN	Uncertain significance	criteria provided, multiple submitters, no conflicts
1297731	NM_031475.3(ESPN):c.2239G>A (p.Gly747Ser)	ESPN	Uncertain significance	criteria provided, multiple submitters, no conflicts
1307782	NM_031475.3(ESPN):c.2069C>T (p.Ser690Leu)	ESPN	Uncertain significance	criteria provided, multiple submitters, no conflicts
1342840	NM_031475.3(ESPN):c.1870G>A (p.Ala624Thr)	ESPN	Uncertain significance	criteria provided, single submitter
1443667	NM_031475.3(ESPN):c.2339_2341del	ESPN	Uncertain significance	criteria provided, multiple submitters, no conflicts
1485690	NM_031475.3(ESPN):c.1A>C (p.Met1Leu)	ESPN	Uncertain significance	criteria provided, single submitter
2071078	NM_031475.3(ESPN):c.1369G>T (p.Ala457Ser)	ESPN	Uncertain significance	criteria provided, multiple submitters, no conflicts
2671695	NM_031475.3(ESPN):c.2263C>T (p.Arg755Cys)	ESPN	Uncertain significance	criteria provided, multiple submitters, no conflicts
3065194	NM_031475.3(ESPN):c.1762G>A (p.Asp588Asn)	ESPN	Uncertain significance	criteria provided, single submitter
3779629	NM_031475.3(ESPN):c.1287del (p.Pro431fs)	ESPN	Uncertain significance	criteria provided, single submitter
3891406	NM_031475.3(ESPN):c.1085C>T (p.Ser362Leu)	ESPN	Uncertain significance	criteria provided, multiple submitters, no conflicts
3891409	NM_031475.3(ESPN):c.904G>A (p.Asp302Asn)	ESPN	Uncertain significance	criteria provided, single submitter
4421	NM_031475.3(ESPN):c.2230G>A (p.Asp744Asn)	ESPN	Uncertain significance	criteria provided, multiple submitters, no conflicts
449818	NM_031475.3(ESPN):c.935C>T (p.Ser312Leu)	ESPN	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 2 · 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
ESPN	Definitive	Autosomal recessive	nonsyndromic genetic hearing loss	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ESPN	Orphanet:231169	Usher syndrome type 1
ESPN	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
ESPN	HGNC:13281	ENSG00000187017	B1AK53	Espin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ESPN	Espin	Multifunctional actin-bundling protein.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ESPN	Scaffold/PPI	no		Ankyrin_rpt, WH2_dom, Ankyrin_rpt-contain_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

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
left testis	1
right testis	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ESPN	184	broad	marker	right testis, left testis, right uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ESPN	1,702

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ESPN	B1AK53	68.76

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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 by outer hair cells of the cochlea	1	203.9×	0.006	ESPN
Sensory processing of sound by inner hair cells of the cochlea	1	163.1×	0.006	ESPN

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
microvillar actin bundle assembly	1	16852.0×	2e-04	ESPN
actin filament bundle assembly	1	455.5×	0.003	ESPN
sensory perception of sound	1	100.9×	0.010	ESPN

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
ESPN	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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ESPN

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)
ESPN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.