Autosomal recessive nonsyndromic hearing loss 102

Summary

Autosomal recessive nonsyndromic hearing loss 102 (MONDO:0014428) is a disease caused by EPS8 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: EPS8 (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 102
Mondo ID	MONDO:0014428
OMIM	615974
DOID	DOID:0110463
UMLS	C3892050
MedGen	856149
GARD	0022652
Is cancer (heuristic)	no

Also known as: autosomal recessive deafness 102 · autosomal recessive nonsyndromic deafness 102 · autosomal recessive nonsyndromic deafness caused by mutation in EPS8 · autosomal recessive nonsyndromic deafness type 102 · autosomal recessive nonsyndromic hearing loss 102 · deafness, autosomal recessive 102 · deafness, autosomal recessive type 102 · DFNB102 · EPS8 autosomal recessive nonsyndromic deafness

Data availability: 19 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 102

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 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 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:

5 uncertain significance, 5 pathogenic, 5 likely pathogenic, 2 conflicting classifications of pathogenicity, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1342940	NM_004447.6(EPS8):c.1424T>G (p.Leu475Ter)	EPS8	Pathogenic	criteria provided, single submitter
155761	NM_004447.6(EPS8):c.88C>T (p.Gln30Ter)	EPS8	Pathogenic	no assertion criteria provided
3601073	NM_004447.6(EPS8):c.1048C>T (p.Gln350Ter)	EPS8	Pathogenic	criteria provided, single submitter
3601074	NM_004447.6(EPS8):c.517-1G>T	EPS8	Pathogenic	criteria provided, single submitter
3601077	NM_004447.6(EPS8):c.811-1G>A	EPS8	Pathogenic	criteria provided, single submitter
3065304	NM_004447.6(EPS8):c.676C>T (p.Gln226Ter)	EPS8	Likely pathogenic	criteria provided, single submitter
3601075	NM_004447.6(EPS8):c.600-1G>A	EPS8	Likely pathogenic	criteria provided, single submitter
3601076	NM_004447.6(EPS8):c.694C>T (p.Arg232Ter)	EPS8	Likely pathogenic	criteria provided, single submitter
997681	NM_004447.6(EPS8):c.1435-2A>T	EPS8	Likely pathogenic	criteria provided, single submitter
997682	GRCh37/hg19 12p12.3(chr12:15800060-15865927)	EPS8	Likely pathogenic	criteria provided, single submitter
1207459	NM_004447.6(EPS8):c.197G>A (p.Arg66His)	EPS8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
761279	NM_004447.6(EPS8):c.871G>T (p.Ala291Ser)	EPS8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1301461	NM_004447.6(EPS8):c.449C>T (p.Ala150Val)	EPS8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1409590	NM_004447.6(EPS8):c.2104C>T (p.Arg702Trp)	EPS8	Uncertain significance	criteria provided, multiple submitters, no conflicts
2505089	NM_004447.6(EPS8):c.1490T>A (p.Ile497Asn)	EPS8	Uncertain significance	criteria provided, single submitter
517643	NM_004447.6(EPS8):c.2177C>T (p.Thr726Ile)	EPS8	Uncertain significance	criteria provided, multiple submitters, no conflicts
560888	NM_004447.6(EPS8):c.205-8A>G	EPS8	Uncertain significance	criteria provided, multiple submitters, no conflicts
508700	NM_004447.6(EPS8):c.104A>G (p.His35Arg)	EPS8	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
509187	NM_004447.6(EPS8):c.1653G>A (p.Ser551=)	EPS8	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
EPS8	Strong	Autosomal recessive	autosomal recessive nonsyndromic hearing loss 102	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EPS8	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
EPS8	HGNC:3420	ENSG00000151491	Q12929	Epidermal growth factor receptor kinase substrate 8	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EPS8	Epidermal growth factor receptor kinase substrate 8	Signaling adapter that controls various cellular protrusions by regulating actin cytoskeleton dynamics and architecture.

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)
EPS8	Scaffold/PPI	no		SH3_domain, PTB/PI_dom, PH-like_dom_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
colonic mucosa	1
jejunal mucosa	1
mucosa of sigmoid colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EPS8	299	ubiquitous	marker	jejunal mucosa, mucosa of sigmoid colon, colonic mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EPS8	1,634

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EPS8	Q12929	2

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	EPS8
Sensory processing of sound by inner hair cells of the cochlea	1	163.1×	0.006	EPS8

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
regulation of actin filament length	1	4213.0×	0.002	EPS8
actin polymerization-dependent cell motility	1	2407.4×	0.002	EPS8
dendritic cell migration	1	1872.4×	0.002	EPS8
behavioral response to ethanol	1	1203.7×	0.002	EPS8
actin crosslink formation	1	1203.7×	0.002	EPS8
exit from mitosis	1	1053.2×	0.002	EPS8
positive regulation of ruffle assembly	1	991.3×	0.002	EPS8
barbed-end actin filament capping	1	802.5×	0.002	EPS8
Rac protein signal transduction	1	561.7×	0.003	EPS8
regulation of Rho protein signal transduction	1	510.7×	0.003	EPS8
regulation of postsynaptic membrane neurotransmitter receptor levels	1	495.6×	0.003	EPS8
actin filament bundle assembly	1	455.5×	0.003	EPS8
adult locomotory behavior	1	300.9×	0.004	EPS8
Rho protein signal transduction	1	247.8×	0.005	EPS8
cellular response to leukemia inhibitory factor	1	159.0×	0.007	EPS8
regulation of cell shape	1	123.0×	0.008	EPS8

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
EPS8	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	EPS8

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)
EPS8	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.