Hearing loss, autosomal dominant 80

Summary

Hearing loss, autosomal dominant 80 (MONDO:0030998) is a disease caused by GREB1L (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: GREB1L (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 27

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hearing loss, autosomal dominant 80
Mondo ID	MONDO:0030998
OMIM	619274
DOID	DOID:0070602
UMLS	C5543289
MedGen	1779667
GARD	0018158
Is cancer (heuristic)	no

Also known as: deafness, autosomal dominant 80 · DFNA80

Data availability: 27 ClinVar variants · 2 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 dominant disease › autosomal dominant nonsyndromic hearing loss › hearing loss, autosomal dominant 80

Related subtypes (75): autosomal dominant nonsyndromic hearing loss 1, autosomal dominant nonsyndromic hearing loss 2A, autosomal dominant nonsyndromic hearing loss 4A, autosomal dominant nonsyndromic hearing loss 6, autosomal dominant nonsyndromic hearing loss 5, autosomal dominant nonsyndromic hearing loss 10, autosomal dominant nonsyndromic hearing loss 11, autosomal dominant nonsyndromic hearing loss 9, autosomal dominant nonsyndromic hearing loss 7, autosomal dominant nonsyndromic hearing loss 12, autosomal dominant nonsyndromic hearing loss 3A, autosomal dominant nonsyndromic hearing loss 13, autosomal dominant nonsyndromic hearing loss 15, autosomal dominant nonsyndromic hearing loss 17, autosomal dominant nonsyndromic hearing loss 16, autosomal dominant nonsyndromic hearing loss 20, autosomal dominant nonsyndromic hearing loss 23, autosomal dominant nonsyndromic hearing loss 25, autosomal dominant nonsyndromic hearing loss 18, autosomal dominant nonsyndromic hearing loss 24, autosomal dominant nonsyndromic hearing loss 22, autosomal dominant nonsyndromic hearing loss 30, autosomal dominant nonsyndromic hearing loss 36, autosomal dominant nonsyndromic hearing loss 21, autosomal dominant nonsyndromic hearing loss 44, autosomal dominant nonsyndromic hearing loss 48, autosomal dominant nonsyndromic hearing loss 41, autosomal dominant nonsyndromic hearing loss 49, autosomal dominant nonsyndromic hearing loss 43, autosomal dominant nonsyndromic hearing loss 28, autosomal dominant nonsyndromic hearing loss 31, autosomal dominant nonsyndromic hearing loss 47, autosomal dominant auditory neuropathy 1, autosomal dominant nonsyndromic hearing loss 53, autosomal dominant nonsyndromic hearing loss 27, autosomal dominant nonsyndromic hearing loss 59, autosomal dominant nonsyndromic hearing loss 3B, autosomal dominant nonsyndromic hearing loss 2B, autosomal dominant nonsyndromic hearing loss 50, autosomal dominant nonsyndromic hearing loss 51, autosomal dominant nonsyndromic hearing loss 64, autosomal dominant nonsyndromic hearing loss 33, autosomal dominant nonsyndromic hearing loss 4B, autosomal dominant nonsyndromic hearing loss 56, autosomal dominant nonsyndromic hearing loss 54, autosomal dominant nonsyndromic hearing loss 58, autosomal dominant nonsyndromic hearing loss 65, autosomal dominant nonsyndromic hearing loss 67, autosomal dominant nonsyndromic hearing loss 40, autosomal dominant nonsyndromic hearing loss 69, autosomal dominant nonsyndromic hearing loss 68, autosomal dominant nonsyndromic hearing loss 70, autosomal dominant nonsyndromic hearing loss 66, hearing loss, autosomal dominant 74, hearing loss, autosomal dominant 77, hearing loss, autosomal dominant 81, hearing loss, autosomal dominant 82, hearing loss, autosomal dominant 83, hearing loss, autosomal dominant 84, hearing loss, autosomal dominant 37, hearing loss, autosomal dominant 75, hearing loss, autosomal dominant 76, hearing loss, autosomal dominant 71, hearing loss, autosomal dominant 72, hearing loss, autosomal dominant 73, hearing loss, autosomal dominant 34, with or without inflammation, hearing loss, autosomal dominant 78, hearing loss, autosomal dominant 79, hearing loss, autosomal dominant 85, hearing loss, autosomal dominant 86, hearing loss, autosomal dominant 87, hearing loss, autosomal dominant 88, hearing loss, autosomal dominant 89, hearing loss, autosomal dominant 90, autosomal dominant nonsyndromic hearing loss 91

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

27 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 7 likely pathogenic, 7 pathogenic, 2 benign, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1333378	NM_001142966.3(GREB1L):c.4576C>T (p.Arg1526Ter)	GREB1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3601152	NM_001142966.3(GREB1L):c.1144G>T (p.Glu382Ter)	GREB1L	Pathogenic	criteria provided, single submitter
3601155	NM_001142966.3(GREB1L):c.1498_1499del (p.Val500fs)	GREB1L	Pathogenic	criteria provided, single submitter
3601157	NM_001142966.3(GREB1L):c.2556+1G>A	GREB1L	Pathogenic	criteria provided, single submitter
3601159	NM_001142966.3(GREB1L):c.5562dup (p.Asp1855Ter)	GREB1L	Pathogenic	criteria provided, single submitter
3601160	NM_001142966.3(GREB1L):c.5761_5762insAT (p.Arg1921fs)	GREB1L	Pathogenic	criteria provided, single submitter
446526	NM_001142966.3(GREB1L):c.982C>T (p.Arg328Ter)	GREB1L	Pathogenic	no assertion criteria provided
446527	NM_001142966.3(GREB1L):c.4368G>T (p.Gln1456His)	GREB1L	Pathogenic	no assertion criteria provided
1333577	NM_001142966.3(GREB1L):c.2594T>A (p.Leu865Ter)	GREB1L	Likely pathogenic	criteria provided, single submitter
3601153	NM_001142966.3(GREB1L):c.1323del (p.Gly441_Leu442insTer)	GREB1L	Likely pathogenic	criteria provided, single submitter
3601156	NM_001142966.3(GREB1L):c.1987_1992del	GREB1L	Likely pathogenic	criteria provided, single submitter
3601158	NM_001142966.3(GREB1L):c.5278G>T (p.Glu1760Ter)	GREB1L	Likely pathogenic	criteria provided, single submitter
3601161	NM_001142966.3(GREB1L):c.768del (p.Ser257fs)	GREB1L	Likely pathogenic	criteria provided, single submitter
3767321	NM_001142966.3(GREB1L):c.1317A>C (p.Lys439Asn)	GREB1L	Likely pathogenic	criteria provided, single submitter
830361	NM_001142966.3(GREB1L):c.848A>G (p.Asn283Ser)	GREB1L	Likely pathogenic	criteria provided, single submitter
3671581	NM_001142966.3(GREB1L):c.3728G>T (p.Gly1243Val)	GREB1L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1806446	NM_001142966.3(GREB1L):c.1426G>A (p.Glu476Lys)	GREB1L	Uncertain significance	criteria provided, single submitter
2671694	NM_001142966.3(GREB1L):c.5362C>A (p.Leu1788Ile)	GREB1L	Uncertain significance	criteria provided, single submitter
3068600	NM_001142966.3(GREB1L):c.683C>T (p.Ser228Phe)	GREB1L	Uncertain significance	criteria provided, single submitter
3254994	NM_001142966.3(GREB1L):c.1708G>A (p.Val570Met)	GREB1L	Uncertain significance	criteria provided, single submitter
3382569	NM_001142966.3(GREB1L):c.2183-2A>G	GREB1L	Uncertain significance	criteria provided, single submitter
3393396	NM_001142966.3(GREB1L):c.5666G>A (p.Arg1889His)	GREB1L	Uncertain significance	criteria provided, single submitter
3893150	NM_001142966.3(GREB1L):c.106A>G (p.Ile36Val)	GREB1L	Uncertain significance	criteria provided, single submitter
929431	NM_001142966.3(GREB1L):c.347C>T (p.Thr116Ile)	GREB1L	Uncertain significance	criteria provided, single submitter
229007	NM_000260.4(MYO7A):c.5246G>A (p.Arg1749Gln)	MYO7A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1257141	NM_001142966.3(GREB1L):c.3555A>G (p.Glu1185=)	GREB1L	Benign	criteria provided, multiple submitters, no conflicts
1285305	NM_001142966.3(GREB1L):c.5541T>C (p.Ser1847=)	GREB1L	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 6 · 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
GREB1L	Strong	Autosomal dominant	hearing loss, autosomal dominant 80	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GREB1L	Orphanet:1848	Renal agenesis, bilateral
GREB1L	Orphanet:93100	Renal agenesis, unilateral
MYO7A	Orphanet:231169	Usher syndrome type 1
MYO7A	Orphanet:231178	Usher syndrome type 2
MYO7A	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
MYO7A	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GREB1L	HGNC:31042	ENSG00000141449	Q9C091	GREB1-like protein	gencc,clinvar
MYO7A	HGNC:7606	ENSG00000137474	Q13402	Unconventional myosin-VIIa	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GREB1L	GREB1-like protein	Plays a major role in early metanephros and genital development.
MYO7A	Unconventional myosin-VIIa	Myosins are actin-based motor molecules with ATPase activity.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · 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	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GREB1L	Other/Unknown	no		GREB1, GREB1_N, GREB1-like_C
MYO7A	Scaffold/PPI	no		IQ_motif_EF-hand-BS, FERM_domain, MyTH4_dom

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
gastrocnemius	1
male germ line stem cell (sensu Vertebrata) in testis	1
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GREB1L	184	broad	marker	buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis, gastrocnemius
MYO7A	186	broad	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GREB1L	637
MYO7A	43

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYO7A	Q13402	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GREB1L	Q9C091	72.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 2 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
The canonical retinoid cycle in rods (twilight vision)	1	519.1×	0.007	MYO7A
Sensory processing of sound	1	308.6×	0.007	MYO7A
Visual phototransduction	1	259.6×	0.007	MYO7A
Sensory processing of sound by outer hair cells of the cochlea	1	203.9×	0.007	MYO7A
Sensory processing of sound by inner hair cells of the cochlea	1	163.1×	0.007	MYO7A
Sensory Perception	1	95.2×	0.011	MYO7A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
pigment granule transport	1	8426.0×	0.004	MYO7A
paramesonephric duct development	1	2106.5×	0.004	GREB1L
phagolysosome assembly	1	1685.2×	0.004	MYO7A
mechanoreceptor differentiation	1	1685.2×	0.004	MYO7A
mesonephric duct development	1	1685.2×	0.004	GREB1L
cardiac ventricle development	1	1203.7×	0.004	GREB1L
equilibrioception	1	1203.7×	0.004	MYO7A
sensory perception of light stimulus	1	936.2×	0.004	MYO7A
male genitalia development	1	443.5×	0.006	GREB1L
eye photoreceptor cell development	1	421.3×	0.006	MYO7A
auditory receptor cell stereocilium organization	1	421.3×	0.006	MYO7A
actin filament-based movement	1	401.2×	0.006	MYO7A
uterus development	1	401.2×	0.006	GREB1L
embryonic heart tube development	1	383.0×	0.006	GREB1L
sensory organ development	1	337.0×	0.006	MYO7A
cardiac muscle cell differentiation	1	337.0×	0.006	GREB1L
retinoic acid receptor signaling pathway	1	324.1×	0.006	GREB1L
ribosome biogenesis	1	312.1×	0.006	GREB1L
metanephros development	1	255.3×	0.006	GREB1L
cochlea development	1	234.1×	0.007	MYO7A
branching involved in ureteric bud morphogenesis	1	183.2×	0.008	GREB1L
morphogenesis of an epithelium	1	172.0×	0.008	GREB1L
outflow tract morphogenesis	1	153.2×	0.008	GREB1L
lysosome organization	1	153.2×	0.008	MYO7A
kidney development	1	70.2×	0.018	GREB1L
actin filament organization	1	59.3×	0.020	MYO7A
intracellular protein localization	1	52.3×	0.022	MYO7A
sensory perception of sound	1	50.5×	0.022	MYO7A
endocytosis	1	47.6×	0.022	MYO7A
visual perception	1	39.8×	0.026	MYO7A

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
GREB1L	0	0
MYO7A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	GREB1L, MYO7A

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GREB1L	0	—
MYO7A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.