Hearing loss, autosomal recessive 120

Summary

Hearing loss, autosomal recessive 120 (MONDO:0859374) is a disease caused by MINAR2 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: MINAR2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hearing loss, autosomal recessive 120
Mondo ID	MONDO:0859374
OMIM	620238
DOID	DOID:0070674
UMLS	C5774309
MedGen	1824082
GARD	0026723
Is cancer (heuristic)	no

Also known as: deafness, autosomal recessive 120

Data availability: 4 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 recessive disease › hearing loss, autosomal recessive › hearing loss, autosomal recessive 120

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 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 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

4 retrieved; paginated sample, class counts are floors:

4 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2443700	NM_001257308.2(MINAR2):c.144G>A (p.Trp48Ter)	MINAR2	Pathogenic	no assertion criteria provided
2443701	NM_001257308.2(MINAR2):c.412_419del (p.Arg138fs)	MINAR2	Pathogenic	no assertion criteria provided
2443702	NM_001257308.2(MINAR2):c.393G>T (p.Lys131Asn)	MINAR2	Pathogenic	no assertion criteria provided
2442246	NM_001386125.1(OBSCN):c.24822C>A (p.Tyr8274Ter)	OBSCN	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
MINAR2	Strong	Autosomal recessive	hearing loss, autosomal recessive 120	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MINAR2	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
OBSCN	Orphanet:99845	Genetic recurrent myoglobinuria

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
MINAR2	HGNC:33914	ENSG00000186367	P59773	Major intrinsically disordered NOTCH2-binding receptor 1-like	gencc,clinvar
OBSCN	HGNC:15719	ENSG00000154358	Q5VST9	Obscurin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MINAR2	Major intrinsically disordered NOTCH2-binding receptor 1-like	Binds cholesterol and may regulate the distribution and homeostasis of cholesterol in hair cells.
OBSCN	Obscurin	Structural component of striated muscles which plays a role in myofibrillogenesis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MINAR2	Other/Unknown	no		MINAR1-like_C, MINAR1-like
OBSCN	Kinase	yes		IQ_motif_EF-hand-BS, DH_dom, Prot_kinase_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
primordial germ cell in gonad	1
skeletal muscle tissue	1
sural nerve	1
apex of heart	1
gastrocnemius	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MINAR2	29	tissue_specific	marker	primordial germ cell in gonad, skeletal muscle tissue, sural nerve
OBSCN	197	ubiquitous	marker	hindlimb stylopod muscle, apex of heart, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
OBSCN	2,042
MINAR2	76

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
OBSCN	Q5VST9	25

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MINAR2	P59773	62.70

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
NRAGE signals death through JNK	1	184.2×	0.010	OBSCN
RHOQ GTPase cycle	1	181.3×	0.010	OBSCN
G alpha (12/13) signalling events	1	137.6×	0.010	OBSCN
RHOA GTPase cycle	1	74.6×	0.013	OBSCN

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
protein localization to M-band	1	4213.0×	0.003	OBSCN
walking behavior	1	1404.3×	0.005	MINAR2
inner ear auditory receptor cell differentiation	1	601.9×	0.007	MINAR2
inner ear receptor cell stereocilium organization	1	421.3×	0.008	MINAR2
exploration behavior	1	324.1×	0.008	MINAR2
homeostasis of number of cells within a tissue	1	221.7×	0.010	MINAR2
sarcomere organization	1	191.5×	0.010	OBSCN
neuron apoptotic process	1	92.6×	0.018	MINAR2
cholesterol homeostasis	1	78.0×	0.018	MINAR2
regulation of small GTPase mediated signal transduction	1	72.0×	0.018	OBSCN
sensory perception of sound	1	50.5×	0.023	MINAR2
gene expression	1	39.9×	0.027	MINAR2
angiogenesis	1	31.2×	0.032	MINAR2

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
MINAR2	0	0
OBSCN	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	1	OBSCN
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MINAR2

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)
MINAR2	0	—
OBSCN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.