Autosomal dominant nonsyndromic hearing loss 41

Summary

Autosomal dominant nonsyndromic hearing loss 41 (MONDO:0011994) is a disease caused by P2RX2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: P2RX2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 18

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant nonsyndromic hearing loss 41
Mondo ID	MONDO:0011994
MeSH	C564272
OMIM	608224
DOID	DOID:0110567
UMLS	C1842371
MedGen	330834
GARD	0018121
Is cancer (heuristic)	no

Also known as: autosomal dominant deafness 41 · autosomal dominant nonsyndromic deafness 41 · autosomal dominant nonsyndromic deafness caused by mutation in P2RX2 · autosomal dominant nonsyndromic deafness type 41 · deafness, autosomal dominant 41 · deafness, autosomal dominant type 41 · DFNA41 · P2RX2 autosomal dominant nonsyndromic deafness

Data availability: 18 ClinVar variants · 3 GenCC gene-disease records · 4 cell lines.

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 › autosomal dominant nonsyndromic hearing loss 41

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 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 80, 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

18 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 4 benign, 3 pathogenic, 1 benign/likely benign, 1 not provided, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
155762	NM_170682.4(P2RX2):c.178G>T (p.Val60Leu)	P2RX2	Pathogenic	no assertion criteria provided
155763	NM_170682.4(P2RX2):c.1057G>C (p.Gly353Arg)	P2RX2	Pathogenic	criteria provided, single submitter
4082203	NM_170682.4(P2RX2):c.178G>C (p.Val60Leu)	P2RX2	Pathogenic	criteria provided, single submitter
987153	NM_170682.4(P2RX2):c.1057G>A (p.Gly353Arg)	P2RX2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
504852	NM_170682.4(P2RX2):c.381+2T>C	P2RX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1185141	NM_170682.4(P2RX2):c.459_554+1dup	P2RX2	Uncertain significance	no assertion criteria provided
1185634	NM_170682.4(P2RX2):c.1055T>G (p.Val352Gly)	P2RX2	Uncertain significance	no assertion criteria provided
1334075	NM_170682.4(P2RX2):c.490C>T (p.Gln164Ter)	P2RX2	Uncertain significance	criteria provided, single submitter
1895432	NM_170682.4(P2RX2):c.1037C>G (p.Ala346Gly)	P2RX2	Uncertain significance	criteria provided, single submitter
2574792	NM_170682.4(P2RX2):c.211_228del (p.Glu71_Ser76del)	P2RX2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2579142	NM_170682.4(P2RX2):c.804_806del (p.Trp268_Asp269delinsCys)	P2RX2	Uncertain significance	criteria provided, single submitter
931212	NM_170682.4(P2RX2):c.905G>C (p.Arg302Thr)	P2RX2	Uncertain significance	criteria provided, single submitter
1283142	NM_170682.4(P2RX2):c.997-40C>T	P2RX2	Benign	criteria provided, multiple submitters, no conflicts
226980	NM_170682.4(P2RX2):c.1325_1335del (p.Ile441_Ser442insTer)	P2RX2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
226984	NM_170682.4(P2RX2):c.468T>C (p.Thr156=)	P2RX2	Benign	criteria provided, multiple submitters, no conflicts
226986	NM_170682.4(P2RX2):c.636-13G>A	P2RX2	Benign	criteria provided, multiple submitters, no conflicts
508104	NM_170682.4(P2RX2):c.173+28_173+41del	P2RX2	Benign	criteria provided, multiple submitters, no conflicts
3062143	NM_170682.4(P2RX2):c.774G>A (p.Lys258=)	P2RX2	not provided	no classification provided

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
P2RX2	Strong	Autosomal dominant	autosomal dominant nonsyndromic hearing loss 41	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
P2RX2	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA

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
P2RX2	HGNC:15459	ENSG00000187848	Q9UBL9	P2X purinoceptor 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
P2RX2	P2X purinoceptor 2	ATP-gated nonselective transmembrane cation channel permeable to potassium, sodium and calcium.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
P2RX2	Other/Unknown	no		P2X_purnocptor, P2X2_purnocptor, P2X_extracellular_dom_sf

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
esophagogastric junction muscularis propria	1
mucosa of stomach	1
right lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
P2RX2	134	tissue_specific	yes	mucosa of stomach, esophagogastric junction muscularis propria, right lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
P2RX2	976

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
P2RX2	Q9UBL9	18

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
Elevation of cytosolic Ca2+ levels	1	713.8×	0.003	P2RX2
Platelet homeostasis	1	278.5×	0.004	P2RX2

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
detection of hypoxic conditions in blood by carotid body chemoreceptor signaling	1	8426.0×	0.002	P2RX2
urinary bladder smooth muscle contraction	1	2808.7×	0.002	P2RX2
response to carbohydrate	1	1685.2×	0.002	P2RX2
peristalsis	1	1532.0×	0.002	P2RX2
positive regulation of calcium ion transport into cytosol	1	1203.7×	0.002	P2RX2
sensory perception of taste	1	1123.5×	0.002	P2RX2
response to ATP	1	991.3×	0.002	P2RX2
behavioral response to pain	1	887.0×	0.002	P2RX2
neuromuscular synaptic transmission	1	601.9×	0.003	P2RX2
skeletal muscle fiber development	1	543.6×	0.003	P2RX2
neuromuscular junction development	1	526.6×	0.003	P2RX2
positive regulation of calcium-mediated signaling	1	421.3×	0.003	P2RX2
response to ischemia	1	251.5×	0.005	P2RX2
calcium ion transmembrane transport	1	210.7×	0.005	P2RX2
sensory perception of sound	1	100.9×	0.010	P2RX2
response to hypoxia	1	95.8×	0.010	P2RX2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
P2RX2	GEFAPIXANT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
P2RX2	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GEFAPIXANT	4	P2RX2
SURAMIN	3	P2RX2
PYRIDOXAL PHOSPHATE ANHYDROUS	3	P2RX2
ELIAPIXANT	2	P2RX2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
P2RX2	96	Binding:67, Functional:29

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

4 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.

Compound	Max phase	Cohort target (bioactivity)
GEFAPIXANT	4	P2RX2
SURAMIN	3	P2RX2
PYRIDOXAL PHOSPHATE ANHYDROUS	3	P2RX2
ELIAPIXANT	2	P2RX2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	P2RX2
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.