Hearing loss, autosomal dominant 73

Summary

Hearing loss, autosomal dominant 73 (MONDO:0033260) is a disease caused by PTPRQ (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: PTPRQ (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 73
Mondo ID	MONDO:0033260
OMIM	617663
DOID	DOID:0080269
UMLS	C4540024
MedGen	1627153
GARD	0018149
Is cancer (heuristic)	no

Also known as: autosomal dominant nonsyndromic deafness 73 · deafness, autosomal dominant 73 · DFNA73

Data availability: 27 ClinVar variants · 3 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 73

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 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 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:

11 benign, 8 uncertain significance, 2 pathogenic, 2 likely pathogenic, 2 benign/likely benign, 1 likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1184601	NM_001145026.2(PTPRQ):c.6024+2T>C	PTPRQ	Pathogenic	criteria provided, single submitter
3764720	NM_001145026.2(PTPRQ):c.6742C>T (p.Gln2248Ter)	PTPRQ	Pathogenic	criteria provided, single submitter
2501401	NM_001145026.2(PTPRQ):c.5657_5658del (p.Asp1885_Ser1886insTer)	PTPRQ	Likely pathogenic	criteria provided, multiple submitters, no conflicts
982616	NM_001145026.2(PTPRQ):c.3G>A (p.Met1Ile)	PTPRQ	Likely pathogenic	criteria provided, single submitter
438482	NM_001145026.2(PTPRQ):c.6881G>A (p.Trp2294Ter)	PTPRQ	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1285598	NM_001145026.2(PTPRQ):c.5606A>G (p.Gln1869Arg)	PTPRQ	Uncertain significance	criteria provided, single submitter
1679944	NM_001145026.2(PTPRQ):c.6299T>G (p.Met2100Arg)	PTPRQ	Uncertain significance	criteria provided, single submitter
1705929	NM_001145026.2(PTPRQ):c.5893C>A (p.Leu1965Met)	PTPRQ	Uncertain significance	criteria provided, single submitter
3376818	NM_001145026.2(PTPRQ):c.3974A>T (p.Asn1325Ile)	PTPRQ	Uncertain significance	criteria provided, single submitter
3731359	NM_001145026.2(PTPRQ):c.1331A>G (p.Glu444Gly)	PTPRQ	Uncertain significance	criteria provided, single submitter
3774565	NM_001145026.2(PTPRQ):c.1990+1G>C	PTPRQ	Uncertain significance	criteria provided, single submitter
423816	NM_001145026.2(PTPRQ):c.6586A>G (p.Met2196Val)	PTPRQ	Uncertain significance	criteria provided, multiple submitters, no conflicts
548548	NM_001145026.2(PTPRQ):c.386T>G (p.Ile129Ser)	PTPRQ	Uncertain significance	criteria provided, single submitter
1174737	NM_001145026.2(PTPRQ):c.2371C>A (p.Gln791Lys)	PTPRQ	Benign	criteria provided, multiple submitters, no conflicts
1174974	NM_001145026.2(PTPRQ):c.2505C>G (p.Leu835=)	PTPRQ	Benign	criteria provided, multiple submitters, no conflicts
1178660	NM_001145026.2(PTPRQ):c.6115+23_6115+24dup	PTPRQ	Benign	criteria provided, multiple submitters, no conflicts
1206469	NM_001145026.2(PTPRQ):c.3607T>C (p.Tyr1203His)	PTPRQ	Likely benign	criteria provided, multiple submitters, no conflicts
1243577	NM_001145026.2(PTPRQ):c.1882+16TTG[7]	PTPRQ	Benign	criteria provided, multiple submitters, no conflicts
1245650	NM_001145026.2(PTPRQ):c.5943-6T>C	PTPRQ	Benign	criteria provided, multiple submitters, no conflicts
1267160	NM_001145026.2(PTPRQ):c.3155-34A>T	PTPRQ	Benign	criteria provided, multiple submitters, no conflicts
1277989	NM_001145026.2(PTPRQ):c.1187-38T>A	PTPRQ	Benign	criteria provided, multiple submitters, no conflicts
1278409	NM_001145026.2(PTPRQ):c.6453+21C>T	PTPRQ	Benign	criteria provided, multiple submitters, no conflicts
1289654	NM_001145026.2(PTPRQ):c.1187-27dup	PTPRQ	Benign	criteria provided, multiple submitters, no conflicts
678764	NM_001145026.2(PTPRQ):c.1233G>A (p.Thr411=)	PTPRQ	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
682569	NM_001145026.2(PTPRQ):c.1934T>A (p.Val645Asp)	PTPRQ	Benign	criteria provided, multiple submitters, no conflicts
682570	NM_001145026.2(PTPRQ):c.2272+15_2272+16insG	PTPRQ	Benign	criteria provided, multiple submitters, no conflicts
805264	NM_001145026.2(PTPRQ):c.5061T>C (p.Pro1687=)	PTPRQ	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 22 · 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
PTPRQ	Definitive	Autosomal recessive	autosomal recessive nonsyndromic hearing loss 84A	11
PTPRR	Definitive	Autosomal recessive	autosomal recessive nonsyndromic hearing loss 84A	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PTPRQ	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
PTPRQ	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
PTPRQ	HGNC:9679	ENSG00000139304	Q9UMZ3	Phosphatidylinositol phosphatase PTPRQ	gencc,clinvar
PTPRR	HGNC:9680	ENSG00000153233	Q15256	Receptor-type tyrosine-protein phosphatase R	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PTPRQ	Phosphatidylinositol phosphatase PTPRQ	Dephosphorylates phosphatidylinositol phosphates, such as phosphatidylinositol 3,4,5-trisphosphate (PIP3) and phosphatidylinositol 3,5-diphosphates, with preference for PIP3.
PTPRR	Receptor-type tyrosine-protein phosphatase R	Sequesters mitogen-activated protein kinases (MAPKs) such as MAPK1, MAPK3 and MAPK14 in the cytoplasm in an inactive form.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Phosphatase	2	83.9×	1e-04

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PTPRQ	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat
PTPRR	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat

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
left lobe of thyroid gland	1
right lung	1
thyroid gland	1
cerebellar cortex	1
endothelial cell	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PTPRQ	119	tissue_specific	marker	thyroid gland, left lobe of thyroid gland, right lung
PTPRR	184	tissue_specific	marker	endothelial cell, right hemisphere of cerebellum, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTPRR	1,437
PTPRQ	535

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTPRQ	Q9UMZ3	1
PTPRR	Q15256	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

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
ERBB2 signaling pathway	1	936.2×	0.004	PTPRR
regulation of fat cell differentiation	1	648.1×	0.004	PTPRQ
negative regulation of epithelial cell migration	1	526.6×	0.004	PTPRR
detection of mechanical stimulus involved in sensory perception of sound	1	468.1×	0.004	PTPRQ
protein dephosphorylation	1	110.9×	0.012	PTPRR
negative regulation of ERK1 and ERK2 cascade	1	108.0×	0.012	PTPRR
in utero embryonic development	1	36.0×	0.032	PTPRR
signal transduction	1	8.0×	0.121	PTPRR

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PTPRQ	0	0
PTPRR	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
PTPRR	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PTPRQ	3.1.3.48	protein-tyrosine-phosphatase
PTPRR	3.1.3.48	protein-tyrosine-phosphatase

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	2	PTPRQ, PTPRR
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
PTPRQ	0	—
PTPRR	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.