autosomal recessive nonsyndromic hearing loss 84A

Summary

autosomal recessive nonsyndromic hearing loss 84A (MONDO:0013249) is a disease caused by PTPRQ (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: PTPRQ (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 67

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive nonsyndromic hearing loss 84A
Mondo ID	MONDO:0013249
OMIM	613391
DOID	DOID:0110529
UMLS	C3150654
MedGen	462004
GARD	0022634
Is cancer (heuristic)	no

Also known as: autosomal recessive deafness 84A · autosomal recessive deafness 84A with vestibular dysfunction · autosomal recessive nonsyndromic deafness 84A · autosomal recessive nonsyndromic deafness caused by mutation in PTPRQ · autosomal recessive nonsyndromic deafness type 84A · autosomal recessive nonsyndromic hearing loss 84A · deafness, autosomal recessive 84 · deafness, autosomal recessive 84A · deafness, autosomal recessive 84a · deafness, autosomal recessive 84A, with vestibular dysfunction · deafness, autosomal recessive type 84A · DFNB84A · PTPRQ autosomal recessive nonsyndromic deafness

Data availability: 67 ClinVar variants · 5 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 84A

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 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 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

67 retrieved; paginated sample, class counts are floors:

17 uncertain significance, 16 pathogenic, 13 likely pathogenic, 11 benign, 4 conflicting classifications of pathogenicity, 3 likely benign, 2 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1217990	NM_001145026.2(PTPRQ):c.1673_1682del (p.Thr558fs)	PTPRQ	Pathogenic	criteria provided, multiple submitters, no conflicts
156332	NM_001145026.2(PTPRQ):c.715A>G (p.Arg239Gly)	PTPRQ	Pathogenic	no assertion criteria provided
156333	NM_001145026.2(PTPRQ):c.837T>A (p.Tyr279Ter)	PTPRQ	Pathogenic	criteria provided, single submitter
1799534	NM_001145026.2(PTPRQ):c.2726del (p.Glu909fs)	PTPRQ	Pathogenic	criteria provided, single submitter
3377236	NM_001145026.2(PTPRQ):c.228G>A (p.Trp76Ter)	PTPRQ	Pathogenic	criteria provided, single submitter
3377523	NM_001145026.2(PTPRQ):c.6453+2dup	PTPRQ	Pathogenic	no assertion criteria provided
3378394	NM_001145026.2(PTPRQ):c.3873+727A>G	PTPRQ	Pathogenic	no assertion criteria provided
3378395	NM_001145026.2(PTPRQ):c.4159del (p.Gln1387fs)	PTPRQ	Pathogenic	no assertion criteria provided
3601705	NM_001145026.2(PTPRQ):c.4869T>A (p.Tyr1623Ter)	PTPRQ	Pathogenic	criteria provided, single submitter
3601706	NM_001145026.2(PTPRQ):c.5239C>T (p.Arg1747Ter)	PTPRQ	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3601709	NM_001145026.2(PTPRQ):c.6454-2A>G	PTPRQ	Pathogenic	criteria provided, single submitter
3764720	NM_001145026.2(PTPRQ):c.6742C>T (p.Gln2248Ter)	PTPRQ	Pathogenic	criteria provided, single submitter
4086104	NM_001145026.2(PTPRQ):c.661G>T (p.Glu221Ter)	PTPRQ	Pathogenic	criteria provided, single submitter
4526207	NC_000012.11:g.(81064272_81066947)_(81067084_81072380)del	PTPRQ	Pathogenic	criteria provided, single submitter
4689666	NM_001145026.2(PTPRQ):c.3624G>A (p.Glu1208=)	PTPRQ	Pathogenic	criteria provided, single submitter
523416	NM_001145026.2(PTPRQ):c.6475C>T (p.Arg2159Ter)	PTPRQ	Pathogenic	criteria provided, multiple submitters, no conflicts
973493	NM_001145026.2(PTPRQ):c.4006C>T (p.Gln1336Ter)	PTPRQ	Pathogenic	criteria provided, multiple submitters, no conflicts
1185053	NM_001145026.2(PTPRQ):c.6194_6453+1del	PTPRQ	Likely pathogenic	no assertion criteria provided
1799533	NM_001145026.2(PTPRQ):c.1291C>T (p.Arg431Ter)	PTPRQ	Likely pathogenic	criteria provided, single submitter
2431060	NM_001145026.2(PTPRQ):c.3308_3309del (p.Leu1103fs)	PTPRQ	Likely pathogenic	criteria provided, single submitter
2501109	NM_001145026.2(PTPRQ):c.3022A>T (p.Asn1008Tyr)	PTPRQ	Likely pathogenic	criteria provided, single submitter
2582600	NM_001145026.2(PTPRQ):c.2621C>A (p.Ser874Ter)	PTPRQ	Likely pathogenic	criteria provided, single submitter
3378396	NM_001145026.2(PTPRQ):c.6602+81_6738+394delinsTTTATAAAATG	PTPRQ	Likely pathogenic	no assertion criteria provided
3601707	NM_001145026.2(PTPRQ):c.5943-2A>T	PTPRQ	Likely pathogenic	criteria provided, single submitter
3601708	NM_001145026.2(PTPRQ):c.6211G>T (p.Glu2071Ter)	PTPRQ	Likely pathogenic	criteria provided, single submitter
3601710	NM_001145026.2(PTPRQ):c.1264C>T (p.Gln422Ter)	PTPRQ	Likely pathogenic	criteria provided, single submitter
3780505	NM_001145026.2(PTPRQ):c.3527del (p.Lys1176fs)	PTPRQ	Likely pathogenic	criteria provided, single submitter
3780507	NM_001145026.2(PTPRQ):c.4732-1G>T	PTPRQ	Likely pathogenic	criteria provided, single submitter
3780508	NM_001145026.2(PTPRQ):c.1187-2A>C	PTPRQ	Likely pathogenic	criteria provided, single submitter
4687898	NM_001145026.2(PTPRQ):c.2T>C (p.Met1Thr)	PTPRQ	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 22 · Orphanet: 8 · 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
CDH23	Orphanet:231169	Usher syndrome type 1
CDH23	Orphanet:2965	Prolactinoma
CDH23	Orphanet:314777	Familial isolated pituitary adenoma
CDH23	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
CDH23	Orphanet:91347	TSH-secreting pituitary adenoma
CDH23	Orphanet:96253	Cushing disease

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

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
CDH23	HGNC:13733	ENSG00000107736	Q9H251	Cadherin-23	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.
CDH23	Cadherin-23	Cadherins are calcium-dependent cell adhesion proteins.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

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	55.9×	8e-04
Other/Unknown	1	0.6×	0.914

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
CDH23	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS

Expression context

Cohort genes with no expression data: 0.

3 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)	3
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
left ovary	1
right ovary	1
ventricular zone	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
CDH23	161	broad	marker	ventricular zone, left ovary, right ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDH23	1,575
PTPRR	1,437
PTPRQ	535

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CDH23	Q9H251	6
PTPRQ	Q9UMZ3	1
PTPRR	Q15256	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 3 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	1	308.6×	0.008	CDH23
Sensory processing of sound by outer hair cells of the cochlea	1	203.9×	0.008	CDH23
Sensory processing of sound by inner hair cells of the cochlea	1	163.1×	0.008	CDH23
Sensory Perception	1	95.2×	0.011	CDH23

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
equilibrioception	1	802.5×	0.010	CDH23
ERBB2 signaling pathway	1	624.1×	0.010	PTPRR
sensory perception of light stimulus	1	624.1×	0.010	CDH23
regulation of fat cell differentiation	1	432.1×	0.010	PTPRQ
obsolete cell-cell adhesion via plasma-membrane adhesion molecules	1	374.5×	0.010	CDH23
negative regulation of epithelial cell migration	1	351.1×	0.010	PTPRR
detection of mechanical stimulus involved in sensory perception of sound	1	312.1×	0.010	PTPRQ
auditory receptor cell stereocilium organization	1	280.9×	0.010	CDH23
calcium-dependent cell-cell adhesion	1	160.5×	0.015	CDH23
cochlea development	1	156.0×	0.015	CDH23
regulation of cytosolic calcium ion concentration	1	127.7×	0.016	CDH23
photoreceptor cell maintenance	1	119.5×	0.016	CDH23
protein dephosphorylation	1	73.9×	0.023	PTPRR
negative regulation of ERK1 and ERK2 cascade	1	72.0×	0.023	PTPRR
calcium ion transport	1	60.4×	0.024	CDH23
locomotory behavior	1	59.8×	0.024	CDH23
homophilic cell-cell adhesion	1	46.8×	0.029	CDH23
neuron projection development	1	40.7×	0.031	CDH23
sensory perception of sound	1	33.6×	0.036	CDH23
visual perception	1	26.5×	0.043	CDH23
in utero embryonic development	1	24.0×	0.045	PTPRR
cell migration	1	20.5×	0.050	CDH23
signal transduction	1	5.3×	0.176	PTPRR

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
CDH23	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: 3; 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	1	CDH23

Undrugged target profiles

3 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	—
CDH23	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.