PTPRQ

Chr 12ADAR

protein tyrosine phosphatase receptor type Q

Also known as: DFNA73, DFNB84, DFNB84A, PTPGMC1, R-PTP-Q

NCBI Gene: 374462ENSG00000139304UniProt: Q9UMZ3OMIM: 603317

This protein tyrosine phosphatase dephosphorylates phosphatidylinositol phosphates, particularly PIP3, and is required for hair bundle maturation in auditory hair cells. Mutations cause autosomal recessive deafness (type 84A) and autosomal dominant deafness (type 73). The gene shows minimal constraint against loss-of-function variants (very low pLI score), suggesting tolerance to haploinsufficiency in most contexts.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.702 OMIM phenotypes
Clinical Summary— PTPRQ
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Gene-Disease Validity (ClinGen)
hearing loss, autosomal recessive · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
46 unique Pathogenic / Likely Pathogenic· 228 VUS of 500 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — PTPRQ
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.70LOEUF
pLI 0.000
Z-score 3.93
OE 0.55 (0.43–0.70)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.00Z-score
OE missense 0.91 (0.86–0.96)
838 obs / 923.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.55 (0.43–0.70)
0≤0.351.4
Missense OE0.91 (0.86–0.96)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 48 / 87.8Missense obs/exp: 838 / 923.4Syn Z: 0.18
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongPTPRQ-related deafnessLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.78top 25%
GOF
0.71top 25%
LOF
0.2581th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNPTPRQTrp2294* protein would lack only six terminal residues and could exert a dominant-negative effect, a possible explanation for allelic deafness, DFNA73, clinically and genetically distinct from DFNB84A.PMID:29309402

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic27
VUS228
Likely Benign96
Benign122
Conflicting7
19
Pathogenic
27
Likely Pathogenic
228
VUS
96
Likely Benign
122
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
0
3
1
19
Likely Pathogenic
25
2
0
0
27
VUS
4
195
17
12
228
Likely Benign
0
17
54
25
96
Benign
2
12
103
5
122
Conflicting
—7
Total4622617743499

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PTPRQ · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Targeted Next-Generation Sequencing Identified Novel Compound Heterozygous Variants in the PTPRQ Gene Causing Autosomal Recessive Hearing Loss in a Chinese Family
Jin Y et al.·Front Genet
2022
Analysis of Receptor-Type Protein Tyrosine Phosphatase Extracellular Regions with Insights from AlphaFold
El Badaoui L et al.·Int J Mol Sci
2024
Whole-exome sequencing identified a novel heterozygous mutation of SALL1 and a new homozygous mutation of PTPRQ in a Chinese family with Townes-Brocks syndrome and hearing loss
Yang G et al.·BMC Med Genomics
2021
Delayed progressive sensorineural hearing loss due to a novel compound heterozygous PTPRQ mutation in a Chinese patient
Qin Y et al.·J Clin Lab Anal
2023
Protein Tyrosine Phosphatase Receptor-type Q: Structure, Activity, and Implications in Human Disease.
Zhang W et al.·Protein Pept Lett
2022
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
PNPT1, MYO15A, PTPRQ, and SLC12A2-associated genetic and phenotypic heterogeneity among hearing impaired assortative mating families in Southern India.
Vanniya S P et al.·Ann Hum Genet
2022
Ultrarare heterozygous pathogenic variants of genes causing dominant forms of early-onset deafness underlie severe presbycusis.
Boucher S et al.·Proc Natl Acad Sci U S A
2020
Whole-genome sequencing, as a powerful diagnostic tool in hearing loss, reveals novel variants in PTPRQ missed by whole-exome sequencing.
Bengl D et al.·BMC Med Genomics
2025
Detailed Clinical Features of PTPRQ-Associated Hearing Loss Identified in a Large Japanese Hearing Loss Cohort.
Sakuma N et al.·Genes (Basel)
2024Cohort
First confirmatory study on PTPRQ as an autosomal dominant non-syndromic hearing loss gene.
Oziębło D et al.·J Transl Med
2019Case report
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients