PTPRQ

Summary

PTPRQ (protein tyrosine phosphatase receptor type Q, HGNC:9679) is a protein-coding gene on chromosome 12q21.31, encoding Phosphatidylinositol phosphatase PTPRQ (Q9UMZ3). Dephosphorylates phosphatidylinositol phosphates, such as phosphatidylinositol 3,4,5-trisphosphate (PIP3) and phosphatidylinositol 3,5-diphosphates, with preference for PIP3.

This locus encodes a member of the type III receptor-like protein-tyrosine phosphatase family. The encoded protein catalyzes the dephosphorylation of phosphotyrosine and phosphatidylinositol and plays roles in cellular proliferation and differentiation. Mutations at this locus have been linked to autosomal recessive deafness.

Source: NCBI Gene 374462 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hearing loss, autosomal recessive (Definitive, ClinGen) — +3 more curated relationships
• Clinical variants (ClinVar): 584 total — 26 pathogenic, 32 likely-pathogenic
• Phenotypes (HPO): 9
• MANE Select transcript: NM_001145026

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9679
Approved symbol	PTPRQ
Name	protein tyrosine phosphatase receptor type Q
Location	12q21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000139304
Ensembl biotype	protein_coding
OMIM	603317
Entrez	374462

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000547376, ENST00000547485, ENST00000547881, ENST00000549355, ENST00000551042, ENST00000551573, ENST00000551624, ENST00000616559, ENST00000623635, ENST00000644991

RefSeq mRNA: 1 — MANE Select: NM_001145026 NM_001145026

CCDS: CCDS73501

Canonical transcript exons

ENST00000644991 — 45 exons

Exon	Start	End
ENSE00001610375	80634945	80635073
ENSE00001647756	80652744	80652834
ENSE00003501628	80649588	80649669
ENSE00003646365	80444741	80444849
ENSE00003712899	80496250	80496531
ENSE00003712989	80657985	80658061
ENSE00003715617	80620154	80620376
ENSE00003717773	80494933	80495094
ENSE00003720940	80484433	80484605
ENSE00003721170	80495999	80496106
ENSE00003721656	80678986	80680273
ENSE00003722590	80542089	80542364
ENSE00003723468	80673169	80673304
ENSE00003724620	80506024	80506206
ENSE00003725342	80472105	80472251
ENSE00003725469	80542730	80542881
ENSE00003727932	80510323	80510443
ENSE00003729608	80616200	80616266
ENSE00003729642	80506569	80506670
ENSE00003731246	80622061	80622134
ENSE00003733228	80534015	80534175
ENSE00003733715	80460653	80460902
ENSE00003734525	80546556	80546697
ENSE00003734592	80493275	80493455
ENSE00003737458	80669339	80669464
ENSE00003740152	80670344	80670492
ENSE00003740375	80534892	80535037
ENSE00003740469	80549465	80549734
ENSE00003741942	80648897	80648923
ENSE00003742506	80632192	80632291
ENSE00003743652	80619384	80619542
ENSE00003744516	80588129	80588452
ENSE00003744783	80468710	80468838
ENSE00003745502	80495192	80495371
ENSE00003746250	80541555	80541845
ENSE00003747080	80457575	80457644
ENSE00003747652	80678602	80678725
ENSE00003749353	80539776	80539944
ENSE00003749360	80610439	80610625
ENSE00003749601	80605059	80605180
ENSE00003750199	80459284	80459483
ENSE00003752575	80669007	80669141
ENSE00003753846	80613592	80613836
ENSE00003788995	80445491	80445717
ENSE00003818100	80444235	80444399

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 74.50.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0332 / max 11.1347, expressed in 10 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127101	0.2850	111
127100	0.1080	35
127102	0.1047	44
127099	0.0405	11
127107	0.0332	10
127103	0.0050	2

Top tissues by expression

133 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
thyroid gland	UBERON:0002046	74.50	gold quality
left lobe of thyroid gland	UBERON:0001120	74.36	gold quality
right lung	UBERON:0002167	73.84	gold quality
right lobe of thyroid gland	UBERON:0001119	73.74	gold quality
adult mammalian kidney	UBERON:0000082	72.76	gold quality
omental fat pad	UBERON:0010414	71.98	gold quality
popliteal artery	UBERON:0002250	70.84	gold quality
tibial artery	UBERON:0007610	70.78	gold quality
skeletal muscle tissue	UBERON:0001134	70.54	gold quality
gastrocnemius	UBERON:0001388	70.32	gold quality
kidney	UBERON:0002113	69.15	gold quality
muscle of leg	UBERON:0001383	69.05	gold quality
right atrium auricular region	UBERON:0006631	67.94	gold quality
lung	UBERON:0002048	67.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	67.02	gold quality
upper lobe of left lung	UBERON:0008952	66.70	gold quality
adipose tissue	UBERON:0001013	65.70	gold quality
ascending aorta	UBERON:0001496	65.40	gold quality
right uterine tube	UBERON:0001302	64.73	gold quality
thoracic aorta	UBERON:0001515	64.64	gold quality
quadriceps femoris	UBERON:0001377	64.14	gold quality
lower esophagus muscularis layer	UBERON:0035833	63.44	gold quality
lower esophagus	UBERON:0013473	63.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	63.40	gold quality
muscle tissue	UBERON:0002385	63.18	gold quality
cerebellar vermis	UBERON:0004720	63.05	gold quality
urinary bladder	UBERON:0001255	62.67	gold quality
right coronary artery	UBERON:0001625	61.81	gold quality
tibial nerve	UBERON:0001323	61.66	gold quality
calcaneal tendon	UBERON:0003701	61.28	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	9231.37
E-CURD-119	yes	8864.34
E-ANND-3	yes	7.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

91 targeting PTPRQ, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-5002-5P	99.76	70.84	1763

Literature-anchored findings (GeneRIF, showing 17)

• Overexpression of PTP-RQ consistently led to reduced differentiation of mesenchymal stem cells into adipocytes via decreasing the phosphatidyl inositol phosphate level in cells, and consequently downregulating Akt/PKB phosphorylation. (PMID:19351528)
• Mutations in PTPRQ are a cause of autosomal-recessive nonsyndromic hearing impairment DFNB84 and associated with vestibular dysfunction. (PMID:20346435)
• Identification of the DFNB84 gene represents the first identification of PTPRQ mutation in human hearing loss. (PMID:20472657)
• PTPRQ crystal structure shows the basis for the dephosphorylating activity of PTPRQ towards phosphatidylinositide substrates. (PMID:23897475)
• novel c.16_17insT (L8fsX18) and c.2714delA (E909fsX922)mutations in PTPRQ presented here further confirms the essential role of PTPRQ in hearing development and auditory function (PMID:25557914)
• Identification of four causative mutations in the PTPRQ gene as a cause of congenital sensorineural hearing loss in a Japanese population. (PMID:25788564)
• two novel compound heterozygous missense mutations, c. 3125 A>G p.D1042G and c.5981 A>G p.E1994G in the PTPRQ gene, were identified as the cause of recessively inherited sensorineural hearing loss in family 1572. (PMID:25919374)
• Confirm contribution of PTPRZ1, and especially PTPRQ, in CRC carcinogenesis and demonstrated that PTPRQ expression is correlated with KRAS mutation. (PMID:26851024)
• PTPRQ may be a useful biomarker for discriminating between patients with Idiopathic normal pressure hydrocephalus and Alzheimer’s disease. (PMID:28714010)
• We identified a heterozygous nonsense mutation, c.6881G>A (p.Trp2294*), in the last coding exon of PTPRQ. PTPRQ has been linked with recessive (DFNB84A), but not dominant deafness. PTPRQTrp2294* protein would lack only six terminal residues and could exert a dominant-negative effect (PMID:29309402)
• The studies findings suggest that the novel compound heterozygous PTPRQ mutations, c.4472C>T (p.T1491M) and c.1973T>C (p.V658A), are the cause of congenital Sensorineural Hearing Loss in a Chinese family. (PMID:29849575)
• First confirmatory study on PTPRQ as an autosomal dominant non-syndromic hearing loss gene. (PMID:31655630)
• Protein tyrosine phosphatase receptor type Q in cerebrospinal fluid reflects ependymal cell dysfunction and is a potential biomarker for adult chronic hydrocephalus. (PMID:33035386)
• PNPT1, MYO15A, PTPRQ, and SLC12A2-associated genetic and phenotypic heterogeneity among hearing impaired assortative mating families in Southern India. (PMID:34374074)
• Protein Tyrosine Phosphatase Receptor-type Q: Structure, Activity, and Implications in Human Disease. (PMID:35546749)
• Delayed progressive sensorineural hearing loss due to a novel compound heterozygous PTPRQ mutation in a Chinese patient. (PMID:37106574)
• Detailed Clinical Features of PTPRQ-Associated Hearing Loss Identified in a Large Japanese Hearing Loss Cohort. (PMID:38674423)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ptprq	ENSMUSG00000035916
rattus_norvegicus	Ptprq	ENSRNOG00000056915

Paralogs (36): CNTN1 (ENSG00000018236), CDON (ENSG00000064309), NEO1 (ENSG00000067141), SDK2 (ENSG00000069188), IGSF9B (ENSG00000080854), IGSF9 (ENSG00000085552), NRCAM (ENSG00000091129), MXRA5 (ENSG00000101825), IGDCC4 (ENSG00000103742), CNTN3 (ENSG00000113805), IGSF21 (ENSG00000117154), CNTN6 (ENSG00000134115), CHL1 (ENSG00000134121), CNTN4 (ENSG00000144619), BOC (ENSG00000144857), SDK1 (ENSG00000146555), HMCN2 (ENSG00000148357), NCAM1 (ENSG00000149294), CNTN5 (ENSG00000149972), IGSF10 (ENSG00000152580), ROBO4 (ENSG00000154133), ROBO3 (ENSG00000154134), NCAM2 (ENSG00000154654), VCAM1 (ENSG00000162692), NFASC (ENSG00000163531), PRTG (ENSG00000166450), ROBO1 (ENSG00000169855), DSCAM (ENSG00000171587), IGDCC3 (ENSG00000174498), VSIG10 (ENSG00000176834), DSCAML1 (ENSG00000177103), CNTN2 (ENSG00000184144), ROBO2 (ENSG00000185008), VSIG10L (ENSG00000186806), DCC (ENSG00000187323), L1CAM (ENSG00000198910)

Protein

Protein identifiers

Phosphatidylinositol phosphatase PTPRQ — Q9UMZ3 (reviewed: Q9UMZ3)

Alternative names: Receptor-type tyrosine-protein phosphatase Q

All UniProt accessions (6): A0A087WZU1, A0A087X0B9, F8VW52, F8VXI2, F8W122, H0YIJ5

UniProt curated annotations — full annotation on UniProt →

Function. Dephosphorylates phosphatidylinositol phosphates, such as phosphatidylinositol 3,4,5-trisphosphate (PIP3) and phosphatidylinositol 3,5-diphosphates, with preference for PIP3. Phosphate can be hydrolyzed from the D3 and D5 positions in the inositol ring. Has low tyrosine-protein phosphatase activity in vitro; however, the relevance of such activity in vivo is unclear. Plays an important role in adipogenesis of mesenchymal stem cells (MSCs). Regulates the phosphorylation state of AKT1 by regulating the levels of PIP3 in MSCs and preadipocyte cells. Required for hair bundle maturation, a process that enables hair cells to detect and transmit sound and balance signals effectively, therefore affecting auditory function. May act by regulating the level of phosphatidylinositol 4,5-bisphosphate (PIP2) level in the basal region of hair bundles.

Subunit / interactions. Interacts with TPRN. TPRN, CLIC5 and PTPQR form concentric rings at the base of stereocilia and may form a complex.

Subcellular location. Cell projection. Stereocilium. Apical cell membrane. Basal cell membrane.

Tissue specificity. In developing kidney, it localizes to the basal membrane of podocytes, beginning when podocyte progenitors can first be identified in the embryonic kidney (at protein level). Expressed in lung and kidney.

Disease relevance. Deafness, autosomal recessive, 84A (DFNB84A) [MIM:613391] A form of non-syndromic deafness characterized by progressive, sensorineural hearing loss and vestibular dysfunction. The disease is caused by variants affecting the gene represented in this entry. Deafness, autosomal dominant, 73 (DFNA73) [MIM:617663] A form of non-syndromic hearing loss characterized by mild to severe bilateral symptoms with variable age of onset from early childhood to the third decade. The disease may be caused by variants affecting the gene represented in this entry.

Induction. Down-regulated during adipogenesis of mesenchymal stem cells.

Similarity. Belongs to the protein-tyrosine phosphatase family. Receptor class 2A subfamily.

RefSeq proteins (1): NP_001138498* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000242	PTP_cat	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR016130	Tyr_Pase_AS	Active_site
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR050713	RTP_Phos/Ushers	Family

Pfam: PF00041, PF00102

Enzyme classification (BRENDA):

• EC 3.1.3.48 — protein-tyrosine-phosphatase (BRENDA: 59 organisms, 501 substrates, 1326 inhibitors, 270 Km, 165 kcat entries)

Substrate kinetics (BRENDA)

70 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-NITROPHENYL PHOSPHATE	0.0008–148	84
6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE	0.0039–0.862	27
P-NITROPHENYL PHOSPHATE	0.0024–10	20
DADEPYLIPQQG	0.0003–0.1	12
PHOSPHOTYROSINE	0.012–30	11
LYSOZYME	0.0003–0.012	5
MYELIN BASIC PROTEIN	0.0001–0.022	5
ACETYL-DADEPY-NH2	0.0228–0.219	4
ACETYL-DADEPYL-NH2	1.1–97.5	4
4,6,8-TRIMETHYL-2-OXO-2H-CHROMEN-7-YL DIHYDROGEN	0.02–0.156	3
SASASPYSASA	0.53–2.3	3
1-NAPHTHYL PHOSPHATE	1.19–1.88	2
3,6-FLUORESCEIN DIPHOSPHATE	15–19	2
4-METHYLUMBELLIFERYL PHOSPHATE	0.953–2.41	2
BOVINE SERUM ALBUMIN	0.0001–0.0003	2

Catalyzed reactions (Rhea), 4 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + phosphate (RHEA:25017)
• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) + phosphate (RHEA:25528)
• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5-bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + phosphate (RHEA:32955)
• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5-bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + phosphate (RHEA:39019)

UniProt features (68 total): domain 19, strand 12, glycosylation site 10, sequence variant 9, helix 9, turn 3, topological domain 2, signal peptide 1, chain 1, active site 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4IKC	X-RAY DIFFRACTION	1.56

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UMZ3-F1	75.35	0.05

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 2233 (phosphocysteine intermediate)

Glycosylation sites (10): 94, 202, 394, 944, 1038, 1080, 1101, 1290, 1295, 1844

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 102 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_DETECTION_OF_MECHANICAL_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_3_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_DETECTION_OF_MECHANICAL_STIMULUS, chr12q21, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (9): regulation of fat cell differentiation (GO:0045598), detection of mechanical stimulus involved in sensory perception of sound (GO:0050910), hematopoietic progenitor cell differentiation (GO:0002244), protein dephosphorylation (GO:0006470), lipid metabolic process (GO:0006629), dephosphorylation (GO:0016311), inner ear morphogenesis (GO:0042472), neuromuscular process controlling balance (GO:0050885), vestibular receptor cell morphogenesis (GO:0060116)

GO Molecular Function (8): protein tyrosine phosphatase activity (GO:0004725), phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity (GO:0016314), phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity (GO:0034485), phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity (GO:0043813), phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity (GO:0052629), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (9): basal plasma membrane (GO:0009925), apical plasma membrane (GO:0016324), signaling receptor complex (GO:0043235), stereocilium base (GO:0120044), plasma membrane (GO:0005886), membrane (GO:0016020), stereocilium (GO:0032420), stereocilium bundle (GO:0032421), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
embryonic morphogenesis	2
phosphatidylinositol trisphosphate phosphatase activity	2
phosphatidylinositol phosphate 5-phosphatase activity	2
phosphatidylinositol-3,5-bisphosphate phosphatase activity	2
plasma membrane region	2
stereocilium	2
fat cell differentiation	1
regulation of cell differentiation	1
sensory perception of sound	1
nervous system process	1
detection of mechanical stimulus involved in sensory perception	1
hemopoiesis	1
cell differentiation	1
dephosphorylation	1
protein modification process	1
primary metabolic process	1
phosphate-containing compound metabolic process	1
ear morphogenesis	1
inner ear development	1
musculoskeletal movement	1
neuromuscular process	1
inner ear morphogenesis	1
cell morphogenesis involved in neuron differentiation	1
vestibular receptor cell development	1
phosphoprotein phosphatase activity	1
phosphatidylinositol-3-phosphate biosynthetic process	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
basal part of cell	1
apical part of cell	1
protein-containing complex	1
membrane	1
cell periphery	1
stereocilium bundle	1
neuron projection	1
actin-based cell projection	1
cluster of actin-based cell projections	1

Protein interactions and networks

STRING

526 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPRQ	MYO6	Q9UM54	540
PTPRQ	USP31	Q70CQ4	519
PTPRQ	TPRN	Q4KMQ1	519
PTPRQ	REDIC1	Q86WS4	505
PTPRQ	SYT1	P21579	484
PTPRQ	NAV3	Q8IVL0	456
PTPRQ	RBBP6	Q7Z6E9	438
PTPRQ	TMTC2	Q8N394	430
PTPRQ	MANF	P55145	426
PTPRQ	UAP1	Q16222	425
PTPRQ	FRS2	Q8WU20	424
PTPRQ	LRRC10	Q5BKY1	423
PTPRQ	TMC1	Q8TDI8	416
PTPRQ	E2F7	Q96AV8	410
PTPRQ	MRPL11	Q9Y3B7	406
PTPRQ	OTOGL	Q3ZCN5	406

IntAct

9 interactions, top by confidence:

A	B	Type	Score
PTPRQ	EZR	psi-mi:“MI:0915”(physical association)	0.000
PTPRQ	AHI1	psi-mi:“MI:0915”(physical association)	0.000
PTPRQ	SNX27	psi-mi:“MI:0915”(physical association)	0.000
NHERF1	PTPRQ	psi-mi:“MI:0915”(physical association)	0.000
ATP2B2	PTPRQ	psi-mi:“MI:0915”(physical association)	0.000
EEA1	PTPRQ	psi-mi:“MI:0915”(physical association)	0.000
NHERF2	PTPRQ	psi-mi:“MI:0915”(physical association)	0.000
PIBF1	PTPRQ	psi-mi:“MI:0915”(physical association)	0.000

ESM2 similar proteins: A2AED3, B1AUH1, B2RU80, B3DK56, B3EX02, F1NWE3, O14522, O42422, O73875, O88488, P08922, P08941, P0C5E4, P16621, P23467, P28827, P28828, P35822, P35992, P53767, P54755, P54757, P54759, Q00546, Q02763, Q02858, Q05546, Q06806, Q06807, Q15262, Q15375, Q2EY13, Q2EY15, Q2VWP7, Q2VWP9, Q5R412, Q5VTL7, Q61772, Q63132, Q64455

Diamond homologs: A0A6I8TCE0, A1L1L3, A2A8L5, A2ALK8, A4IFW2, A7MBJ4, B0V2N1, B0X4T2, B1AUH1, B2RU80, B3DK56, B9EKR1, E9Q0N2, E9Q612, F1NWE3, O13016, O14522, O35239, O55082, O82656, O88488, P04157, P06800, P08575, P0C5E4, P10586, P16621, P17706, P18031, P20417, P23467, P23468, P23470, P23471, P26045, P28191, P28192, P28827, P28828, P29074

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

584 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	26
Likely pathogenic	32
Uncertain significance	243
Likely benign	109
Benign	152

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1184601	NM_001145026.2(PTPRQ):c.6024+2T>C	Pathogenic
1217990	NM_001145026.2(PTPRQ):c.1673_1682del (p.Thr558fs)	Pathogenic
1297696	NM_001145026.2(PTPRQ):c.1560del (p.Gln519_Tyr520insTer)	Pathogenic
156332	NM_001145026.2(PTPRQ):c.715A>G (p.Arg239Gly)	Pathogenic
156333	NM_001145026.2(PTPRQ):c.837T>A (p.Tyr279Ter)	Pathogenic
1799534	NM_001145026.2(PTPRQ):c.2726del (p.Glu909fs)	Pathogenic
285868	NM_001145026.2(PTPRQ):c.5390-1G>T	Pathogenic
3340153	NM_001145026.2(PTPRQ):c.473_474insTA (p.Val159fs)	Pathogenic
3377236	NM_001145026.2(PTPRQ):c.228G>A (p.Trp76Ter)	Pathogenic
3377523	NM_001145026.2(PTPRQ):c.6453+2dup	Pathogenic
3378394	NM_001145026.2(PTPRQ):c.3873+727A>G	Pathogenic
3378395	NM_001145026.2(PTPRQ):c.4159del (p.Gln1387fs)	Pathogenic
3383438	NM_001145026.2(PTPRQ):c.4826del (p.Ser1609fs)	Pathogenic
3393554	NM_001145026.2(PTPRQ):c.5775del (p.Phe1925fs)	Pathogenic
3601705	NM_001145026.2(PTPRQ):c.4869T>A (p.Tyr1623Ter)	Pathogenic
3601709	NM_001145026.2(PTPRQ):c.6454-2A>G	Pathogenic
3764720	NM_001145026.2(PTPRQ):c.6742C>T (p.Gln2248Ter)	Pathogenic
3898735	NM_001145026.2(PTPRQ):c.4173_4182del (p.Met1390_Tyr1391insTer)	Pathogenic
4086104	NM_001145026.2(PTPRQ):c.661G>T (p.Glu221Ter)	Pathogenic
4294339	NM_001145026.2(PTPRQ):c.4015+1G>A	Pathogenic
4526207	NC_000012.11:g.(81064272_81066947)_(81067084_81072380)del	Pathogenic
4689666	NM_001145026.2(PTPRQ):c.3624G>A (p.Glu1208=)	Pathogenic
499563	NM_001145026.2(PTPRQ):c.3867_3871del (p.Tyr1289_Lys1291delinsTer)	Pathogenic
523416	NM_001145026.2(PTPRQ):c.6475C>T (p.Arg2159Ter)	Pathogenic
597495	NM_001145026.2(PTPRQ):c.1359+2T>C	Pathogenic
973493	NM_001145026.2(PTPRQ):c.4006C>T (p.Gln1336Ter)	Pathogenic
1180826	NM_001145026.2(PTPRQ):c.6775del (p.Leu2259fs)	Likely pathogenic
1185053	NM_001145026.2(PTPRQ):c.6194_6453+1del	Likely pathogenic
1799533	NM_001145026.2(PTPRQ):c.1291C>T (p.Arg431Ter)	Likely pathogenic
2431060	NM_001145026.2(PTPRQ):c.3308_3309del (p.Leu1103fs)	Likely pathogenic

SpliceAI

7377 predictions. Top by Δscore:

Variant	Effect	Δscore
12:80444850:G:GG	donor_gain	1.0000
12:80445489:A:AG	acceptor_gain	1.0000
12:80445490:G:GG	acceptor_gain	1.0000
12:80445670:G:GT	donor_gain	1.0000
12:80468756:A:T	donor_gain	1.0000
12:80472248:GATG:G	donor_gain	1.0000
12:80472249:ATGGT:A	donor_loss	1.0000
12:80472252:G:A	donor_loss	1.0000
12:80472252:G:GG	donor_gain	1.0000
12:80472253:T:TT	donor_loss	1.0000
12:80484431:A:AG	acceptor_gain	1.0000
12:80484432:G:GG	acceptor_gain	1.0000
12:80484565:G:GT	donor_gain	1.0000
12:80484601:ATGAG:A	donor_loss	1.0000
12:80484602:TGAGG:T	donor_loss	1.0000
12:80484603:G:GT	donor_gain	1.0000
12:80484603:GAGGT:G	donor_loss	1.0000
12:80484604:AGGT:A	donor_loss	1.0000
12:80484605:GGTA:G	donor_loss	1.0000
12:80484606:G:A	donor_loss	1.0000
12:80484607:T:A	donor_loss	1.0000
12:80493452:GTTG:G	donor_gain	1.0000
12:80494918:A:AG	acceptor_gain	1.0000
12:80494918:ACT:A	acceptor_gain	1.0000
12:80494919:C:G	acceptor_gain	1.0000
12:80494920:T:TA	acceptor_gain	1.0000
12:80494923:A:AG	acceptor_gain	1.0000
12:80494927:A:AG	acceptor_gain	1.0000
12:80494928:A:G	acceptor_gain	1.0000
12:80494931:A:AG	acceptor_gain	1.0000

AlphaMissense

15071 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:80620180:T:A	W1848R	0.999
12:80620180:T:C	W1848R	0.999
12:80669043:G:C	G2110R	0.999
12:80669073:T:A	W2120R	0.999
12:80669073:T:C	W2120R	0.999
12:80669357:T:A	W2149R	0.999
12:80669357:T:C	W2149R	0.999
12:80669451:T:C	L2180P	0.999
12:80670386:T:A	W2199R	0.999
12:80670386:T:C	W2199R	0.999
12:80670488:T:C	C2233R	0.999
12:80670490:C:G	C2233W	0.999
12:80670491:A:C	S2234R	0.999
12:80673169:T:A	S2234R	0.999
12:80673169:T:G	S2234R	0.999
12:80679003:T:A	W2327R	0.999
12:80679003:T:C	W2327R	0.999
12:80445553:T:A	W118R	0.998
12:80445553:T:C	W118R	0.998
12:80459346:T:A	W217R	0.998
12:80459346:T:C	W217R	0.998
12:80620182:G:C	W1848C	0.998
12:80620182:G:T	W1848C	0.998
12:80669345:T:C	C2145R	0.998
12:80669359:G:C	W2149C	0.998
12:80669359:G:T	W2149C	0.998
12:80678998:T:C	L2325P	0.998
12:80679005:G:C	W2327C	0.998
12:80679005:G:T	W2327C	0.998
12:80457578:G:C	A174P	0.997

dbSNP variants (sampled 300 via entrez): RS1000010815 (12:80609667 C>G), RS1000033973 (12:80559268 T>A,C), RS1000062633 (12:80498805 T>C,G), RS1000072020 (12:80540890 C>G,T), RS1000075603 (12:80525567 A>G), RS1000109526 (12:80676486 T>C), RS1000119084 (12:80454707 T>C), RS1000119778 (12:80628290 G>T), RS1000128631 (12:80587446 A>G), RS1000130037 (12:80477173 T>A,G), RS1000132973 (12:80668488 T>C), RS1000161916 (12:80547101 A>G,T), RS1000183664 (12:80448939 G>T), RS1000209998 (12:80471579 G>A,C,T), RS1000215458 (12:80505427 G>A)

Disease associations

OMIM: gene MIM:603317 | disease phenotypes: MIM:613391, MIM:617663, MIM:128600, MIM:220290, MIM:607197

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive nonsyndromic hearing loss 84A	Definitive	Autosomal recessive
hearing loss, autosomal recessive	Definitive	Unknown
hearing loss, autosomal dominant 73	Strong	Autosomal dominant
autosomal dominant nonsyndromic hearing loss	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hearing loss, autosomal recessive	Definitive	AR

Mondo (8): hearing loss disorder (MONDO:0005365), autosomal recessive nonsyndromic hearing loss 84A (MONDO:0013249), hearing loss, autosomal dominant 73 (MONDO:0033260), ear malformation (MONDO:0007500), hearing loss, autosomal recessive (MONDO:0019588), flatfoot (MONDO:0005293), sensorineural hearing loss disorder (MONDO:0020678), autosomal dominant nonsyndromic hearing loss (MONDO:0019587)

Orphanet (2): Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635)

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0001270	Motor delay
HP:0001751	Abnormal vestibular function
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0011463	Childhood onset

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D005413	Flatfoot	C05.330.488.655.250; C05.330.495.681.250; C05.660.585.512.380.813.250; C16.131.621.585.512.500.681.250
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
C564609	Deafness, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Receptor tyrosine phosphatase (RTP) family

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
dicyclohexyl phthalate	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Estradiol	affects cotreatment, decreases expression	1
Fenofibrate	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT00486577	PHASE2/PHASE3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	PHASE2/PHASE3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	PHASE2/PHASE3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	PHASE2/PHASE3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	PHASE1/PHASE2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
NCT01621256	PHASE1/PHASE2	COMPLETED	Efficacy, Safety, and Tolerability of Ancrod in Patients With Sudden Hearing Loss
NCT06370351	PHASE1/PHASE2	RECRUITING	A Phase I/II Clinical Trial with SENS-501 in Children Suffering from Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations
NCT06545175	PHASE1/PHASE2	RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
NCT07304024	PHASE1/PHASE2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound
NCT01109576	EARLY_PHASE1	COMPLETED	Workshops for Veterans With Vision and Hearing Loss