PTPRR

Summary

PTPRR (protein tyrosine phosphatase receptor type R, HGNC:9680) is a protein-coding gene on chromosome 12q15, encoding Receptor-type tyrosine-protein phosphatase R (Q15256). Sequesters mitogen-activated protein kinases (MAPKs) such as MAPK1, MAPK3 and MAPK14 in the cytoplasm in an inactive form. It is a selective cancer dependency (DepMap: 14.9% of cell lines).

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and a single intracellular catalytic domain, and thus represents a receptor-type PTP. Silencing of this gene has been associated with colorectal cancer. Multiple transcript variants encoding different isoforms have been found for this gene. This gene shares a symbol (PTPRQ) with another gene, protein tyrosine phosphatase, receptor type, Q (GeneID 374462), which is also located on chromosome 12.

Source: NCBI Gene 5801 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hearing loss, autosomal recessive (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 14
• Clinical variants (ClinVar): 710 total — 26 pathogenic, 32 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 14.9% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_002849

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9680
Approved symbol	PTPRR
Name	protein tyrosine phosphatase receptor type R
Location	12q15
Locus type	gene with protein product
Status	Approved
Aliases	PTPBR7, PTP-SL, EC-PTP, PCPTP1
Ensembl gene	ENSG00000153233
Ensembl biotype	protein_coding
OMIM	602853
Entrez	5801

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000283228, ENST00000342084, ENST00000378778, ENST00000440835, ENST00000537619, ENST00000547752, ENST00000548220, ENST00000549107, ENST00000549308, ENST00000550661, ENST00000551219

RefSeq mRNA: 4 — MANE Select: NM_002849 NM_001207015, NM_001207016, NM_002849, NM_130846

CCDS: CCDS44945, CCDS55847, CCDS55848, CCDS8998

Canonical transcript exons

ENST00000283228 — 14 exons

Exon	Start	End
ENSE00000937354	70892679	70892977
ENSE00001252923	70920333	70920738
ENSE00001681055	70761471	70761626
ENSE00001757470	70764665	70764778
ENSE00003477613	70754191	70754301
ENSE00003498792	70656704	70656817
ENSE00003518632	70684704	70684783
ENSE00003560279	70698265	70698349
ENSE00003584631	70684127	70684264
ENSE00003604563	70638079	70639277
ENSE00003616319	70701137	70701323
ENSE00003635984	70745818	70746086
ENSE00003637926	70662495	70662605
ENSE00003688267	70660940	70661097

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 90.27.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1080 / max 25.7158, expressed in 35 samples.

FANTOM5 promoters (22 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132084	2.2983	133
132083	0.4497	89
132082	0.3014	64
127101	0.2850	111
132074	0.2356	58
132069	0.1313	72
127100	0.1080	35
127102	0.1047	44
132085	0.0779	21
132071	0.0694	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	90.27	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.65	gold quality
cerebellar cortex	UBERON:0002129	87.53	gold quality
cerebellar hemisphere	UBERON:0002245	87.48	gold quality
cerebellum	UBERON:0002037	86.69	gold quality
prefrontal cortex	UBERON:0000451	84.93	gold quality
entorhinal cortex	UBERON:0002728	83.92	gold quality
jejunal mucosa	UBERON:0000399	83.64	gold quality
mucosa of transverse colon	UBERON:0004991	82.72	gold quality
Brodmann (1909) area 46	UBERON:0006483	82.36	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.01	gold quality
orbitofrontal cortex	UBERON:0004167	81.64	gold quality
frontal cortex	UBERON:0001870	81.38	gold quality
cerebellar vermis	UBERON:0004720	81.12	gold quality
middle temporal gyrus	UBERON:0002771	80.43	gold quality
neocortex	UBERON:0001950	80.17	gold quality
right frontal lobe	UBERON:0002810	80.16	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.03	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.96	gold quality
secondary oocyte	CL:0000655	78.66	gold quality
primary visual cortex	UBERON:0002436	78.48	gold quality
cerebral cortex	UBERON:0000956	78.34	gold quality
superior frontal gyrus	UBERON:0002661	78.33	gold quality
cingulate cortex	UBERON:0003027	78.26	gold quality
Brodmann (1909) area 23	UBERON:0013554	78.19	gold quality
temporal lobe	UBERON:0001871	78.15	gold quality
anterior cingulate cortex	UBERON:0009835	78.06	gold quality
rectum	UBERON:0001052	77.39	gold quality
paraflocculus	UBERON:0005351	76.76	gold quality
Brodmann (1909) area 10	UBERON:0013541	76.62	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	60.70
E-MTAB-6678	yes	8.44
E-ANND-3	yes	4.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

107 targeting PTPRR, 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-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 14.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 13)

• determined high-resolution structures of all of the human family members of Mitogen-Activated Protein Kinase-specific protein tyrosine phosphatases (PMID:16441242)
• expression of the PTPRR-1 isoform was inactivated in colorectal cancer cells as a result of de novo CpG island methylation and enrichment of transcription-repressive histone-tail marks, mainly H3K27me3 (PMID:20015382)
• the protein tyrosine phosphatase receptor type R gene may play a role in conferring risk of major depressive disorder in females (PMID:22100128)
• Methylation of the PTPRR promoter has an important role in the metastasis and may be a biomarker of invasive cervical cancer (PMID:22330137)
• 3 genes identified by association study and supported by ocular expression and/or replication, UHRF1BP1L, PTPRR, and PPFIA2, are novel candidates for myopic development within the MYP3 locus that should be further studied. (PMID:23422819)
• High expression of PTP receptors R and Z1 was observed in all examined cases of colorectal carcinoma, adenoma and normal colon tissue in this study. (PMID:24242166)
• The methylation index of PTPRR recovered from scrapings of uterine cervix adenocarcinomas is significantly higher than in normal controls. (PMID:24407576)
• Results show that PTPRR is an early and direct target of the androgen receptor which negatively regulates the RAS/ERK1/2 pathway suggesting that its loss in prostate cancer cells is one factor that might contribute to activation of the RAS/ERK1/2 pathway. (PMID:25592066)
• The PTPRR genes were related to possible endophenotypes for suicidal behaviour such as anger, depression-anxiety and fatigue. (PMID:28327445)
• The development of MDD may be related with the polymorphism of ERK-rs12678428 and PTPRR-rs1513105. (PMID:28467119)
• Results suggest that protein tyrosine phosphatase receptor type R (PTPRR) expression might have utility as a prognostic marker for predicting overall survival. (PMID:31653698)
• Identification of PTPRR and JAG1 as key genes in castration-resistant prostate cancer by integrated bioinformatics methods(). (PMID:32133801)
• Re-expression of epigenetically silenced PTPRR by histone acetylation sensitizes RAS-mutant lung adenocarcinoma to SHP2 inhibition. (PMID:38280930)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptprr	ENSDARG00000105744
mus_musculus	Ptprr	ENSMUSG00000020151
rattus_norvegicus	Ptprr	ENSRNOG00000004483

Paralogs (35): PTPRN (ENSG00000054356), PTPRU (ENSG00000060656), PTPN3 (ENSG00000070159), PTPN21 (ENSG00000070778), PTPN18 (ENSG00000072135), PTPN23 (ENSG00000076201), PTPRH (ENSG00000080031), PTPRC (ENSG00000081237), PTPN4 (ENSG00000088179), PTPRS (ENSG00000105426), PTPRZ1 (ENSG00000106278), PTPN5 (ENSG00000110786), PTPN6 (ENSG00000111679), PTPRB (ENSG00000127329), PTPN12 (ENSG00000127947), PTPRE (ENSG00000132334), PTPRA (ENSG00000132670), PTPN22 (ENSG00000134242), PTPRF (ENSG00000142949), PTPN7 (ENSG00000143851), PTPRG (ENSG00000144724), PTPRJ (ENSG00000149177), PTPRO (ENSG00000151490), PTPN14 (ENSG00000152104), PTPRK (ENSG00000152894), PTPRD (ENSG00000153707), PTPRN2 (ENSG00000155093), PTPN13 (ENSG00000163629), PTPN9 (ENSG00000169410), PTPRM (ENSG00000173482), PTPN2 (ENSG00000175354), PTPN11 (ENSG00000179295), PTPRT (ENSG00000196090), PTPN1 (ENSG00000196396), PTPN20 (ENSG00000204179)

Protein

Protein identifiers

Receptor-type tyrosine-protein phosphatase R — Q15256 (reviewed: Q15256)

Alternative names: Ch-1PTPase, NC-PTPCOM1, Protein-tyrosine phosphatase PCPTP1

All UniProt accessions (3): Q15256, F8VU63, F8VVE9

UniProt curated annotations — full annotation on UniProt →

Function. Sequesters mitogen-activated protein kinases (MAPKs) such as MAPK1, MAPK3 and MAPK14 in the cytoplasm in an inactive form. The MAPKs bind to a dephosphorylated kinase interacting motif, phosphorylation of which by the protein kinase A complex releases the MAPKs for activation and translocation into the nucleus.

Subunit / interactions. Interacts with MAPKs.

Subcellular location. Secreted Cell membrane Cytoplasm. Perinuclear region Cytoplasm. Perinuclear region.

Tissue specificity. Detected in cerebrospinal fluid (at protein level). Expressed in brain, placenta, small intestine, stomach, uterus and weakly in the prostate. Isoform alpha has been observed only in the brain. Isoform gamma is expressed in brain, placenta and uterus. Isoform delta is expressed in brain, kidney, placenta, prostate, small intestine and uterus.

Similarity. Belongs to the protein-tyrosine phosphatase family. Receptor class 7 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q15256-1	Alpha	yes
Q15256-3	Gamma
Q15256-4	Delta
Q15256-5	4

RefSeq proteins (4): NP_001193944, NP_001193945, NP_002840, NP_570897 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000242	PTP_cat	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR008356	Tyr_Pase_KIM-con	Family
IPR016130	Tyr_Pase_AS	Active_site
IPR016334	Tyr_Pase_rcpt_R/non-rcpt_5	Family
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR059011	PTPRR_N	Domain

Pfam: PF00102, PF26155

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), 1 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)

UniProt features (50 total): helix 13, strand 13, splice variant 5, sequence variant 4, binding site 3, modified residue 2, glycosylation site 2, topological domain 2, signal peptide 1, chain 1, sequence conflict 1, transmembrane region 1, domain 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2A8B	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15256-F1	72.59	0.40

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): 588 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (3): 554; 588–594; 632

Post-translational modifications (2): 272, 339

Glycosylation sites (2): 23, 129

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 315 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, AP1_01, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, MODULE_516, 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, KEGG_MAPK_SIGNALING_PATHWAY, MODULE_64, GOBP_REGULATION_OF_EPITHELIAL_CELL_MIGRATION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP

GO Biological Process (7): in utero embryonic development (GO:0001701), protein dephosphorylation (GO:0006470), signal transduction (GO:0007165), negative regulation of epithelial cell migration (GO:0010633), ERBB2 signaling pathway (GO:0038128), negative regulation of ERK1 and ERK2 cascade (GO:0070373), dephosphorylation (GO:0016311)

GO Molecular Function (6): protein tyrosine phosphatase activity (GO:0004725), transmembrane receptor protein tyrosine phosphatase activity (GO:0005001), protein kinase binding (GO:0019901), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (8): obsolete extracellular space (GO:0005615), cytosol (GO:0005829), plasma membrane (GO:0005886), cell junction (GO:0030054), perinuclear region of cytoplasm (GO:0048471), extracellular region (GO:0005576), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoplasm	2
chordate embryonic development	1
dephosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
epithelial cell migration	1
regulation of epithelial cell migration	1
negative regulation of cell migration	1
negative regulation of multicellular organismal process	1
ERBB signaling pathway	1
negative regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
phosphate-containing compound metabolic process	1
phosphoprotein phosphatase activity	1
protein tyrosine phosphatase activity	1
transmembrane receptor protein phosphatase activity	1
kinase binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1264 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPRR	PTS	Q03393	889
PTPRR	MAPK1	P28482	727
PTPRR	DUSP1	P28562	623
PTPRR	MAP2K1	Q02750	614
PTPRR	DUSP12	Q9UNI6	598
PTPRR	DUSP6	Q16828	506
PTPRR	CTNNB1	P35222	484
PTPRR	ZNF582	Q96NG8	479
PTPRR	PTPN11	Q06124	477
PTPRR	CDH1	P12830	473
PTPRR	STAT5A	P42229	429
PTPRR	TBC1D31	Q96DN5	427
PTPRR	RPS6KA3	P51812	422
PTPRR	GADD45B	O75293	408
PTPRR	DUSP5	Q16690	398

IntAct

40 interactions, top by confidence:

A	B	Type	Score
SS18	ARID1A	psi-mi:“MI:0914”(association)	0.760
PTPRR	MAPK1	psi-mi:“MI:0914”(association)	0.680
MAPK1	PTPRR	psi-mi:“MI:2364”(proximity)	0.680
PTPRR	MAPK1	psi-mi:“MI:0915”(physical association)	0.680
PTPRR	MAPK1	psi-mi:“MI:0403”(colocalization)	0.680
MAPK14	PTPRR	psi-mi:“MI:0915”(physical association)	0.660
PTPRR	MAPK14	psi-mi:“MI:0915”(physical association)	0.660
MAPK14	PTPRR	psi-mi:“MI:0403”(colocalization)	0.660
ERBB2	PTPRR	psi-mi:“MI:0915”(physical association)	0.510
PTPRR	ERBB2	psi-mi:“MI:0915”(physical association)	0.510
PTPRR	INSR	psi-mi:“MI:0915”(physical association)	0.510
INSR	PTPRR	psi-mi:“MI:0915”(physical association)	0.510
PTPRR	LMTK2	psi-mi:“MI:0915”(physical association)	0.370
PTPRR	AATK	psi-mi:“MI:0915”(physical association)	0.370
PTPRR	ERBB4	psi-mi:“MI:0915”(physical association)	0.370
PTPRR	EGFR	psi-mi:“MI:0915”(physical association)	0.370
PTPRR	ERBB3	psi-mi:“MI:0915”(physical association)	0.370
PTPRR	TEK	psi-mi:“MI:0915”(physical association)	0.370
PTPRR	RET	psi-mi:“MI:0915”(physical association)	0.370
PTPRR	RYK	psi-mi:“MI:0915”(physical association)	0.370
PTPRR	ROR1	psi-mi:“MI:0915”(physical association)	0.370
PTPRR	ROR2	psi-mi:“MI:0915”(physical association)	0.370
PTPRR	IGF1R	psi-mi:“MI:0915”(physical association)	0.370
PTPRR	PTK7	psi-mi:“MI:0915”(physical association)	0.370
PTPRR	EPHA2	psi-mi:“MI:0915”(physical association)	0.370
PTPRR	Mst1r	psi-mi:“MI:0915”(physical association)	0.370
PTPRR	NTRK1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (133): MAPK1 (Affinity Capture-MS), MAPK14 (Affinity Capture-MS), PTPRR (Affinity Capture-MS), PTPRR (Affinity Capture-MS), MAPK1 (Co-localization), PTPRR (Two-hybrid), PTPRR (Two-hybrid), PTPRR (Two-hybrid), PTPRR (Two-hybrid), PTPRR (Two-hybrid), PTPRR (Two-hybrid), PTPRR (Two-hybrid), PTPRR (Two-hybrid), PTPRR (Two-hybrid), PTPRR (Two-hybrid)

ESM2 similar proteins: A1L1L3, B3NKK1, B4IMC3, B4NSS9, G5EC24, G5EGA9, G5EGU2, H2KZM6, H2KZW3, O08617, O55082, P04157, P06800, P08575, P18052, P18475, P28192, P29349, P29351, P34138, P34337, P34442, P35235, P41499, P42083, P42159, P81718, Q05209, Q06124, Q10656, Q15256, Q20402, Q22712, Q4JDL3, Q5I124, Q5I128, Q5I137, Q5I138, Q5I139, Q5I141

Diamond homologs: A0A6I8TCE0, A1L1L3, A2ALK8, A4IFW2, B0V2N1, B0X4T2, B1AUH1, B2GV87, B2RU80, B3DK56, B9EKR1, E9Q0N2, E9Q612, F1NWE3, G5EC24, G5EGJ9, H2KZM6, O02695, O08617, O13016, O35239, O55082, P06800, P16620, P17706, P18031, P18052, P18433, P20417, P23467, P23468, P23469, P23470, P23471, P26045, P28191, P29074, P29350, P29351, P29352

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
PTPRR	down-regulates	MAPK14	dephosphorylation
PTPRR	“down-regulates activity”	STAT3	dephosphorylation
PTPRR	“down-regulates activity”	PXN	dephosphorylation
PTPRR	“down-regulates activity”	MAPK7	dephosphorylation
PTPRR	“down-regulates activity”	MAPK1	dephosphorylation
MAPK1	“up-regulates activity”	PTPRR	phosphorylation
MAPK3	“up-regulates activity”	PTPRR	phosphorylation
PRKACA	“down-regulates activity”	PTPRR	phosphorylation
Gbeta	“up-regulates activity”	PTPRR	phosphorylation
ERK1/2	“up-regulates activity”	PTPRR	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Constitutive Signaling by Aberrant PI3K in Cancer	7	37.0×	4e-08
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	9	36.3×	3e-10
RAF/MAP kinase cascade	10	25.4×	3e-10
PIP3 activates AKT signaling	9	25.0×	4e-09
MITF-M-regulated melanocyte development	5	23.8×	5e-05
Signaling by Interleukins	5	13.4×	6e-04
Cytokine Signaling in Immune system	5	8.5×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	7	109.2×	3e-11
cell surface receptor protein tyrosine kinase signaling pathway	12	77.2×	6e-18
protein autophosphorylation	9	48.4×	2e-11
epidermal growth factor receptor signaling pathway	5	45.9×	4e-06
positive regulation of epithelial cell proliferation	5	45.2×	4e-06
positive regulation of MAPK cascade	12	35.8×	4e-14
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	11	31.9×	2e-12
positive regulation of ERK1 and ERK2 cascade	8	25.2×	6e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	26
Likely pathogenic	32
Uncertain significance	341
Likely benign	112
Benign	153

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

3246 predictions. Top by Δscore:

Variant	Effect	Δscore
12:70656818:C:CC	acceptor_gain	1.0000
12:70662489:TCTTA:T	donor_loss	1.0000
12:70662490:CTTAC:C	donor_loss	1.0000
12:70662491:TTA:T	donor_loss	1.0000
12:70662492:TAC:T	donor_loss	1.0000
12:70662494:C:CT	donor_loss	1.0000
12:70662601:CATTT:C	acceptor_gain	1.0000
12:70662602:ATTT:A	acceptor_gain	1.0000
12:70662603:TTT:T	acceptor_gain	1.0000
12:70662604:TT:T	acceptor_gain	1.0000
12:70662604:TTC:T	acceptor_loss	1.0000
12:70662605:TC:T	acceptor_loss	1.0000
12:70662606:C:CC	acceptor_gain	1.0000
12:70662606:CTGGA:C	acceptor_loss	1.0000
12:70662607:T:A	acceptor_loss	1.0000
12:70684121:TCATA:T	donor_loss	1.0000
12:70684122:CATAC:C	donor_loss	1.0000
12:70684123:ATAC:A	donor_loss	1.0000
12:70684124:TACCT:T	donor_loss	1.0000
12:70684125:A:AC	donor_gain	1.0000
12:70684126:C:CC	donor_gain	1.0000
12:70684126:CCT:C	donor_gain	1.0000
12:70684176:T:TA	donor_gain	1.0000
12:70684260:TAGCC:T	acceptor_gain	1.0000
12:70684261:AGCC:A	acceptor_gain	1.0000
12:70684262:GCC:G	acceptor_gain	1.0000
12:70684263:CC:C	acceptor_gain	1.0000
12:70684263:CCC:C	acceptor_gain	1.0000
12:70684264:CC:C	acceptor_gain	1.0000
12:70684265:C:CC	acceptor_gain	1.0000

AlphaMissense

4332 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:70656802:T:A	R594S	1.000
12:70656802:T:G	R594S	1.000
12:70656803:C:G	R594T	1.000
12:70656812:C:T	G591E	1.000
12:70661050:C:A	W552C	1.000
12:70661050:C:G	W552C	1.000
12:70661052:A:G	W552R	1.000
12:70661052:A:T	W552R	1.000
12:70684158:A:T	V489D	1.000
12:70684195:A:G	W477R	1.000
12:70684195:A:T	W477R	1.000
12:70684233:G:T	A464D	1.000
12:70698286:G:T	R420S	1.000
12:70639227:A:G	L644P	0.999
12:70639241:A:C	F639L	0.999
12:70639241:A:T	F639L	0.999
12:70639242:A:G	F639S	0.999
12:70639243:A:G	F639L	0.999
12:70639250:C:A	Q636H	0.999
12:70639250:C:G	Q636H	0.999
12:70639262:T:A	Q632H	0.999
12:70639262:T:G	Q632H	0.999
12:70639277:T:A	R627S	0.999
12:70639277:T:G	R627S	0.999
12:70656704:C:A	R627I	0.999
12:70656704:C:G	R627T	0.999
12:70656713:C:G	R624P	0.999
12:70656714:G:T	R624S	0.999
12:70656716:A:G	L623P	0.999
12:70656761:A:G	L608P	0.999

dbSNP variants (sampled 300 via entrez): RS1000001821 (12:70777730 C>A,T), RS1000008629 (12:70733161 A>G), RS1000026827 (12:70905197 T>G), RS1000034748 (12:70689763 G>A), RS1000046336 (12:70773184 C>G), RS1000047129 (12:70686330 C>T), RS1000062120 (12:70898700 G>GA), RS1000069110 (12:70862153 G>A), RS1000071368 (12:70740932 A>C), RS1000088268 (12:70759297 A>G), RS1000090823 (12:70814012 C>T), RS1000104301 (12:70739390 A>G), RS1000105753 (12:70648349 A>G), RS1000136308 (12:70855766 T>A,G), RS1000142244 (12:70722805 A>G)

Disease associations

OMIM: gene MIM:602853 | 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

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000407	Sensorineural hearing impairment

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001858_4	Refractive error	5.000000e-09
GCST003124_9	Mild influenza (H1N1) infection	4.000000e-25
GCST003125_8	Influenza A (H1N1) infection	3.000000e-18
GCST003996_33	Monobrow	9.000000e-21
GCST006291_27	Spherical equivalent or myopia (age of diagnosis)	1.000000e-13
GCST006412_78	Intraocular pressure	1.000000e-08
GCST007993_26	Asthma (adult onset)	7.000000e-07
GCST007995_41	Asthma (childhood onset)	4.000000e-08
GCST009158_13	Uterine fibroids	3.000000e-08
GCST010002_218	Refractive error	5.000000e-26
GCST010241_317	Apolipoprotein A1 levels	2.000000e-08
GCST010241_405	Apolipoprotein A1 levels	2.000000e-10
GCST010242_103	HDL cholesterol levels	2.000000e-08
GCST90011899_29	Aspartate aminotransferase levels	4.000000e-27

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)
EFO:0007906	synophrys measurement
EFO:0004847	age at onset
EFO:0004695	intraocular pressure measurement
EFO:1002011	adult onset asthma
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004736	aspartate aminotransferase measurement

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: yes

ChEMBL targets (1): CHEMBL3425390 (SINGLE PROTEIN)

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

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases abundance, increases expression	4
Copper	increases expression, affects cotreatment, decreases expression, affects binding	3
Benzo(a)pyrene	affects methylation, increases expression	2
Formaldehyde	increases expression, decreases expression	2
Progesterone	increases expression, affects cotreatment	2
Silicon Dioxide	increases expression	2
bisphenol A	affects cotreatment, decreases methylation	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
2-palmitoylglycerol	increases expression	1
oligofectamine	increases expression	1
abrine	increases expression	1
ormosil	affects binding, increases expression	1
NSC 689534	affects binding, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Chelating Agents	increases expression, affects binding	1
Curcumin	decreases expression	1
Demecolcine	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Lead	affects expression	1
Oxygen	increases expression	1
Phthalic Acids	increases methylation	1
Polyethylene Glycols	affects binding, increases expression	1
Rotenone	decreases expression	1
Sarin	decreases expression	1
Smoke	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3430030	Binding	Inhibition of recombinant PTP-SL (unknown origin) using OMFP as substrate after 1 hr by fluorescence assay	Perspective: Tyrosine phosphatases as novel targets for antiplatelet therapy. — Bioorg Med Chem

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