PTPRK

Summary

PTPRK (protein tyrosine phosphatase receptor type K, HGNC:9674) is a protein-coding gene on chromosome 6q22.33, encoding Receptor-type tyrosine-protein phosphatase kappa (Q15262). Regulation of processes involving cell contact and adhesion such as growth control, tumor invasion, and metastasis.

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 two tandem catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP mu (MAM) domain, an Ig-like domain and four fibronectin type III-like repeats. This PTP was shown to mediate homophilic intercellular interaction, possibly through the interaction with beta- and gamma-catenin at adherens junctions. Expression of this gene was found to be stimulated by TGF-beta 1, which may be important for the inhibition of keratinocyte proliferation.

Source: NCBI Gene 5796 — RefSeq curated summary.

At a glance

• GWAS associations: 26
• Clinical variants (ClinVar): 193 total
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 3 cancer types
• MANE Select transcript: NM_002844

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9674
Approved symbol	PTPRK
Name	protein tyrosine phosphatase receptor type K
Location	6q22.33
Locus type	gene with protein product
Status	Approved
Aliases	R-PTP-kappa
Ensembl gene	ENSG00000152894
Ensembl biotype	protein_coding
OMIM	602545
Entrez	5796

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 23 protein_coding, 8 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000368202, ENST00000368205, ENST00000368207, ENST00000368210, ENST00000368213, ENST00000368215, ENST00000368226, ENST00000392449, ENST00000415046, ENST00000415055, ENST00000429595, ENST00000434424, ENST00000490332, ENST00000495748, ENST00000498284, ENST00000524481, ENST00000524534, ENST00000525459, ENST00000531050, ENST00000531466, ENST00000532331, ENST00000532751, ENST00000876486, ENST00000876487, ENST00000876488, ENST00000930831, ENST00000930832, ENST00000930833, ENST00000950858, ENST00000950859, ENST00000950860, ENST00000950861, ENST00000950862, ENST00000950863, ENST00000950864

RefSeq mRNA: 6 — MANE Select: NM_002844 NM_001135648, NM_001291981, NM_001291982, NM_001291983, NM_001291984, NM_002844

CCDS: CCDS47473, CCDS5137, CCDS75517, CCDS78179

Canonical transcript exons

ENST00000368226 — 30 exons

Exon	Start	End
ENSE00001883289	127968785	127970280
ENSE00002170574	127996901	127996988
ENSE00002188417	127998720	127998904
ENSE00002210494	127973022	127973157
ENSE00002220256	127990769	127990885
ENSE00002241247	127991294	127991391
ENSE00002242528	127973664	127973827
ENSE00002243269	127992673	127992709
ENSE00002259739	127983242	127983377
ENSE00002260634	127982831	127982980
ENSE00002272479	127981116	127981289
ENSE00002277876	127976657	127976782
ENSE00002296359	127976923	127977054
ENSE00002302514	127985721	127985875
ENSE00002316125	127995462	127995538
ENSE00003466930	128009130	128009268
ENSE00003480723	128064758	128064794
ENSE00003508782	128322039	128322310
ENSE00003522631	128082437	128082638
ENSE00003533687	128397566	128397688
ENSE00003559558	128242521	128242602
ENSE00003570488	128083715	128083824
ENSE00003618154	128520259	128520599
ENSE00003625813	128240035	128240150
ENSE00003641852	128067519	128067792
ENSE00003648694	128218922	128219096
ENSE00003657054	128089690	128089992
ENSE00003664146	128078813	128078918
ENSE00003679245	128005084	128005244
ENSE00003783990	128184432	128184725

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 99.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.1947 / max 3279.7436, expressed in 1522 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75484	55.9169	1504
75480	0.5937	330
75467	0.3289	34
75468	0.1483	31
75485	0.1077	49
75481	0.0992	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	99.10	gold quality
colonic epithelium	UBERON:0000397	94.90	gold quality
gall bladder	UBERON:0002110	94.82	gold quality
duodenum	UBERON:0002114	93.91	gold quality
calcaneal tendon	UBERON:0003701	93.65	gold quality
superior frontal gyrus	UBERON:0002661	93.52	gold quality
islet of Langerhans	UBERON:0000006	93.31	gold quality
rectum	UBERON:0001052	93.16	gold quality
stromal cell of endometrium	CL:0002255	91.26	gold quality
pancreas	UBERON:0001264	91.25	gold quality
stomach	UBERON:0000945	90.88	gold quality
prefrontal cortex	UBERON:0000451	90.86	gold quality
urinary bladder	UBERON:0001255	90.74	gold quality
liver	UBERON:0002107	90.21	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.03	gold quality
primary visual cortex	UBERON:0002436	89.96	gold quality
body of pancreas	UBERON:0001150	89.94	gold quality
body of stomach	UBERON:0001161	89.89	gold quality
placenta	UBERON:0001987	89.77	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.75	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.54	gold quality
smooth muscle tissue	UBERON:0001135	89.43	gold quality
frontal cortex	UBERON:0001870	89.21	gold quality
popliteal artery	UBERON:0002250	88.70	gold quality
tibial artery	UBERON:0007610	88.70	gold quality
tonsil	UBERON:0002372	88.64	gold quality
cerebral cortex	UBERON:0000956	88.57	gold quality
fundus of stomach	UBERON:0001160	88.52	gold quality
mucosa of stomach	UBERON:0001199	88.36	gold quality
cortical plate	UBERON:0005343	88.18	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	92.01
E-CURD-119	yes	13.58
E-ANND-3	yes	8.92
E-GEOD-99795	no	17.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SMAD3, SMAD4

miRNA regulators (miRDB)

149 targeting PTPRK, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 34)

• RPTP-kappa is a key regulator of EGFR tyrosine phosphorylation and function in human keratinocytes (PMID:16263724)
• the crystal structure of catalytically active, monomeric D1 domain of RPTPkappa at 1.9 A. RPTPkappa is monomeric in solution and crystal structure. (PMID:16672235)
• EGF receptor is activated in human keratinocytes by oxidative inhibition of receptor-type protein-tyrosine phosphatase kappa by ultraviolet irradiation (PMID:16849327)
• EBNA1 apparently disables TGF-beta signaling, which subsequently decreases transcription of the PTPRK tumor suppressor (PMID:17720884)
• PTPRK influences transactivating activity of beta-catenin in non-tumoral and neoplastic cells by regulating the balance between signaling and adhesive beta-catenin, thus providing biochemical basis for the hypothesis of PTPRK as a tumor suppressor gene. (PMID:18276111)
• overexpression of GnT-V in a hepatoma cell line not only induced the addition of beta1,6 GlcNAc branch to N-glycan of RPTPkappa but also decreased the protein level of RPTPkappa (PMID:19236842)
• These data indicate that PPTRK positively regulates ERK1/2 phosphorylation, which impacts CD4(+) T cell development. (PMID:19800317)
• These data describe a novel mechanism of cross-talk between EGFR and TGF-beta pathways, in which RPTP-kappa functions to integrate growth-promoting and growth-inhibiting signaling pathways. (PMID:19864455)
• Our results suggest that GnT-V could decrease human hepatoma SMMC-7721 cell adhesion and promote cell proliferation partially through RPTPkappa. (PMID:19911372)
• PTPkappa was scissored by the processed form of proprotein convertase 5, and galectin-3 binding protein which is over-produced in colon cancer cells and tissues. (PMID:21094132)
• PTPRK is a negative regulator of adhesion, invasion, migration, and proliferation of breast cancer cells. (PMID:23552869)
• Tumor derived mutations of protein tyrosine phosphatase receptor type k affect its function and alter sensitivity to chemotherapeutics in glioma. (PMID:23696788)
• PTPRK showed lower mRNA expression in duodenal mucose of celiac disease patients. (PMID:23820479)
• High expression of PTPRK is associated with prostate cancer. (PMID:24002526)
• Findings strongly indicate that the tyrosine phosphorylation of CD133, which is dephosphorylated by PTPRK, regulates AKT signaling and has a critical role in colon cancer progression. (PMID:24882578)
• By regulating phosphorylation of SRC, RPTPkappa promotes the pathogenic action of rheumatoid arthritis fibroblast-like synoviocytes, mediating cross-activation of growth factor and inflammatory cytokine signalling by TGFbeta in RA FLS. (PMID:25378349)
• Notch and TGF-beta act in concert to stimulate induction of PTPRK, which suppresses EGFR activation in human keratinocytes. (PMID:25609089)
• PTPRK underexpression leads to STAT3 activation and contributes to nasal NK/T-cell lymphoma pathogenesis (PMID:25612622)
• PTPRK-RSPO3 fusions and RNF43 mutations were found to be characteristic genetic features of traditional serrated adenomas (TSAs). (PMID:26924569)
• PTPRK plays dual roles in coordinating angiogenesis. It plays a positive role in cell proliferation, adhesion and tubule formation, but suppresses cell migration, in particular, the FGF-promoted migration. (PMID:28259897)
• The present study identified RSPO fusion transcripts, including three novel transcripts, in one-third of colorectal Traditional serrated adenoma (TSA) and showed that PTPRK-RSPO3 fusions were the predominant cause of RSPO overexpression in colorectal TSA. (PMID:28543708)
• Study found a significant association between PTPRK genetic variants and the risk and age at onset of Alzheimer’s disease in two independent samples, and provided initial evidence of several genetic variants in PTPRK influencing the risk of cancer and cholesterol levels. (PMID:28987514)
• PTPRK was identified as a direct target of miR-1260b, and PTPRK expression was inversely correlated with miR-1260b in non-small cell lung cancer cell lines and clinical tissues (PMID:29628123)
• Study show that RAS at the Golgi is selectively activated by apoptogenic stimuli and antagonizes cell survival by suppressing ERK activity through the induction of PTPRkappa, which targets CRAF for dephosphorylation. RAS oncogenic potential is strictly dependent on its sublocalization, with Golgi complex-located RAS antagonizing tumor development. (PMID:30185827)
• These results suggested that PTPRK functions as a novel tumor suppressor in NSCLC, and its suppressive ability may be involved in STAT3 activation. (PMID:30838170)
• The authors report here that the homophilic receptor PTPRK is stabilized at cell-cell contacts in epithelial cells. PTPRK directly and selectively dephosphorylates at least five substrates, including Afadin, PARD3 and delta-catenin family members, which are all important cell-cell adhesion regulators. (PMID:30924770)
• Knockdown of PTPRK potentiates the pro-oncogenic CD133-AKT pathway in colon cancer cells. (PMID:30947381)
• the lower PTPRK expression was observed in Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) positive cancer stem cells (CSCs) population, suggesting the role of PTPRK downregulation in primary as well as acquired resistance to cytotoxic drugs. (PMID:31027318)
• The tumor suppressor PTPRK promotes ZNRF3 internalization and is required for Wnt inhibition in the Spemann organizer. (PMID:31934854)
• Simulation of multiple microenvironments shows a pivot role of RPTPs on the control of Epithelial-to-Mesenchymal Transition. (PMID:33068671)
• A MET-PTPRK kinase-phosphatase rheostat controls ZNRF3 and Wnt signaling. (PMID:34590584)
• Investigation of cell signalings and therapeutic targets in PTPRK-RSPO3 fusion-positive colorectal cancer. (PMID:36129915)
• Determinants of receptor tyrosine phosphatase homophilic adhesion: Structural comparison of PTPRK and PTPRM extracellular domains. (PMID:36436563)
• PTPRK, an EGFR Phosphatase, Is Decreased in CeD Biopsies and Intestinal Organoids. (PMID:36611909)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptprk	ENSDARG00000063416
danio_rerio		ENSDARG00000115646
mus_musculus	Ptprk	ENSMUSG00000019889
rattus_norvegicus	Ptprk	ENSRNOG00000047605

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), PTPRR (ENSG00000153233), 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 kappa — Q15262 (reviewed: Q15262)

All UniProt accessions (10): Q15262, E9PGC5, E9PMV4, E9PRW2, H0Y6P5, H0Y6V4, H0YD44, H0YDP9, Q5TG12, Q6P493

UniProt curated annotations — full annotation on UniProt →

Function. Regulation of processes involving cell contact and adhesion such as growth control, tumor invasion, and metastasis. Negative regulator of EGFR signaling pathway. Forms complexes with beta-catenin and gamma-catenin/plakoglobin. Beta-catenin may be a substrate for the catalytic activity of PTPRK/PTP-kappa.

Subcellular location. Cell junction. Adherens junction. Cell membrane.

Tissue specificity. High levels in lung, brain and colon; less in liver, pancreas, stomach, kidney, placenta and mammary carcinoma.

Post-translational modifications. This protein undergoes proteolytic processing.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q15262-1	1	yes
Q15262-2	2
Q15262-3	3
Q15262-4	4

RefSeq proteins (6): NP_001129120, NP_001278910, NP_001278911, NP_001278912, NP_001278913, NP_002835* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000242	PTP_cat	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR000998	MAM_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR016130	Tyr_Pase_AS	Active_site
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050348	Protein-Tyr_Phosphatase	Family
IPR057598	Fn3_PTPRU	Domain

Pfam: PF00041, PF00102, PF00629, PF07679, PF23144

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 (101 total): strand 41, helix 16, glycosylation site 12, domain 8, sequence conflict 7, binding site 3, splice variant 3, active site 2, topological domain 2, signal peptide 1, chain 1, turn 1, site 1, modified residue 1, transmembrane region 1, disulfide bond 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2C7S	X-RAY DIFFRACTION	1.95
8A1F	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15262-F1	82.64	0.53

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 (3): 1082 (phosphocysteine intermediate); 1376 (phosphocysteine intermediate); 643–644 (cleavage)

Ligand- & substrate-binding residues (3): 1050; 1082–1088; 1126

Post-translational modifications (1): 856

Disulfide bonds (1): 216–270

Glycosylation sites (12): 101, 140, 211, 416, 424, 436, 462, 552, 586, 590, 607, 690

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-182971	EGFR downregulation

MSigDB gene sets: 356 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, RRAGTTGT_UNKNOWN, GOBP_CELLULAR_RESPONSE_TO_UV, PAL_PRMT5_TARGETS_UP, GOBP_KERATINOCYTE_PROLIFERATION, GCANCTGNY_MYOD_Q6, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOZGIT_ESR1_TARGETS_DN, GOBP_FOCAL_ADHESION_ASSEMBLY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOCC_CELL_SURFACE, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GOBP_NEUROGENESIS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_JUNCTION_ORGANIZATION

GO Biological Process (16): protein dephosphorylation (GO:0006470), cell adhesion (GO:0007155), signal transduction (GO:0007165), transforming growth factor beta receptor signaling pathway (GO:0007179), negative regulation of cell population proliferation (GO:0008285), negative regulation of keratinocyte proliferation (GO:0010839), cell migration (GO:0016477), negative regulation of cell migration (GO:0030336), neuron projection development (GO:0031175), protein localization to cell surface (GO:0034394), cellular response to reactive oxygen species (GO:0034614), cellular response to UV (GO:0034644), negative regulation of cell cycle (GO:0045786), negative regulation of DNA-templated transcription (GO:0045892), focal adhesion assembly (GO:0048041), dephosphorylation (GO:0016311)

GO Molecular Function (8): protein tyrosine phosphatase activity (GO:0004725), transmembrane receptor protein tyrosine phosphatase activity (GO:0005001), beta-catenin binding (GO:0008013), protein kinase binding (GO:0019901), gamma-catenin binding (GO:0045295), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (10): centriole (GO:0005814), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), adherens junction (GO:0005912), cell surface (GO:0009986), membrane (GO:0016020), cell junction (GO:0030054), leading edge membrane (GO:0031256), sperm head-tail coupling apparatus (GO:0120212), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by EGFR	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cellular process	2
negative regulation of cellular process	2
protein binding	2
dephosphorylation	1
protein modification process	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cell population proliferation	1
regulation of cell population proliferation	1
regulation of keratinocyte proliferation	1
keratinocyte proliferation	1
negative regulation of epithelial cell proliferation	1
cell motility	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
neuron development	1
plasma membrane bounded cell projection organization	1
intracellular protein localization	1
response to reactive oxygen species	1
cellular response to oxidative stress	1
cellular response to oxygen-containing compound	1
response to UV	1
cellular response to light stimulus	1
cell cycle	1
regulation of cell cycle	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
cell-substrate junction assembly	1
cell-matrix adhesion	1
phosphate-containing compound metabolic process	1
phosphoprotein phosphatase activity	1
protein tyrosine phosphatase activity	1
transmembrane receptor protein phosphatase activity	1

Protein interactions and networks

STRING

1709 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPRK	RSPO2	Q6UXX9	791
PTPRK	PDIK1L	Q8N165	740
PTPRK	MAP3K21	Q5TCX8	733
PTPRK	GUCY2F	P51841	716
PTPRK	RSPO3	Q9BXY4	700
PTPRK	MYLK2	Q9H1R3	690
PTPRK	PTS	Q03393	604
PTPRK	CDH17	Q12864	602
PTPRK	EGFR	P00533	583
PTPRK	CTNNB1	P35222	581
PTPRK	EIF3E	P60228	575
PTPRK	GORAB	Q5T7V8	525
PTPRK	AKT2	P31751	518
PTPRK	THEMIS	Q8N1K5	510
PTPRK	BMP7	P18075	503

IntAct

115 interactions, top by confidence:

A	B	Type	Score
ARL4C	RGS12	psi-mi:“MI:0914”(association)	0.640
ANKRD46	ATRN	psi-mi:“MI:0914”(association)	0.640
LOX	PTPRK	psi-mi:“MI:0915”(physical association)	0.580
PTPRK	LOX	psi-mi:“MI:0915”(physical association)	0.580
RPL28	MAGEB2	psi-mi:“MI:0914”(association)	0.560
PTPRK	TK1	psi-mi:“MI:0915”(physical association)	0.550
CLEC4A	SEMA7A	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
DEFA5	NUDT19	psi-mi:“MI:0914”(association)	0.530
PTPRU	GOLIM4	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
SLC39A9	B4GALT5	psi-mi:“MI:0914”(association)	0.530
MMP26	SLC25A20	psi-mi:“MI:0914”(association)	0.530
CMA1	MANBA	psi-mi:“MI:0914”(association)	0.530
LGALS1	LAMA5	psi-mi:“MI:0914”(association)	0.530
EVA1B	NRP1	psi-mi:“MI:0914”(association)	0.530
GPRC5B	STXBP3	psi-mi:“MI:0914”(association)	0.530
ZNF785	TRIO	psi-mi:“MI:0914”(association)	0.530
DSCAM	PTPRK	psi-mi:“MI:0915”(physical association)	0.400
DSCAML1	PTPRK	psi-mi:“MI:0915”(physical association)	0.400
GADD45A	PTPRK	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (337): PTPRK (Affinity Capture-MS), PTPRK (Affinity Capture-MS), PTPRK (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), ATRN (Affinity Capture-MS), CACNA2D2 (Affinity Capture-MS), ECE1 (Affinity Capture-MS), CES3 (Affinity Capture-MS), TCTN2 (Affinity Capture-MS), LRP1B (Affinity Capture-MS), INSR (Affinity Capture-MS), PXDN (Affinity Capture-MS), FRAS1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), LAMA5 (Affinity Capture-MS)

ESM2 similar proteins: A0A1S4GGP7, B1Q236, B8V7Q1, B8VIW9, F1QSQ0, F8W3X3, G5EDK5, H2A0L8, O02466, O15943, O44386, O44730, P28827, P34616, P35822, P55289, P70408, Q02763, Q02858, Q03600, Q03763, Q06807, Q09165, Q15262, Q19319, Q24247, Q24298, Q5RJH3, Q60ZN5, Q61495, Q68SP4, Q6W3B0, Q7TMD7, Q7TSF0, Q7TSF1, Q86SJ6, Q86WI1, Q8JHW2, Q8VHN7, Q8WXG9

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

5 interactions.

A	Effect	B	Mechanism
PTPRK	“up-regulates activity”	ZNRF3	dephosphorylation
PTPRK	“down-regulates activity”	STAT3	dephosphorylation
PTPRK	unknown	EGFR	dephosphorylation
PTPRK	“down-regulates activity”	PROM1	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 138 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
Signaling by SCF-KIT	6	16.0×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	5	28.3×	5e-04
T cell costimulation	6	18.1×	5e-04
semaphorin-plexin signaling pathway	5	16.2×	4e-03
negative regulation of T cell receptor signaling pathway	5	14.8×	4e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 3 cancer types — BLCA, CCRCC, NSCLC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	150
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

9242 predictions. Top by Δscore:

Variant	Effect	Δscore
6:127970281:C:CC	acceptor_gain	1.0000
6:127970288:A:AC	acceptor_gain	1.0000
6:127970288:A:C	acceptor_gain	1.0000
6:127970292:C:CT	acceptor_gain	1.0000
6:127973017:CTCA:C	donor_loss	1.0000
6:127973019:CACC:C	donor_loss	1.0000
6:127973020:A:AC	donor_gain	1.0000
6:127973021:C:CC	donor_gain	1.0000
6:127973021:C:CG	donor_loss	1.0000
6:127973021:CCG:C	donor_gain	1.0000
6:127973153:CATTT:C	acceptor_gain	1.0000
6:127973154:ATTT:A	acceptor_gain	1.0000
6:127973155:TTT:T	acceptor_gain	1.0000
6:127973155:TTTCT:T	acceptor_loss	1.0000
6:127973156:TT:T	acceptor_gain	1.0000
6:127973158:C:CC	acceptor_gain	1.0000
6:127973158:CTGAA:C	acceptor_loss	1.0000
6:127973159:T:G	acceptor_loss	1.0000
6:127973165:C:CT	acceptor_gain	1.0000
6:127973166:A:T	acceptor_gain	1.0000
6:127976655:A:AC	donor_gain	1.0000
6:127976655:ACT:A	donor_gain	1.0000
6:127976656:C:CC	donor_gain	1.0000
6:127976656:CT:C	donor_gain	1.0000
6:127976656:CTC:C	donor_gain	1.0000
6:127976795:CGTTT:C	acceptor_gain	1.0000
6:127976799:T:C	acceptor_gain	1.0000
6:127976799:T:TC	acceptor_gain	1.0000
6:127981114:A:AC	donor_gain	1.0000
6:127981114:ACGT:A	donor_gain	1.0000

AlphaMissense

9493 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:127976685:C:G	R1313P	1.000
6:127976988:A:G	W1259R	1.000
6:127976988:A:T	W1259R	1.000
6:127981285:A:G	L1180P	1.000
6:127982944:C:G	A1141P	1.000
6:127982956:C:G	A1137P	1.000
6:127983252:A:T	V1125D	1.000
6:127983257:A:C	N1123K	1.000
6:127983257:A:T	N1123K	1.000
6:127983264:C:G	R1121P	1.000
6:127983265:G:T	R1121S	1.000
6:127983285:A:T	V1114D	1.000
6:127983300:T:A	D1109V	1.000
6:127983300:T:C	D1109G	1.000
6:127983300:T:G	D1109A	1.000
6:127983301:C:G	D1109H	1.000
6:127983303:A:T	V1108D	1.000
6:127983321:G:T	A1102D	1.000
6:127983322:C:G	A1102P	1.000
6:127983330:A:G	L1099P	1.000
6:127983333:A:C	M1098R	1.000
6:127983353:G:C	C1091W	1.000
6:127983355:A:G	C1091R	1.000
6:127983357:C:T	G1090D	1.000
6:127983358:C:G	G1090R	1.000
6:127983366:C:T	G1087E	1.000
6:127983367:C:G	G1087R	1.000
6:127983367:C:T	G1087R	1.000
6:127983372:C:A	G1085V	1.000
6:127983372:C:T	G1085D	1.000

dbSNP variants (sampled 300 via entrez): RS1000009045 (6:128412236 G>A), RS1000010379 (6:128325018 C>G,T), RS1000013842 (6:128080971 C>T), RS1000021043 (6:128278680 A>G), RS1000023139 (6:127971521 A>G), RS1000031402 (6:128121713 T>C), RS1000037038 (6:128240910 A>G), RS1000039582 (6:128056429 CTT>C,CT,CTTT,CTTTT,CTTTTT), RS1000044264 (6:128281245 T>A), RS1000048695 (6:128118188 T>C), RS1000055639 (6:128434501 C>A), RS1000062402 (6:128182662 A>T), RS1000066305 (6:128393559 G>A), RS1000067551 (6:128375674 T>C), RS1000072396 (6:128428480 C>T)

Disease associations

OMIM: gene MIM:602545 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST000612_24	Celiac disease	3.000000e-14
GCST001198_54	Multiple sclerosis	6.000000e-09
GCST002541_57	Menarche (age at onset)	2.000000e-09
GCST004132_4	Crohn’s disease	7.000000e-06
GCST004862_120	Itch intensity from mosquito bite adjusted by bite size	9.000000e-06
GCST005038_67	Allergic disease (asthma, hay fever or eczema)	2.000000e-10
GCST005209_1	Hodgkin’s lymphoma	2.000000e-08
GCST005211_2	Nodular sclerosis Hodgkin lymphoma	4.000000e-06
GCST005523_23	Celiac disease	1.000000e-18
GCST006268_514	Reaction time	1.000000e-08
GCST006617_4	Uterine fibroid size (maximum volume)	4.000000e-07
GCST007798_78	Asthma	7.000000e-15
GCST007800_72	Asthma (childhood onset)	2.000000e-15
GCST008151_90	Waist circumference	7.000000e-07
GCST008160_90	Waist circumference	7.000000e-07
GCST008477_2	Emphysema annual change measurement in smokers (adjusted lung density)	6.000000e-06
GCST008916_127	Asthma	1.000000e-11
GCST009391_79	Metabolite levels	1.000000e-06
GCST009720_41	Asthma	3.000000e-11
GCST009798_84	Asthma	3.000000e-10
GCST009874_4	Celiac disease	2.000000e-20
GCST010042_77	Asthma	2.000000e-17
GCST010043_146	Asthma	9.000000e-19
GCST010654_2	Arterial stiffness (brachial-femoral pulse wave velocity)	5.000000e-07
GCST012167_7	Adiponectin levels	7.000000e-06
GCST90014325_3	Asthma	7.000000e-11

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0008393	reaction time measurement
EFO:0009410	uterine fibroid measurement
EFO:0007626	emphysema imaging measurement
EFO:0004517	arterial stiffness measurement
EFO:0004502	adiponectin measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

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

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, decreases expression	5
Aflatoxin B1	decreases methylation, affects expression, decreases expression	4
bisphenol A	affects cotreatment, increases methylation, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Acetaminophen	decreases expression, increases expression, affects response to substance	3
Cisplatin	decreases expression, increases reaction	3
Valproic Acid	affects expression, decreases expression	3
methacrylaldehyde	decreases expression, increases oxidation, increases abundance, affects cotreatment	2
Acrolein	affects cotreatment, decreases expression, increases oxidation, increases abundance	2
Estradiol	affects expression, affects cotreatment, increases expression	2
Ozone	affects cotreatment, decreases expression, increases oxidation, increases abundance	2
Tobacco Smoke Pollution	affects expression, increases methylation	2
Cadmium Chloride	increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression, increases oxidation	1
deoxynivalenol	decreases expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
tanshinone	decreases expression	1
nickel chloride	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
cupric chloride	decreases expression	1
coumarin	increases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1H4	Abcam A-549 PTPRK KO 2	Cancer cell line	Male
CVCL_B2PM	Abcam A-549 PTPRK KO 1	Cancer cell line	Male
CVCL_TH68	HAP1 PTPRK (-) 1	Cancer cell line	Male
CVCL_TH69	HAP1 PTPRK (-) 2	Cancer cell line	Male
CVCL_TH70	HAP1 PTPRK (-) 3	Cancer cell line	Male
CVCL_TH71	HAP1 PTPRK (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome