PTPRT

Summary

PTPRT (protein tyrosine phosphatase receptor type T, HGNC:9682) is a protein-coding gene on chromosome 20q12-q13.11, encoding Receptor-type tyrosine-protein phosphatase T (O14522). May be involved in both signal transduction and cellular adhesion in the CNS. In precision oncology, PTPRT Promoter Hypermethylation confers sensitivity to JSI-124 + Stattic in Head And Neck Squamous Cell Carcinoma (CIViC Level D).

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 intracellular catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP (MAM) domain, Ig-like and fibronectin type III-like repeats. The protein domain structure and the expression pattern of the mouse counterpart of this PTP suggest its roles in both signal transduction and cellular adhesion in the central nervous system. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported.

Source: NCBI Gene 11122 — RefSeq curated summary.

At a glance

• GWAS associations: 27
• Clinical variants (ClinVar): 272 total — 6 likely-pathogenic
• Phenotypes (HPO): 2
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer driver (intOGen): activating (oncogene-like) across 7 cancer types
• MANE Select transcript: NM_007050

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9682
Approved symbol	PTPRT
Name	protein tyrosine phosphatase receptor type T
Location	20q12-q13.11
Locus type	gene with protein product
Status	Approved
Aliases	RPTPrho, KIAA0283
Ensembl gene	ENSG00000196090
Ensembl biotype	protein_coding
OMIM	608712
Entrez	11122

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000356100, ENST00000373184, ENST00000373187, ENST00000373190, ENST00000373193, ENST00000373198, ENST00000373201, ENST00000485499, ENST00000617474

RefSeq mRNA: 5 — MANE Select: NM_007050 NM_001394024, NM_001394025, NM_001394026, NM_007050, NM_133170

CCDS: CCDS42874, CCDS68127

Canonical transcript exons

ENST00000373187 — 31 exons

Exon	Start	End
ENSE00000662140	42791195	42791466
ENSE00001127453	42885807	42885932
ENSE00001127981	42780218	42780299
ENSE00001289737	42118403	42118500
ENSE00001290774	42110333	42110487
ENSE00001291858	42248687	42248822
ENSE00001293417	42128754	42128830
ENSE00001295075	42756462	42756636
ENSE00001296212	42236229	42236258
ENSE00001298748	42104569	42104718
ENSE00001299388	42084682	42084845
ENSE00001303056	42315723	42315996
ENSE00001303836	42352084	42352285
ENSE00001304010	42161352	42161542
ENSE00001304469	42115199	42115315
ENSE00001304649	42098421	42098552
ENSE00001305193	42472266	42472562
ENSE00001310313	42119935	42119971
ENSE00001314457	42102124	42102297
ENSE00001315163	42677866	42678159
ENSE00001315899	42106786	42106921
ENSE00001316436	42282489	42282525
ENSE00001317939	42081882	42082017
ENSE00001320070	42141915	42142002
ENSE00001320663	42771435	42771550
ENSE00001322891	42350628	42350730
ENSE00001324256	42199240	42199388
ENSE00001326438	42085728	42085853
ENSE00001329888	42448220	42448329
ENSE00003936403	43189646	43189906
ENSE00003936780	42072756	42080932

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 90.29.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2477 / max 70.6912, expressed in 193 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187297	0.9455	168
187296	0.2846	99
187295	0.0177	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 10	UBERON:0013541	90.29	gold quality
middle temporal gyrus	UBERON:0002771	88.05	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.11	gold quality
frontal pole	UBERON:0002795	84.97	gold quality
superior frontal gyrus	UBERON:0002661	84.84	gold quality
prefrontal cortex	UBERON:0000451	84.44	gold quality
Brodmann (1909) area 46	UBERON:0006483	83.90	gold quality
primary visual cortex	UBERON:0002436	83.84	gold quality
frontal cortex	UBERON:0001870	83.03	gold quality
orbitofrontal cortex	UBERON:0004167	82.81	gold quality
postcentral gyrus	UBERON:0002581	82.60	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.04	gold quality
neocortex	UBERON:0001950	81.97	gold quality
bronchial epithelial cell	CL:0002328	81.69	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.37	gold quality
epithelium of bronchus	UBERON:0002031	81.10	gold quality
occipital lobe	UBERON:0002021	80.79	gold quality
parietal lobe	UBERON:0001872	80.63	gold quality
right frontal lobe	UBERON:0002810	80.11	gold quality
bronchus	UBERON:0002185	79.95	gold quality
entorhinal cortex	UBERON:0002728	79.82	gold quality
cingulate cortex	UBERON:0003027	79.25	gold quality
cerebral cortex	UBERON:0000956	79.18	gold quality
anterior cingulate cortex	UBERON:0009835	79.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.24	gold quality
cortical plate	UBERON:0005343	77.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.86	gold quality
telencephalon	UBERON:0001893	75.72	gold quality
CA1 field of hippocampus	UBERON:0003881	74.96	silver quality
right uterine tube	UBERON:0001302	73.82	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	1446.23
E-ENAD-27	yes	116.74
E-HCAD-35	yes	69.03
E-GEOD-81608	yes	18.81
E-GEOD-83139	yes	8.83
E-ANND-3	yes	7.83
E-MTAB-5061	no	3.21

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYCN

Literature-anchored findings (GeneRIF, showing 18)

• alterations of the PTPRT-mediated signaling pathway by PTPRT phosphatase domain mutation may not play a critical role in the development of common human cancers (PMID:17223850)
• STAT3 is a substrate of receptor protein tyrosine phosphatase T (PMID:17360477)
• brain-specific PTPRT regulates synapse formation through interaction with cell adhesion molecules, and this function and the phosphatase activity are attenuated through tyrosine phosphorylation by the synaptic tyrosine kinase Fyn. (PMID:19816407)
• Data show that paxillin is a direct substrate of PTPRT and that PTPRT specifically regulates paxillin phosphorylation at tyrosine residue 88(Y88). (PMID:20133777)
• [review] High-throughput mutational analysis identifies loss-of-function mutations in six PTPs in human colon cancers, providing critical cancer genetics evidence that PTPs can act as tumour suppressor genes. (PMID:21517784)
• The catalytic domain point mutants show a decreased thermal and thermodynamic stability and decreased activation energy relative to phosphatase activity, when compared to wild- type (PMID:22389709)
• tumor-specific mutational events in the PTPRT gene can serve as direct drivers for tumor growth by inducing hyperactivation of STAT3, a potent oncogenic transcription factor and PTPRT substrate (PMID:24395800)
• Data show that hepatitis B virus X protein mutant HBxDelta127 enhances proliferation of hepatoma cells through up-regulating miR-215 targeting protein tyrosine phosphatase, receptor type T (PTPRT). (PMID:24434140)
• Data reported evidence that rs2866943 polymorphism in PTPRT 3’-UTR was involved in the occurrence of esophageal squamous cell carcinoma by acting as a protective factor while rs6029959 acts as a risk factor. (PMID:25967969)
• PTPRT promoter methylation is significantly associated with sensitivity to STAT3 inhibition in HNSCC cells, suggesting that PTPRT promoter methylation may serve as a predictive biomarker for responsiveness to STAT3 inhibitors in clinical development (PMID:25982282)
• The single cell genotyping not only confirmed the co-occurrence of the PTPRT, CAND1 and DOCK6 mutations in the same AML clone but also revealed a clonal hierarchy, as the PTPRT mutation was likely acquired after the CAND1 and DOCK6 mutations. (PMID:27244256)
• A novel de novo 20q13.11q13.12 microdeletion was found in a boy with neurodevelopmental disorders. The established function of the PTPRT gene suggests that haploinsuficiency of this gene may result in the clinical features observed in our patient: stereotype movements, nervous tics, social and emotional disturbances and attention-span deficits. (PMID:28796977)
• PTPRT epigenetic silencing defines lung cancer with STAT3 activation and can direct STAT3 targeted therapies. (PMID:31595832)
• Study revealed a significantly higher prevalence of PTPRT and JAK2 mutations in lung adenocarcinomas among African Americans compared with European Americans. Patients carrying these mutations have a concomitant increase in IL-6/STAT3 signaling and miR-21 expression. (PMID:31844068)
• PTPRT Could Be a Treatment Predictive and Prognostic Biomarker for Breast Cancer. (PMID:34414233)
• Association of PTPRT Mutations with Cancer Metastasis in Multiple Cancer Types. (PMID:35789644)
• Novel genetic variants linked to prelabor rupture of membranes among Chinese pregnant women. (PMID:37054626)
• Downregulation of PTPRT elevates the expression of survivin and promotes the proliferation, migration, and invasion of lung adenocarcinoma. (PMID:38216925)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptprt	ENSDARG00000074781
danio_rerio	ptprt	ENSDARG00000097572
mus_musculus	Ptprt	ENSMUSG00000053141
rattus_norvegicus	Ptprt	ENSRNOG00000032656

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), PTPRR (ENSG00000153233), PTPRD (ENSG00000153707), PTPRN2 (ENSG00000155093), PTPN13 (ENSG00000163629), PTPN9 (ENSG00000169410), PTPRM (ENSG00000173482), PTPN2 (ENSG00000175354), PTPN11 (ENSG00000179295), PTPN1 (ENSG00000196396), PTPN20 (ENSG00000204179)

Protein

Protein identifiers

Receptor-type tyrosine-protein phosphatase T — O14522 (reviewed: O14522)

Alternative names: Receptor-type tyrosine-protein phosphatase rho

All UniProt accessions (7): A0A075B6H0, A0A087X1J1, B1AJR6, B1AJR8, B1AJR9, B1AJS0, O14522

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in both signal transduction and cellular adhesion in the CNS.

Subcellular location. Membrane.

Tissue specificity. Expressed in colon, lung, heart and testis, as well as in fetal and adult brain. Not detected in muscle and peripheral blood leukocytes.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O14522-3	3	yes
O14522-1	1

RefSeq proteins (5): NP_001380953, NP_001380954, NP_001380955, NP_008981, NP_573400 (=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
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	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
IPR051622	R-tyr_protein_phosphatases	Family
IPR057598	Fn3_PTPRU	Domain

Pfam: PF00041, PF00102, PF00629, 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 (90 total): sequence variant 28, strand 12, helix 11, glycosylation site 10, domain 8, binding site 3, sequence conflict 3, active site 2, topological domain 2, splice variant 2, turn 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, transmembrane region 1, disulfide bond 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2OOQ	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14522-F1	83.99	0.55

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 (2): 1084 (phosphocysteine intermediate); 1378 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (3): 1052; 1084–1090; 1128

Post-translational modifications (1): 1208

Disulfide bonds (1): 213–267

Glycosylation sites (10): 78, 98, 137, 208, 421, 510, 547, 601, 654, 684

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 200 (showing top): BENPORATH_ES_WITH_H3K27ME3, MODULE_255, GOBP_RESPONSE_TO_PEPTIDE, TGCACTT_MIR519C_MIR519B_MIR519A, AAGTCCA_MIR422B_MIR422A, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, MODULE_317, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS, GOBP_CELL_CELL_ADHESION, SMID_BREAST_CANCER_LUMINAL_B_UP, CLIMENT_BREAST_CANCER_COPY_NUMBER_UP, GOBP_RESPONSE_TO_INTERLEUKIN_6, WANG_CISPLATIN_RESPONSE_AND_XPC_DN, TGAGATT_MIR216

GO Biological Process (10): protein dephosphorylation (GO:0006470), cell adhesion (GO:0007155), homophilic cell-cell adhesion (GO:0007156), signal transduction (GO:0007165), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), negative regulation of cell migration (GO:0030336), neuron projection development (GO:0031175), cellular response to interleukin-6 (GO:0071354), negative regulation of receptor signaling pathway via STAT (GO:1904893), dephosphorylation (GO:0016311)

GO Molecular Function (15): protein tyrosine phosphatase activity (GO:0004725), transmembrane receptor protein tyrosine phosphatase activity (GO:0005001), beta-catenin binding (GO:0008013), thiolester hydrolase activity (GO:0016790), protein phosphatase binding (GO:0019903), protein homodimerization activity (GO:0042803), alpha-catenin binding (GO:0045294), gamma-catenin binding (GO:0045295), cadherin binding (GO:0045296), alpha-actinin binding (GO:0051393), delta-catenin binding (GO:0070097), STAT family protein binding (GO:0097677), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (3): plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	4
cellular process	2
cellular anatomical structure	2
dephosphorylation	1
protein modification process	1
cell-cell adhesion	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
enzyme-linked receptor protein signaling pathway	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
response to interleukin-6	1
cellular response to cytokine stimulus	1
negative regulation of signal transduction	1
cell surface receptor signaling pathway via STAT	1
regulation of receptor signaling pathway via STAT	1
phosphate-containing compound metabolic process	1
phosphoprotein phosphatase activity	1
protein tyrosine phosphatase activity	1
transmembrane receptor protein phosphatase activity	1
hydrolase activity, acting on ester bonds	1
phosphatase binding	1
identical protein binding	1
protein dimerization activity	1
cell adhesion molecule binding	1
actinin binding	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

2324 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPRT	PTS	Q03393	723
PTPRT	CTNNB1	P35222	573
PTPRT	CDH1	P12830	519
PTPRT	PTPN14	Q15678	509
PTPRT	CSMD1	Q96PZ7	507
PTPRT	ADGRA1	Q86SQ6	458
PTPRT	LRP1B	Q9NZR2	442
PTPRT	KNDC1	Q76NI1	429
PTPRT	EXD2	Q9NVH0	423
PTPRT	PTPRU	P78399	418
PTPRT	PTPN13	Q12923	410
PTPRT	STAT3	P40763	406
PTPRT	CLSTN3	Q9BQT9	404
PTPRT	PTPN3	P26045	391
PTPRT	OTX2	P32243	383

IntAct

37 interactions, top by confidence:

A	B	Type	Score
PTPRT	PTPRT	psi-mi:“MI:0915”(physical association)	0.550
PTPRT	PTPRT	psi-mi:“MI:0914”(association)	0.550
DSCAM	PTPRT	psi-mi:“MI:0915”(physical association)	0.540
DSCAML1	PTPRT	psi-mi:“MI:0915”(physical association)	0.540
PTPRT	DSCAM	psi-mi:“MI:0407”(direct interaction)	0.540
DSCAML1	PTPRT	psi-mi:“MI:0407”(direct interaction)	0.540
PTPRT		psi-mi:“MI:0915”(physical association)	0.520
Nlgn1	PTPRT	psi-mi:“MI:0915”(physical association)	0.520
PTPRT	Nlgn2	psi-mi:“MI:0915”(physical association)	0.520
Nrxn1	PTPRT	psi-mi:“MI:0915”(physical association)	0.520
Nrxn3	PTPRT	psi-mi:“MI:0915”(physical association)	0.520
Nlgn2	PTPRT	psi-mi:“MI:0915”(physical association)	0.520
PTPRT	Nlgn1	psi-mi:“MI:0915”(physical association)	0.520
PTPRT	Nrxn1	psi-mi:“MI:0915”(physical association)	0.520
PTPRT	Nrxn3	psi-mi:“MI:0915”(physical association)	0.520
PTPRN	PTPRT	psi-mi:“MI:0915”(physical association)	0.510
PTPRT	PTPRN	psi-mi:“MI:0915”(physical association)	0.510
PTPRT	RMND1	psi-mi:“MI:0915”(physical association)	0.400
CD58	PTPRT	psi-mi:“MI:0915”(physical association)	0.400
GRB2	PTPRT	psi-mi:“MI:0915”(physical association)	0.400
Fyn	PTPRT	psi-mi:“MI:0915”(physical association)	0.400
EGFR	PTPRT	psi-mi:“MI:0915”(physical association)	0.370
ERBB2	PTPRT	psi-mi:“MI:0915”(physical association)	0.370
ERBB4	PTPRT	psi-mi:“MI:0915”(physical association)	0.370
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): PTPRT (Two-hybrid), PTPRT (Two-hybrid), PTPRT (Two-hybrid), PTPRT (Affinity Capture-MS), ATP2A2 (Affinity Capture-MS), PHKA1 (Proximity Label-MS), PHKB (Proximity Label-MS), PTPRT (Affinity Capture-MS), RMND1 (Affinity Capture-MS), PTPRT (Affinity Capture-MS), PTPRT (Affinity Capture-RNA), PTPRT (Affinity Capture-MS)

ESM2 similar proteins: A2AED3, B0CLX4, B2RU80, B3DK56, B3EX02, E2RK30, F1NWE3, O14522, O70458, O70535, O88488, P08922, P08941, P08F94, P0C5E4, P17948, P20352, P23467, P28827, P28828, P35822, P35969, P35992, P42702, P42703, P53767, P97378, Q15262, Q2EY13, Q2EY15, Q2VWP7, Q2VWP9, Q589G5, Q5RFR6, Q5VJ70, Q5VTL7, Q5XNR9, Q62959, Q63132, Q65Z14

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

4 interactions.

A	Effect	B	Mechanism
PTPRT	“down-regulates activity”	PXN	dephosphorylation
PTPRT	“down-regulates activity”	STAT3	dephosphorylation
FYN	“down-regulates activity”	PTPRT	phosphorylation

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 7 cancer types — ESCA, HCC, HNSC, MEL, OVT, PAAD, STAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	6
Uncertain significance	179
Likely benign	27
Benign	35

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
402164	NM_007050.6(PTPRT):c.1561-3C>T	Likely pathogenic
402165	NM_007050.6(PTPRT):c.206T>C (p.Val69Ala)	Likely pathogenic
545234	NC_000020.11:g.(?42232174)(42274201_?)del	Likely pathogenic
545235	NC_000020.11:g.(?42303583)(42488707_?)del	Likely pathogenic
545236	NC_000020.11:g.(?42461895)(42648116_?)del	Likely pathogenic
545237	NC_000020.11:g.(?42472130)(42562200_?)del	Likely pathogenic

SpliceAI

9270 predictions. Top by Δscore:

Variant	Effect	Δscore
20:42084680:A:AC	donor_gain	1.0000
20:42084681:C:CC	donor_gain	1.0000
20:42084703:C:A	donor_gain	1.0000
20:42084719:A:AC	donor_gain	1.0000
20:42084720:C:CC	donor_gain	1.0000
20:42085722:ACTT:A	donor_loss	1.0000
20:42085723:CTT:C	donor_loss	1.0000
20:42085724:TTAC:T	donor_loss	1.0000
20:42085725:TACCC:T	donor_loss	1.0000
20:42085726:A:AC	donor_gain	1.0000
20:42085726:AC:A	donor_gain	1.0000
20:42085727:C:CC	donor_gain	1.0000
20:42085727:CC:C	donor_gain	1.0000
20:42085849:CAGAA:C	acceptor_gain	1.0000
20:42085852:AA:A	acceptor_gain	1.0000
20:42098553:C:CC	acceptor_gain	1.0000
20:42102117:GGCTT:G	donor_loss	1.0000
20:42102118:GCTTA:G	donor_loss	1.0000
20:42102119:CTT:C	donor_loss	1.0000
20:42102120:TTA:T	donor_loss	1.0000
20:42102121:T:TG	donor_loss	1.0000
20:42102122:A:AC	donor_gain	1.0000
20:42102122:AC:A	donor_loss	1.0000
20:42102122:ACAT:A	donor_gain	1.0000
20:42102122:ACATC:A	donor_gain	1.0000
20:42102123:C:CA	donor_gain	1.0000
20:42102123:CA:C	donor_gain	1.0000
20:42102123:CAT:C	donor_gain	1.0000
20:42102123:CATC:C	donor_gain	1.0000
20:42102123:CATCC:C	donor_gain	1.0000

AlphaMissense

9472 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:42081913:C:G	R1414P	1.000
20:42084800:A:G	W1340R	1.000
20:42084800:A:T	W1340R	1.000
20:42084823:A:T	V1332D	1.000
20:42098486:A:G	W1261R	1.000
20:42098486:A:T	W1261R	1.000
20:42102293:A:G	L1182P	1.000
20:42104687:A:G	L1141P	1.000
20:42104694:C:G	A1139P	1.000
20:42106874:A:G	L1101P	1.000
20:42106901:C:T	G1092D	1.000
20:42106902:C:G	G1092R	1.000
20:42106916:C:T	G1087E	1.000
20:42106917:C:A	G1087W	1.000
20:42110335:G:C	C1084W	1.000
20:42110437:C:A	W1050C	1.000
20:42110437:C:G	W1050C	1.000
20:42110439:A:G	W1050R	1.000
20:42110439:A:T	W1050R	1.000
20:42115307:A:C	C997W	1.000
20:42115309:A:G	C997R	1.000
20:42118434:A:T	V984D	1.000
20:42118471:A:G	W972R	1.000
20:42118471:A:T	W972R	1.000
20:42315817:C:T	G682D	1.000
20:42315818:C:G	G682R	1.000
20:42315979:A:T	V628D	1.000
20:42448240:C:A	G514W	1.000
20:42448262:C:A	W506C	1.000
20:42448262:C:G	W506C	1.000

dbSNP variants (sampled 300 via entrez): RS1000009150 (20:42294739 C>T), RS1000009835 (20:42600731 A>G), RS1000010258 (20:42924485 T>C), RS1000010999 (20:42180637 A>G), RS1000012470 (20:42244439 C>A,G), RS1000015621 (20:42699293 C>A,T), RS1000017104 (20:43084809 G>A), RS1000021145 (20:42100009 C>A), RS1000021903 (20:42973048 G>T), RS1000023168 (20:42285724 T>C), RS1000024453 (20:42344305 C>G), RS1000026068 (20:42468878 C>T), RS1000027838 (20:42683017 T>C), RS1000028020 (20:42812276 A>C,T), RS1000028446 (20:43085172 A>G)

Disease associations

OMIM: gene MIM:608712 | disease phenotypes: MIM:181500, MIM:209850

GenCC curated gene-disease

Mondo (4): schizophrenia (MONDO:0005090), autism (MONDO:0005260), intellectual disability (MONDO:0001071), autism spectrum disorder (MONDO:0005258)

Orphanet (3): NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0100753	Schizophrenia
HP:0000717	Autism

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST002127_37	Periodontitis (Mean PAL)	9.000000e-06
GCST002304_13	Fractional exhaled nitric oxide (childhood)	2.000000e-06
GCST002304_8	Fractional exhaled nitric oxide (childhood)	8.000000e-06
GCST002498_14	Age-related nuclear cataracts	2.000000e-06
GCST002828_7	Urate levels in obese individuals	6.000000e-06
GCST002875_14	Diisocyanate-induced asthma	2.000000e-06
GCST003253_10	Microalbuminuria	4.000000e-06
GCST004068_51	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	2.000000e-06
GCST005236_4	Problematic alcohol use in trauma-exposed individuals	5.000000e-06
GCST006105_5	Eye morphology	6.000000e-06
GCST007017_20	Serum bilirubin levels x Mediterranean diet adherence interaction in metabolic syndrome	3.000000e-06
GCST007094_235	Diastolic blood pressure	2.000000e-09
GCST007099_194	Systolic blood pressure	2.000000e-08
GCST007817_2	Facial attractiveness (male raters)	6.000000e-07
GCST008152_72	Weight	2.000000e-06
GCST008162_6	Hip circumference	2.000000e-06
GCST008559_9	Anxiety and stress-related disorders	5.000000e-07
GCST009195_5	Temporal pole volume	8.000000e-06
GCST009391_991	Metabolite levels	4.000000e-06
GCST009514_6	Recurrence of mild malaria attacks	7.000000e-07
GCST009515_2	Recurrence of malaria infection (mild or asymptomatic)	4.000000e-07
GCST009524_199	Household income (MTAG)	6.000000e-09
GCST010396_238	Gut microbiota (bacterial taxa, hurdle binary method)	5.000000e-06
GCST010396_311	Gut microbiota (bacterial taxa, hurdle binary method)	6.000000e-06
GCST011743_67	HDL cholesterol levels in HIV infection	8.000000e-06
GCST012331_2	BMI x SSRI levels interaction in schizophrenia or bipolar disorder	2.000000e-08
GCST90000514_31	Gastroesophageal reflux disease	9.000000e-09

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0005536	nitric oxide exhalation measurement
EFO:0004531	urate measurement
EFO:0006995	response to diisocyanate
EFO:0008483	response to trauma exposure
EFO:0009458	alcohol use disorder measurement
EFO:0004570	bilirubin measurement
EFO:0008111	diet measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0009892	facial attractiveness measurement
EFO:0004338	body weight
EFO:0010098	stress-related disorder
EFO:0010475	deoxycholate measurement
EFO:0004952	disease recurrence
EFO:0009695	household income
EFO:0007874	gut microbiome measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004340	body mass index
EFO:0005658	response to selective serotonin reuptake inhibitor

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
PTPRT Promoter Hypermethylation	JSI-124 + Stattic	Head And Neck Squamous Cell Carcinoma	Sensitivity/Response	CIViC D	EID817

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

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases methylation, increases mutagenesis	2
terbufos	increases methylation	1
sodium arsenite	increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Amphotericin B	increases expression	1
Copper	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Fonofos	increases methylation	1
Niclosamide	decreases expression	1
Parathion	increases methylation	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Triclosan	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety