PTPRZ1

Summary

PTPRZ1 (protein tyrosine phosphatase receptor type Z1, HGNC:9685) is a protein-coding gene on chromosome 7q31.32, encoding Receptor-type tyrosine-protein phosphatase zeta (P23471). Protein tyrosine phosphatase that negatively regulates oligodendrocyte precursor proliferation in the embryonic spinal cord.

This gene encodes a member of the receptor protein tyrosine phosphatase family. Expression of this gene is restricted to the central nervous system (CNS), and it may be involved in the regulation of specific developmental processes in the CNS. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 5803 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 327 total
• Druggable target: yes
• MANE Select transcript: NM_002851

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9685
Approved symbol	PTPRZ1
Name	protein tyrosine phosphatase receptor type Z1
Location	7q31.32
Locus type	gene with protein product
Status	Approved
Aliases	PTP18, RPTPB, phosphacan
Ensembl gene	ENSG00000106278
Ensembl biotype	protein_coding
OMIM	176891
Entrez	5803

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 17 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000393386, ENST00000449182, ENST00000468641, ENST00000470504, ENST00000471837, ENST00000474500, ENST00000483028, ENST00000483995, ENST00000489114, ENST00000650681, ENST00000650728, ENST00000650826, ENST00000651065, ENST00000651320, ENST00000651390, ENST00000651841, ENST00000651842, ENST00000651863, ENST00000652054, ENST00000652298, ENST00000652708, ENST00000878583, ENST00000878584, ENST00000912208, ENST00000912209

RefSeq mRNA: 5 — MANE Select: NM_002851 NM_001206838, NM_001206839, NM_001369395, NM_001369396, NM_002851

CCDS: CCDS34740, CCDS56505, CCDS94187

Canonical transcript exons

ENST00000393386 — 30 exons

Exon	Start	End
ENSE00000719430	122044422	122044568
ENSE00000882003	122053910	122054038
ENSE00000882004	122054941	122055087
ENSE00000919395	121967951	121968130
ENSE00000919399	121983665	121983822
ENSE00000919400	121983967	121984117
ENSE00000919404	122010334	122013889
ENSE00001136915	122042608	122042743
ENSE00001136943	122028552	122028643
ENSE00001288229	122059753	122059888
ENSE00001288259	122051866	122051939
ENSE00001288262	122051428	122051521
ENSE00001288280	122040816	122040979
ENSE00001288286	122039454	122039588
ENSE00001288312	122034095	122034115
ENSE00001288344	122019124	122019268
ENSE00001288360	122004614	122004660
ENSE00001288365	121997880	121998006
ENSE00001288373	121996382	121996566
ENSE00001288392	121976785	121976851
ENSE00001288397	121976173	121976268
ENSE00001288403	121972541	121972692
ENSE00001958628	122061080	122062036
ENSE00002400146	122058800	122058942
ENSE00003465205	121928156	121928221
ENSE00003544318	122036600	122036682
ENSE00003618007	122034282	122034378
ENSE00003625049	122031474	122031559
ENSE00003682109	122038755	122038889
ENSE00003850169	121873161	121873557

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 99.83.

FANTOM5 (CAGE): breadth broad, TPM avg 42.6034 / max 3473.5458, expressed in 563 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80825	20.5633	491
80824	19.9468	496
80823	0.9771	231
80827	0.4824	183
80826	0.2825	94
80828	0.1684	54
80832	0.1134	67
80831	0.0694	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.83	gold quality
ganglionic eminence	UBERON:0004023	99.59	gold quality
cortical plate	UBERON:0005343	99.40	gold quality
endothelial cell	CL:0000115	98.70	gold quality
amygdala	UBERON:0001876	98.38	gold quality
CA1 field of hippocampus	UBERON:0003881	98.27	gold quality
cranial nerve II	UBERON:0000941	98.22	gold quality
caudate nucleus	UBERON:0001873	97.94	gold quality
nucleus accumbens	UBERON:0001882	97.79	gold quality
embryo	UBERON:0000922	97.73	gold quality
corpus callosum	UBERON:0002336	97.70	gold quality
lateral globus pallidus	UBERON:0002476	97.63	gold quality
substantia nigra	UBERON:0002038	97.53	gold quality
subthalamic nucleus	UBERON:0001906	97.48	gold quality
temporal lobe	UBERON:0001871	97.47	gold quality
midbrain	UBERON:0001891	97.39	gold quality
Ammon’s horn	UBERON:0001954	97.31	gold quality
hypothalamus	UBERON:0001898	97.29	gold quality
putamen	UBERON:0001874	97.25	gold quality
substantia nigra pars compacta	UBERON:0001965	97.04	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.03	gold quality
inferior vagus X ganglion	UBERON:0005363	96.73	gold quality
entorhinal cortex	UBERON:0002728	96.68	gold quality
medulla oblongata	UBERON:0001896	96.67	gold quality
superior vestibular nucleus	UBERON:0007227	96.58	gold quality
telencephalon	UBERON:0001893	96.48	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.34	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.20	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.20	gold quality
cingulate cortex	UBERON:0003027	96.16	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	5138.66
E-HCAD-35	yes	3292.40
E-MTAB-9435	yes	2706.80
E-GEOD-180759	yes	2700.95
E-HCAD-25	yes	2573.43
E-MTAB-6819	yes	1402.01
E-HCAD-56	yes	909.71
E-MTAB-8221	yes	270.20
E-CURD-114	yes	65.87
E-GEOD-84465	yes	30.88
E-ANND-3	yes	15.13
E-MTAB-9388	yes	14.21
E-MTAB-8060	no	52.34

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, ELK1, EPAS1

miRNA regulators (miRDB)

76 targeting PTPRZ1, 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-429	100.00	73.44	2698
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-199A-3P	99.75	70.48	929

Literature-anchored findings (GeneRIF, showing 40)

• PTPRZ1 has a role in oligodendrocyte survival and in recovery from demyelinating disease (PMID:12355066)
• RPTPzeta has a novel role in regulating glioblastoma cell motility (PMID:14555979)
• RPTPbeta/zeta is a receptor of HARP in human endothelial cells (PMID:15797857)
• PTPRA and PTPRZ may have roles in gastric cancer progression including lymphovascular invasion and liver/peritoneal dissemination (PMID:16338072)
• In AZ-521 cells, which mainly express RPTPbeta, VacA, after binding to RPTPbeta in non-lipid raft microdomains on the cell surface, is localized with RPTPbeta in lipid rafts in a temperature- and VacA concentration-dependent process. (PMID:17030583)
• Data suggest that increased tyrosine phosphorylation of receptor protein tyrosine phosphatase beta/zeta substrates in pleiotrophin-stimulated cells is sufficient to coordinately stimulate the functions needed for an epithelial-mesenchymal transition. (PMID:17098867)
• Midkine, pleiotrophin (PTN), and their receptors syndecan-3 and receptor protein tyrosine phosphatase beta/zeta, were highly expressed in the striatum during developmen (PMID:17368428)
• phosphorylation of ALK in PTN-stimulated cells is mediated through the PTN/RPTPbeta/zeta signaling pathway (PMID:17681947)
• the PTN/RPTPbeta/zeta signaling pathway may be constitutively activated and potentially function to constitutively activate ALK in human breast cancer (PMID:17706593)
• the effect of the shorter basic peptide P(122-131) on DU145 cells, which express HARP and its receptor RPTPB, suggested interference, under anchorage-independent conditions, of P(122-131) with a HARP autocrine loop in an RPTPB -dependent fashion. (PMID:17727841)
• Pleiotrophin receptor (PTPRZ1) is expressed in embryonic stem cells and mediates important signals for survival, proliferation, and maintenance of pluripotency state. (PMID:17823238)
• results from the immunohistochemical analyses of rPTPbeta/zeta expression should prompt further evaluation of this protein as a novel oligodendroglioma marker. (PMID:18003890)
• PTPRZ1 is unlikely to be related to the development of schizophrenia in the Japanese population (PMID:18186075)
• the cleavage sites in the extracellular juxtamembrane region of Ptprz by tumor necrosis factor-alpha converting enzyme and matrix metalloproteinase 9. (PMID:18713734)
• GnT-Vb-mediated glycosylation of RPTPbeta promotes galectin-1 binding and RPTPbeta levels of retention on the cell surface. (PMID:18838383)
• PTN through its receptor RPTPbeta/zeta is a mediator of the stimulatory effects of eNOS/NO on human endothelial and prostate cancer cell migration (PMID:19058221)
• these data suggest that alpha(v)beta(3) is a key molecule that determines the stimulatory or inhibitory effect of pleiotrophin on cell migration. (PMID:19141530)
• phosphacan was present in the evolving astroglial scar after human traumatic spinal cord injury, and, therefore, might play an important role in the blockade of successful CNS regeneration. (PMID:19604403)
• findings implicate PTPRG, PTPRZ and CNTNs as a group of receptors and ligands involved in the manifold recognition events that underlie the construction of neural networks (PMID:20133774)
• preferential activation of PTPRZ1 by HIF-2 results at least in part from cooperative binding of HIF-2 and ELK1 to nearby sites on the PTPRZ1 promoter region (PMID:20224786)
• results demonstrate that P(122-131) inhibits biological activities that are related to the induction of a transformed phenotype in PCa cells, by interacing with RPTPbeta-zeta and interfering with other pleiotrophin receptors (PMID:20738847)
• RPTP-beta is a key regulator of Met function. (PMID:21454675)
• molecular basis for the substrate recognition of Ptprz. (PMID:21890632)
• report the cocrystal structure of the carbonic anhydrase-like domain of PTPRZ bound to tandem Ig repeats of CNTN1 and binding assays to show that PTPRZ binds specifically to CNTN1 expressed at the surface of oligodendrocyte precursor cells (PMID:21969550)
• Studies indicate that RPTPzeta is an RPTP for which a link between ligand-dependent dimerization and inhibition of the intracellular tyrosine phosphatase activity has been clearly established. (PMID:22682003)
• Enhanced RPTPbeta/zeta signaling can contribute to schizophrenia phenotypes and support both construct and face validity for PTPRZ1-transgenic mice as a model for multiple schizophrenia phenotypes. (PMID:22832403)
• Loss of RPTPZ promotes prostate cancer metastasi. (PMID:23060448)
• The results of this study suggested that pleiotrophin inhibition of PTPRZ1 contributes to the homeostatic self-renewal of OPCs and that this process is mediated by the tonic activation of beta-catenin/TCF-dependent transcription. (PMID:23100427)
• PTPRZ1 was highly expressed in human neuroendocrine tumor tissues and PTPRZ1 is an oncogenic tyrosine phosphatase in small-cell lung carcinoma. (PMID:23170925)
• Receptor-type Protein tyrosine phosphatase beta regulates met phosphorylation and function in head and neck squamous cell carcinoma. (PMID:23226095)
• PTPRZ1 is affected in a contiguous gene deletion syndrome (PMID:23570448)
• Protein tyrosine phosphatase zeta enhances proliferation by increasing beta-catenin nuclear expression in VHL-inactive human renal cell carcinoma cells. (PMID:23588815)
• Data suggest that CSF-1R-independent actions of IL-34 via receptor-type protein-tyrosine phosphatase zeta (PTP-zeta) might be considered in evaluating IL-34 roles in development and disease. (PMID:23744080)
• Ligand independent activation of anaplastic lymphoma kinase (ALK) results when the cytokine pleiotrophin (PTN) interacts with its receptor, the receptor protein tyrosine phosphatase beta-zeta (RPTPbeta-zeta). Review) (PMID:23777859)
• 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)
• Data indicate that the fusion arose from translocation events involving introns 3 or 8 of protein tyrosine phosphatase, receptor-type, Z polypeptide 1 (PTPRZ1) and intron 1 of hepatocyte growth factor receptor MET. (PMID:25135958)
• Distinct domains of PTPRZ-B are differentially required for migration and proliferation of glioma cells, respectively. (PMID:25238264)
• Data indicate that enhanced MET oncoprotein RNA expression by fusion with receptor-type tyrosine-protein phosphatase zeta (PTPRZ1). (PMID:25935522)
• Confirm contribution of PTPRZ1, and especially PTPRQ, in CRC carcinogenesis and demonstrated that PTPRQ expression is correlated with KRAS mutation. (PMID:26851024)
• these data indicate that PTN-PTPRZ-A signaling controls the timing of oligodendrocyte precursor cell differentiation in vivo, in which the CS moiety of PTPRZ receptors maintains them in a monomeric active state until its ligand binding. (PMID:27445335)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptprz1b	ENSDARG00000020871
danio_rerio	ptprz1a	ENSDARG00000051814
mus_musculus	Ptprz1	ENSMUSG00000068748
rattus_norvegicus	Ptprz1	ENSRNOG00000006030

Paralogs (35): PTPRN (ENSG00000054356), PTPRU (ENSG00000060656), PTPN3 (ENSG00000070159), PTPN21 (ENSG00000070778), PTPN18 (ENSG00000072135), PTPN23 (ENSG00000076201), PTPRH (ENSG00000080031), PTPRC (ENSG00000081237), PTPN4 (ENSG00000088179), PTPRS (ENSG00000105426), 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), PTPRT (ENSG00000196090), PTPN1 (ENSG00000196396), PTPN20 (ENSG00000204179)

Protein

Protein identifiers

Receptor-type tyrosine-protein phosphatase zeta — P23471 (reviewed: P23471)

Alternative names: Protein-tyrosine phosphatase receptor type Z polypeptide 1, Protein-tyrosine phosphatase receptor type Z polypeptide 2, R-PTP-zeta-2

All UniProt accessions (11): P23471, A0A494C036, A0A494C055, A0A494C087, A0A494C0U4, A0A494C0V2, A0A494C1B4, A0A494C1F0, A0A494C1H9, A0A494C1J5, A0A494C1R4

UniProt curated annotations — full annotation on UniProt →

Function. Protein tyrosine phosphatase that negatively regulates oligodendrocyte precursor proliferation in the embryonic spinal cord. Required for normal differentiation of the precursor cells into mature, fully myelinating oligodendrocytes. May play a role in protecting oligondendrocytes against apoptosis. May play a role in the establishment of contextual memory, probably via the dephosphorylation of proteins that are part of important signaling cascades.

Subunit / interactions. The carbonic-anhydrase like domain interacts with CNTN1 (contactin). Interacts with PTN. Interaction with PTN promotes formation of homooligomers; oligomerization impairs phosphatase activity. Interacts (via chondroitin sulfate chains) with MDK (via C-terminal); this interaction is inhibited by PTN; this interaction promotes neuronal migration.

Subcellular location. Cell membrane. Secreted Secreted.

Tissue specificity. Specifically expressed in the central nervous system, where it is localized in the Purkinje cell layer of the cerebellum, the dentate gyrus, and the subependymal layer of the anterior horn of the lateral ventricle. Developmentally regulated in the brain.

Similarity. Belongs to the protein-tyrosine phosphatase family. Receptor class 5 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P23471-1	1	yes
P23471-2	2
P23471-3	3

RefSeq proteins (5): NP_001193767, NP_001193768, NP_001356324, NP_001356325, NP_002842* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000242	PTP_cat	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR001148	CA_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR016130	Tyr_Pase_AS	Active_site
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR036398	CA_dom_sf	Homologous_superfamily
IPR041887	Alpha_CARP_receptor-type	Domain
IPR050348	Protein-Tyr_Phosphatase	Family

Pfam: PF00041, PF00102, PF00194

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 (136 total): strand 39, glycosylation site 24, helix 21, compositionally biased region 9, region of interest 7, turn 7, modified residue 5, domain 4, binding site 3, sequence variant 3, sequence conflict 3, topological domain 2, disulfide bond 2, splice variant 2, signal peptide 1, chain 1, active site 1, site 1, transmembrane region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8FN9	X-RAY DIFFRACTION	1.8
5AWX	X-RAY DIFFRACTION	1.86
8FN8	X-RAY DIFFRACTION	1.89
3JXF	X-RAY DIFFRACTION	2
3S97	X-RAY DIFFRACTION	2.3
5H08	X-RAY DIFFRACTION	2.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23471-F1	55.23	0.24

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): 1933 (phosphocysteine intermediate); 2223 (ancestral active site)

Ligand- & substrate-binding residues (3): 1901; 1933–1939; 1977

Post-translational modifications (5): 637, 639, 1684, 1687, 2055

Disulfide bonds (2): 56–240, 133–264

Glycosylation sites (24): 105, 134, 223, 232, 324, 381, 497, 501, 552, 587, 602, 629, 637, 677, 997, 1017, 1050, 1082, 1122, 1457 …

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-449836	Other interleukin signaling
R-HSA-9851151	MDK and PTN in ALK signaling

MSigDB gene sets: 232 (showing top): GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_COGNITION, GOBP_BEHAVIOR, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, MODULE_255, JAEGER_METASTASIS_DN, TTTGTAG_MIR520D, GOBP_POSITIVE_REGULATION_OF_GLIAL_CELL_DIFFERENTIATION, MODULE_317, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_MYELINATION, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (14): hematopoietic progenitor cell differentiation (GO:0002244), protein dephosphorylation (GO:0006470), signal transduction (GO:0007165), axonogenesis (GO:0007409), central nervous system development (GO:0007417), learning or memory (GO:0007611), neuron projection development (GO:0031175), regulation of myelination (GO:0031641), peptidyl-tyrosine dephosphorylation (GO:0035335), negative regulation of neuron apoptotic process (GO:0043524), oligodendrocyte differentiation (GO:0048709), positive regulation of oligodendrocyte differentiation (GO:0048714), regulation of oligodendrocyte progenitor proliferation (GO:0070445), dephosphorylation (GO:0016311)

GO Molecular Function (6): protein tyrosine phosphatase activity (GO:0004725), transmembrane receptor protein tyrosine phosphatase activity (GO:0005001), integrin binding (GO:0005178), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (6): extracellular region (GO:0005576), plasma membrane (GO:0005886), synapse (GO:0045202), perineuronal net (GO:0072534), membrane (GO:0016020), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Interleukins	1
Signaling by ALK	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of cellular process	2
cellular anatomical structure	2
hemopoiesis	1
cell differentiation	1
dephosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
nervous system development	1
system development	1
behavior	1
cognition	1
neuron development	1
plasma membrane bounded cell projection organization	1
myelination	1
regulation of nervous system development	1
protein dephosphorylation	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
central nervous system development	1
glial cell differentiation	1
positive regulation of glial cell differentiation	1
oligodendrocyte differentiation	1
regulation of oligodendrocyte differentiation	1
oligodendrocyte progenitor proliferation	1
regulation of neural precursor cell proliferation	1
phosphate-containing compound metabolic process	1
phosphoprotein phosphatase activity	1
protein tyrosine phosphatase activity	1
transmembrane receptor protein phosphatase activity	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
phosphatase activity	1

Protein interactions and networks

STRING

2306 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPRZ1	PTN	P21246	998
PTPRZ1	ACAN	P16112	990
PTPRZ1	BCAN	Q96GW7	988
PTPRZ1	NCAN	O14594	972
PTPRZ1	VCAN	P13611	951
PTPRZ1	MDK	P21741	909
PTPRZ1	NRCAM	Q92823	906
PTPRZ1	NCAM1	P13591	875
PTPRZ1	CNTNAP1	P78357	853
PTPRZ1	HMGB1	P09429	765
PTPRZ1	CNTN1	Q12860	752
PTPRZ1	SDC1	P18827	743
PTPRZ1	HAPLN2	Q9GZV7	739
PTPRZ1	PTS	Q03393	710
PTPRZ1	NFASC	O94856	702

IntAct

148 interactions, top by confidence:

A	B	Type	Score
ITGAV	ITGB3	psi-mi:“MI:0915”(physical association)	0.930
PTPRZ1	CNTN1	psi-mi:“MI:0915”(physical association)	0.610
PTPRZ1	CNTN1	psi-mi:“MI:0407”(direct interaction)	0.610
ALK	PTPRZ1	psi-mi:“MI:0915”(physical association)	0.540
PTPRZ1	ALK	psi-mi:“MI:0203”(dephosphorylation reaction)	0.540
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
ITGB3	PTPRZ1	psi-mi:“MI:0403”(colocalization)	0.460
PTPRZ1	ITGB3	psi-mi:“MI:0915”(physical association)	0.460
PTPRZ1	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
PDZD2	PTPRZ1	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRZ1	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRZ1	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRZ1	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRZ1	SNTG1	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRZ1	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRZ1	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
DLG3	PTPRZ1	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRZ1	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRZ1	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRZ1	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRZ1	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRZ1	FRMPD2	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRZ1	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRZ1	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRZ1	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRZ1	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (53): PTPRZ1 (Affinity Capture-MS), PTPRZ1 (Affinity Capture-Western), VEGFA (Affinity Capture-Western), VEGFA (Co-localization), PTN (Co-localization), PTPRZ1 (Affinity Capture-Western), PTPRZ1 (Affinity Capture-MS), IL34 (Reconstituted Complex), PTPRZ1 (Biochemical Activity), PTPRZ1 (Co-purification), LGALS1 (Affinity Capture-Western), PTPRZ1 (Affinity Capture-Western), PTPRZ1 (Affinity Capture-Western), PTPRZ1 (Affinity Capture-Western), FYN (Two-hybrid)

ESM2 similar proteins: A0JPP4, B7ZCC9, B9EKR1, E9Q7X6, J3KML8, O00592, O57604, P13611, P23471, P30005, P34910, P52549, P70628, Q01036, Q06093, Q1XI86, Q28858, Q2TA21, Q2TBJ9, Q3MIW9, Q3TNW5, Q3TYV2, Q5XI99, Q62059, Q62656, Q62781, Q68FD9, Q69558, Q6MG22, Q6R8J2, Q7TST5, Q80XH2, Q86TY3, Q8BT18, Q8BUE7, Q8C633, Q8IZF6, Q8N3K9, Q8VD58, Q8WXI7

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

4 interactions.

A	Effect	B	Mechanism
PTPRZ1	down-regulates	ALK	dephosphorylation
EPAS1	“up-regulates quantity by expression”	PTPRZ1	“transcriptional regulation”
PTPRZ1	“up-regulates activity”	CTNNB1	dephosphorylation
PTPRZ1	“down-regulates activity”	ARHGAP35	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 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
Dopamine Neurotransmitter Release Cycle	5	35.0×	2e-05
Assembly and cell surface presentation of NMDA receptors	9	32.2×	1e-09
Neurexins and neuroligins	11	30.5×	2e-11
Protein-protein interactions at synapses	7	26.2×	9e-07
Non-integrin membrane-ECM interactions	6	13.0×	3e-04
RHOA GTPase cycle	6	6.3×	4e-03
Extracellular matrix organization	7	6.2×	3e-03
RAF/MAP kinase cascade	7	6.0×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	53.9×	4e-11
protein localization to synapse	6	47.4×	6e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	7	35.8×	4e-07
receptor clustering	5	32.2×	5e-05
protein-containing complex assembly	10	11.7×	2e-06
cell-cell adhesion	11	11.5×	7e-07
protein localization to plasma membrane	6	6.7×	7e-03
chemical synaptic transmission	7	5.6×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	280
Likely benign	17
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

4395 predictions. Top by Δscore:

Variant	Effect	Δscore
7:121893414:G:GT	donor_gain	1.0000
7:121928152:ATAG:A	acceptor_loss	1.0000
7:121928153:T:G	acceptor_gain	1.0000
7:121928153:TA:T	acceptor_loss	1.0000
7:121928154:A:AG	acceptor_gain	1.0000
7:121928154:AG:A	acceptor_loss	1.0000
7:121928154:AGATT:A	acceptor_gain	1.0000
7:121928155:G:GT	acceptor_gain	1.0000
7:121928155:GA:G	acceptor_gain	1.0000
7:121928155:GAT:G	acceptor_gain	1.0000
7:121928155:GATT:G	acceptor_gain	1.0000
7:121928155:GATTG:G	acceptor_gain	1.0000
7:121928217:TACAG:T	donor_loss	1.0000
7:121928218:ACAG:A	donor_loss	1.0000
7:121928219:CAG:C	donor_loss	1.0000
7:121928220:AG:A	donor_loss	1.0000
7:121928221:GGTAA:G	donor_loss	1.0000
7:121928222:G:GA	donor_loss	1.0000
7:121928223:T:A	donor_loss	1.0000
7:121967945:CCCTA:C	acceptor_loss	1.0000
7:121967947:CTAG:C	acceptor_loss	1.0000
7:121967948:TAG:T	acceptor_loss	1.0000
7:121967949:AGGAG:A	acceptor_loss	1.0000
7:121967950:G:GA	acceptor_loss	1.0000
7:121967950:GGA:G	acceptor_gain	1.0000
7:121968043:G:GG	donor_gain	1.0000
7:121972539:A:AG	acceptor_gain	1.0000
7:121972539:AGT:A	acceptor_gain	1.0000
7:121972539:AGTG:A	acceptor_gain	1.0000
7:121972540:G:GG	acceptor_gain	1.0000

AlphaMissense

15278 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:122038791:G:C	G1802R	1.000
7:122040873:T:A	W1899R	1.000
7:122040873:T:C	W1899R	1.000
7:122040970:T:A	V1931D	1.000
7:122040977:C:G	C1933W	1.000
7:122053976:T:A	W2107R	1.000
7:122053976:T:C	W2107R	1.000
7:121996447:T:A	W332R	0.999
7:121996447:T:C	W332R	0.999
7:121996449:G:C	W332C	0.999
7:121996449:G:T	W332C	0.999
7:121997940:T:C	C392R	0.999
7:121997942:C:G	C392W	0.999
7:122019231:T:C	C1651R	0.999
7:122036669:C:A	A1785D	0.999
7:122036678:T:A	V1788D	0.999
7:122038783:C:A	A1799D	0.999
7:122038786:C:A	A1800D	0.999
7:122038792:G:A	G1802D	0.999
7:122038821:T:A	W1812R	0.999
7:122038821:T:C	W1812R	0.999
7:122038864:T:A	I1826K	0.999
7:122038873:T:C	L1829P	0.999
7:122039472:T:A	W1841R	0.999
7:122039472:T:C	W1841R	0.999
7:122040875:G:C	W1899C	0.999
7:122040875:G:T	W1899C	0.999
7:122040975:T:C	C1933R	0.999
7:122040976:G:A	C1933Y	0.999
7:122040978:A:C	S1934R	0.999

dbSNP variants (sampled 300 via entrez): RS1000023669 (7:122034558 C>A,T), RS1000027996 (7:121912575 C>G,T), RS1000039311 (7:122013633 T>C), RS1000062124 (7:121919412 T>C), RS1000088927 (7:121919110 C>T), RS1000089243 (7:121920834 A>C,G), RS1000098004 (7:121978916 G>A), RS1000131853 (7:122008700 G>A), RS1000150936 (7:121959398 G>A,C), RS1000156484 (7:121913558 A>G), RS1000158799 (7:122028135 G>A), RS1000171128 (7:121938651 C>G), RS1000171862 (7:121894530 T>C), RS1000180172 (7:122041011 A>G), RS1000185245 (7:122048132 T>A,C)

Disease associations

OMIM: gene MIM:176891 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004494_1	Hand grip strength	6.000000e-07
GCST004744_28	Lung adenocarcinoma	3.000000e-06
GCST006979_213	Heel bone mineral density	5.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006941	grip strength measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295730 (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

ChEMBL bioactivities

5 potent at pChembl≥5 of 5 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.00	IC50	100	nM	CHEMBL4285054
7.00	IC50	100	nM	CHEMBL4278170
6.10	IC50	800	nM	CHEMBL4286807
5.46	IC50	3500	nM	CHEMBL4286401
5.30	IC50	5000	nM	CHEMBL4293314

PubChem BioAssay actives

5 with measured affinity, of 43 total; 5 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[4-(trifluoromethylsulfanyl)phenyl]-N-[[4-(trifluoromethylsulfanyl)phenyl]methyl]methanamine	1402953: Inhibition of human recombinant PTPRZ1 using pNPP as substrate by fluorescence spectrometric analysis	ic50	0.1000	uM
1-(trifluoromethylsulfanyl)-4-[[4-(trifluoromethylsulfanyl)phenoxy]methyl]benzene	1402953: Inhibition of human recombinant PTPRZ1 using pNPP as substrate by fluorescence spectrometric analysis	ic50	0.1000	uM
2-[4-(trifluoromethylsulfanyl)phenyl]-N-[[4-(trifluoromethylsulfanyl)phenyl]methyl]acetamide	1402953: Inhibition of human recombinant PTPRZ1 using pNPP as substrate by fluorescence spectrometric analysis	ic50	0.8000	uM
1-(trifluoromethylsulfonyl)-4-[[4-(trifluoromethylsulfonyl)phenoxy]methyl]benzene	1402951: Inhibition of PTPRZ1 (unknown origin) using pNPP as substrate preincubated for 15 mins followed by substrate addition measured after 10 mins by spectrophotometric analysis	ic50	3.5000	uM
N-benzyl-4-(trifluoromethylsulfanyl)aniline	1402953: Inhibition of human recombinant PTPRZ1 using pNPP as substrate by fluorescence spectrometric analysis	ic50	5.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	5
sodium arsenite	affects methylation, increases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Calcitriol	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
tungsten carbide	affects binding, decreases expression	1
methylmercuric chloride	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects methylation	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
3,4-dichloroaniline	decreases expression	1
arsenite	decreases expression, decreases methylation	1
cobaltous chloride	decreases expression	1
CGP 52608	increases reaction, affects binding	1
methyl-beta-cyclodextrin	affects localization, decreases reaction	1
dimethylarsinous acid	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
LDN 193189	increases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Bacterial Toxins	decreases reaction, affects localization	1
Benzo(a)pyrene	increases methylation	1
Carbamazepine	affects expression	1
Cobalt	affects binding, decreases expression	1
Cytarabine	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Diuron	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4253959	Binding	Inhibition of PTPRZ1 in human HeLa cells assessed as increase in EGF-induced tryrosine phosphorylation at 0.1 to 10 uM incubated for 10 mins after EGF stimulation for 10 mins by ELISA relative to control	Development of inhibitors of receptor protein tyrosine phosphatase β/ζ (PTPRZ1) as candidates for CNS disorders. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1MA	HyCyte NCI-H520 KO-hPTPRZ1	Cancer cell line	Male

Clinical trials (associated diseases)

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