PTPRU

Summary

PTPRU (protein tyrosine phosphatase receptor type U, HGNC:9683) is a protein-coding gene on chromosome 1p35.3, encoding Receptor-type tyrosine-protein phosphatase U (Q92729). Tyrosine-protein phosphatase which dephosphorylates CTNNB1.

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. This PTP was thought to play roles in cell-cell recognition and adhesion. Studies of the similar gene in mice suggested the role of this PTP in early neural development. The expression of this gene was reported to be regulated by phorbol myristate acetate (PMA) or calcium ionophore in Jurkat T lymphoma cells. Alternatively spliced transcript variants have been reported.

Source: NCBI Gene 10076 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nephrotic syndrome, type 6 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 23
• Clinical variants (ClinVar): 806 total — 5 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes
• MANE Select transcript: NM_133178

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9683
Approved symbol	PTPRU
Name	protein tyrosine phosphatase receptor type U
Location	1p35.3
Locus type	gene with protein product
Status	Approved
Aliases	PTPRO, hPTP-J, PCP-2, FMI, PTP
Ensembl gene	ENSG00000060656
Ensembl biotype	protein_coding
OMIM	602454
Entrez	10076

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000345512, ENST00000373779, ENST00000415600, ENST00000428026, ENST00000460170, ENST00000465525, ENST00000492954, ENST00000493601, ENST00000526080, ENST00000527027, ENST00000531385, ENST00000940165, ENST00000940166, ENST00000940167, ENST00000940168

RefSeq mRNA: 4 — MANE Select: NM_133178 NM_001195001, NM_005704, NM_133177, NM_133178

CCDS: CCDS334, CCDS335, CCDS44098, CCDS53290

Canonical transcript exons

ENST00000373779 — 30 exons

Exon	Start	End
ENSE00000762209	29311456	29311553
ENSE00000762212	29315372	29315507
ENSE00000762213	29316002	29316151
ENSE00000762214	29317748	29317921
ENSE00001065073	29279456	29279657
ENSE00001065079	29279012	29279121
ENSE00001065086	29258505	29258776
ENSE00001065087	29259261	29259342
ENSE00001065089	29259449	29259564
ENSE00001065097	29259870	29260044
ENSE00001156797	29255275	29255406
ENSE00001345409	29275448	29275756
ENSE00001826408	29325599	29326800
ENSE00003475729	29303855	29304045
ENSE00003475960	29325191	29325326
ENSE00003480679	29312552	29312706
ENSE00003485069	29260610	29260903
ENSE00003490691	29305352	29305428
ENSE00003511895	29320685	29320825
ENSE00003523919	29282676	29282949
ENSE00003562207	29323631	29323788
ENSE00003574518	29291869	29292026
ENSE00003580932	29283940	29283976
ENSE00003587397	29311643	29311759
ENSE00003614207	29280039	29280141
ENSE00003615782	29284731	29284869
ENSE00003633306	29323371	29323496
ENSE00003644823	29310744	29310780
ENSE00003681096	29304774	29304849
ENSE00003849939	29236522	29236717

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 95.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.1289 / max 120.2588, expressed in 1360 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1859	6.8801	1311
1860	0.8627	408
201440	0.2308	104
1862	0.1085	65
1861	0.0468	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endocervix	UBERON:0000458	95.46	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.98	gold quality
ectocervix	UBERON:0012249	91.96	gold quality
tibial nerve	UBERON:0001323	91.66	gold quality
endometrium epithelium	UBERON:0004811	91.06	silver quality
sural nerve	UBERON:0015488	90.78	gold quality
cortical plate	UBERON:0005343	90.76	gold quality
nasal cavity epithelium	UBERON:0005384	90.38	gold quality
right uterine tube	UBERON:0001302	89.24	gold quality
trigeminal ganglion	UBERON:0001675	88.59	gold quality
nasal cavity mucosa	UBERON:0001826	88.03	gold quality
substantia nigra pars reticulata	UBERON:0001966	87.88	gold quality
substantia nigra pars compacta	UBERON:0001965	87.64	gold quality
minor salivary gland	UBERON:0001830	87.58	gold quality
adenohypophysis	UBERON:0002196	87.53	gold quality
right ovary	UBERON:0002118	87.19	gold quality
gastrocnemius	UBERON:0001388	87.16	gold quality
left ovary	UBERON:0002119	87.15	gold quality
body of uterus	UBERON:0009853	86.84	gold quality
right lung	UBERON:0002167	86.61	gold quality
muscle of leg	UBERON:0001383	86.51	gold quality
upper lobe of left lung	UBERON:0008952	86.46	gold quality
left uterine tube	UBERON:0001303	86.31	gold quality
prefrontal cortex	UBERON:0000451	86.15	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.09	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.95	gold quality
mouth mucosa	UBERON:0003729	85.72	gold quality
mucosa of stomach	UBERON:0001199	85.63	gold quality
upper lobe of lung	UBERON:0008948	85.60	gold quality
right frontal lobe	UBERON:0002810	85.52	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR4A2, PITX3, TAL1

miRNA regulators (miRDB)

77 targeting PTPRU, 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-4692	100.00	67.32	2066
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826

Literature-anchored findings (GeneRIF, showing 9)

• Expressed in a cell density-dependent fashion, PCP-2 interacts directly with its substrate beta-catenin, independent of the tyrosine phosphorylation state of beta-catenin. (PMID:12501215)
• Reduced expression of both synaptopodin and GLEPP1 is associated with poor response to steroid therapy in primary focal segmental glomerulosclerosis. (PMID:16564554)
• PCP-2 may play an important role in the maintenance of epithelial integrity, and a loss of its regulatory function may be an alternative mechanism for activating beta-catenin signaling. (PMID:16574648)
• Gene expression of GLEPP-1 is decreased in podocytes from women with preeclampsia. (PMID:19528353)
• High PTPRU expression is associated with glioma growth and motility. (PMID:24876153)
• PTPRU is required for gastric cancer cell proliferation and migration. (PMID:25337216)
• Transwell and wound-healing assays showed that miR-574-5p promotes the migration and invasion of NSCLC cells. Furthermore, miR-574-5p enhanced the tyrosine phosphorylation of beta-catenin by repressing PTPRU expression in vitro. (PMID:27761023)
• The receptor PTPRU is a redox sensitive pseudophosphatase. (PMID:32591542)
• PTPRU, a quiescence-induced receptor tyrosine phosphatase negatively regulates osteogenic differentiation of human mesenchymal stem cells. (PMID:36332481)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptprua	ENSDARG00000092638
danio_rerio	ptprub	ENSDARG00000101081
mus_musculus	Ptpru	ENSMUSG00000028909
rattus_norvegicus	Ptpru	ENSRNOG00000013515

Paralogs (35): PTPRN (ENSG00000054356), 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), PTPRT (ENSG00000196090), PTPN1 (ENSG00000196396), PTPN20 (ENSG00000204179)

Protein

Protein identifiers

Receptor-type tyrosine-protein phosphatase U — Q92729 (reviewed: Q92729)

Alternative names: Pancreatic carcinoma phosphatase 2, Protein-tyrosine phosphatase J, Protein-tyrosine phosphatase pi, Protein-tyrosine phosphatase receptor omicron, Receptor-type protein-tyrosine phosphatase psi

All UniProt accessions (1): Q92729

UniProt curated annotations — full annotation on UniProt →

Function. Tyrosine-protein phosphatase which dephosphorylates CTNNB1. Regulates CTNNB1 function both in cell adhesion and signaling. May function in cell proliferation and migration and play a role in the maintenance of epithelial integrity. May play a role in megakaryocytopoiesis.

Subunit / interactions. Forms homooligomeric complexes which mediate cell homotypic adhesion. Interacts (via the cytoplasmic juxtamembrane domain) with CTNNB1; may mediate interaction with the cadherin/catenin adhesion complex. Interacts with KIT. May interact with AP3B1.

Subcellular location. Cell junction. Cell membrane.

Tissue specificity. High levels in brain, pancreas, and skeletal muscle; less in colon, kidney, liver, stomach, and uterus; not expressed in placenta and spleen. Also detected in heart, prostate, lung, thymus, testis and ovary. Ubiquitously expressed in brain. Expressed by hematopoietic stem cells.

Post-translational modifications. The extracellular domain is proteolytically processed through cleavage within the fibronectin type-III 4 domain. In addition to the 190 kDa full-length protein, proteolytic products of 100 kDa, 80 kDa and 73 kDa are observed. N-glycosylated. Phosphorylated on tyrosine residues upon activation of KIT with stem cell factor (SCF). The 73 kDa proteolytic product is not phosphorylated.

Induction. Up-regulated upon cell contact (at protein level). Down-regulated by phorbol ester (at protein level) and calcium ionophore but up-regulated by phorbol ester in megakaryocytic cells.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q92729-1	1	yes
Q92729-2	2
Q92729-3	3
Q92729-4	4, PTPRO

RefSeq proteins (4): NP_001181930, NP_005695, NP_573438, NP_573439* (*=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
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 (68 total): strand 12, domain 8, sequence conflict 8, helix 8, sequence variant 6, modified residue 4, splice variant 4, binding site 3, glycosylation site 3, region of interest 2, active site 2, topological domain 2, mutagenesis site 2, signal peptide 1, chain 1, disulfide bond 1, transmembrane region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6SUB	X-RAY DIFFRACTION	1.72
6SUC	X-RAY DIFFRACTION	1.97

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92729-F1	81.84	0.51

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): 1085 (phosphocysteine intermediate); 1380 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (3): 1053; 1085–1091; 1129

Post-translational modifications (4): 848, 853, 863, 865

Disulfide bonds (1): 210–264

Glycosylation sites (3): 75, 410, 685

Mutagenesis-validated functional residues (2):

Position	Phenotype
1085	loss of phosphatase activity toward ctnnb1. loss of the inhibitory effect on ctnnb1 transcriptional activity without eff
1380	no effect on phosphatase activity toward ctnnb1. loss of the inhibitory effect on ctnnb1 transcriptional activity withou

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1433557	Signaling by SCF-KIT

MSigDB gene sets: 558 (showing top): ATF_B, GOBP_EPITHELIUM_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CELL_CHEMOTAXIS, GOBP_REGULATION_OF_CELL_CELL_ADHESION_MEDIATED_BY_CADHERIN, GOBP_RETINAL_GANGLION_CELL_AXON_GUIDANCE, GOBP_RENAL_SYSTEM_PROCESS_INVOLVED_IN_REGULATION_OF_BLOOD_VOLUME, MODULE_64, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_NEUROGENESIS, CREBP1_Q2

GO Biological Process (15): protein dephosphorylation (GO:0006470), cell adhesion (GO:0007155), signal transduction (GO:0007165), cell surface receptor protein tyrosine phosphatase signaling pathway (GO:0007185), negative regulation of cell population proliferation (GO:0008285), negative regulation of cell migration (GO:0030336), animal organ regeneration (GO:0031100), neuron projection development (GO:0031175), homotypic cell-cell adhesion (GO:0034109), protein localization to cell surface (GO:0034394), response to glucocorticoid (GO:0051384), negative regulation of canonical Wnt signaling pathway (GO:0090090), positive regulation of cell-cell adhesion mediated by cadherin (GO:2000049), dephosphorylation (GO:0016311), cell differentiation (GO:0030154)

GO Molecular Function (6): protein tyrosine phosphatase activity (GO:0004725), transmembrane receptor protein tyrosine phosphatase activity (GO:0005001), beta-catenin binding (GO:0008013), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (4): plasma membrane (GO:0005886), cell-cell junction (GO:0005911), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by Receptor Tyrosine Kinases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
dephosphorylation	1
protein modification process	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
enzyme-linked receptor protein signaling pathway	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
regeneration	1
animal organ development	1
neuron development	1
plasma membrane bounded cell projection organization	1
cell-cell adhesion	1
intracellular protein localization	1
response to corticosteroid	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
positive regulation of cell-cell adhesion	1
cell-cell adhesion mediated by cadherin	1
regulation of cell-cell adhesion mediated by cadherin	1
phosphate-containing compound metabolic process	1
cellular developmental process	1
phosphoprotein phosphatase activity	1
protein tyrosine phosphatase activity	1
transmembrane receptor protein phosphatase activity	1
protein binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
membrane	1
cell periphery	1
anchoring junction	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

74 interactions, top by confidence:

A	B	Type	Score
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
CA10	WDHD1	psi-mi:“MI:0914”(association)	0.640
SCGB1D1	FAM234B	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
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
PTPRU	GOLIM4	psi-mi:“MI:0914”(association)	0.530
TAFA4	NRP1	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
SGCA	GPR180	psi-mi:“MI:0914”(association)	0.530
PTPRU	PTPRU	psi-mi:“MI:0407”(direct interaction)	0.510
PTPRU	PTPRU	psi-mi:“MI:0914”(association)	0.510
PTPRU	KIT	psi-mi:“MI:0915”(physical association)	0.400
ERBB2	PTPRU	psi-mi:“MI:0915”(physical association)	0.370
incE	STX7	psi-mi:“MI:0914”(association)	0.350
KATNIP		psi-mi:“MI:0914”(association)	0.350
CACNA1C	IGLL5	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
CACNA1C	DISP2	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
rl10_rl10l_human	ANKRD28	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC2D	TMEM120B	psi-mi:“MI:0914”(association)	0.350
CTLA4	TMEM120B	psi-mi:“MI:0914”(association)	0.350
CDH5	NBAS	psi-mi:“MI:0914”(association)	0.350
ST8SIA4	FAM234B	psi-mi:“MI:0914”(association)	0.350

BioGRID (132): PTPRU (Affinity Capture-MS), PTPRU (Affinity Capture-MS), EGFR (Biochemical Activity), PTPRU (Two-hybrid), ARL2 (Affinity Capture-MS), ARHGAP5 (Proximity Label-MS), NHS (Proximity Label-MS), NHSL1 (Proximity Label-MS), ST7 (Proximity Label-MS), TMEM57 (Proximity Label-MS), ABI2 (Proximity Label-MS), PTPRK (Affinity Capture-MS), GOLIM4 (Affinity Capture-MS), PTPRU (Affinity Capture-MS), PTPRU (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5NSM8, A0A1L8HYT7, A2AJX4, B1AUH1, B3DK56, B3EX02, E2RK30, E9PZ36, F1RWC3, F8W3R9, O54767, O60494, O70244, P08922, P08F94, P20239, P47984, P56677, P79953, P86091, P97435, P98072, P98073, P98074, Q0IIH7, Q0V8T3, Q0V8T5, Q2QI47, Q3UZ09, Q5VYJ5, Q63132, Q66TN7, Q6DIV5, Q6YI48, Q769J6, Q78DX7, Q7M761, Q7RTY7, Q7RTY8, Q7RTZ1

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

1 interactions.

A	Effect	B	Mechanism
PTPRU	“down-regulates activity”	CTNNB1	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	6
Uncertain significance	468
Likely benign	163
Benign	83

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
2110028	NM_030667.3(PTPRO):c.1241C>G (p.Ser414Ter)	Pathogenic
2110029	NM_030667.3(PTPRO):c.1949del (p.Ser650fs)	Pathogenic
30110	NM_030667.3(PTPRO):c.2627+1G>T	Pathogenic
30111	NM_030667.3(PTPRO):c.2829+1G>A	Pathogenic
3656259	NM_030667.3(PTPRO):c.2803_2806del (p.Asp935fs)	Pathogenic
1068336	NM_030667.3(PTPRO):c.2712-2del	Likely pathogenic
2116990	NM_030667.3(PTPRO):c.2305-1G>C	Likely pathogenic
3574470	NM_030667.3(PTPRO):c.1758del (p.Val587fs)	Likely pathogenic
3574482	NM_030667.3(PTPRO):c.2027del (p.Lys676fs)	Likely pathogenic
3574503	NM_030667.3(PTPRO):c.2712-1G>A	Likely pathogenic
599583	NM_133178.4(PTPRU):c.2531C>T (p.Pro844Leu)	Likely pathogenic

SpliceAI

5567 predictions. Top by Δscore:

Variant	Effect	Δscore
1:29236715:CAGGT:C	donor_loss	1.0000
1:29236716:AG:A	donor_loss	1.0000
1:29236717:GG:G	donor_loss	1.0000
1:29236718:GT:G	donor_loss	1.0000
1:29236719:T:A	donor_loss	1.0000
1:29255270:CACA:C	acceptor_loss	1.0000
1:29255271:ACAG:A	acceptor_loss	1.0000
1:29255273:A:AG	acceptor_gain	1.0000
1:29255273:AGCT:A	acceptor_gain	1.0000
1:29255273:AGCTG:A	acceptor_gain	1.0000
1:29255274:G:GG	acceptor_gain	1.0000
1:29255274:G:GT	acceptor_loss	1.0000
1:29255274:GC:G	acceptor_gain	1.0000
1:29255274:GCT:G	acceptor_gain	1.0000
1:29255274:GCTG:G	acceptor_gain	1.0000
1:29255274:GCTGG:G	acceptor_gain	1.0000
1:29255405:CG:C	donor_gain	1.0000
1:29255406:GG:G	donor_gain	1.0000
1:29255407:G:GG	donor_gain	1.0000
1:29255407:GTA:G	donor_loss	1.0000
1:29255408:T:A	donor_loss	1.0000
1:29258500:TCCA:T	acceptor_loss	1.0000
1:29258501:CCA:C	acceptor_loss	1.0000
1:29258502:CA:C	acceptor_loss	1.0000
1:29258503:A:AG	acceptor_gain	1.0000
1:29258503:AG:A	acceptor_gain	1.0000
1:29258504:G:GG	acceptor_gain	1.0000
1:29258504:GG:G	acceptor_gain	1.0000
1:29258504:GGC:G	acceptor_gain	1.0000
1:29258504:GGCT:G	acceptor_gain	1.0000

AlphaMissense

9398 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:29255354:G:C	W51C	1.000
1:29255354:G:T	W51C	1.000
1:29260018:C:T	S275F	1.000
1:29260622:C:A	P288H	1.000
1:29260634:C:A	P292Q	1.000
1:29260664:T:C	L302P	1.000
1:29279077:T:A	W507R	1.000
1:29279077:T:C	W507R	1.000
1:29279079:G:C	W507C	1.000
1:29279079:G:T	W507C	1.000
1:29303984:T:C	L879P	1.000
1:29315449:A:T	D1112V	1.000
1:29255352:T:A	W51R	0.999
1:29255352:T:C	W51R	0.999
1:29258594:T:A	C99S	0.999
1:29258594:T:C	C99R	0.999
1:29258595:G:A	C99Y	0.999
1:29258595:G:C	C99S	0.999
1:29258596:T:G	C99W	0.999
1:29258728:G:C	W143C	0.999
1:29258728:G:T	W143C	0.999
1:29258748:T:A	V150D	0.999
1:29258750:A:C	S151R	0.999
1:29258752:C:A	S151R	0.999
1:29258752:C:G	S151R	0.999
1:29258756:T:C	F153L	0.999
1:29258758:C:A	F153L	0.999
1:29258758:C:G	F153L	0.999
1:29258761:G:C	W154C	0.999
1:29258761:G:T	W154C	0.999

dbSNP variants (sampled 300 via entrez): RS1000009883 (1:29247034 G>A), RS1000025973 (1:29321380 G>A), RS1000029095 (1:29258235 G>A), RS1000098528 (1:29326359 C>A), RS1000101692 (1:29240523 G>A,T), RS1000130680 (1:29271965 C>T), RS1000151230 (1:29326560 T>C), RS1000152138 (1:29313272 G>A), RS1000182564 (1:29270225 G>A), RS1000225126 (1:29310307 TG>T), RS1000240608 (1:29277747 G>T), RS1000261183 (1:29319838 G>A), RS1000276266 (1:29298411 G>A), RS1000345417 (1:29263903 G>T), RS1000356081 (1:29307224 C>A,G,T)

Disease associations

OMIM: gene MIM:602454 | disease phenotypes: MIM:614196, MIM:614800, MIM:616483

GenCC curated gene-disease

Disease	Classification	Inheritance
nephrotic syndrome, type 6	Strong	Autosomal recessive
familial idiopathic steroid-resistant nephrotic syndrome	Supportive	Autosomal dominant

Mondo (5): nephrotic syndrome, type 6 (MONDO:0013619), short stature-optic atrophy-Pelger-Huët anomaly syndrome (MONDO:0013889), infantile liver failure syndrome 2 (MONDO:0014659), focal segmental glomerulosclerosis (MONDO:0100313), familial idiopathic steroid-resistant nephrotic syndrome (MONDO:0019006)

Orphanet (2): Hereditary steroid-resistant nephrotic syndrome (Orphanet:656), Short stature-optic atrophy-Pelger-Huët anomaly syndrome (Orphanet:391677)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000100	Nephrotic syndrome
HP:0000707	Abnormality of the nervous system
HP:0000737	Irritability
HP:0000969	Edema
HP:0001945	Fever
HP:0001967	Diffuse mesangial sclerosis
HP:0002027	Abdominal pain
HP:0002315	Headache
HP:0002586	Peritonitis
HP:0003073	Hypoalbuminemia
HP:0003621	Juvenile onset
HP:0003774	Stage 5 chronic kidney disease
HP:0005576	Tubulointerstitial fibrosis
HP:0011947	Respiratory tract infection
HP:0012579	Minimal change glomerulonephritis
HP:0012622	Chronic kidney disease
HP:0031504	Foamy urine
HP:0100539	Periorbital edema

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST000821_8	Bipolar disorder and schizophrenia	4.000000e-07
GCST001332_1	Cognitive function	1.000000e-08
GCST001928_2	Pediatric non-alcoholic fatty liver disease activity score	7.000000e-06
GCST003372_37	Glomerular filtration rate (creatinine)	7.000000e-12
GCST004227_15	Obstetric antiphospholipid syndrome	1.000000e-06
GCST004946_45	Schizophrenia	3.000000e-10
GCST005316_366	Intelligence (MTAG)	1.000000e-08
GCST005352_30	Paclitaxel disposition in epithelial ovarian cancer	4.000000e-06
GCST006269_386	General cognitive ability	2.000000e-10
GCST006269_793	General cognitive ability	3.000000e-09
GCST006585_2768	Blood protein levels	4.000000e-08
GCST007277_1	Tourette syndrome	2.000000e-06
GCST009195_2	Temporal pole volume	4.000000e-06
GCST009642_4	Impaired insulin sensitivity in response to n-3 PUFA supplementation	1.000000e-06
GCST010241_374	Apolipoprotein A1 levels	4.000000e-10
GCST010242_370	HDL cholesterol levels	2.000000e-10
GCST010397_60	Gut microbiota (bacterial taxa, rank normal transformation method)	4.000000e-06
GCST010536_11	Carotid plaque maximum area	1.000000e-06
GCST010537_9	Mean area of carotid plaque	5.000000e-07
GCST011105_3	Metamizole-induced agranulocytosis or neutropenia	1.000000e-06
GCST011981_11	Homeostasis model assessment of insulin resistance	1.000000e-07
GCST90000025_910	Appendicular lean mass	6.000000e-12
GCST90002392_157	Mean corpuscular volume	6.000000e-16

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004323	mental process
EFO:0004337	intelligence
EFO:0004471	insulin sensitivity measurement
EFO:0009131	response to polyunsaturated fatty acid supplementation
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007874	gut microbiome measurement
EFO:0006501	carotid plaque build
EFO:0004501	HOMA-IR
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1961785 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases expression	4
aristolochic acid I	decreases expression	1
dicrotophos	increases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	decreases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
quercitrin	decreases expression	1
perfluorooctanoic acid	affects cotreatment, increases expression	1
aflatoxin B2	increases methylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
nutlin 3	increases expression	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Acrolein	decreases expression, increases abundance, affects cotreatment	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Cosmetics	increases expression, affects cotreatment	1
Dexamethasone	decreases expression	1
Estradiol	affects expression	1
Flame Retardants	affects cotreatment, increases expression	1
Naled	affects expression	1
Ozone	increases abundance, affects cotreatment, decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1961835	Binding	Effect on RORB(NR1F2) dependent reporter activity in HEK293 cells at 20 uM	Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. — Nature

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1178	DMS 79	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01129557	PHASE4	TERMINATED	Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease
NCT02399462	PHASE4	WITHDRAWN	Acthar for Treatment of Post-transplant FSGS
NCT02585804	PHASE4	COMPLETED	Treating to Reduce Albuminuria and Normalize Hemodynamic Function in Focal ScLerosis With dApagliflozin Trial Effects
NCT02633046	PHASE4	COMPLETED	Acthar for Treatment-Resistant or Treatment-Intolerant Proteinuria
NCT07219121	PHASE4	RECRUITING	Sparsentan in Posttransplant Immunoglobulin A Nephropathy or Focal Segmental Glomerulosclerosis
NCT01164098	PHASE3	TERMINATED	Rituximab to Prevent Recurrence of Proteinuria
NCT02683889	PHASE3	COMPLETED	Use of Acthar in Patients With FSGS That Will be Undergoing Renal Transplantation
NCT03298698	PHASE3	UNKNOWN	Efficacy of Rituximab in Comparison to Continued Corticosteroid Treatment in Idiopathic Nephrotic Syndrome
NCT03493685	PHASE3	COMPLETED	Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS)
NCT05183646	PHASE3	RECRUITING	A Study of the Efficacy and Safety of DMX-200 in Patients With FSGS Who Are Receiving an ARB
NCT07220083	PHASE3	RECRUITING	A Study to Find Out if BI 764198 Helps Adults and Adolescents With a Kidney Condition Called Focal Segmental Glomerulosclerosis (FSGS)
NCT00550342	PHASE2	WITHDRAWN	Rituximab Treatment of Focal Segmental Glomerulosclerosis
NCT00814255	PHASE2	COMPLETED	Novel Therapies for Resistant FSGS (FONTII): Phase II Clinical Trial
NCT01613118	PHASE2	COMPLETED	Randomized, Double-Blind, Safety and Efficacy Study of RE-021 (Sparsentan) in Focal Segmental Glomerulosclerosis
NCT02592798	PHASE2	COMPLETED	Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Adults and Children 6 Years and Older With Excessive Loss of Protein in the Urine Due to Either Focal Segmental Glomerulosclerosis (FSGS) or Minimal Change Disease (MCD)
NCT03366337	PHASE2	COMPLETED	A Phase 2 Trial of the Safety and Efficacy of Bardoxolone Methyl in Patients With Rare Chronic Kidney Diseases - PHOENIX
NCT03448692	PHASE2	TERMINATED	A Study to Evaluate PF-06730512 in Adults With Focal Segmental Glomerulosclerosis (FSGS)
NCT03536754	PHASE2	COMPLETED	A Study of CCX140-B in Subjects With FSGS
NCT03598036	PHASE2	TERMINATED	Dose-Exploration Evaluating the Efficacy and Safety of Voclosporin in Subjects With Focal Segmental Glomerulosclerosis
NCT03649152	PHASE2	COMPLETED	Safety and Effectiveness of Propagermanium in Focal Segmental Glomerulosclerosis Participants Receiving Irbesartan
NCT03703908	PHASE2	TERMINATED	A Study of CCX140-B in Subjects With Primary FSGS and Nephrotic Syndrome
NCT04009668	PHASE2	COMPLETED	Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease
NCT04573920	PHASE2	ACTIVE_NOT_RECRUITING	Atrasentan in Patients With Proteinuric Glomerular Diseases
NCT05003986	PHASE2	RECRUITING	Study of Sparsentan Treatment in Pediatrics With Proteinuric Glomerular Diseases
NCT05267262	PHASE2	COMPLETED	Study to Evaluate R3R01 in Patients With Alport Syndrome and Patients With Focal Segmental Glomerulosclerosis
NCT05441826	PHASE2	TERMINATED	Efficacy and Safety of VB119 in Subjects With Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS)
NCT06500702	PHASE2	RECRUITING	A Study to Evaluate the Efficacy and Safety of Frexalimab, Brivekimig, or Rilzabrutinib in Participants Aged 16 to 75 Years With Primary Focal Segmental Glomerulosclerosis or Minimal Change Disease
NCT06664814	PHASE2	RECRUITING	An Open-Label Phase 2 Study of N-Acetyl-D-Mannosamine (ManNAc) in Subjects With Primary Focal Segmental Glomerulosclerosis
NCT06983028	PHASE2	RECRUITING	Atacicept in Multiple Glomerular Diseases
NCT07268638	PHASE2	RECRUITING	A Study of Praliciguat in Participants With Focal Segmental Glomerulosclerosis (FSGS)
NCT07614477	PHASE2	RECRUITING	Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of EVER001 in Participants With Selected Proteinuric Glomerular Diseases
NCT00464321	PHASE1	COMPLETED	Safety Study of GC1008 in Patients With Focal Segmental Glomerulosclerosis (FSGS) of Single Doses of GC1008 in Patients With Treatment Resistant Idiopathic FSGS
NCT00782561	PHASE1	TERMINATED	Safety and Pharmacokinetics of FG-3019 in Adolescents and Adults With Focal Segmental Glomerulosclerosis (FSGS)
NCT00816478	PHASE1	TERMINATED	Effect of Oral Galactose on Focal Segmental Glomerulosclerosis (FSGS) Permeability Factor
NCT00816504	PHASE1	WITHDRAWN	Effect of Galactose on Permeblity Factor in Patients With FSGS and CKD Stage 5
NCT02382874	PHASE1	UNKNOWN	Allogenic AD-MSC Transplantation in Idiopathic Nephrotic Syndrome (Focal Segmental Glomerulosclerosis)
NCT02693366	PHASE1	COMPLETED	Stem Cell Therapy for Patients With Focal Segmental Glomerulosclerosis
NCT05942625	PHASE1	RECRUITING	A First in Human Study to Evaluate Safety, Tolerability, Pharmacology of HS-10390 in Healthy Subjects
NCT05955872	PHASE1	COMPLETED	A Study Evaluating the Relative Bioavailability and Food Effect of a Tablet Formulation of VX-147
NCT06529796	PHASE1	COMPLETED	Evaluation of the Pharmacokinetics and Safety of Inaxaplin in Participants With Mild or Moderate Hepatic Impairment