PTPRB

Summary

PTPRB (protein tyrosine phosphatase receptor type B, HGNC:9665) is a protein-coding gene on chromosome 12q15, encoding Receptor-type tyrosine-protein phosphatase beta (P23467). Plays an important role in blood vessel remodeling and angiogenesis. In precision oncology, PTPRB Loss-of-function confers sensitivity to Vatalanib + Sunitinib in Angiosarcoma (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 contains an extracellular domain, a single transmembrane segment and one intracytoplasmic catalytic domain, thus belongs to receptor type PTP. The extracellular region of this PTP is composed of multiple fibronectin type_III repeats, which was shown to interact with neuronal receptor and cell adhesion molecules, such as contactin and tenascin C. This protein was also found to interact with sodium channels, and thus may regulate sodium channels by altering tyrosine phosphorylation status. The functions of the interaction partners of this protein implicate the roles of this PTP in cell adhesion, neurite growth, and neuronal differentiation. Alternate transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5787 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 377 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 5 cancer types
• MANE Select transcript: NM_001109754

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9665
Approved symbol	PTPRB
Name	protein tyrosine phosphatase receptor type B
Location	12q15
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000127329
Ensembl biotype	protein_coding
OMIM	176882
Entrez	5787

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000261266, ENST00000334414, ENST00000538174, ENST00000538708, ENST00000547715, ENST00000548122, ENST00000549400, ENST00000550358, ENST00000550857, ENST00000551525, ENST00000552253, ENST00000952654

RefSeq mRNA: 5 — MANE Select: NM_001109754 NM_001109754, NM_001206971, NM_001206972, NM_001330204, NM_002837

CCDS: CCDS44943, CCDS44944, CCDS55845, CCDS55846, CCDS81713

Canonical transcript exons

ENST00000334414 — 34 exons

Exon	Start	End
ENSE00001176657	70571824	70572087
ENSE00001176665	70576382	70576645
ENSE00001176673	70581036	70581302
ENSE00001244013	70515870	70521511
ENSE00001618774	70552777	70553020
ENSE00001778550	70555160	70555309
ENSE00003499258	70587007	70587267
ENSE00003501377	70589964	70590233
ENSE00003519360	70637341	70637429
ENSE00003523115	70609069	70609339
ENSE00003524510	70596049	70596327
ENSE00003551578	70635671	70636066
ENSE00003578127	70592282	70592545
ENSE00003592678	70622390	70622646
ENSE00003611209	70594467	70594724
ENSE00003714766	70538155	70538231
ENSE00003715333	70540858	70540957
ENSE00003716660	70571026	70571289
ENSE00003718613	70534488	70534651
ENSE00003720947	70566435	70566704
ENSE00003725332	70562844	70563107
ENSE00003729083	70539827	70539844
ENSE00003729881	70544557	70544663
ENSE00003729934	70536025	70536159
ENSE00003736777	70539939	70540022
ENSE00003738766	70559343	70559624
ENSE00003739210	70538924	70539014
ENSE00003739656	70534833	70534955
ENSE00003741136	70555870	70556148
ENSE00003741240	70524471	70524591
ENSE00003748909	70569675	70569938
ENSE00003749840	70532035	70532170
ENSE00003751122	70560671	70560934
ENSE00003754272	70539625	70539706

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 97.90.

FANTOM5 (CAGE): breadth broad, TPM avg 7.1079 / max 199.5876, expressed in 721 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132055	2.6629	299
132047	1.9987	487
132049	0.7815	370
132045	0.5092	222
132050	0.2996	169
132051	0.2133	124
132057	0.2097	105
132046	0.1387	84
132048	0.1205	64
132056	0.0770	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	97.90	gold quality
lower lobe of lung	UBERON:0008949	96.94	gold quality
visceral pleura	UBERON:0002401	96.87	gold quality
right lung	UBERON:0002167	93.14	gold quality
heart right ventricle	UBERON:0002080	92.57	gold quality
pleura	UBERON:0000977	92.42	gold quality
parietal pleura	UBERON:0002400	92.18	gold quality
upper lobe of lung	UBERON:0008948	91.83	gold quality
upper lobe of left lung	UBERON:0008952	91.56	gold quality
lung	UBERON:0002048	91.32	gold quality
colonic epithelium	UBERON:0000397	90.89	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.07	gold quality
apex of heart	UBERON:0002098	90.01	gold quality
skin of hip	UBERON:0001554	89.50	gold quality
subcutaneous adipose tissue	UBERON:0002190	89.29	gold quality
adipose tissue	UBERON:0001013	89.07	gold quality
renal medulla	UBERON:0000362	88.97	gold quality
biceps brachii	UBERON:0001507	88.65	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.31	gold quality
connective tissue	UBERON:0002384	88.23	gold quality
omental fat pad	UBERON:0010414	88.19	gold quality
peritoneum	UBERON:0002358	88.15	gold quality
metanephros cortex	UBERON:0010533	87.23	gold quality
superficial temporal artery	UBERON:0001614	86.42	gold quality
cardiac ventricle	UBERON:0002082	86.33	gold quality
calcaneal tendon	UBERON:0003701	86.17	gold quality
heart left ventricle	UBERON:0002084	86.10	gold quality
gall bladder	UBERON:0002110	85.77	gold quality
seminal vesicle	UBERON:0000998	85.68	gold quality
heart	UBERON:0000948	84.91	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-11268	yes	3199.50
E-GEOD-131882	yes	2849.34
E-CURD-119	yes	2545.26
E-ANND-2	yes	2229.22
E-GEOD-130473	yes	756.38
E-GEOD-135922	yes	620.27
E-MTAB-10553	yes	57.51
E-HCAD-1	yes	42.15
E-CURD-46	yes	29.38
E-MTAB-8410	yes	28.71
E-HCAD-35	yes	21.02
E-HCAD-9	yes	18.86
E-MTAB-6678	yes	13.40
E-MTAB-9067	yes	7.08
E-GEOD-130148	yes	5.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

277 targeting PTPRB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-LET-7F-2-3P	99.98	70.98	2588

Literature-anchored findings (GeneRIF, showing 19)

• The PTP1B has been observed over expressed in human breast cancer patients, suggesting its role in cell proliferation. (PMID:15638728)
• the Ser127Gly polymorphism in PTPRB is associated with substance abuse vulnerability in three independent case-control samples, but was not associated with alcoholism in Japanese subjects (PMID:18361428)
• These results reveal a novel role for HPTPbeta in modulating Ang-1-Tie2 signaling and endothelial cell survival. (PMID:19116766)
• vascular endothelial protein tyrosine phosphatase contributes to endothelial morphogenesis. Silencing of VE-PTP expression was accompanied by increased VEGF receptor-2 tyrosine phosphorylation and activation of downstream signaling pathways. (PMID:19136612)
• Suggest that VE-PTP, in cooperation with integrins, regulates the spreading and migration of endothelial cells during angiogenesis. (PMID:20301196)
• zinc(II) ions regulate receptor protein-tyrosine phosphatase beta activity at picomolar concentrations. (PMID:22275360)
• these results suggest that the polarized redistribution of VE-PTP in response to shear stress plays an important role in the regulation of endothelial cells function by blood flow. (PMID:24451369)
• The endothelial phosphatase PTPRB, a negative regulator of vascular growth factor tyrosine kinases, harbored predominantly truncating mutations in 10 of 39 angiosarcoma tumors. (PMID:24633157)
• Results provide evidence that PTPRB and PLCG1 mutations are driving events in a subset of secondary angiosarcomas. (PMID:24795022)
• VE-PTP activates TIE2 and stabilizes retinal and choroidal blood vessels (PMID:25180601)
• PTPRB was down-regulated in non-small-cell lung cancer patients and was associated with patient overall survival. (PMID:27314562)
• STIM1-induced Ca(2+) signaling activates Pyk2 to inhibit the interaction of VE-PTP and VE-cadherin and hence increase endothelial permeability. (PMID:28385807)
• Collagen regulates the ability of endothelial progenitor cells to protect hypoxic myocardium through a mechanism involving miR-377/VE-PTP axis. (PMID:30044046)
• PTPRB overexpression decreased vimentin expression and promoted E-cadherin expression, consistent with promotion of EMT, while PTPRB knockdown had the opposite effect. (PMID:31040266)
• The search for substrates of VE-PTP revealed that proteins relevant for the regulation of endothelial junctions and of cell adhesion are over-represented among the potential targets of VE-PTP, supporting the concept that VEPTP is an important regulator of vascular integrity and junctional signaling. (PMID:31427368)
• Study found PTPRB negatively correlated with miR-624 expression in osteosarcoma (OS) tissues. PTPRB was confirmed as a downstream target of miR-624. (PMID:31829261)
• PSMD11, PTPRM and PTPRB as novel biomarkers of pancreatic cancer progression. (PMID:32663515)
• Novel rare mutation in a conserved site of PTPRB causes human hypoplastic left heart syndrome. (PMID:36148623)
• The variants in PTPRB, TRAF3IP3, and DISC1 genes were associated with Graves’ disease in the Chinese population. (PMID:36397361)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptprb	ENSDARG00000076624
mus_musculus	Ptprb	ENSMUSG00000020154
rattus_norvegicus	Ptprb	ENSRNOG00000055293

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), 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 beta — P23467 (reviewed: P23467)

Alternative names: Vascular endothelial protein tyrosine phosphatase

All UniProt accessions (5): P23467, F8VSD5, F8VU56, H0YHE8, Q6ZR19

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in blood vessel remodeling and angiogenesis. Not necessary for the initial formation of blood vessels, but is essential for their maintenance and remodeling. Can induce dephosphorylation of TEK/TIE2, CDH5/VE-cadherin and KDR/VEGFR-2. Regulates angiopoietin-TIE2 signaling in endothelial cells. Acts as a negative regulator of TIE2, and controls TIE2 driven endothelial cell proliferation, which in turn affects blood vessel remodeling during embryonic development and determines blood vessel size during perinatal growth. Essential for the maintenance of endothelial cell contact integrity and for the adhesive function of VE-cadherin in endothelial cells and this requires the presence of plakoglobin.

Subunit / interactions. Monomer. Interacts with TEK. Interacts via fibronectin type-III 17 domain with CDH5. Detected in a complex with CNTN1 and NRCAM. Interacts (phosphorylated form) with FYN and GRB2. Interacts with IGFBP2.

Subcellular location. Membrane.

Induction. Up-regulated by hypoxia.

Similarity. Belongs to the protein-tyrosine phosphatase family. Receptor class 3 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
P23467-1	1	yes
P23467-2	2
P23467-3	3
P23467-4	4

RefSeq proteins (5): NP_001103224, NP_001193900, NP_001193901, NP_001317133, NP_002828 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000242	PTP_cat	Domain
IPR000387	Tyr_Pase_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
IPR041201	PTPRJ_TM	Domain
IPR050713	RTP_Phos/Ushers	Family

Pfam: PF00041, PF00102, PF18861

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 (97 total): glycosylation site 26, domain 18, strand 16, helix 10, sequence variant 7, sequence conflict 4, binding site 3, splice variant 3, turn 3, topological domain 2, signal peptide 1, chain 1, active site 1, modified residue 1, transmembrane region 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
2HC1	X-RAY DIFFRACTION	1.3
2HC2	X-RAY DIFFRACTION	1.4
2H03	X-RAY DIFFRACTION	1.65
2I4G	X-RAY DIFFRACTION	1.65
2I5X	X-RAY DIFFRACTION	1.7
2I4E	X-RAY DIFFRACTION	1.75
2I3R	X-RAY DIFFRACTION	1.85
2I3U	X-RAY DIFFRACTION	1.85
8JBN	X-RAY DIFFRACTION	1.99
8JBY	X-RAY DIFFRACTION	1.99
2AHS	X-RAY DIFFRACTION	2.1
2I4H	X-RAY DIFFRACTION	2.15
2H02	X-RAY DIFFRACTION	2.3
2H04	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23467-F1	80.67	0.09

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 1904 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (3): 1870; 1904–1910; 1948

Post-translational modifications (1): 1981

Glycosylation sites (26): 28, 53, 75, 172, 198, 267, 321, 414, 421, 479, 544, 574, 598, 652, 721, 829, 1040, 1096, 1163, 1185 …

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 245 (showing top): MORF_ITGA2, REACTOME_INNATE_IMMUNE_SYSTEM, KAAB_FAILED_HEART_ATRIUM_DN, GOCC_SECRETORY_GRANULE, GOBP_OSTEOBLAST_DIFFERENTIATION, MORF_RAD51L3, CAIRO_HEPATOBLASTOMA_CLASSES_DN, MORF_PRKCA, GOBP_BLOOD_VESSEL_MORPHOGENESIS, LANDIS_ERBB2_BREAST_PRENEOPLASTIC_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, NIKOLSKY_BREAST_CANCER_12Q13_Q21_AMPLICON, BIOCARTA_SPRY_PATHWAY, MORF_THPO, GOBP_OSSIFICATION

GO Biological Process (8): angiogenesis (GO:0001525), osteoblast differentiation (GO:0001649), protein dephosphorylation (GO:0006470), phosphate-containing compound metabolic process (GO:0006796), glial cell migration (GO:0008347), dephosphorylation (GO:0016311), developmental process (GO:0032502), negative regulation of osteoblast differentiation (GO:0045668)

GO Molecular Function (7): transmembrane receptor protein tyrosine phosphatase activity (GO:0005001), transmembrane receptor protein tyrosine kinase inhibitor activity (GO:0030293), cadherin binding (GO:0045296), phosphoprotein phosphatase activity (GO:0004721), protein tyrosine phosphatase activity (GO:0004725), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): plasma membrane (GO:0005886), specific granule membrane (GO:0035579), signaling receptor complex (GO:0043235), tertiary granule membrane (GO:0070821), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
secretory granule membrane	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
ossification	1
cell differentiation	1
dephosphorylation	1
protein modification process	1
metabolic process	1
cell migration	1
gliogenesis	1
phosphate-containing compound metabolic process	1
biological_process	1
osteoblast differentiation	1
negative regulation of cell differentiation	1
regulation of osteoblast differentiation	1
protein tyrosine phosphatase activity	1
transmembrane receptor protein phosphatase activity	1
transmembrane receptor protein tyrosine kinase activity	1
protein tyrosine kinase inhibitor activity	1
signaling receptor inhibitor activity	1
cell adhesion molecule binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
phosphoprotein phosphatase activity	1
binding	1
catalytic activity	1
membrane	1
cell periphery	1
specific granule	1
protein-containing complex	1
tertiary granule	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1572 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPRB	PTN	P21246	991
PTPRB	CDH5	P33151	949
PTPRB	PTS	Q03393	858
PTPRB	MDK	P21741	826
PTPRB	IGFBP2	P18065	806
PTPRB	TEK	Q02763	787
PTPRB	CNTNAP1	P78357	743
PTPRB	CNTN1	Q12860	707
PTPRB	ANGPT1	Q15389	698
PTPRB	TIE1	P35590	690
PTPRB	KDR	P35968	689
PTPRB	CDH17	Q12864	679
PTPRB	NFASC	O94856	673
PTPRB	CTNNB1	P35222	638
PTPRB	NRCAM	Q92823	618

IntAct

43 interactions, top by confidence:

A	B	Type	Score
EGFR	PTPRB	psi-mi:“MI:0915”(physical association)	0.690
PTPRB	GHR	psi-mi:“MI:0407”(direct interaction)	0.680
PTPRB	GHR	psi-mi:“MI:0203”(dephosphorylation reaction)	0.680
MAPK3	PTPRB	psi-mi:“MI:0203”(dephosphorylation reaction)	0.620
PTPRB	MAPK1	psi-mi:“MI:0203”(dephosphorylation reaction)	0.440
PTPRB	MET	psi-mi:“MI:0203”(dephosphorylation reaction)	0.440
PTPRB	RRBP1	psi-mi:“MI:0915”(physical association)	0.400
PTPRB	MADD	psi-mi:“MI:0915”(physical association)	0.400
PTPRB	FLT1	psi-mi:“MI:0915”(physical association)	0.400
PTPRB	PCMT1	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
PTPRB	RRP8	psi-mi:“MI:0914”(association)	0.350
PTPRB	PTPRB	psi-mi:“MI:0914”(association)	0.310
PTPRB	CDH2	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000
PTPRB	TEC	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000
PTPRB	ERBB2	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000
PTPRB	PDGFRB	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000
PTPRB	PXN	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000
PTPRB	LCK	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000
PTPRB	CTNNB1	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000
PTPRB	INSR	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000
PTPRB	CSK	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000
PTPRB	GAB1	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000
PTPRB	ALK	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000
PTPRB	GRIN2B	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000
PTPRB	NTRK1	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000
PTPRB	PDPK1	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000
PTPRB	NSF	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000

BioGRID (40): MAGI3 (Two-hybrid), EGFR (Biochemical Activity), PTPRB (Affinity Capture-Western), VEGFA (Affinity Capture-Western), VEGFA (Co-localization), PTN (Co-localization), PTPRB (Two-hybrid), RABEP2 (Proximity Label-MS), GOPC (Proximity Label-MS), PTPRG (Proximity Label-MS), PTPRB (Affinity Capture-RNA), MAGI3 (Affinity Capture-Western), MAGI3 (Reconstituted Complex), MADD (Proximity Label-MS), RRBP1 (Proximity Label-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, 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

19 interactions.

A	Effect	B	Mechanism
PTPRB	up-regulates	MAPK3	dephosphorylation
PTPRB	down-regulates	GHR	dephosphorylation
PTPRB	down-regulates	MET	dephosphorylation
PTPRB	down-regulates	ALK	dephosphorylation
PTPRB	down-regulates	MAPK1	dephosphorylation
PTPRB	“down-regulates activity”	MET	dephosphorylation
PTPRB	“down-regulates activity”	KDR	dephosphorylation
PTPRB	up-regulates	Gbeta	dephosphorylation
PTPRB	up-regulates	ERK1/2	dephosphorylation
PTPRB	“down-regulates activity”	NOS3	dephosphorylation
PTPRB	“down-regulates activity”	TEK	dephosphorylation
PTPRB	“up-regulates activity”	CDH5	dephosphorylation
PTPRB	“down-regulates activity”	SRC	dephosphorylation
PTPRB	down-regulates	INSR	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 32 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
Negative regulation of the PI3K/AKT network	5	46.4×	6e-06
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	9	29.0×	3e-09
Constitutive Signaling by Aberrant PI3K in Cancer	6	25.4×	7e-06
PIP3 activates AKT signaling	10	22.3×	3e-09
RAF/MAP kinase cascade	8	16.3×	3e-06
Intracellular signaling by second messengers	5	15.2×	3e-04
Signaling by Receptor Tyrosine Kinases	8	13.8×	6e-06
Diseases of signal transduction by growth factor receptors and second messengers	7	13.3×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	7	57.8×	7e-09
cell surface receptor protein tyrosine kinase signaling pathway	8	46.3×	3e-09
insulin receptor signaling pathway	5	37.0×	2e-05
protein autophosphorylation	6	29.1×	6e-06
positive regulation of MAPK cascade	9	24.2×	1e-08
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	9	23.5×	1e-08
positive regulation of angiogenesis	5	19.2×	2e-04
protein phosphorylation	7	15.9×	2e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 5 cancer types — ANGS, MEL, OVT, PLMESO, THYM.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	256
Likely benign	17
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

5014 predictions. Top by Δscore:

Variant	Effect	Δscore
12:70532028:CTCTT:C	donor_loss	1.0000
12:70532029:TCTTA:T	donor_loss	1.0000
12:70532030:CTTA:C	donor_loss	1.0000
12:70532031:TTA:T	donor_loss	1.0000
12:70532032:TA:T	donor_loss	1.0000
12:70532171:C:CC	acceptor_gain	1.0000
12:70534552:CAAA:C	donor_gain	1.0000
12:70534831:A:AC	donor_gain	1.0000
12:70534832:C:CC	donor_gain	1.0000
12:70534832:CA:C	donor_gain	1.0000
12:70534832:CACCG:C	donor_gain	1.0000
12:70534845:AAACT:A	donor_gain	1.0000
12:70534850:C:CA	donor_gain	1.0000
12:70534955:CCTAG:C	acceptor_loss	1.0000
12:70534956:C:CA	acceptor_loss	1.0000
12:70534957:T:C	acceptor_loss	1.0000
12:70536023:A:AC	donor_gain	1.0000
12:70536024:C:CC	donor_gain	1.0000
12:70536024:CT:C	donor_gain	1.0000
12:70536024:CTCGG:C	donor_gain	1.0000
12:70536043:CTGGG:C	donor_gain	1.0000
12:70536044:TGGGT:T	donor_gain	1.0000
12:70536155:TTGCC:T	acceptor_gain	1.0000
12:70536157:GCCCT:G	acceptor_loss	1.0000
12:70536158:CC:C	acceptor_gain	1.0000
12:70536159:CC:C	acceptor_gain	1.0000
12:70536160:C:CC	acceptor_gain	1.0000
12:70536161:T:A	acceptor_loss	1.0000
12:70538153:A:AC	donor_gain	1.0000
12:70538154:C:CT	donor_gain	1.0000

AlphaMissense

14590 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000029166 (12:70588902 G>A), RS1000038120 (12:70609538 G>A,C), RS1000050496 (12:70526344 A>C,G), RS1000101420 (12:70518344 C>G,T), RS1000104277 (12:70601742 A>T), RS1000145722 (12:70592948 A>G), RS1000152810 (12:70604841 T>A,C), RS1000182762 (12:70638367 C>T), RS1000194234 (12:70552303 G>A), RS1000221191 (12:70597086 T>G), RS1000239741 (12:70552515 GAAGA>G), RS1000249518 (12:70585799 C>T), RS1000252521 (12:70558870 T>A,C), RS1000286038 (12:70562177 G>A), RS1000295905 (12:70564911 G>A)

Disease associations

OMIM: gene MIM:176882 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002363_8	Response to anti-retroviral therapy (ddI/d4T) in HIV-1 infection (Grade 3 peripheral neuropathy)	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0000180	HIV-1 infection

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2706 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 321 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3931971	RAZUPROTAFIB	2	321

Clinical evidence (CIViC)

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

Variant	Therapy	Indication	Effect	Level	CIViC
PTPRB Loss-of-function	Vatalanib + Sunitinib	Angiosarcoma	Sensitivity/Response	CIViC D	EID1895

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

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 13e [PMID: 16759857]	Inhibition	7.15	pIC50
razuprotafib	Inhibition	6.15	pIC50

Binding affinities (BindingDB)

87 measured of 98 human assays (98 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[4-[(2S)-2-(4-cyclopropyl-1,3-thiazol-2-yl)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]ethyl]phenyl]sulfamic acid	IC50	0.01 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]-2-[4-(3,3,3-trifluoropropyl)-1,3-thiazol-2-yl]ethyl]phenyl]sulfamic acid	IC50	0.08 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[2-[(4-chlorophenyl)sulfonylmethyl]-1,3-thiazol-4-yl]-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]ethyl]phenyl]sulfamic acid	IC50	0.08 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]-2-(4-thiophen-3-yl-1,3-thiazol-2-yl)ethyl]phenyl]sulfamic acid	IC50	0.09 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]-2-(4-propyl-1,3-thiazol-2-yl)ethyl]phenyl]sulfamic acid	IC50	0.1 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethyl-5-methyl-1,3-thiazol-2-yl)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]ethyl]phenyl]sulfamic acid	IC50	0.1 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(2-ethyl-1,3-thiazol-4-yl)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]ethyl]phenyl]sulfamic acid	IC50	0.1 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[[(2S)-2-(ethoxycarbonylamino)-3-phenylpropanoyl]amino]-2-(4-ethyl-1,3-thiazol-2-yl)ethyl]phenyl]sulfamic acid	IC50	0.14 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethyl-1,3-thiazol-2-yl)-2-[(2-phenylacetyl)amino]ethyl]phenyl]sulfamic acid	IC50	0.157 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethyl-1,3-thiazol-2-yl)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]ethyl]phenyl]sulfamic acid	IC50	0.162 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-tert-butyl-1,3-thiazol-2-yl)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]ethyl]phenyl]sulfamic acid	IC50	0.2 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethoxycarbonyl-1,3-thiazol-2-yl)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]ethyl]phenyl]sulfamic acid	IC50	0.2 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(2-cyclopropyl-1,3-thiazol-4-yl)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]ethyl]phenyl]sulfamic acid	IC50	0.2 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[3-(3-chlorophenyl)propanoylamino]-2-(4-ethyl-1,3-thiazol-2-yl)ethyl]phenyl]sulfamic acid	IC50	0.2 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[(5-propyl-1,3,4-thiadiazol-2-yl)amino]-2-(2-thiophen-2-yl-1,3-thiazol-4-yl)ethyl]phenyl]sulfamic acid	IC50	0.2 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-2-(4-thiophen-3-yl-1,3-thiazol-2-yl)ethyl]phenyl]sulfamic acid	IC50	0.24 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]-2-[4-(2,2,2-trifluoroethyl)-1,3-thiazol-2-yl]ethyl]phenyl]sulfamic acid	IC50	0.3 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]-2-(5-phenyl-1,3-thiazol-2-yl)ethyl]phenyl]sulfamic acid	IC50	0.3 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-2-(4-tert-butyl-1,3-thiazol-2-yl)ethyl]phenyl]sulfamic acid	IC50	0.3 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethyl-1,3-thiazol-2-yl)-2-[[(2S)-2-(methoxycarbonylamino)-4-methylpentanoyl]amino]ethyl]phenyl]sulfamic acid	IC50	0.3 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethyl-1,3-thiazol-2-yl)-2-[[(2S)-2-[(3-methoxy-3-oxopropanoyl)amino]-3-phenylpropanoyl]amino]ethyl]phenyl]sulfamic acid	IC50	0.3 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethyl-1,3-thiazol-2-yl)-2-[[2-(3-fluorophenyl)acetyl]amino]ethyl]phenyl]sulfamic acid	IC50	0.3 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]-2-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)ethyl]phenyl]sulfamic acid	IC50	0.4 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[2-(furan-2-yl)-1,3-thiazol-4-yl]-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]ethyl]phenyl]sulfamic acid	IC50	0.4 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[(5-benzyl-1,3,4-thiadiazol-2-yl)amino]-2-(2-thiophen-2-yl-1,3-thiazol-4-yl)ethyl]phenyl]sulfamic acid	IC50	0.6 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]-2-(4-methyl-1,3-thiazol-2-yl)ethyl]phenyl]sulfamic acid	IC50	1 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4,5-dimethyl-1,3-thiazol-2-yl)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]ethyl]phenyl]sulfamic acid	IC50	1 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]-2-[4-(methoxymethyl)-1,3-thiazol-2-yl]ethyl]phenyl]sulfamic acid	IC50	1 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(5,6-dihydro-4H-cyclopenta[d][1,3]thiazol-2-yl)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]ethyl]phenyl]sulfamic acid	IC50	1 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]-2-(2-methyl-1,3-thiazol-4-yl)ethyl]phenyl]sulfamic acid	IC50	1 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-2-(4-ethyl-1,3-thiazol-2-yl)ethyl]phenyl]sulfamic acid	IC50	1 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethyl-1,3-thiazol-2-yl)-2-[[(2S)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]ethyl]phenyl]sulfamic acid	IC50	1 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[2-(tert-butylsulfonylmethyl)-1,3-thiazol-4-yl]-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]ethyl]phenyl]sulfamic acid	IC50	2 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethyl-1,3-thiazol-2-yl)-2-(3-phenylpropanoylamino)ethyl]phenyl]sulfamic acid	IC50	2 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[[2-(4-ethyl-2,3-dioxopiperazin-1-yl)acetyl]amino]-2-(4-ethyl-1,3-thiazol-2-yl)ethyl]phenyl]sulfamic acid	IC50	2 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethyl-1,3-thiazol-2-yl)-2-[[2-(5-methyl-2,4-dioxo-1,3-diazinan-1-yl)acetyl]amino]ethyl]phenyl]sulfamic acid	IC50	2 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[[5-(2-methoxy-2-oxoethyl)-1,3,4-thiadiazol-2-yl]amino]-2-(2-thiophen-2-yl-1,3-thiazol-4-yl)ethyl]phenyl]sulfamic acid	IC50	2 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]-2-(2-pyrazin-2-yl-1,3-thiazol-4-yl)ethyl]phenyl]sulfamic acid	IC50	3 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethyl-1,3-thiazol-2-yl)-2-[[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]ethyl]phenyl]sulfamic acid	IC50	3 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethyl-1,3-thiazol-2-yl)-2-[3-(2-methoxyphenyl)propanoylamino]ethyl]phenyl]sulfamic acid	IC50	3 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[(5-methyl-1,3,4-thiadiazol-2-yl)amino]-2-(2-phenyl-1,3-thiazol-4-yl)ethyl]phenyl]sulfamic acid	IC50	3 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethyl-1,3-thiazol-2-yl)-2-[[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]ethyl]phenyl]sulfamic acid	IC50	4 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]-2-(2-thiophen-2-yl-1,3-thiazol-4-yl)ethyl]phenyl]sulfamic acid	IC50	5 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-[[(2S)-2-(methoxycarbonylamino)-3-phenylpropanoyl]amino]-2-(1,3-thiazol-2-yl)ethyl]phenyl]sulfamic acid	IC50	6 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethyl-1,3-thiazol-2-yl)-2-[3-(4-methoxyphenyl)propanoylamino]ethyl]phenyl]sulfamic acid	IC50	6 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethyl-1,3-thiazol-2-yl)-2-[[2-(3-methoxyphenyl)acetyl]amino]ethyl]phenyl]sulfamic acid	IC50	8 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethyl-1,3-thiazol-2-yl)-2-[3-(3-methoxyphenyl)propanoylamino]ethyl]phenyl]sulfamic acid	IC50	10 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethyl-1,3-thiazol-2-yl)-2-[[2-(2-fluorophenyl)acetyl]amino]ethyl]phenyl]sulfamic acid	IC50	12 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethyl-1,3-thiazol-2-yl)-2-[[2-(2-hydroxyphenyl)acetyl]amino]ethyl]phenyl]sulfamic acid	IC50	14 nM	US-10220048: Compositions and methods for treating ocular diseases
[4-[(2S)-2-(4-ethyl-1,3-thiazol-2-yl)-2-[[2-(methoxycarbonylamino)acetyl]amino]ethyl]phenyl]sulfamic acid	IC50	20 nM	US-10220048: Compositions and methods for treating ocular diseases

ChEMBL bioactivities

517 potent at pChembl≥5 of 540 total, top 22 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL3928885
10.10	IC50	0.08	nM	CHEMBL3935358
10.10	IC50	0.08	nM	CHEMBL3948990
10.05	IC50	0.09	nM	CHEMBL3963181
10.00	IC50	0.1	nM	CHEMBL3907615
10.00	IC50	0.1	nM	CHEMBL3962687
10.00	IC50	0.1	nM	CHEMBL3967271
9.85	IC50	0.14	nM	CHEMBL3945835
9.80	IC50	0.157	nM	CHEMBL3921571
9.79	IC50	0.162	nM	CHEMBL3891215
9.70	IC50	0.2	nM	CHEMBL3956877
9.70	IC50	0.2	nM	CHEMBL3900884
9.70	IC50	0.2	nM	CHEMBL3946325
9.70	IC50	0.2	nM	CHEMBL3966138
9.70	IC50	0.2	nM	CHEMBL3924295
9.62	IC50	0.24	nM	CHEMBL3973378
9.52	IC50	0.3	nM	CHEMBL3981985
9.52	IC50	0.3	nM	CHEMBL3953372
9.52	IC50	0.3	nM	CHEMBL3975815
9.52	IC50	0.3	nM	CHEMBL3898194
9.52	IC50	0.3	nM	CHEMBL3974482
9.52	IC50	0.3	nM	CHEMBL3984069

PubChem BioAssay actives

63 with measured affinity, of 209 total; 50 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
[4-[(2S)-2-(4-ethyl-1,3-thiazol-2-yl)-2-[[(2S)-2-methoxycarbonyl-4-methylpentanoyl]amino]ethyl]phenyl]sulfamic acid	456624: Inhibition of human protein-tyrosine phosphatase beta	ic50	0.0003	uM
azane;[4-[3-methoxy-2-methoxycarbonyl-3-oxo-2-[[4-(sulfoamino)phenyl]methyl]propyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.0600	uM
azane;[4-[2,2-bis(3-methyl-1,2,4-oxadiazol-5-yl)-5-phenylpentyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.0700	uM
azane;[4-[2,2-bis(methoxycarbonyl)-5-(1-phenyltetrazol-5-yl)sulfonylpentyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.0800	uM
azane;[4-[2,2-bis(3-methyl-1,2,4-oxadiazol-5-yl)-3-[4-(sulfoamino)phenyl]propyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.0800	uM
azane;[4-[2-ethoxycarbonyl-2-methoxycarbonyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.0900	uM
azane;[3-[3-methoxy-2-methoxycarbonyl-3-oxo-2-[[4-(sulfoamino)phenyl]methyl]propyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.1000	uM
[25,26,27,28-tetrahydroxy-11,17,23-tris(phosphonomethyl)-2,8,14,20-tetrathiapentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(24),3,5,7(28),9,11,13(27),15(26),16,18,21(25),22-dodecaen-5-yl]methylphosphonic acid	455687: Inhibition of human recombinant PTPbeta	ic50	0.1300	uM
azane;4-[3-methoxy-2-methoxycarbonyl-3-oxo-2-[[4-(sulfoamino)phenyl]methyl]propyl]benzoic acid	269825: Inhibition of HPTPbeta	ic50	0.1400	uM
azane;[4-[5-(benzenesulfonyl)-2,2-bis(methoxycarbonyl)pentyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.1500	uM
azane;[4-[2,2-bis(methoxycarbonyl)-5-phenylpentyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.1500	uM
azane;[4-[2,2-bis(methoxycarbonyl)-5-(1-phenyltetrazol-5-yl)sulfanylpentyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.2000	uM
[4-(2-benzyl-3-methoxy-2-methoxycarbonyl-3-oxopropyl)phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ki	0.2000	uM
azane;[4-[3-(3-cyanophenyl)-2,2-bis(3-methyl-1,2,4-oxadiazol-5-yl)propyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.2100	uM
5-[2-cyclohexyl-4-[4-fluoro-2-(trifluoromethyl)phenyl]phenyl]-1,2-oxazole-3-carboxylic acid	405513: Inhibition of PtpB	ki	0.2200	uM
azane;[4-[3-(3-methoxyphenyl)-2,2-bis(3-methyl-1,2,4-oxadiazol-5-yl)propyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.2300	uM
azane;[4-[4-ethoxy-2,2-bis(methoxycarbonyl)-4-oxobutyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.2300	uM
azane;[4-[3-methoxy-2-methoxycarbonyl-3-oxo-2-(phenylmethoxymethyl)propyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.2700	uM
azane;[4-[3-methoxy-2-methoxycarbonyl-2-[(3-methoxycarbonylphenyl)methyl]-3-oxopropyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.2900	uM
azane;[4-[3-methoxy-2-methoxycarbonyl-3-oxo-2-[(3-sulfamoylphenyl)methyl]propyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.3000	uM
azane;[4-[3-methoxy-2-methoxycarbonyl-2-[(3-methoxyphenyl)methyl]-3-oxopropyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.3300	uM
azane;[4-[3-(4-methoxyphenyl)-2,2-bis(3-methyl-1,2,4-oxadiazol-5-yl)propyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.3400	uM
azane;[4-[6-methoxy-2,2-bis(methoxycarbonyl)-6-oxohexyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.3800	uM
azane;[4-[3-methoxy-2-methoxycarbonyl-2-[(4-methoxyphenyl)methyl]-3-oxopropyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.3900	uM
4-[[(5Z)-2,4-dioxo-5-[(4-phenylmethoxyphenyl)methylidene]-1,3-thiazolidin-3-yl]methyl]benzoic acid	300025: Inhibition of human protein-tyrosine phosphatase beta	ic50	0.4000	uM
azane;[4-[2-ethoxycarbonyl-3-methoxy-3-oxo-2-(phenylmethoxycarbonylamino)propyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.4000	uM
azane;[4-[3-methoxy-2-methoxycarbonyl-2-[(4-methoxycarbonylphenyl)methyl]-3-oxopropyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.4100	uM
azane;[4-[2,2-bis(methoxycarbonyl)-5-methylsulfonylpentyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.4200	uM
azane;[4-[3-methoxy-2-methoxycarbonyl-3-oxo-2-[(4-sulfamoylphenyl)methyl]propyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.4300	uM
azane;[4-[2-ethoxycarbonyl-3-methoxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxopropyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.4500	uM
3-[2-(3-chlorophenyl)ethynyl]-6-hydroxy-2-[4-[2-oxo-2-(propylamino)ethoxy]phenyl]-1-benzofuran-5-carboxylic acid	755768: Inhibition of recombinant PTPbeta (unknown origin) using pNPP as substrate by spectrophotometric analysis	ic50	0.4700	uM
(2R)-2-[2,6-dibromo-4-(6-bromonaphtho[3,2-b][1]benzofuran-11-yl)phenoxy]-3-phenylpropanoic acid	165341: The compound was tested in vitro for the inhibitory activity against Protein-tyrosine phosphatase beta (SH-PTP1) (human PTPases.)	ic50	0.5000	uM
azane;[4-[3-methoxy-2-methoxycarbonyl-3-oxo-2-(pyridin-4-ylmethyl)propyl]phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	0.5700	uM
2-[2,6-dibromo-4-(6-bromonaphtho[3,2-b][1]benzothiol-11-yl)phenoxy]acetic acid	165341: The compound was tested in vitro for the inhibitory activity against Protein-tyrosine phosphatase beta (SH-PTP1) (human PTPases.)	ic50	0.6000	uM
[4-[[(3-methoxyphenyl)sulfonyl-(4-phenyl-1,3-thiazol-2-yl)amino]methyl]phenyl]sulfamic acid	1920416: Inhibition of recombinant human PTPbeta using DiFMUP as substrate preincubated for 10 mins followed by substrate addition and measured after 2 hrs	ic50	0.9676	uM
[4-[[(4-thiophen-2-yl-1,3-thiazol-2-yl)amino]methyl]phenyl]sulfamic acid	1920416: Inhibition of recombinant human PTPbeta using DiFMUP as substrate preincubated for 10 mins followed by substrate addition and measured after 2 hrs	ic50	0.9950	uM
azane;[4-(3-methoxy-2-methoxycarbonyl-3-oxopropyl)phenyl]sulfamic acid	269825: Inhibition of HPTPbeta	ic50	1.0000	uM
[4-[[(3-fluorophenyl)sulfonyl-(4-thiophen-2-yl-1,3-thiazol-2-yl)amino]methyl]phenyl]sulfamic acid	1920416: Inhibition of recombinant human PTPbeta using DiFMUP as substrate preincubated for 10 mins followed by substrate addition and measured after 2 hrs	ic50	1.0710	uM
4-[[(5Z)-2,4-dioxo-5-[(4-phenoxyphenyl)methylidene]-1,3-thiazolidin-3-yl]methyl]benzoic acid	300025: Inhibition of human protein-tyrosine phosphatase beta	ic50	1.1000	uM
[4-[[(3-fluorophenyl)sulfonyl-(4-phenyl-1,3-thiazol-2-yl)amino]methyl]phenyl]sulfamic acid	1920416: Inhibition of recombinant human PTPbeta using DiFMUP as substrate preincubated for 10 mins followed by substrate addition and measured after 2 hrs	ic50	1.2440	uM
[4-[[(3-chlorophenyl)sulfonyl-(4-phenyl-1,3-thiazol-2-yl)amino]methyl]phenyl]sulfamic acid	1920416: Inhibition of recombinant human PTPbeta using DiFMUP as substrate preincubated for 10 mins followed by substrate addition and measured after 2 hrs	ic50	1.3170	uM
[4-[[(3-methoxyphenyl)sulfonyl-(4-thiophen-2-yl-1,3-thiazol-2-yl)amino]methyl]phenyl]sulfamic acid	1920416: Inhibition of recombinant human PTPbeta using DiFMUP as substrate preincubated for 10 mins followed by substrate addition and measured after 2 hrs	ic50	1.4140	uM
[4-[(N-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carbonyl]anilino)methyl]phenyl]sulfamic acid	1920416: Inhibition of recombinant human PTPbeta using DiFMUP as substrate preincubated for 10 mins followed by substrate addition and measured after 2 hrs	ic50	1.4530	uM
[4-[(N-[2-(2,4-dichlorophenoxy)acetyl]anilino)methyl]phenyl]sulfamic acid	1920416: Inhibition of recombinant human PTPbeta using DiFMUP as substrate preincubated for 10 mins followed by substrate addition and measured after 2 hrs	ic50	1.6840	uM
[4-[(N-[2-(3-fluorophenyl)acetyl]anilino)methyl]phenyl]sulfamic acid	1920416: Inhibition of recombinant human PTPbeta using DiFMUP as substrate preincubated for 10 mins followed by substrate addition and measured after 2 hrs	ic50	1.7150	uM
[4-[[(3-chlorophenyl)sulfonyl-(4-thiophen-2-yl-1,3-thiazol-2-yl)amino]methyl]phenyl]sulfamic acid	1920416: Inhibition of recombinant human PTPbeta using DiFMUP as substrate preincubated for 10 mins followed by substrate addition and measured after 2 hrs	ic50	1.7450	uM
[4-[(N-[2-(4-bromo-3-fluorophenyl)acetyl]anilino)methyl]phenyl]sulfamic acid	1920416: Inhibition of recombinant human PTPbeta using DiFMUP as substrate preincubated for 10 mins followed by substrate addition and measured after 2 hrs	ic50	1.7750	uM
[4-[[(4-methoxyphenyl)sulfonyl-(4-thiophen-2-yl-1,3-thiazol-2-yl)amino]methyl]phenyl]sulfamic acid	1920416: Inhibition of recombinant human PTPbeta using DiFMUP as substrate preincubated for 10 mins followed by substrate addition and measured after 2 hrs	ic50	1.8060	uM
[4-[[(4-methoxyphenyl)sulfonyl-(4-phenyl-1,3-thiazol-2-yl)amino]methyl]phenyl]sulfamic acid	1920416: Inhibition of recombinant human PTPbeta using DiFMUP as substrate preincubated for 10 mins followed by substrate addition and measured after 2 hrs	ic50	2.0660	uM
[4-[[(2-chloropyridine-3-carbonyl)-(4-phenyl-1,3-thiazol-2-yl)amino]methyl]phenyl]sulfamic acid	1920416: Inhibition of recombinant human PTPbeta using DiFMUP as substrate preincubated for 10 mins followed by substrate addition and measured after 2 hrs	ic50	2.9760	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression	4
nickel chloride	increases expression	2
(+)-JQ1 compound	decreases expression	2
Oxygen	increases expression	2
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, affects methylation, increases methylation	1
trichostatin A	increases expression	1
sodium arsenite	decreases expression	1
nickel sulfate	decreases expression	1
1-nitropyrene	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-(oxalylamino)benzoic acid	decreases activity	1
clothianidin	decreases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Leflunomide	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Ethanol	affects cotreatment, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Cocaine	decreases expression	1
Copper	affects binding, increases expression	1
Doxorubicin	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Folic Acid	affects cotreatment, increases expression	1
Nickel	decreases expression	1
Silicon Dioxide	decreases expression	1
Tretinoin	increases expression	1

ChEMBL screening assays

36 unique, capped per target: 35 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1050900	Binding	Inhibition of PTPRB	Knowledge-based characterization of similarity relationships in the human protein-tyrosine phosphatase family for rational inhibitor design. — J Med Chem
CHEMBL4626315	ADMET	Inhibition of PTPB (unknown origin) expressed in Escherichia coli BL21 using p-nitrophenyl phosphate as substrate measured after 30 mins by UV-vis spectrophotometric method	Highly Potent and Selective N-Aryl Oxamic Acid-Based Inhibitors for Mycobacterium tuberculosis Protein Tyrosine Phosphatase B. — J Med Chem

Clinical trials (associated diseases)

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