PTPN22

Summary

PTPN22 (protein tyrosine phosphatase non-receptor type 22, HGNC:9652) is a protein-coding gene on chromosome 1p13.2, encoding Tyrosine-protein phosphatase non-receptor type 22 (Q9Y2R2). Acts as a negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules.

This gene encodes of member of the non-receptor class 4 subfamily of the protein-tyrosine phosphatase family. The encoded protein is a lymphoid-specific intracellular phosphatase that associates with the molecular adapter protein CBL and may be involved in regulating CBL function in the T-cell receptor signaling pathway. Mutations in this gene may be associated with a range of autoimmune disorders including Type 1 Diabetes, rheumatoid arthritis, systemic lupus erythematosus and Graves’ disease. Alternatively spliced transcript variants encoding distinct isoforms have been described.

Source: NCBI Gene 26191 — RefSeq curated summary.

At a glance

• Gene–disease (curated): systemic lupus erythematosus (Supportive, GenCC) — +3 more curated relationships
• GWAS associations: 80
• Clinical variants (ClinVar): 7 total
• Phenotypes (HPO): 214
• Druggable target: yes
• Transcription factor: yes — 18 downstream targets (CollecTRI)
• MANE Select transcript: NM_015967

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9652
Approved symbol	PTPN22
Name	protein tyrosine phosphatase non-receptor type 22
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	Lyp, Lyp1, Lyp2
Ensembl gene	ENSG00000134242
Ensembl biotype	protein_coding
OMIM	600716
Entrez	26191

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 16 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000359785, ENST00000420377, ENST00000460620, ENST00000469077, ENST00000484147, ENST00000525799, ENST00000528414, ENST00000529045, ENST00000532224, ENST00000534519, ENST00000538253, ENST00000910046, ENST00000910047, ENST00000910048, ENST00000910049, ENST00000910050, ENST00000910051, ENST00000910052, ENST00000910053, ENST00000941803, ENST00000941804

RefSeq mRNA: 4 — MANE Select: NM_015967 NM_001193431, NM_001308297, NM_012411, NM_015967

CCDS: CCDS76191, CCDS863, CCDS864

Canonical transcript exons

ENST00000359785 — 21 exons

Exon	Start	End
ENSE00001835701	113871537	113871712
ENSE00003466968	113859352	113859460
ENSE00003474612	113834910	113834993
ENSE00003482869	113837590	113838407
ENSE00003484167	113856382	113856441
ENSE00003503879	113819577	113819654
ENSE00003508988	113859002	113859078
ENSE00003523586	113833111	113833138
ENSE00003524691	113838544	113838620
ENSE00003533668	113852027	113852104
ENSE00003543076	113854907	113855049
ENSE00003545617	113857738	113857776
ENSE00003586805	113829949	113830029
ENSE00003610476	113858478	113858573
ENSE00003611117	113813811	113814969
ENSE00003643552	113825142	113825172
ENSE00003657188	113848540	113848626
ENSE00003657203	113829592	113829707
ENSE00003678524	113834309	113834439
ENSE00003679549	113856548	113856619
ENSE00003745864	113854471	113854537

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 90.90.

FANTOM5 (CAGE): breadth broad, TPM avg 8.0074 / max 707.0876, expressed in 718 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13915	7.3037	706
13914	0.5287	150
13912	0.1286	39
13913	0.0393	23
13916	0.0070	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	90.90	gold quality
bone marrow	UBERON:0002371	90.44	gold quality
monocyte	CL:0000576	89.10	gold quality
leukocyte	CL:0000738	89.05	gold quality
mononuclear cell	CL:0000842	89.04	gold quality
granulocyte	CL:0000094	88.64	gold quality
buccal mucosa cell	CL:0002336	87.85	silver quality
blood	UBERON:0000178	87.74	gold quality
calcaneal tendon	UBERON:0003701	85.54	gold quality
superficial temporal artery	UBERON:0001614	84.91	gold quality
lymph node	UBERON:0000029	84.57	gold quality
epithelium of nasopharynx	UBERON:0001951	83.22	gold quality
spleen	UBERON:0002106	82.36	gold quality
vermiform appendix	UBERON:0001154	82.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.88	gold quality
jejunal mucosa	UBERON:0000399	81.65	gold quality
trabecular bone tissue	UBERON:0002483	80.94	gold quality
colonic epithelium	UBERON:0000397	79.38	gold quality
amniotic fluid	UBERON:0000173	78.63	gold quality
small intestine Peyer’s patch	UBERON:0003454	77.89	gold quality
gall bladder	UBERON:0002110	77.61	gold quality
rectum	UBERON:0001052	77.49	gold quality
mucosa of transverse colon	UBERON:0004991	76.41	gold quality
small intestine	UBERON:0002108	76.08	gold quality
right lung	UBERON:0002167	75.92	gold quality
caecum	UBERON:0001153	75.78	gold quality
upper lobe of left lung	UBERON:0008952	75.36	gold quality
thymus	UBERON:0002370	75.11	gold quality
upper lobe of lung	UBERON:0008948	74.38	gold quality
tibia	UBERON:0000979	73.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-122	yes	32.37
E-GEOD-135922	yes	23.63
E-CURD-88	yes	22.69
E-CURD-112	yes	13.83
E-ANND-3	yes	11.55
E-MTAB-6678	yes	5.34

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

18 targets.

Target	Regulation
CCL5	Activation
CD40	Activation
CD86	Activation
CXCL10	Activation
CXCL8	Repression
ICAM1	Activation
IFIT1	Activation
IFIT2	Activation
IFNB1	Activation
IFNG	Activation
IL1B	Repression
IL6	Repression
IRF7	Activation
ISG15	Activation
MX1	Activation
NOD2	Activation
TBX21	Activation
TNF	Repression

Upstream regulators (CollecTRI, top): FOXP3, IRF5

miRNA regulators (miRDB)

68 targeting PTPN22, 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-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4658	99.77	64.94	514

Literature-anchored findings (GeneRIF, showing 40)

• data demonstrate a novel interaction between Lyp and the adaptor Grb2 and are consistent with a negative regulatory role for Lyp in T-cell signaling. (PMID:11882361)
• Lyp may play an antagonistic role in signaling by the Bcr-Abl fusion protein (PMID:12764153)
• Minor allele is associated with rheumatoid arthritis and type I diabetes, suggesting it as a risk factor for autoimmune disease. (PMID:15208781)
• PTPN22 may have a role in regulating the immune system and the development of autoimmunity (PMID:15273934)
• general association of the PTPN22 locus with autoimmune disease such as typse 1 diabetes. (PMID:15504986)
• Individuals lacking the C allele of PTPN22 may have reduced capacity to downregulate T-cell responses and may therefore be more susceptible to autoimmunity. (PMID:15620463)
• PTPN22 1858T allele may confer differential susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Spanish population. (PMID:15641066)
• Association of a missense single nucleotide polymorphism in codon 620 of the PTPN22 with rheumatoid arthritis from a UK caucasian population. (PMID:15641088)
• Results provide compelling evidence that the lymphoid-specific phosphatase encoded by PTPN22 is a critical player in multiple autoimmune disorders. (PMID:15734872)
• REVIEW: current data suggest that the PTPN22 620W allele is likely to be a general risk factor for the development of humoral autoimmunity (PMID:15790351)
• The association of PTPN22 1858C>T poymorphism in Dutch cohort of juvenile type 1 diabetes and rheumatoid arthritis cohort was confirmed. (PMID:15875058)
• PTPN22 gene plays a role in the pathogenesis of rheumatoid arthritis and juvenile idiopathic arthritis. (PMID:15934099)
• These observations confirm the association of RA susceptibility with the PTPN22 1858T allele. (PMID:15986374)
• Missense R620W polymorphism may have an influence on the development of generalised vitiligo and provide further evidence for autoimmunity as an aetiological factor with respect to this disease. (PMID:16015369)
• The R620W C/T polymorphism of PTPN22 is associated with SLE independently of the association of PDCD1. (PMID:16052172)
• R620W polymorphism of PTPN22 is not major risk allele for SLE susceptibility in Caucasians from northern America, the UK, or Finland, but it appears to be risk factor for concurrent autoimmune diseases of autoimmune thyroid disease and SLE. (PMID:16052563)
• Our results do not support potential involvement of PTPN22 gene polymorphism in the susceptibility or clinical expression of giant cell arteritis (PMID:16078327)
• C1858T polymorphism is unlikely to be associated in psoriasis (PMID:16098055)
• PTPN22 polymorphism is a risk factor for rheumatoid arthritis in Finns, but not for juvenile idiopathic arthritis. (PMID:16107870)
• Data suggest that the PTPN22 1858 single nucleotide polymorphism has no, or only a negligible, effect on celiac disease susceptibility in the studied Spanish population. (PMID:16112033)
• The influence of PTPN22 in autoimmunity was shown by demonstrating single nucleotide polymorphism (SNP) C1858T in Colombian patients with four autoimmune diseases. (PMID:16163373)
• analyses identified two SNPs on a single common haplotype that are associated with theumatoid arthritis (RA) independent of R620W, suggesting that R620W and at least one variant in the PTPN22 gene region influence RA susceptibility (PMID:16175503)
• Review summarizes recent developments and current understanding of the way in which the PTPN22 gene encoding lymphoid tyrosine phosphatase contributes to T-cell activation, and how aberrant function of PTPN22 might trigger autoimmunity. (PMID:16229750)
• T cells from carriers of the allele predisposing to autoimmune diseases produce less interleukin-2 upon TCR stimulation, and the encoded phosphatase has higher catalytic activity and is a more potent negative regulator of T lymphocyte activation. (PMID:16273109)
• This study is the first to show linkage of PTPN22 to rheumatoid factor positive- rheumatopid arthritis, consistent with PTPN22 as a new rheumatoid arthritis gene. (PMID:16277672)
• data suggest that the codon 620 polymorphism of the PTPN22 gene does not have a causal role for autoimmune thyroid diseases in the Japanese (PMID:16279843)
• The PTPN22 620W allele appears to be involved in the pathogenesis of Wegener granulomatosis, and antineutrophil cytoplasmic antibodies positivity seems to be the hallmark. (PMID:16320352)
• significant association between variation of PTPN22 1858 C/T polymorphism & strong association in females with type 1 diabetes mellitus. No significant difference was observed between distribution of PTPN22 C/T in Hashimoto thyroiditis or Addison disease. (PMID:16322396)
• PTPN22 is associated with an earlier age of onset of rheumatoid arthritis and has a stronger effect in males than in females. (PMID:16380915)
• the 620W allele of protein tyrosine phosphatase PTPN22 does not play a major role in Crohn’s disease and multiple sclerosis (PMID:16391555)
• The 620W risk allele was increased in 293 nonthymoma patients without anti-titin antibodies (odds ratio, 1.97; 95% confidence interval, 1.32-2.97, p = 0.00059) but not in nonthymoma patients with anti-titin antibodies or in thymoma patients. (PMID:16437561)
• Variant R620W of PTPN22 play a role in susceptibility to psoriatic arthritis in men. (PMID:16456530)
• analysis of substrates of human protein-tyrosine phosphatase PTPN22 (PMID:16461343)
• The type 1 diabetes association with PTPN22 is confirmed, and the promoter -1123G > C SNP is a more likely causative variant in PTPN22. (PMID:16470599)
• The PTPN22 1858T variant was associated with future development of rheumatoid arthritis. (PMID:16507117)
• Moderate association of the R620W variant of PTPN22 with psoriatic arthritis in the Toronto population only. (PMID:16507123)
• The strong effect of PTPN22 on type 1 diabetes susceptibility was more pronounced in malesand in subjects with non-DR4-DQ8/low-risk HLA genotypes. (PMID:16614815)
• PTPN22 1858T allele is associated with rheumatoid arthritis irrespective of autoantibody production. (PMID:16635271)
• There is association between type 1 diabetes and the PTPN22,1858T allele, in the Ukrainian population. (PMID:16671953)
• PTPN22 gene (1858T)does not confer risk for primary biliary cirrhosis (PBC) and does not account for the frequent presence of other autoimmune diseases in patients with PBC. (PMID:16671954)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ptpn22	ENSMUSG00000027843
rattus_norvegicus	Ptpn22	ENSRNOG00000019614

Paralogs (35): PTPRN (ENSG00000054356), PTPRU (ENSG00000060656), PTPN3 (ENSG00000070159), PTPN21 (ENSG00000070778), PTPN18 (ENSG00000072135), PTPN23 (ENSG00000076201), PTPRH (ENSG00000080031), PTPRC (ENSG00000081237), PTPN4 (ENSG00000088179), PTPRS (ENSG00000105426), PTPRZ1 (ENSG00000106278), PTPN5 (ENSG00000110786), PTPN6 (ENSG00000111679), PTPRB (ENSG00000127329), PTPN12 (ENSG00000127947), PTPRE (ENSG00000132334), PTPRA (ENSG00000132670), 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

Tyrosine-protein phosphatase non-receptor type 22 — Q9Y2R2 (reviewed: Q9Y2R2)

Alternative names: Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP, Lymphoid phosphatase, PEST-domain phosphatase

All UniProt accessions (8): A0A0A0MTD9, A0A0A0MTE6, A0A0B4J1S7, Q9Y2R2, E9PM87, E9PMK2, E9PMT0, F5H2S8

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules. Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating ‘Tyr-394’ residue. Dephosphorylates ZAP70 at its activating ‘Tyr-493’ residue. Dephosphorylates the immune system activator SKAP2. Positively regulates toll-like receptor (TLR)-induced type 1 interferon production. Promotes host antiviral responses mediated by type 1 interferon. Regulates NOD2-induced pro-inflammatory cytokine secretion and autophagy. Acts as an activator of NLRP3 inflammasome assembly by mediating dephosphorylation of ‘Tyr-861’ of NLRP3. Dephosphorylates phospho-anandamide (p-AEA), an endocannabinoid to anandamide (also called N-arachidonoylethanolamide).

Subunit / interactions. Interacts with CSK. Interacts with LPXN. Interacts with CBL. Interacts with TRAF3 (via MATH domain); the interaction promotes TRAF3 polyubiquitination.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in bone marrow, B and T-cells, PBMCs, natural killer cells, monocytes, dendritic cells and neutrophils. Both isoform 1 and 4 are predominantly expressed in lymphoid tissues and cells. Isoform 1 is expressed in thymocytes and both mature B and T-cells.

Post-translational modifications. Phosphorylation on Ser-35 by PKC/PRKCD abrogates its ability to dephosphorylate and inactivate the SRC family kinases.

Disease relevance. Systemic lupus erythematosus (SLE) [MIM:152700] A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Disease susceptibility is associated with variants affecting the gene represented in this entry. Type 1 diabetes mellitus (T1D) [MIM:222100] A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Rheumatoid arthritis (RA) [MIM:180300] An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Disease susceptibility is associated with variants affecting the gene represented in this entry. Vitiligo (VTLG) [MIM:193200] A pigmentary disorder of the skin and mucous membranes. It is characterized by circumscribed depigmented macules and patches, commonly on extensor aspects of extremities, on the face or neck and in skin folds. Vitiligo is a progressive disorder in which some or all of the melanocytes in the affected skin are selectively destroyed. It is a multifactorial disorder with a complex etiology probably including autoimmune mechanisms, and is associated with an elevated risk of other autoimmune diseases. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Activity regulation. Down-regulated by phosphorylation.

Induction. By muramyl-dipeptide and lipopolysaccharide.

Miscellaneous. Due to intron retention. Lacks most of the phosphatase domain and functions as a dominant negative isoform of the full length PTPN22.

Similarity. Belongs to the protein-tyrosine phosphatase family. Non-receptor class 4 subfamily.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9Y2R2-1	1, LyP1	yes
Q9Y2R2-2	2, LyP2
Q9Y2R2-3	3
Q9Y2R2-4	4, LYP3
Q9Y2R2-5	5
Q9Y2R2-6	6, PTPN22.6

RefSeq proteins (4): NP_001180360, NP_001295226, NP_036543, NP_057051* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000242	PTP_cat	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR016130	Tyr_Pase_AS	Active_site
IPR016276	PTPN22	Family
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR047170	PTN12/18/22	Family
IPR047253	PTN22_cat	Domain

Pfam: PF00102

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), 2 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)
• N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine phosphate + H2O = N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + phosphate (RHEA:56532)

UniProt features (65 total): strand 16, helix 12, splice variant 8, sequence conflict 7, modified residue 5, sequence variant 4, mutagenesis site 4, region of interest 2, binding site 2, chain 1, domain 1, disulfide bond 1, active site 1, turn 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
9YG0	X-RAY DIFFRACTION	1.76
2P6X	X-RAY DIFFRACTION	1.9
9YG3	X-RAY DIFFRACTION	1.96
9YG1	X-RAY DIFFRACTION	1.97
9YDM	X-RAY DIFFRACTION	1.99
7AAM	X-RAY DIFFRACTION	2.15
3BRH	X-RAY DIFFRACTION	2.2
3H2X	X-RAY DIFFRACTION	2.2
9YG2	X-RAY DIFFRACTION	2.26
4J51	X-RAY DIFFRACTION	2.3
3OLR	X-RAY DIFFRACTION	2.5
2QCT	X-RAY DIFFRACTION	2.8
3OMH	X-RAY DIFFRACTION	2.9
2QCJ	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2R2-F1	59.45	0.36

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): 227 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (2): 227–233; 274

Post-translational modifications (5): 684, 692, 35, 449, 635

Disulfide bonds (1): 129–227

Mutagenesis-validated functional residues (4):

Position	Phenotype
35	loss of phosphorylation by pkc/prkcd.
36	no effect on phosphorylation by pkc/prkcd.
129	decreases activity 2 fold.
231	decreases activity 7 fold.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-202427	Phosphorylation of CD3 and TCR zeta chains
R-HSA-202430	Translocation of ZAP-70 to Immunological synapse

MSigDB gene sets: 905 (showing top): GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_B_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_MAP_KINASE_ACTIVITY, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_AUTOPHAGY, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID

GO Biological Process (43): lipid metabolic process (GO:0006629), autophagy (GO:0006914), negative regulation of autophagy (GO:0010507), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), T cell differentiation (GO:0030217), lipopolysaccharide-mediated signaling pathway (GO:0031663), positive regulation of type I interferon production (GO:0032481), response to lipopolysaccharide (GO:0032496), negative regulation of interleukin-6 production (GO:0032715), negative regulation of interleukin-8 production (GO:0032717), negative regulation of tumor necrosis factor production (GO:0032720), positive regulation of type II interferon production (GO:0032729), regulation of natural killer cell proliferation (GO:0032817), positive regulation of toll-like receptor 3 signaling pathway (GO:0034141), positive regulation of toll-like receptor 4 signaling pathway (GO:0034145), phosphoanandamide dephosphorylation (GO:0035644), negative regulation of JUN kinase activity (GO:0043508), regulation of innate immune response (GO:0045088), T cell receptor signaling pathway (GO:0050852), regulation of B cell receptor signaling pathway (GO:0050855), negative regulation of T cell receptor signaling pathway (GO:0050860), negative regulation of T cell activation (GO:0050868), positive regulation of ERK1 and ERK2 cascade (GO:0070374), negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070433), cellular response to muramyl dipeptide (GO:0071225), positive regulation of NLRP3 inflammasome complex assembly (GO:1900227), regulation of non-canonical NF-kappaB signal transduction (GO:1901222), positive regulation of protein K63-linked ubiquitination (GO:1902523), negative regulation of p38MAPK cascade (GO:1903753), positive regulation of defense response to virus by host (GO:0002230), immune system process (GO:0002376), regulation of leukocyte migration (GO:0002685), protein dephosphorylation (GO:0006470), dephosphorylation (GO:0016311), positive regulation of interferon-alpha production (GO:0032727), positive regulation of interferon-beta production (GO:0032728), positive regulation of toll-like receptor 7 signaling pathway (GO:0034157), positive regulation of toll-like receptor 9 signaling pathway (GO:0034165), positive regulation of protein import into nucleus (GO:0042307)

GO Molecular Function (9): protein tyrosine phosphatase activity (GO:0004725), non-membrane spanning protein tyrosine phosphatase activity (GO:0004726), phosphatase activity (GO:0016791), SH3 domain binding (GO:0017124), kinase binding (GO:0019900), ubiquitin protein ligase binding (GO:0031625), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic side of plasma membrane (GO:0009898), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
TCR signaling	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
gene expression	2
regulation of gene expression	2
positive regulation of cytokine production	2
negative regulation of cytokine production	2
positive regulation of pattern recognition receptor signaling pathway	2
cytoplasm	2
primary metabolic process	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
lymphocyte differentiation	1
T cell activation	1
cell surface receptor signaling pathway	1
cellular response to lipopolysaccharide	1
regulation of type I interferon production	1
type I interferon production	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
interleukin-6 production	1
regulation of interleukin-6 production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
natural killer cell proliferation	1
regulation of natural killer cell activation	1
regulation of lymphocyte proliferation	1
toll-like receptor 3 signaling pathway	1
regulation of toll-like receptor 3 signaling pathway	1
positive regulation of intracellular signal transduction	1

Protein interactions and networks

STRING

2366 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPN22	C1QBP	Q07021	942
PTPN22	HLA-DRB1	P01911	931
PTPN22	CSK	P41240	930
PTPN22	CD8A	P01732	891
PTPN22	PADI4	Q9UM07	864
PTPN22	CTLA4	P16410	843
PTPN22	JAK1	P23458	839
PTPN22	STAT4	Q14765	819
PTPN22	TNFAIP3	P21580	789
PTPN22	IRF5	Q13568	786
PTPN22	FCRL3	Q96P31	780
PTPN22	Q5Y7H0	Q5Y7H0	758
PTPN22	BANK1	Q8NDB2	751
PTPN22	ZAP70	P43403	737
PTPN22	TRAF3	Q13114	725

IntAct

53 interactions, top by confidence:

A	B	Type	Score
PTPN22	LCK	psi-mi:“MI:0914”(association)	0.780
PTPN22	LCK	psi-mi:“MI:0407”(direct interaction)	0.780
PTPN22	LCK	psi-mi:“MI:0203”(dephosphorylation reaction)	0.780
CD247	PTPN22	psi-mi:“MI:0915”(physical association)	0.630
PTPN22	CD247	psi-mi:“MI:0407”(direct interaction)	0.630
PTPN22	CD247	psi-mi:“MI:0915”(physical association)	0.630
EGFR	PTPN22	psi-mi:“MI:0915”(physical association)	0.630
PTPN22	EGFR	psi-mi:“MI:0915”(physical association)	0.630
PTPN22	SKAP2	psi-mi:“MI:0407”(direct interaction)	0.610
PTPN22	SKAP2	psi-mi:“MI:0203”(dephosphorylation reaction)	0.610
SKAP2	PTPN22	psi-mi:“MI:0915”(physical association)	0.610
PTPN22	ZAP70	psi-mi:“MI:0407”(direct interaction)	0.600
PTPN22	ZAP70	psi-mi:“MI:0203”(dephosphorylation reaction)	0.600
PSTPIP1	PTPN22	psi-mi:“MI:0915”(physical association)	0.590
PTPN22	PSTPIP1	psi-mi:“MI:0915”(physical association)	0.590
PTPN22	Traf3	psi-mi:“MI:0407”(direct interaction)	0.540
PTPN22	Traf3	psi-mi:“MI:0915”(physical association)	0.540
PTPN22	GRB2	psi-mi:“MI:0407”(direct interaction)	0.540
PTPN22	GRB2	psi-mi:“MI:0915”(physical association)	0.540
PTPN22	PRKCD	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (61): PTPN22 (Two-hybrid), PTPN22 (Biochemical Activity), PTPN22 (Biochemical Activity), PTPN22 (PCA), PTPN22 (Affinity Capture-Luminescence), PSTPIP2 (Affinity Capture-MS), TBC1D31 (Proximity Label-MS), KIF7 (Proximity Label-MS), CSK (Proximity Label-MS), LZTS2 (Proximity Label-MS), CEP131 (Proximity Label-MS), PIBF1 (Proximity Label-MS), KIAA0753 (Proximity Label-MS), MIB1 (Proximity Label-MS), MED4 (Proximity Label-MS)

ESM2 similar proteins: A1ZA92, A1ZAC4, B3NLX1, B4GBA9, B4GT53, B4P6W7, B4P8I0, B6VQ60, B7ZQJ9, G5EBL2, G5EEU2, P25158, P25823, P34344, P34423, P52351, Q05209, Q08119, Q09293, Q09354, Q09377, Q0V9S3, Q10077, Q18317, Q1XG89, Q23238, Q23647, Q24617, Q24747, Q28Z18, Q290S5, Q2KHT3, Q2NKX8, Q32KD2, Q504Y3, Q5RA75, Q621Q3, Q7TPV2, Q7ZXG4, Q86BY9

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

9 interactions.

A	Effect	B	Mechanism
PTPN22	down-regulates	CD247	dephosphorylation
PTPN22	down-regulates	LCK	dephosphorylation
PTPN22	down-regulates	ZAP70	dephosphorylation
PRKCD	down-regulates	PTPN22	phosphorylation
PTPN22	“down-regulates activity”	LCK	dephosphorylation
PTPN22	“down-regulates activity”	CD247	dephosphorylation
PTPN22	“down-regulates activity”	ZAP70	dephosphorylation
PTPN22	“up-regulates activity”	NLRP3	dephosphorylation
PTPN22	down-regulates	CBL	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 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
FCGR3A-mediated phagocytosis	5	40.7×	1e-05
Constitutive Signaling by Aberrant PI3K in Cancer	6	33.1×	6e-06
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	6	25.2×	1e-05
PIP3 activates AKT signaling	7	20.3×	6e-06
RAF/MAP kinase cascade	5	13.3×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	5	87.8×	1e-06
epidermal growth factor receptor signaling pathway	5	51.6×	9e-06
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	16.3×	7e-04
protein phosphorylation	5	14.2×	1e-03
intracellular signal transduction	8	12.7×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2912 predictions. Top by Δscore:

Variant	Effect	Δscore
1:113825140:A:AC	donor_gain	1.0000
1:113825141:C:CC	donor_gain	1.0000
1:113825141:CT:C	donor_gain	1.0000
1:113825171:CT:C	acceptor_gain	1.0000
1:113825173:C:CC	acceptor_gain	1.0000
1:113829582:T:C	donor_gain	1.0000
1:113829595:ACT:A	donor_gain	1.0000
1:113829596:CTC:C	donor_gain	1.0000
1:113829947:A:AC	donor_gain	1.0000
1:113829948:C:CC	donor_gain	1.0000
1:113829948:CAAT:C	donor_gain	1.0000
1:113834999:CAAAA:C	acceptor_gain	1.0000
1:113835000:A:T	acceptor_gain	1.0000
1:113835003:A:AC	acceptor_gain	1.0000
1:113848645:C:CT	acceptor_gain	1.0000
1:113848645:C:T	acceptor_gain	1.0000
1:113848650:CAAA:C	acceptor_gain	1.0000
1:113848653:A:AC	acceptor_gain	1.0000
1:113848653:A:C	acceptor_gain	1.0000
1:113857732:ACTTA:A	donor_loss	1.0000
1:113857734:TTA:T	donor_loss	1.0000
1:113857735:TAC:T	donor_loss	1.0000
1:113857737:C:T	donor_loss	1.0000
1:113857774:GATC:G	acceptor_loss	1.0000
1:113857775:ATCTG:A	acceptor_loss	1.0000
1:113857776:TCT:T	acceptor_loss	1.0000
1:113857777:CTGG:C	acceptor_loss	1.0000
1:113857778:T:A	acceptor_loss	1.0000
1:113858476:A:AC	donor_gain	1.0000
1:113858477:C:CC	donor_gain	1.0000

AlphaMissense

5337 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:113855013:A:G	W193R	0.999
1:113855013:A:T	W193R	0.999
1:113855011:C:A	W193C	0.997
1:113855011:C:G	W193C	0.997
1:113854522:C:A	R233S	0.996
1:113854522:C:G	R233S	0.996
1:113856401:A:G	L174P	0.996
1:113858507:A:G	W114R	0.996
1:113858507:A:T	W114R	0.996
1:113852037:A:T	V273D	0.995
1:113854523:C:G	R233T	0.995
1:113854537:A:C	S228R	0.995
1:113854537:A:T	S228R	0.995
1:113854908:T:G	S228R	0.995
1:113854909:G:C	C227W	0.995
1:113854911:A:G	C227R	0.995
1:113858545:G:T	A101D	0.995
1:113848613:A:G	L281P	0.993
1:113852058:C:G	R266P	0.993
1:113854532:C:T	G230D	0.993
1:113854523:C:A	R233M	0.992
1:113856601:A:G	W143R	0.992
1:113856601:A:T	W143R	0.992
1:113857759:G:C	C129W	0.992
1:113859371:T:A	R59S	0.992
1:113859371:T:G	R59S	0.992
1:113814916:A:G	W805R	0.990
1:113814916:A:T	W805R	0.990
1:113854920:A:G	C224R	0.990
1:113848602:C:G	A285P	0.989

dbSNP variants (sampled 300 via entrez): RS1000012779 (1:113861150 T>C), RS1000069243 (1:113865159 C>T), RS1000070216 (1:113859587 A>G,T), RS1000083995 (1:113840177 T>C), RS1000259686 (1:113828699 G>A), RS1000271004 (1:113862653 T>A,C), RS1000308745 (1:113871478 C>A,G), RS1000316092 (1:113849115 T>A), RS1000320194 (1:113847822 C>T), RS1000496425 (1:113868336 G>A), RS1000505031 (1:113818294 A>G), RS1000572265 (1:113820282 C>T), RS1000675975 (1:113861487 G>A), RS1000705701 (1:113851417 G>T), RS1000728678 (1:113853331 T>A)

Disease associations

OMIM: gene MIM:600716 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
systemic lupus erythematosus	Supportive	Unknown
rheumatoid arthritis	Limited	Unknown
type 1 diabetes mellitus 1	Limited	Autosomal recessive
autoimmune disease	Limited	Autosomal dominant

Mondo (4): rheumatoid arthritis (MONDO:0008383), type 1 diabetes mellitus 1 (MONDO:0009100), systemic lupus erythematosus (MONDO:0007915), autoimmune disease (MONDO:0007179)

Orphanet (0):

HPO phenotypes

214 total (30 of 214 shown, HPO-id order):

HPO	Term
HP:0000024	Prostatitis
HP:0000071	Ureteral stenosis
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000099	Glomerulonephritis
HP:0000126	Hydronephrosis
HP:0000155	Oral ulcer
HP:0000163	Abnormal oral cavity morphology
HP:0000206	Glossitis
HP:0000246	Sinusitis
HP:0000360	Tinnitus
HP:0000365	Hearing impairment
HP:0000366	Abnormality of the nose
HP:0000388	Otitis media
HP:0000389	Chronic otitis media
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000421	Epistaxis
HP:0000488	Retinopathy
HP:0000491	Keratitis
HP:0000499	Abnormal eyelash morphology
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000520	Proptosis
HP:0000534	Abnormal eyebrow morphology
HP:0000541	Retinal detachment
HP:0000554	Uveitis
HP:0000572	Visual loss

GWAS associations

80 associations (top):

Study	Trait	p-value
GCST000038_7	Type 1 diabetes	2.000000e-80
GCST000038_9	Type 1 diabetes	8.000000e-24
GCST000040_2	Rheumatoid arthritis	6.000000e-25
GCST000043_3	Type 1 diabetes	5.000000e-26
GCST000054_3	Type 1 diabetes	1.000000e-07
GCST000070_3	Rheumatoid arthritis	2.000000e-11
GCST000207_19	Crohn’s disease	1.000000e-08
GCST000232_4	Rheumatoid arthritis	6.000000e-42
GCST000258_6	Type 1 diabetes	1.000000e-40
GCST000392_19	Type 1 diabetes	9.000000e-85
GCST000420_5	Rheumatoid arthritis	2.000000e-21
GCST000662_1	Vitiligo	1.000000e-07
GCST000879_51	Crohn’s disease	4.000000e-09
GCST000917_4	Rheumatoid arthritis	1.000000e-08
GCST001191_15	Type 1 diabetes	2.000000e-111
GCST001474_13	Hypothyroidism	3.000000e-13
GCST001611_4	Myasthenia gravis	8.000000e-10
GCST001729_13	Crohn’s disease	2.000000e-15
GCST001762_676	Obesity-related traits	2.000000e-06
GCST001937_47	Breast cancer	2.000000e-08
GCST002318_95	Rheumatoid arthritis	9.000000e-170
GCST002323_2	Rheumatoid arthritis	5.000000e-33
GCST002373_3	Thyroid peroxidase antibody levels	2.000000e-08
GCST002876_9	Type 1 diabetes and autoimmune thyroid diseases	7.000000e-20
GCST003097_2	Pediatric autoimmune diseases	8.000000e-11
GCST003155_36	Systemic lupus erythematosus	1.000000e-28
GCST003156_9	Systemic lupus erythematosus	1.000000e-15
GCST003251_19	Late-onset myasthenia gravis	7.000000e-06
GCST003620_3	Systemic lupus erythematosus or rheumatoid arthritis	2.000000e-35
GCST003622_67	Systemic lupus erythematosus	8.000000e-13

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0005134	amino acid measurement
EFO:0007874	gut microbiome measurement
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0004587	lymphocyte count
EFO:0000482	event free survival time
EFO:0004866	autoantibody measurement
EFO:0009706	latent autoimmune diabetes in adults
EFO:0009924	Drugs used in diabetes use measurement
EFO:0009933	Thyroid preparation use measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D001172	Arthritis, Rheumatoid	C05.550.114.154; C05.799.114; C17.300.775.099; C20.111.199
D001327	Autoimmune Diseases	C20.111
D008180	Lupus Erythematosus, Systemic	C17.300.480; C20.111.590

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2889 (SINGLE PROTEIN), CHEMBL5739544 (PROTEIN-PROTEIN INTERACTION)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2476601	PTPN22		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Protein tyrosine phosphatases non-receptor type (PTPN)

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
compound 8a [PMID: 23713581]	Inhibition	6.77	pIC50
NC1	Inhibition	5.37	pKi
I-C11	Inhibition	5.34	pIC50

Binding affinities (BindingDB)

242 measured of 363 human assays (379 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
5-(tosylmethyl)-2-furoic acid	IC50	23 nM
cid_694792	KI	60 nM
N-[3-[(2-methoxyphenyl)sulfamoyl]-4-(1-pyrrolidinyl)phenyl]-3-methyl-2-thiophenecarboxamide	IC50	163 nM
4-[5-[(Z)-[3-(4-nitrophenyl)-4-oxidanylidene-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl]benzoic acid	IC50	216 nM
CHEMBL2396721	IC50	310 nM
1-(2,6-dichlorophenyl)-3-(2-phenylethyl)thiourea	IC50	342 nM
cid_3578672	IC50	342 nM
1-[[1-(1-phenylethyl)-3-pyrrolidinyl]methyl]-3-(2,4,6-trimethylphenyl)thiourea	IC50	343 nM
4-[[2-bromanyl-4-[(E)-2-cyano-2-(3-fluorophenyl)ethenyl]phenoxy]methyl]benzoic acid	IC50	400 nM
2-[2-chloranyl-6-ethoxy-4-[(E)-[2-(naphthalen-2-ylamino)-4-oxidanylidene-1,3-thiazol-5-ylidene]methyl]phenoxy]ethanoic acid	IC50	440 nM
cid_67062	IC50	485 nM
MLS000409155	IC50	498 nM
SMR000311544	IC50	500 nM
cid_2162931	IC50	567 nM
1-(3-chloro-4-methoxyphenyl)-3-[2-(4-methyl-1-piperidinyl)ethyl]thiourea	IC50	720 nM
MLS-0109562.0001	IC50	727 nM
MLS000621546	IC50	740 nM
N’-(5-chloro-2-methoxyphenyl)-N-[(1-methyl-1H-indol-3-yl)methyl]-N-(3-morpholin-4-ylpropyl)thiourea	IC50	754 nM
SMR000624920	IC50	804 nM
SMR000143195	IC50	810 nM
2-[4-[(E)-[[4-[2-(4-chloroanilino)-1,3-thiazol-4-yl]benzoyl]hydrazinylidene]methyl]phenoxy]acetic acid	IC50	924 nM
SMR001268769	IC50	927 nM
MLS000679877	IC50	937 nM
3-[(5E)-5-[[4-[(4-chlorophenyl)methoxy]-3-methoxyphenyl]methylidene]-4-oxo-2-sulfanylidene-3-thiazolidinyl]benzoic acid	IC50	953 nM
(5-methyl-2-thiophenyl)-[4-(phenylmethyl)-1-piperazinyl]methanethione	IC50	997 nM
MLS001008494	IC50	1030 nM
N’-(4-chloro-2-methoxyphenyl)-N-[(1-methyl-1H-indol-3-yl)methyl]-N-(3-morpholin-4-ylpropyl)thiourea	IC50	1030 nM
2-[4-[(Z)-[2-(4-fluoroanilino)-4-keto-2-thiazolin-5-ylidene]methyl]phenoxy]acetic acid methyl ester	IC50	1050 nM
1-(3-chloro-4-methoxyphenyl)-3-[3-(1-pyrrolidinyl)propyl]thiourea	IC50	1120 nM
2-[3-[2-hydroxyethyl(dimethyl)azaniumyl]propanoylamino]-2-methyl-propane-1-sulfonate	EC50	1160 nM
2-[2-chloranyl-6-methoxy-4-[(Z)-[3-[2-[(4-methylphenyl)amino]-2-oxidanylidene-ethyl]-2,4-bis(oxidanylidene)-1,3-thiazolidin-5-ylidene]methyl]phenoxy]ethanoic acid	IC50	1180 nM
2-[2,6-bis(chloranyl)-4-[(Z)-[3-[2-[(4-methylphenyl)amino]-2-oxidanylidene-ethyl]-2,4-bis(oxidanylidene)-1,3-thiazolidin-5-ylidene]methyl]phenoxy]ethanoic acid	IC50	1200 nM
3-(2-{(E)-[1-(4-chlorophenyl)-2,5-dioxoimidazolidin-4-ylidene]methyl}-1H-pyrrol-1-yl)benzoic acid	IC50	1230 nM
3-[(5E)-5-[1-(2-chlorobenzyl)-2-keto-indolin-3-ylidene]-4-keto-2-thioxo-thiazolidin-3-yl]propionic acid	IC50	1230 nM
MLS000516376	IC50	1230 nM
MLS000737363	IC50	1240 nM
3-(3-chloranyl-4-methoxy-phenyl)-1-(3-methylbutyl)-1-(1-propan-2-ylpiperidin-4-yl)thiourea	IC50	1260 nM
4-[3-[(5Z)-4-keto-2-thioxo-5-veratrylidene-thiazolidin-3-yl]propanoylamino]benzoic acid	IC50	1270 nM
SMR000549393	IC50	1290 nM
2-[4-[[[4-[2-(4-chloroanilino)-1,3-thiazol-4-yl]benzoyl]hydrazinylidene]methyl]phenoxy]acetic acid	IC50	1300 nM
MLS000577024	IC50	1300 nM
2-(2,3-dihydro-1H-inden-5-yl)-N-[2-[(2-methoxyphenyl)amino]-2-oxidanylidene-ethyl]-N-propyl-ethanamide	IC50	1320 nM
cid_3390606	IC50	1360 nM
(4-ethoxyphenyl)-(4-methyl-1-piperazinyl)methanethione	IC50	1420 nM
1-ethyl-6-methyl-3-[(E)-2-phenylethenyl]pyrimido[5,4-e][1,2,4]triazine-5,7-dione	EC50	1440 nM
cid_9595040	IC50	1490 nM
cid_7693352	IC50	1510 nM
(5Z)-2-azanylidene-3-(4-fluorophenyl)-5-[(4-hydroxyphenyl)methylidene]-1,3-thiazolidin-4-one	IC50	1550 nM
2-hydroxy-4-({4-[5-(2-methyl-3-phenyl-2-propen-1-ylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]butanoyl}amino)benzoic acid	IC50	1560 nM
1,3,6-Trimethyl-1H-pyrimido[5,4-e][1,2,4]triazine-5,7-dione	EC50	1610 nM

ChEMBL bioactivities

326 potent at pChembl≥5 of 551 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.96	Ki	110	nM	CHEMBL2396719
6.95	IC50	113	nM	CHEMBL1701224
6.92	IC50	120	nM	SODIUM ORTHOVANAD
6.85	Ki	140	nM	CHEMBL6103296
6.77	IC50	171	nM	CHEMBL2396718
6.77	IC50	170	nM	CHEMBL2396719
6.60	IC50	250	nM	CHEMBL2396719
6.60	IC50	250	nM	CHEMBL6078598
6.60	IC50	250	nM	CHEMBL6103296
6.60	IC50	249	nM	CHEMBL1701224
6.59	IC50	259	nM	CHEMBL2396719
6.59	IC50	259	nM	CHEMBL2396723
6.58	IC50	263	nM	CHEMBL2396720
6.58	IC50	260	nM	CHEMBL6133607
6.57	IC50	270	nM	CHEMBL1650888
6.54	IC50	290	nM	CHEMBL6120825
6.52	IC50	300	nM	CHEMBL2396717
6.51	IC50	310	nM	CHEMBL2396721
6.47	IC50	340	nM	CHEMBL1650889
6.47	IC50	340	nM	CHEMBL1650890
6.43	IC50	369	nM	CHEMBL1701224
6.42	Ki	380	nM	CHEMBL6078571
6.42	IC50	380	nM	CHEMBL1650891
6.41	IC50	390	nM	CHEMBL442448
6.39	IC50	410	nM	CHEMBL1650892
6.38	IC50	420	nM	CHEMBL6148148
6.37	IC50	430	nM	CHEMBL6103444
6.36	IC50	440	nM	CHEMBL6082988
6.32	IC50	480	nM	CHEMBL1649599
6.30	Ki	500	nM	CHEMBL6048572
6.29	IC50	508	nM	CHEMBL6078571
6.28	IC50	530	nM	CHEMBL6146280
6.28	IC50	520	nM	CHEMBL1650893
6.28	IC50	527	nM	CHEMBL1701224
6.26	IC50	550	nM	CHEMBL2396722
6.26	IC50	550	nM	CHEMBL6142357
6.25	IC50	560	nM	CHEMBL1650894
6.22	IC50	602	nM	CHEMBL1408081
6.21	IC50	610	nM	CHEMBL2396714
6.21	IC50	610	nM	CHEMBL1650895
6.20	IC50	630	nM	CHEMBL2316908
6.20	IC50	630	nM	CHEMBL6133408
6.20	IC50	626	nM	CHEMBL1701224
6.19	IC50	640	nM	CHEMBL1650896
6.19	IC50	650	nM	CHEMBL1650897
6.19	IC50	650	nM	CHEMBL1650898
6.17	IC50	680	nM	CHEMBL2396713
6.17	IC50	670	nM	CHEMBL2396724
6.15	IC50	710	nM	CHEMBL1650899
6.13	IC50	740	nM	CHEMBL1650900

PubChem BioAssay actives

167 with measured affinity, of 520 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
3-[2-(3-chlorophenyl)ethynyl]-2-[4-[2-(cyclopropylamino)-2-oxoethoxy]phenyl]-6-hydroxy-1-benzofuran-5-carboxylic acid	755730: Competitive inhibition of N-terminal 6xHis-tagged LYP catalytic domain (1 to 303) (unknown origin) expressed in Escherichia coli BL21(DE3) using pNPP as substrate by Dixon plot analysis	ki	0.1100	uM
3-[2-(3-chlorophenyl)ethynyl]-6-hydroxy-2-[4-[2-oxo-2-(propylamino)ethoxy]phenyl]-1-benzofuran-5-carboxylic acid	755782: Inhibition of N-terminal 6xHis-tagged LYP catalytic domain (1 to 303) (unknown origin) expressed in Escherichia coli BL21(DE3) using pNPP as substrate by spectrophotometric analysis	ic50	0.1710	uM
3-[2-(3-chlorophenyl)ethynyl]-2-[4-[2-[(3,4-dimethoxyphenyl)methylamino]-2-oxoethoxy]phenyl]-6-hydroxy-1-benzofuran-5-carboxylic acid	755782: Inhibition of N-terminal 6xHis-tagged LYP catalytic domain (1 to 303) (unknown origin) expressed in Escherichia coli BL21(DE3) using pNPP as substrate by spectrophotometric analysis	ic50	0.2590	uM
2-[4-(2-anilino-2-oxoethoxy)phenyl]-3-[2-(3-chlorophenyl)ethynyl]-6-hydroxy-1-benzofuran-5-carboxylic acid	755782: Inhibition of N-terminal 6xHis-tagged LYP catalytic domain (1 to 303) (unknown origin) expressed in Escherichia coli BL21(DE3) using pNPP as substrate by spectrophotometric analysis	ic50	0.2630	uM
3-[1-[4-[(4-bromonaphthalen-1-yl)amino]-4-oxobutyl]triazol-4-yl]-6-hydroxy-2-(4-methylphenyl)-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	0.2700	uM
3-[2-(3-chlorophenyl)ethynyl]-6-hydroxy-2-[3-[2-oxo-2-(4-propan-2-ylanilino)ethoxy]phenyl]-1-benzofuran-5-carboxylic acid	755782: Inhibition of N-terminal 6xHis-tagged LYP catalytic domain (1 to 303) (unknown origin) expressed in Escherichia coli BL21(DE3) using pNPP as substrate by spectrophotometric analysis	ic50	0.3000	uM
2-[4-[2-(1-adamantylamino)-2-oxoethoxy]phenyl]-3-[2-(3-chlorophenyl)ethynyl]-6-hydroxy-1-benzofuran-5-carboxylic acid	755782: Inhibition of N-terminal 6xHis-tagged LYP catalytic domain (1 to 303) (unknown origin) expressed in Escherichia coli BL21(DE3) using pNPP as substrate by spectrophotometric analysis	ic50	0.3100	uM
6-hydroxy-2-(4-methoxyphenyl)-3-[1-[4-(naphthalen-1-ylamino)-4-oxobutyl]triazol-4-yl]-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	0.3400	uM
6-hydroxy-2-(4-methoxyphenyl)-3-[1-[4-[(4-nitronaphthalen-1-yl)amino]-4-oxobutyl]triazol-4-yl]-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	0.3400	uM
3-[1-[4-[(4-chloronaphthalen-1-yl)amino]-4-oxobutyl]triazol-4-yl]-6-hydroxy-2-(4-methylphenyl)-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	0.3800	uM
3-[(5Z)-5-[[5-(4-hydroxy-3-methoxycarbonylphenyl)thiophen-2-yl]methylidene]-2,4-dioxo-1,3-thiazolidin-3-yl]propanoic acid	332012: Inhibition of lymphoid specific tyrosine phosphatase	ic50	0.3900	uM
6-hydroxy-2-(4-methylphenyl)-3-[1-[4-(naphthalen-1-ylamino)-4-oxobutyl]triazol-4-yl]-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	0.4100	uM
6-hydroxy-2-(4-methylphenyl)-3-[1-[4-oxo-4-(pyren-1-ylamino)butyl]triazol-4-yl]-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	0.4800	uM
6-hydroxy-3-[1-[4-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-4-oxobutyl]triazol-4-yl]-2-(3-methylphenyl)-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	0.5200	uM
3-[2-(3-chlorophenyl)ethynyl]-2-[4-[2-[4-(3,4-dichlorophenyl)piperidin-1-yl]-2-oxoethoxy]phenyl]-6-hydroxy-1-benzofuran-5-carboxylic acid	755782: Inhibition of N-terminal 6xHis-tagged LYP catalytic domain (1 to 303) (unknown origin) expressed in Escherichia coli BL21(DE3) using pNPP as substrate by spectrophotometric analysis	ic50	0.5500	uM
3-[1-[4-[(4-chloronaphthalen-1-yl)amino]-4-oxobutyl]triazol-4-yl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	0.5600	uM
3-[1-[4-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-4-oxobutyl]triazol-4-yl]-6-hydroxy-2-(3-methylphenyl)-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	0.6100	uM
3-[2-(3,4-dichlorophenyl)ethynyl]-6-hydroxy-2-[4-(trifluoromethoxy)phenyl]-1-benzofuran-5-carboxylic acid	755782: Inhibition of N-terminal 6xHis-tagged LYP catalytic domain (1 to 303) (unknown origin) expressed in Escherichia coli BL21(DE3) using pNPP as substrate by spectrophotometric analysis	ic50	0.6100	uM
6-hydroxy-3-[2-(4-phenoxyphenyl)ethynyl]-2-phenyl-1-benzofuran-5-carboxylic acid	725276: Inhibition of LYP (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	0.6300	uM
6-hydroxy-2-(4-methylphenyl)-3-[1-[4-[(4-nitronaphthalen-1-yl)amino]-4-oxobutyl]triazol-4-yl]-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	0.6400	uM
3-[1-(4-anilino-4-oxobutyl)triazol-4-yl]-6-hydroxy-2-(3-methylphenyl)-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	0.6500	uM
3-[1-[4-(benzylamino)-4-oxobutyl]triazol-4-yl]-6-hydroxy-2-(3-methylphenyl)-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	0.6500	uM
3-[2-(3-chlorophenyl)ethynyl]-2-[4-[2-[2-(2,4-dichlorophenyl)ethylamino]-2-oxoethoxy]phenyl]-6-hydroxy-1-benzofuran-5-carboxylic acid	755782: Inhibition of N-terminal 6xHis-tagged LYP catalytic domain (1 to 303) (unknown origin) expressed in Escherichia coli BL21(DE3) using pNPP as substrate by spectrophotometric analysis	ic50	0.6700	uM
3-[2-(3-chlorophenyl)ethynyl]-6-hydroxy-2-[4-(trifluoromethoxy)phenyl]-1-benzofuran-5-carboxylic acid	755782: Inhibition of N-terminal 6xHis-tagged LYP catalytic domain (1 to 303) (unknown origin) expressed in Escherichia coli BL21(DE3) using pNPP as substrate by spectrophotometric analysis	ic50	0.6800	uM
3-[1-[4-[(4-bromonaphthalen-1-yl)amino]-4-oxobutyl]triazol-4-yl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	0.7100	uM
3-[1-[4-(benzylamino)-4-oxobutyl]triazol-4-yl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	0.7400	uM
6-hydroxy-3-[1-[2-(naphthalen-1-ylamino)-2-oxoethyl]triazol-4-yl]-2-phenyl-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	0.7700	uM
3-[1-[4-(cyclohexylamino)-4-oxobutyl]triazol-4-yl]-6-hydroxy-2-(4-methylphenyl)-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	0.9000	uM
6-hydroxy-3-[1-[3-(naphthalen-1-ylamino)-3-oxopropyl]triazol-4-yl]-2-phenyl-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	0.9100	uM
5-[(4-phenylmethoxyphenyl)methyl-(4-phenylphenyl)sulfonylamino]-1-benzofuran-2-carboxylic acid	2133933: Competitive inhibition of N-terminal His-tagged LYP catalytic domain (1 to 294 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using pNPP as substrate assessed as inhibition constant by Lineweaver-Burk plot analysis	ki	0.9300	uM
3-[1-[4-(benzylamino)-4-oxobutyl]triazol-4-yl]-6-hydroxy-2-(4-methylphenyl)-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	0.9700	uM
3-[(5E)-5-[[5-(1,3-benzothiazol-2-yl)furan-2-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]propanoic acid	332012: Inhibition of lymphoid specific tyrosine phosphatase	ic50	0.9800	uM
3-[2-(3-chlorophenyl)ethynyl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid	725276: Inhibition of LYP (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	0.9900	uM
3-[2-[(Z)-[3-[2-(2,4-dimethylanilino)-2-oxoethyl]-2,4-dioxo-1,3-thiazolidin-5-ylidene]methyl]pyrrol-1-yl]benzoic acid	332012: Inhibition of lymphoid specific tyrosine phosphatase	ic50	1.0000	uM
6-hydroxy-3-iodo-1-methyl-2-[3-[[2-oxo-2-(4-thiophen-3-ylanilino)acetyl]amino]phenyl]indole-5-carboxylic acid	1182541: Inhibition of LYP (unknown origin)	ic50	1.0500	uM
naphthalene-1,2-dione	1182274: Inhibition of LYP (unknown origin) using DiFMUP substrate incubated for 2 hrs	ic50	1.1000	uM
6-hydroxy-2-(4-methylphenyl)-3-[1-[4-oxo-4-(quinolin-8-ylamino)butyl]triazol-4-yl]-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	1.1100	uM
6-hydroxy-2-(4-methylphenyl)-3-[1-[2-(naphthalen-1-ylamino)-2-oxoethyl]triazol-4-yl]-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	1.1800	uM
4-[(5E)-5-[[5-(1,3-benzothiazol-2-yl)furan-2-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]butanoic acid	332012: Inhibition of lymphoid specific tyrosine phosphatase	ic50	1.3000	uM
3-[2-(3,5-difluorophenyl)ethynyl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid	725276: Inhibition of LYP (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	1.3000	uM
5-[(4-chloro-3-nitrophenyl)sulfonyl-[[4-(4-methoxyphenyl)phenyl]methyl]amino]-1-benzofuran-2-carboxylic acid	2133933: Competitive inhibition of N-terminal His-tagged LYP catalytic domain (1 to 294 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using pNPP as substrate assessed as inhibition constant by Lineweaver-Burk plot analysis	ki	1.3400	uM
6-hydroxy-2-(4-methylphenyl)-3-[1-[3-(naphthalen-1-ylamino)-3-oxopropyl]triazol-4-yl]-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	1.3500	uM
6-hydroxy-3-[1-[4-[(4-nitronaphthalen-1-yl)amino]-4-oxobutyl]triazol-4-yl]-2-phenyl-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	1.4900	uM
2-hydroxy-5-[5-[(Z)-[3-(2-methoxy-2-oxoethyl)-2,4-dioxo-1,3-thiazolidin-5-ylidene]methyl]thiophen-2-yl]benzoic acid	332012: Inhibition of lymphoid specific tyrosine phosphatase	ic50	1.8000	uM
6-hydroxy-2-(4-methylphenyl)-3-[1-[6-(naphthalen-1-ylamino)-6-oxohexyl]triazol-4-yl]-1-benzofuran-5-carboxylic acid	566809: Inhibition of recombinant LyP assessed as hydrolysis of DiFMUP	ic50	1.8000	uM
3-ethynyl-6-hydroxy-2-(4-phenylphenyl)-1-benzofuran-5-carboxylic acid	755782: Inhibition of N-terminal 6xHis-tagged LYP catalytic domain (1 to 303) (unknown origin) expressed in Escherichia coli BL21(DE3) using pNPP as substrate by spectrophotometric analysis	ic50	1.8200	uM
3-[2-[(Z)-[3-[2-(2-methylanilino)-2-oxoethyl]-2,4-dioxo-1,3-thiazolidin-5-ylidene]methyl]pyrrol-1-yl]benzoic acid	332012: Inhibition of lymphoid specific tyrosine phosphatase	ic50	1.9000	uM
4-[(E)-3-(3-nitrophenyl)-3-oxoprop-1-enyl]benzoic acid	1664545: Competitive inhibition of LYP (unknown origin) assessed as inhibition constant using varying level of pNPP as substrate by Lineweaver-Burk plot analysis	ki	1.9000	uM
2-[(5Z)-5-[(E)-3-(furan-2-yl)prop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-methylbutanoic acid	332012: Inhibition of lymphoid specific tyrosine phosphatase	ic50	1.9000	uM
2-(1-carboxyethoxy)-5-[(2S)-3-[4-(3-hydroxy-2-methoxycarbonylphenoxy)butylamino]-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]-3-oxopropyl]benzoic acid	210268: Inhibition of T-cell Protein Tyrosine Phosphatase (TCPTP)	ki	1.9700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	4
Benzo(a)pyrene	decreases methylation, increases methylation, decreases expression	2
Nickel	affects expression, increases expression, decreases reaction	2
Magnetite Nanoparticles	increases expression, affects cotreatment	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	increases expression	1
triphenyl phosphate	affects expression	1
titanium dioxide	increases expression	1
trichostatin A	affects expression, decreases reaction	1
sulforaphane	increases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Irinotecan	increases expression	1
Temozolomide	decreases expression	1
Amphotericin B	decreases expression	1
Arsenic	affects methylation	1
Benzene	increases expression	1
Capsaicin	increases expression	1
Clorgyline	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Succimer	affects cotreatment, increases expression	1
Estradiol	affects expression	1
Ethyl Methanesulfonate	increases expression	1
Folic Acid	affects expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	increases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression, affects response to substance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Tretinoin	increases expression	1
Vanadates	increases expression	1

ChEMBL screening assays

137 unique, capped per target: 122 binding, 10 functional, 5 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1070016	Binding	Inhibition of Lyp expressed in Escherichia coli assessed as inhibition of p-nitrophenyl phosphate hydrolysis at pH 7 by spectrophotometry	Salicylic acid based small molecule inhibitor for the oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2). — J Med Chem
CHEMBL1737900	Functional	PUBCHEM_BIOASSAY: SAR LYP1 Fluorescent Assay using pCAP substrate for In Vitro dose response studies - Set 2. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID1779, AID1784, AID2135, AID449727]	PubChem BioAssay data set
CHEMBL4625400	ADMET	Inhibition of LYP (unknown origin) at 25 uM using pNPP as substrate relative to control	A chalcone derivative binds a putative allosteric site of YopH: Inhibition of a virulence factor of Yersinia. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00056667	PHASE4	COMPLETED	Relaxation Response Training for the Treatment of Rheumatoid Arthritis
NCT00094341	PHASE4	COMPLETED	Preference of Rheumatoid Arthritis (RA) Patients of Enbrel® (Etanercept) Auto-Injector Versus Enbrel® Pre-Filled Syringes
NCT00099554	PHASE4	COMPLETED	Effectiveness and Safety of Enbrel® (Etanercept) in Rheumatoid Arthritis Subjects Who Have Failed Remicade® (Infliximab)
NCT00111410	PHASE4	COMPLETED	Evaluating the Effect of Anakinra (r-metHuIL-1ra) on Vaccine AntibodyResponse in Subjects With Rheumatoid Arthritis (RA)
NCT00115219	PHASE4	COMPLETED	Evaluating Efficacy and Safety of Etanercept 50 mg Twice Weekly (BIW) in Rheumatoid Arthritis (RA) Subjects Who Are Sub-Optimal Responders to Etanercept 50 mg Once Weekly (QW)
NCT00121043	PHASE4	COMPLETED	Evaluating Kineret® (Anakinra) in Rheumatoid Arthritis (RA) Subjects Using aSelf-Reported Questionnaire
NCT00132418	PHASE4	COMPLETED	Study of Enbrel in Rheumatoid Arthritis (RA) Subjects With Comorbid Disorders
NCT00157872	PHASE4	COMPLETED	A Study of Rofecoxib Versus Naproxen in the Treatment of Chinese Patient With Rheumatoid Arthritis (0966-231)
NCT00195494	PHASE4	COMPLETED	Study Comparing Etanercept and Methotrexate vs. Methotrexate Alone in Rheumatoid Arthritis
NCT00208364	PHASE4	TERMINATED	A Two Centre Study to Assess the Long-term Performance of the Pinnacle™ Cup With a Metal-on-Metal Bearing in Primary Total Hip Replacement
NCT00208377	PHASE4	TERMINATED	A Multi-centre Study to Assess the Long-term Performance of the DePuy ASR™ System in Primary Hip Resurfacing Surgery
NCT00208390	PHASE4	TERMINATED	A Multi-centre Study to Assess the Long-term Performance of the Summit™ Hip in Primary Total Hip Replacement
NCT00208429	PHASE4	WITHDRAWN	A Multi-centre Study to Assess the Long-term Performance of the Pinnacle™ Cup With a Polyethylene-on-metal Bearing in Primary Total Hip Replacement
NCT00208455	PHASE4	TERMINATED	A Multi-centre Study to Assess the Long-term Performance of the DePuy PROXIMA™ Hip in Primary Total Hip Replacement
NCT00209859	PHASE4	COMPLETED	Methotrexate and Cyclosporine in Treatment of Early Rheumatoid Arthritis
NCT00216177	PHASE4	UNKNOWN	Comparison of Adalimumab and Infliximab Treatment of Rheumatoid Arthritis
NCT00233558	PHASE4	TERMINATED	Open-Label Steroid Reduction Study of Adalimumab With Methotrexate in Patients With Active Rheumatoid Arthritis
NCT00234234	PHASE4	COMPLETED	Predictors of the Response to Adalimumab in Rheumatoid Arthritis
NCT00234897	PHASE4	COMPLETED	Efficacy of HUMIRA in Subjects With Active Rheumatoid Arthritis
NCT00244556	PHASE4	COMPLETED	Study Comparing Enbrel (Etanercept) Plus Methotrexate Versus Enbrel Alone in Active Rheumatoid Arthritis Despite Current Methotrexate Therapy
NCT00252668	PHASE4	COMPLETED	Study Evaluating the Combination of Etanercept and Methotrexate in Rheumatoid Arthritis Subjects
NCT00259610	PHASE4	COMPLETED	Treatment of Early Aggressive Rheumatoid Arthritis (TEAR)
NCT00291915	PHASE4	UNKNOWN	Multicenter Randomized Prospective Trial Comparing Methotrexate Alone or in Combination With Adalimumab in Early Arthritis
NCT00319917	PHASE4	COMPLETED	A Double Blind Placebo Controlled Study to Assess the Efficacy on Joint Damage in RA Patients
NCT00334620	PHASE4	COMPLETED	Effectiveness of Radon Spa Therapy in Multimodal Rehabilitative Treatment of Rheumatoid Arthritis
NCT00346294	PHASE4	COMPLETED	An Open-Label Study to Assess the Rate of Failure of an Enbrel® (Etanercept) SureClick™ Auto-injector in Subjects With Rheumatoid Arthritis
NCT00356473	PHASE4	COMPLETED	Effects of Atorvastatin on Disease Activity and HDL Cholesterol Function in Patients With Rheumatoid Arthritis
NCT00369187	PHASE4	COMPLETED	Study of a Large Protein Molecule Administered With Escalating Doses of Recombinant Human Hyaluronidase
NCT00385528	PHASE4	COMPLETED	Effects of a Multi-Faceted Psychiatric Intervention Targeted at the Complex Medically Ill: a Randomized Controlled Trial
NCT00396747	PHASE4	COMPLETED	A Comparison of Methotrexate Alone or Combined to Infliximab or to Pulse Methylprednisolone in Early Rheumatoid Arthritis: A Magnetic Resonance Imaging Study
NCT00420927	PHASE4	COMPLETED	Study of the Optimal Protocol for Methotrexate and Adalimumab Combination Therapy in Early Rheumatoid Arthritis
NCT00422227	PHASE4	COMPLETED	Study Comparing Etanercept With Usual DMARD Therapy in Subjects With Rheumatoid Arthritis in the Asia Pacific Region
NCT00424502	PHASE4	COMPLETED	A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to a TNF-Blocker.
NCT00434200	PHASE4	UNKNOWN	Rheumatoid Arthritis Patients in Training
NCT00439062	PHASE4	COMPLETED	Treatment of Rheumatoid Arthritis With Roxithromycin
NCT00447759	PHASE4	COMPLETED	The Standard Care Versus Celecoxib Outcome Trial
NCT00462072	PHASE4	COMPLETED	Centocor Microarray Study of Patients
NCT00462345	PHASE4	COMPLETED	A Study of MabThera (Rituximab) in Combination With Methotrexate in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNF Therapies.
NCT00480272	PHASE4	COMPLETED	Prospective Study on Intensive Early Rheumatoid Arthritis Treatment
NCT00502853	PHASE4	COMPLETED	A Pilot Study of MabThera (Rituximab) Evaluated by MRI in Patients With Rheumatoid Arthritis.