SYK

Summary

SYK (spleen associated tyrosine kinase, HGNC:11491) is a protein-coding gene on chromosome 9q22.2, encoding Tyrosine-protein kinase SYK (P43405). Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). In precision oncology, SYK OVEREXPRESSION is associated with resistance to Paclitaxel in Ovarian Cancer (CIViC Level D).

This gene encodes a member of the family of non-receptor type Tyr protein kinases. This protein is widely expressed in hematopoietic cells and is involved in coupling activated immunoreceptors to downstream signaling events that mediate diverse cellular responses, including proliferation, differentiation, and phagocytosis. It is thought to be a modulator of epithelial cell growth and a potential tumour suppressor in human breast carcinomas. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6850 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 82 with systemic inflammation (Strong, GenCC)
• GWAS associations: 17
• Clinical variants (ClinVar): 115 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 51
• Druggable target: yes — 54 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_003177

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11491
Approved symbol	SYK
Name	spleen associated tyrosine kinase
Location	9q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000165025
Ensembl biotype	protein_coding
OMIM	600085
Entrez	6850

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 15 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000375746, ENST00000375747, ENST00000375751, ENST00000375754, ENST00000476708, ENST00000865872, ENST00000865873, ENST00000865874, ENST00000865875, ENST00000865876, ENST00000865877, ENST00000865878, ENST00000865879, ENST00000970482, ENST00000970483, ENST00000970484

RefSeq mRNA: 4 — MANE Select: NM_003177 NM_001135052, NM_001174167, NM_001174168, NM_003177

CCDS: CCDS47992, CCDS6688

Canonical transcript exons

ENST00000375754 — 14 exons

Exon	Start	End
ENSE00001176425	90864589	90864667
ENSE00001176435	90888515	90888627
ENSE00001176447	90887749	90887889
ENSE00001176458	90878764	90878953
ENSE00001176467	90877571	90877780
ENSE00001176477	90874672	90874849
ENSE00001176486	90874204	90874291
ENSE00001176494	90867131	90867199
ENSE00001176505	90865048	90865097
ENSE00001176518	90862206	90862344
ENSE00001176524	90845434	90845594
ENSE00001468273	90895528	90898549
ENSE00001468302	90843858	90844315
ENSE00003843040	90801819	90801893

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 97.31.

FANTOM5 (CAGE): breadth broad, TPM avg 14.4341 / max 487.2953, expressed in 885 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97319	12.4094	860
97323	0.9855	130
97321	0.6664	248
97320	0.0984	42
97322	0.0738	31
97317	0.0733	30
97324	0.0720	38
97318	0.0554	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	97.31	gold quality
mononuclear cell	CL:0000842	96.84	gold quality
leukocyte	CL:0000738	96.81	gold quality
granulocyte	CL:0000094	95.15	gold quality
blood	UBERON:0000178	95.13	gold quality
epithelium of nasopharynx	UBERON:0001951	94.97	gold quality
bone marrow cell	CL:0002092	93.04	gold quality
bone marrow	UBERON:0002371	92.84	gold quality
vermiform appendix	UBERON:0001154	92.68	gold quality
trabecular bone tissue	UBERON:0002483	92.46	gold quality
lymph node	UBERON:0000029	91.84	gold quality
spleen	UBERON:0002106	91.36	gold quality
esophagus squamous epithelium	UBERON:0006920	89.70	gold quality
jejunal mucosa	UBERON:0000399	89.23	gold quality
caecum	UBERON:0001153	88.70	gold quality
tonsil	UBERON:0002372	88.40	gold quality
rectum	UBERON:0001052	87.83	gold quality
amniotic fluid	UBERON:0000173	87.62	gold quality
duodenum	UBERON:0002114	87.12	gold quality
thymus	UBERON:0002370	86.91	gold quality
ileal mucosa	UBERON:0000331	86.82	gold quality
epithelium of esophagus	UBERON:0001976	86.39	gold quality
mucosa of transverse colon	UBERON:0004991	86.01	gold quality
thyroid gland	UBERON:0002046	85.86	gold quality
palpebral conjunctiva	UBERON:0001812	85.77	gold quality
right lobe of thyroid gland	UBERON:0001119	85.70	gold quality
left lobe of thyroid gland	UBERON:0001120	85.69	gold quality
small intestine	UBERON:0002108	85.57	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.51	gold quality
endometrium epithelium	UBERON:0004811	85.51	silver quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	37.27
E-HCAD-35	yes	34.91
E-CURD-122	yes	22.58
E-ANND-3	yes	17.41
E-MTAB-9067	yes	15.71
E-HCAD-25	yes	15.36
E-MTAB-10042	yes	4.53
E-MTAB-6386	no	686.41

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREM, ETS2, JUN, NR0B2, POU2F2, PPARG, SPI1, TP53, TXK

miRNA regulators (miRDB)

106 targeting SYK, 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-6798-5P	100.00	65.77	699
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-6132	99.60	65.83	1554

Literature-anchored findings (GeneRIF, showing 40)

• Syk kinase is required for the sequential events of Fc gamma IIa receptor-mediated phagocytosis leading to particle uptake by the receptor-bearing monocyte or neutrophil. (PMID:11441091)
• Primary arrest of circulating platelets on collagen involves phosphorylation of Syk, cortactin and focal adhesion kinase (PMID:11988077)
• Syk/hSlo interaction does not affect the electrical features of BK channels in osteosarcoma cells. (PMID:12009018)
• Proteasome-dependent regulation of Syk tyrosine kinase levels in basophils (PMID:12209081)
• actin-linking proteins moesin and ezrin directly interact with Syk in an ITAM-dependent manner (PMID:12387735)
• mechanism of IL-2-activated SYK regulation of Akt-dependent cell survival in NK cells (PMID:12393431)
• Our data suggest that reduced Syk expression in breast cancers is associated with distant metastasis and poor prognosis. (PMID:12445683)
• This protein suppresses the cell motility and nuclear factor kappa B-mediated secretion of urokinase type plasminogen activator by inhibiting the phosphatidylinositol 3’-kinase activity in breast cancer cells. (PMID:12477728)
• Syk kinase is up-regulated specifically in activated/effector T cells generated by stimulation with anti-CD3 or antigen, and perhaps may serve as both novel indicator for immune activation and target for manipulation of ongoing immune responses. (PMID:12682251)
• H2O2 induces NF-kappaB activation, not through serine phosphorylation or degradation of IkappaBalpha, but through Syk-mediated tyrosine phosphorylation of IkappaBalpha (PMID:12711606)
• Nuclear Syk possesses biological activities associated with tumor suppression in mammary epithelial cells. (PMID:12907655)
• “Syk was first isolated and characterized by Zioncheck et al. and is known to be associated with high affinity IgE receptor…and involved in the signaling pathway after cross-linking of this receptor by antigen in mast cells and basophils.” p. 1685 (PMID:14646171)
• role in lipopolysaccharide-induced c-Jun NH2-terminal kinase activation in human neutrophils (PMID:14699155)
• Hypermethylation leads to lose of the syk gene expression in human breast carcinoma and may be correlated to oncogenesis, metastasis of breast carcinoma. (PMID:15059510)
• The interplay between Syk and ZAP-70 in thymocytes, certain T cells, and B-chronic lymphocytic leukemia cells will modulate the amplitude of antigen-mediated receptor signaling. (PMID:15059847)
• The expression of the Syk gene may play an important role in suppressing growth and metastasis of breast cancer. (PMID:15062056)
• A Syk-dependent signaling cascade controls anti-myeloperoxidase IgM ANCA-dependent neutrophil adhesion and apoptosis. (PMID:15163542)
• data indicate that Syk kinase plays an important role in the translocation of hematopoietic lineage cell-specific protein 1 (HS1) into lipid rafts (PMID:15166239)
• Methylation of Syk promoter is correlated to oncogenesis and metastasis of gastric carcinoma. (PMID:15188513)
• Syk acts a negative control element of EGFR signalling. (PMID:15337524)
• x-ray structure of spleen tyrosine kinase bound to Gleevec (PMID:15507431)
• C-terminal SH2 domain of p85 PI-3 kinase was sufficient for mediating an interaction with tyrosine-phosphorylated Syk (PMID:15536084)
• propose that Syk is involved in signaling pathways induced by integrin engagement in airway epithelial cells; Syk-mediated signaling regulates IL-6 and ICAM-1 expression and may be important in the pathophysiology of lung inflammation (PMID:15557085)
• there is a complex interplay between PKCalpha, Syk, and Src involving physical interaction, phosphorylation, translocation within the cell, and functional activity regulation (PMID:15583006)
• Results demonstrated that the lysosomal change accompanied with the activation of lysosomal enzymes is a primary step in BCR-crosslinking-mediated apoptosis and Syk is responsible for this step through the fusion of BCR-carrying endosomes to lysosomes. (PMID:15670211)
• c-Cbl plays a regulatory role in glycoprotein VI (GPVI)/Fc receptor gamma (FcRgamma)-chain-dependent platelet activation through its interaction with Syk (PMID:15701717)
• These results demonstrate that Syk participates in CXCL12-induced cell polarization, which occurs in concert with cell adhesion mediated by beta1 integrin. (PMID:15707999)
• The SYK is present in the majority of mediastinal B cell lymphomas. (PMID:15744341)
• Novel role for Syk in the maintenance of a bipolar phenotype by regulating lamellipodium formation, which is a critical prerequisite for site-directed migration of leukocytes. (PMID:15754322)
• HS1 Tyr phosphorylation catalyzed by Syk and Lyn plays a crucial role in the translocation of the protein to the membrane and is involved in the cytoskeleton rearrangement triggered by thrombin in human platelets (PMID:15795233)
• Syk-transfected cells formed significantly fewer metastatic tumor lesions than control cells. Syk is novel regulator of metastatic behavior of melanoma cells. (PMID:15955106)
• Dectin-1 activates Syk tyrosine kinase in macrophages for reactive oxygen production (PMID:15956283)
• Data reveal a complex process controlling the association and catalytic activity of protein tyrosine kinases syk and lyn with the human erythrocyte membrane. (PMID:16085052)
• CD21 activation triggered Cbl tyrosine phosphorylation, which interacts with SH2 domains of p85 subunit, SH2 domains of Crk-L and with tyrosine phosphorylated Syk kinase. CD21 activation triggers dissociation of Cbl-Vav complex. (PMID:16289966)
• Shiga toxin (Stx)was found to activate Syk and induce rapid tyrosine phosphorylation of several proteins, one protein being clathrin heavy chain. (PMID:16371508)
• Syk plays an indispensable role in complement-mediated phagocytosis by regulating both actin dynamics and the RhoA activation pathway, and these functions of Syk lead to phagosome formation and pathogen engulfment. (PMID:16449524)
• the cross-talk between Syk and Lck regulates hypoxia/reoxygenation-induced breast cancer progression (PMID:16474166)
• Taken together, these findings indicate that C3bi targets the phagocytic cargo, and engagement or diversion of the Syk route determines the phagocyte response. (PMID:16501050)
• Overview discusses the role of Syk that is essential to complement-mediated phagocytosis. (PMID:16754322)
• identify novel regulatory mechanisms of leukocyte rolling on selectins with a strong dependency on lipid raft integrity and Syk activity (PMID:16849645)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	syk	ENSDARG00000008186
mus_musculus	Syk	ENSMUSG00000021457
rattus_norvegicus	Syk	ENSRNOG00000012160

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), BTK (ENSG00000010671), FYN (ENSG00000010810), STYK1 (ENSG00000060140), TNK2 (ENSG00000061938), TXK (ENSG00000074966), JAK2 (ENSG00000096968), ABL1 (ENSG00000097007), PTK6 (ENSG00000101213), HCK (ENSG00000101336), BMX (ENSG00000102010), CSK (ENSG00000103653), TYK2 (ENSG00000105397), JAK3 (ENSG00000105639), FRK (ENSG00000111816), ITK (ENSG00000113263), ZAP70 (ENSG00000115085), PTK2B (ENSG00000120899), SRMS (ENSG00000125508), TEC (ENSG00000135605), BLK (ENSG00000136573), ABL2 (ENSG00000143322), FER (ENSG00000151422), JAK1 (ENSG00000162434), PTK2 (ENSG00000169398), TNK1 (ENSG00000174292), YES1 (ENSG00000176105), FES (ENSG00000182511), LCK (ENSG00000182866), SRC (ENSG00000197122), LYN (ENSG00000254087)

Protein

Protein identifiers

Tyrosine-protein kinase SYK — P43405 (reviewed: P43405)

Alternative names: Spleen tyrosine kinase, p72-Syk

All UniProt accessions (1): P43405

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development. Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include DEPTOR, VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK. Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition. Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. In addition to its function downstream of BCR also plays a role in T-cell receptor signaling. Also plays a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade. Required for the stimulation of neutrophil phagocytosis by IL15. Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Involved in interleukin-3/IL3-mediated signaling pathway in basophils. Also functions downstream of receptors mediating cell adhesion. Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Also plays a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response.

Subunit / interactions. Interacts with LYN; phosphorylates SYK. Interacts with RHOH (phosphorylated); regulates mast cells activation. Interacts with NFAM1 (phosphorylated); probably involved in BCR signaling. Interacts with VAV1 (via SH2 domain); phosphorylates VAV1 upon BCR activation. Interacts with GAB2 (phosphorylated); probably involved in IgE Fc receptor signaling. Interacts (via its SH2 domains) with CD79A (via its phosphorylated ITAM domain); the interaction stimulates SYK autophosphorylation and activation. Interacts with FCRL3. Interacts (via SH2 domains) with FCER1G (via ITAM domain); activates SYK and mediates neutrophils and macrophages integrin-mediated activation. Interaction with FCER1G in basophils triggers IL3-induced IL4 production. Interacts with ITGB2 and FGR; involved in ITGB2 downstream signaling. Interacts with ITGB3; upon activation by ITGB3 promotes platelet adhesion. Interacts (via SH2 domains) with TYROBP (via ITAM domain); involved in neutrophils and macrophages integrin-mediated activation. Interacts with MSN and SELPLG; mediates the selectin-dependent activation of SYK by SELPLG. Interacts with BLNK (via SH2 domain). Interacts (via the second SH2 domain) with USP25 (via C-terminus); phosphorylates USP25 and regulates USP25 intracellular levels. Interacts (via SH2 domains) with CLEC1B (dimer). Interacts with CLEC7A; participates in leukocyte activation in presence of fungal pathogens. Interacts (phosphorylated) with SLA; may regulate SYK through CBL recruitment. Interacts with YWHAG; attenuates BCR-induced membrane translocation and activation of SYK. Interacts (via SH2 domains) with GCSAM; the interaction increases after B-cell receptor stimulation, resulting in enhanced SYK autophosphorylation and activity. Interacts with TNS2; leading to the phosphorylation of SYK. Interacts with FLNA (via filamin repeat 5); docks SYK to the plasma membrane. Interacts with CEACAM1; lipopolysaccharide activated neutrophils induce phosphorylation of SYK resulting in the formation of a complex including TLR4 and the phosphorylated form of SYK and CEACAM1, which in turn, recruits PTPN6 that dephosphorylates SYK, reducing the production of reactive oxygen species (ROS) and lysosome disruption, leading to a reduction of the inflammasome activity. Interacts (via SH2 domains) with CEACAM20 (phosphorylated form); the interaction further enhances CEACAM20 phosphorylation. Interacts with IL15RA. Interacts with MPL/TPOR; this interaction negatively regulates THPO-mediated ERK1/2 signaling. (Microbial infection) Interacts with Epstein-Barr virus LMP2A.

Subcellular location. Cell membrane. Cytoplasm. Cytosol.

Tissue specificity. Widely expressed in hematopoietic cells (at protein level). Expressed in neutrophils (at protein level). Within the B-cell compartment, expressed from pro- and pre-B cells to plasma cells.

Post-translational modifications. Ubiquitinated by CBLB after BCR activation; which promotes proteasomal degradation. Autophosphorylated. Phosphorylated on tyrosine residues by LYN following receptors engagement. Phosphorylation on Tyr-323 creates a binding site for CBL, an adapter protein that serves as a negative regulator of BCR-stimulated calcium ion signaling. Phosphorylation at Tyr-348 creates a binding site for VAV1. Phosphorylation on Tyr-348 and Tyr-352 enhances the phosphorylation and activation of phospholipase C-gamma and the early phase of calcium ion mobilization via a phosphoinositide 3-kinase-independent pathway. Phosphorylated on tyrosine residues in response to IL15. Phosphorylation on Ser-297 is very common, it peaks 5 minutes after BCR stimulation, and creates a binding site for YWHAG. Phosphorylation at Tyr-630 creates a binding site for BLNK. Dephosphorylated by PTPN6.

Disease relevance. Immunodeficiency 82 with systemic inflammation (IMD82) [MIM:619381] An autosomal dominant immunologic disorder with onset in early childhood. It is characterized by recurrent infections with various organisms, and multi-organ inflammation that manifests as colitis, hepatitis, arthritis and dermatitis. Patients have a propensity for the development of lymphoma, usually in adulthood. Disease severity is variable. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Autoinhibited. Intramolecular binding of the interdomains A and B (also called linker region) to parts of the catalytic domain keep the catalytic center in an inactive conformation. The phosphorylation of the interdomains or the binding of the SH2 domains with dually phosphorylated ITAM domains on transmembrane proteins disrupt those intramolecular interactions allowing the kinase domain to adopt an active conformation. The phosphorylation of SYK and of the ITAM domains which is responsible for SYK activation is essentially mediated by SRC subfamily kinases, like LYN, upon transmembrane receptors engagement. May also be negatively regulated by PTPN6 through dephosphorylation. Downstream signaling adapters and intermediates like BLNK or RHOH may mediate positive and/or negative feedback regulation. Negatively regulated by CBL and CBLB through ubiquitination and probable degradation. Phosphorylates SH3BP2 which in turn may regulate SYK through LYN.

Domain organisation. The SH2 domains mediate the interaction of SYK with the phosphorylated ITAM domains of transmembrane proteins. Some proteins like CLEC1B have a partial ITAM domain (also called hemITAM) containing a single YxxL motif. The interaction with SYK requires CLEC1B homodimerization.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P43405-1	Long	yes
P43405-2	Short

RefSeq proteins (4): NP_001128524, NP_001167638, NP_001167639, NP_003168* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000980	SH2	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR012234	Tyr_kinase_non-rcpt_SYK/ZAP70	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR023420	Kinase_SYK/ZAP-70_inter-SH2_sf	Homologous_superfamily
IPR035838	SYK/ZAP-70_N_SH2	Domain
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR050198	Non-receptor_tyrosine_kinases	Family

Pfam: PF00017, PF07714

Enzyme classification (BRENDA):

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)
• EC 2.7.12.1 — dual-specificity kinase (BRENDA: 51 organisms, 125 substrates, 188 inhibitors, 14 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
ATP	0.019–0.1185	7
HISTONE H1	0.006–0.012	5
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (106 total): modified residue 31, strand 28, helix 25, sequence variant 6, domain 3, turn 2, region of interest 2, mutagenesis site 2, sequence conflict 2, binding site 2, chain 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

93 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4YJR	X-RAY DIFFRACTION	1.32
4YJQ	X-RAY DIFFRACTION	1.34
4FYO	X-RAY DIFFRACTION	1.4
5LMA	X-RAY DIFFRACTION	1.43
3BUW	X-RAY DIFFRACTION	1.45
6ZCS	X-RAY DIFFRACTION	1.47
5TIU	X-RAY DIFFRACTION	1.49
8XQ1	X-RAY DIFFRACTION	1.5
8BI2	X-RAY DIFFRACTION	1.51
4YJT	X-RAY DIFFRACTION	1.52
1XBB	X-RAY DIFFRACTION	1.57
4RX8	X-RAY DIFFRACTION	1.59
4PX6	X-RAY DIFFRACTION	1.6
4YJO	X-RAY DIFFRACTION	1.6
8RRQ	X-RAY DIFFRACTION	1.6
6HM7	X-RAY DIFFRACTION	1.64
4YJV	X-RAY DIFFRACTION	1.65
6ZCX	X-RAY DIFFRACTION	1.66
4YJU	X-RAY DIFFRACTION	1.67
4I0T	X-RAY DIFFRACTION	1.7
5CXZ	X-RAY DIFFRACTION	1.7
6ZCR	X-RAY DIFFRACTION	1.73
6ZCU	X-RAY DIFFRACTION	1.73
4FZ7	X-RAY DIFFRACTION	1.75
4RX9	X-RAY DIFFRACTION	1.75
8RRZ	X-RAY DIFFRACTION	1.75
4XG7	X-RAY DIFFRACTION	1.76
5CY3	X-RAY DIFFRACTION	1.76
5TT7	X-RAY DIFFRACTION	1.77
4FL1	X-RAY DIFFRACTION	1.79

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43405-F1	84.52	0.64

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): 494 (proton acceptor)

Ligand- & substrate-binding residues (2): 377–385; 402

Post-translational modifications (31): 44, 47, 131, 202, 256, 295, 296, 297, 316, 317, 319, 323, 345, 348, 350, 352, 364, 379, 384, 484 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
297	abolishes ywhag binding.
630	loss of interaction with blnk.

Function

Pathways and Gene Ontology

Reactome pathways

47 pathways

ID	Pathway
R-HSA-114604	GPVI-mediated activation cascade
R-HSA-2029481	FCGR activation
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-2029485	Role of phospholipids in phagocytosis
R-HSA-2424491	DAP12 signaling
R-HSA-2454202	Fc epsilon receptor (FCERI) signaling
R-HSA-2730905	Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-2871796	FCERI mediated MAPK activation
R-HSA-2871809	FCERI mediated Ca+2 mobilization
R-HSA-354192	Integrin signaling
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-5621480	Dectin-2 family
R-HSA-9020558	Interleukin-2 signaling
R-HSA-912631	Regulation of signaling by CBL
R-HSA-9664323	FCGR3A-mediated IL10 synthesis
R-HSA-9664422	FCGR3A-mediated phagocytosis
R-HSA-9674555	Signaling by CSF3 (G-CSF)
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9705462	Inactivation of CSF3 (G-CSF) signaling
R-HSA-9706374	FLT3 signaling through SRC family kinases
R-HSA-983695	Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
R-HSA-109582	Hemostasis
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1280218	Adaptive Immune System
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-2172127	DAP12 interactions

MSigDB gene sets: 0 (showing top):

GO Biological Process (91): angiogenesis (GO:0001525), cell activation (GO:0001775), lymph vessel development (GO:0001945), positive regulation of receptor internalization (GO:0002092), stimulatory C-type lectin receptor signaling pathway (GO:0002223), adaptive immune response (GO:0002250), macrophage activation involved in immune response (GO:0002281), neutrophil activation involved in immune response (GO:0002283), leukocyte activation involved in immune response (GO:0002366), serotonin secretion by platelet (GO:0002554), cell surface pattern recognition receptor signaling pathway (GO:0002752), negative regulation of inflammatory response to antigenic stimulus (GO:0002862), protein phosphorylation (GO:0006468), protein import into nucleus (GO:0006606), leukocyte cell-cell adhesion (GO:0007159), integrin-mediated signaling pathway (GO:0007229), animal organ morphogenesis (GO:0009887), regulation of platelet activation (GO:0010543), regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803), peptidyl-tyrosine phosphorylation (GO:0018108), leukotriene biosynthetic process (GO:0019370), calcium-mediated signaling (GO:0019722), platelet activation (GO:0030168), B cell differentiation (GO:0030183), neutrophil chemotaxis (GO:0030593), positive regulation of protein-containing complex assembly (GO:0031334), receptor internalization (GO:0031623), positive regulation of type I interferon production (GO:0032481), positive regulation of granulocyte macrophage colony-stimulating factor production (GO:0032725), positive regulation of interleukin-10 production (GO:0032733), positive regulation of interleukin-12 production (GO:0032735), positive regulation of interleukin-3 production (GO:0032752), positive regulation of interleukin-4 production (GO:0032753), positive regulation of interleukin-6 production (GO:0032755), positive regulation of interleukin-8 production (GO:0032757), positive regulation of tumor necrosis factor production (GO:0032760), positive regulation of mast cell cytokine production (GO:0032765), regulation of superoxide anion generation (GO:0032928), positive regulation of superoxide anion generation (GO:0032930), positive regulation of cell adhesion mediated by integrin (GO:0033630)

GO Molecular Function (19): phosphotyrosine residue binding (GO:0001784), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), signaling receptor binding (GO:0005102), integrin binding (GO:0005178), ATP binding (GO:0005524), interleukin-15 receptor binding (GO:0016170), kinase activity (GO:0016301), protein kinase binding (GO:0019901), phosphatase binding (GO:0019902), Toll-like receptor binding (GO:0035325), SH2 domain binding (GO:0042169), phospholipase binding (GO:0043274), scaffold protein binding (GO:0097110), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (9): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), B cell receptor complex (GO:0019815), early phagosome (GO:0032009), protein-containing complex (GO:0032991), T cell receptor complex (GO:0042101), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Fcgamma receptor (FCGR) dependent phagocytosis	3
Fc epsilon receptor (FCERI) signaling	3
C-type lectin receptors (CLRs)	2
Platelet activation, signaling and aggregation	1
DAP12 interactions	1
Innate Immune System	1
Signal Transduction	1
Platelet Aggregation (Plug Formation)	1
Interleukin-2 family signaling	1
Interleukin-3, Interleukin-5 and GM-CSF signaling	1
Anti-inflammatory response favouring Leishmania parasite infection	1
Leishmania phagocytosis	1
Cytokine Signaling in Immune system	1
SARS-CoV Infections	1
Signaling by CSF3 (G-CSF)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune response	4
cellular anatomical structure	3
innate immune response activating cell surface receptor signaling pathway	2
myeloid cell activation involved in immune response	2
protein kinase activity	2
protein binding	2
signaling receptor binding	2
enzyme binding	2
plasma membrane signaling receptor complex	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cellular process	1
multicellular organismal process	1
vasculature development	1
anatomical structure development	1
regulation of receptor internalization	1
receptor internalization	1
positive regulation of receptor-mediated endocytosis	1
cellular response to lectin	1
leukocyte activation involved in immune response	1
macrophage activation	1
neutrophil activation	1
cell activation involved in immune response	1
leukocyte activation	1
serotonin secretion involved in inflammatory response	1
platelet degranulation	1
establishment of localization in cell	1
exocytic process	1
pattern recognition receptor signaling pathway	1
inflammatory response to antigenic stimulus	1
regulation of inflammatory response to antigenic stimulus	1
negative regulation of inflammatory response	1
negative regulation of immune response	1
phosphorylation	1
protein modification process	1
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
cell-cell adhesion	1

Protein interactions and networks

STRING

4648 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYK	LCP2	Q13094	998
SYK	BLNK	Q8WV28	998
SYK	FCER1G	P30273	998
SYK	VAV1	P15498	998
SYK	TYROBP	O43914	997
SYK	CARD9	Q9H257	997
SYK	CLEC7A	Q9BXN2	995
SYK	CD79B	P40259	993
SYK	CD79A	P11912	992
SYK	PLCG2	P16885	987
SYK	BTK	Q06187	987
SYK	LYN	P07948	986
SYK	SRC	P12931	976
SYK	VAV3	Q9UKW4	969
SYK	CD247	P20963	967

IntAct

182 interactions, top by confidence:

A	B	Type	Score
SYK	STAT3	psi-mi:“MI:0915”(physical association)	0.870
STAT3	SYK	psi-mi:“MI:0915”(physical association)	0.870
PYCARD	CASP1	psi-mi:“MI:0914”(association)	0.860
SYK	USP25	psi-mi:“MI:0915”(physical association)	0.830
USP25	SYK	psi-mi:“MI:0915”(physical association)	0.830
SH3BP2	VAV1	psi-mi:“MI:0914”(association)	0.790
LCK	SYK	psi-mi:“MI:0915”(physical association)	0.750
LCK	SYK	psi-mi:“MI:0914”(association)	0.750
SYK	FLT3	psi-mi:“MI:0407”(direct interaction)	0.740
SYK	CBL	psi-mi:“MI:0217”(phosphorylation reaction)	0.740
CBL	SYK	psi-mi:“MI:0217”(phosphorylation reaction)	0.740
CBL	SYK	psi-mi:“MI:0407”(direct interaction)	0.740

BioGRID (342): IL17RA (Affinity Capture-Western), TRAF6 (Affinity Capture-Western), TRAF3IP2 (Affinity Capture-Western), SYK (Affinity Capture-Western), SYK (Two-hybrid), SH2D2A (Two-hybrid), USP25 (Two-hybrid), SYK (Affinity Capture-Western), SYK (Affinity Capture-Western), FAM46A (Two-hybrid), SYK (Affinity Capture-Luminescence), SYK (Two-hybrid), SYK (Two-hybrid), HCLS1 (Co-localization), CTTN (Co-localization)

ESM2 similar proteins: A7A1P0, A8WZ92, B4IT27, B5VNQ3, B6A7Q3, C0RW22, F1N9Y5, G5EC24, H2KZW3, O01798, O12990, O19064, O35495, O60674, O94921, P08458, P22517, P23458, P23561, P26818, P27466, P32865, P34635, P34892, P35626, P42159, P42687, P43405, P48025, P51813, P52332, P53356, P83104, Q00537, Q00655, Q09639, Q10056, Q12469, Q17833, Q24145

Diamond homologs: A0JNB0, A1Y2K1, F1N9Y5, G5EBZ8, G5ECJ6, O35346, O45539, O54967, P00519, P00520, P00521, P00522, P00523, P00524, P00525, P00530, P00533, P00534, P00535, P00541, P00542, P03949, P05480, P06239, P06240, P06241, P08103, P08630, P08631, P09760, P09769, P10447, P11273, P12931, P13115, P13116, P13388, P14084, P14085, P14234

SIGNOR signaling

91 interactions.

A	Effect	B	Mechanism
SYK	up-regulates	VAV1	phosphorylation
VAV1	up-regulates	SYK	binding
SYK	down-regulates	SNCA	phosphorylation
SYK	down-regulates	MAPT	phosphorylation
CHEK1	down-regulates	SYK	phosphorylation
SYK	up-regulates	IKZF1	phosphorylation
R406	down-regulates	SYK	“chemical inhibition”
“Fostamatinib disodium”	down-regulates	SYK	“chemical inhibition”
SYK	“up-regulates activity”	IL15RA	phosphorylation
SYK	“down-regulates activity”	LCK	phosphorylation
SYK	“up-regulates activity”	MAP4K1	phosphorylation
SYK	“up-regulates activity”	PLCG1	phosphorylation
SYK	“up-regulates activity”	PRKCA	phosphorylation
SYK	“up-regulates activity”	SYK	phosphorylation
SYK	“up-regulates activity”	TUBA4A	phosphorylation
SYK	“up-regulates activity”	BTK	phosphorylation
2-[[7-(3,4-dimethoxyphenyl)-5-imidazo[1,2-c]pyrimidinyl]amino]-3-pyridinecarboxamide	“down-regulates activity”	SYK	“chemical inhibition”
BCR-Mk	“up-regulates activity”	SYK	binding
BCR-Ml	“up-regulates activity”	SYK	binding
BCR-Dk	“up-regulates activity”	SYK	binding
BCR-Dl	“up-regulates activity”	SYK	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 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
Regulation of KIT signaling	7	77.9×	2e-10
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	8	76.9×	5e-12
PI3K events in ERBB2 signaling	6	74.6×	5e-09
GAB1 signalosome	6	70.5×	6e-09
Constitutive Signaling by EGFRvIII	5	66.1×	2e-07
Regulation of signaling by CBL	7	64.4×	6e-10
Signaling by ALK	6	63.4×	1e-08
Signal regulatory protein family interactions	5	62.2×	3e-07

GO biological processes:

GO term	Partners	Fold	FDR
Fc-gamma receptor signaling pathway involved in phagocytosis	6	68.0×	4e-08
stimulatory C-type lectin receptor signaling pathway	5	59.1×	1e-06
Fc-epsilon receptor signaling pathway	5	59.1×	1e-06
T cell costimulation	9	54.4×	1e-11
peptidyl-tyrosine phosphorylation	8	54.4×	2e-10
leukocyte migration	5	50.3×	3e-06
negative regulation of inflammatory response to antigenic stimulus	5	48.5×	3e-06
epidermal growth factor receptor signaling pathway	11	44.0×	8e-13

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	47
Likely benign	11
Benign	28

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
989389	NM_003177.7(SYK):c.1649C>A (p.Ser550Tyr)	Pathogenic
989237	NM_003177.7(SYK):c.1350G>A (p.Met450Ile)	Likely pathogenic
989387	NM_003177.7(SYK):c.1024C>A (p.Pro342Thr)	Likely pathogenic

SpliceAI

2348 predictions. Top by Δscore:

Variant	Effect	Δscore
9:90801891:CAGGT:C	donor_loss	1.0000
9:90801892:AG:A	donor_loss	1.0000
9:90801893:GG:G	donor_loss	1.0000
9:90844271:G:GT	donor_gain	1.0000
9:90844272:A:T	donor_gain	1.0000
9:90844285:GGAA:G	donor_gain	1.0000
9:90844286:G:T	donor_gain	1.0000
9:90844286:GAA:G	donor_gain	1.0000
9:90845586:A:T	donor_gain	1.0000
9:90845590:TTCCT:T	donor_gain	1.0000
9:90845591:TCCT:T	donor_gain	1.0000
9:90845593:CT:C	donor_gain	1.0000
9:90845593:CTG:C	donor_loss	1.0000
9:90845594:TG:T	donor_loss	1.0000
9:90845595:G:GG	donor_gain	1.0000
9:90845596:T:G	donor_loss	1.0000
9:90845597:GAGT:G	donor_loss	1.0000
9:90845598:AGTA:A	donor_loss	1.0000
9:90862200:TTCTA:T	acceptor_loss	1.0000
9:90862201:TCTA:T	acceptor_loss	1.0000
9:90862202:CTA:C	acceptor_loss	1.0000
9:90862203:TA:T	acceptor_loss	1.0000
9:90862204:A:AG	acceptor_gain	1.0000
9:90862204:AG:A	acceptor_gain	1.0000
9:90862205:G:GA	acceptor_gain	1.0000
9:90862205:GG:G	acceptor_gain	1.0000
9:90862299:G:GT	donor_gain	1.0000
9:90862299:G:T	donor_gain	1.0000
9:90862343:AGG:A	donor_loss	1.0000
9:90862344:GGTAC:G	donor_loss	1.0000

AlphaMissense

4178 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:90843951:G:T	G18V	1.000
9:90843971:G:C	A25P	1.000
9:90844304:T:A	W136R	1.000
9:90844304:T:C	W136R	1.000
9:90845452:G:C	A146P	1.000
9:90845477:T:C	L154P	1.000
9:90845486:T:C	L157P	1.000
9:90845518:T:A	W168R	1.000
9:90845518:T:C	W168R	1.000
9:90845585:G:T	G190V	1.000
9:90845590:T:C	F192L	1.000
9:90845592:C:A	F192L	1.000
9:90845592:C:G	F192L	1.000
9:90845594:T:C	L193P	1.000
9:90862241:T:C	L205P	1.000
9:90862327:T:C	F234L	1.000
9:90862329:C:A	F234L	1.000
9:90862329:C:G	F234L	1.000
9:90864590:T:C	L240P	1.000
9:90864623:T:C	L251S	1.000
9:90874777:T:C	L370P	1.000
9:90874800:G:C	G378R	1.000
9:90874801:G:A	G378D	1.000
9:90874806:G:C	G380R	1.000
9:90874806:G:T	G380C	1.000
9:90874807:G:A	G380D	1.000
9:90874807:G:T	G380V	1.000
9:90874812:T:A	F382I	1.000
9:90874812:T:C	F382L	1.000
9:90874812:T:G	F382V	1.000

dbSNP variants (sampled 300 via entrez): RS1000004238 (9:90810003 G>A), RS1000020787 (9:90869701 C>G), RS1000027779 (9:90851192 A>G,T), RS1000072503 (9:90845619 C>T), RS1000074552 (9:90870091 ACT>A), RS1000092663 (9:90830928 C>T), RS1000112503 (9:90810988 T>C), RS1000183112 (9:90842460 CAT>C), RS1000194712 (9:90824831 C>G), RS1000236176 (9:90867349 G>A), RS1000256617 (9:90816430 C>T), RS1000267256 (9:90867611 A>G), RS1000286773 (9:90858150 G>A), RS1000314178 (9:90822772 G>A,T), RS1000315248 (9:90864121 C>T)

Disease associations

OMIM: gene MIM:600085 | disease phenotypes: MIM:619381, MIM:300755

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 82 with systemic inflammation	Strong	Autosomal dominant

Mondo (5): immunodeficiency 82 with systemic inflammation (MONDO:0030308), long QT syndrome (MONDO:0002442), colitis (MONDO:0005292), arthritic joint disease (MONDO:0005578), immunodeficiency disease (MONDO:0021094)

Orphanet (1): Immunodeficiency-systemic inflammation-lymphoma predisposition syndrome (Orphanet:695807)

HPO phenotypes

51 total (30 of 51 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000155	Oral ulcer
HP:0000403	Recurrent otitis media
HP:0000988	Skin rash
HP:0001369	Arthritis
HP:0001386	Joint swelling
HP:0001581	Recurrent skin infections
HP:0001744	Splenomegaly
HP:0001824	Weight loss
HP:0001903	Anemia
HP:0001954	Recurrent fever
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002027	Abdominal pain
HP:0002039	Anorexia
HP:0002041	Intractable diarrhea
HP:0002090	Pneumonia
HP:0002110	Bronchiectasis
HP:0002583	Colitis
HP:0002588	Duodenal ulcer
HP:0002716	Lymphadenopathy
HP:0002719	Recurrent infections
HP:0002722	Recurrent abscess formation
HP:0002729	Follicular hyperplasia
HP:0002749	Osteomalacia
HP:0002754	Osteomyelitis
HP:0002850	Decreased circulating total IgM
HP:0003073	Hypoalbuminemia
HP:0003228	Hypernatremia
HP:0003460	Decreased circulating total IgA

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000993_1	Vascular dementia	7.000000e-11
GCST001198_36	Multiple sclerosis	9.000000e-07
GCST001461_4	Type 2 diabetes	5.000000e-06
GCST004373_11	Atrial fibrillation	6.000000e-06
GCST004616_201	Platelet distribution width	2.000000e-11
GCST005025_19	Anti-saccade response	9.000000e-06
GCST007124_5	Multiple sclerosis and HDL levels (pleiotropy)	1.000000e-06
GCST007600_13	Alzheimer’s disease	5.000000e-06
GCST008951_2	Chromosomal aberration frequency (total)	2.000000e-07
GCST009209_8	Frontal pole volume	6.000000e-07
GCST009391_1419	Metabolite levels	1.000000e-06
GCST90002393_307	Monocyte count	2.000000e-11
GCST90002395_54	Mean platelet volume	6.000000e-09
GCST90002397_686	Mean spheric corpuscular volume	1.000000e-12
GCST90002400_379	Plateletcrit	9.000000e-11
GCST90002401_485	Platelet distribution width	2.000000e-25
GCST90002402_64	Platelet count	9.000000e-18

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width
EFO:0006874	antisaccade response measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009860	chromosomal aberration frequency
EFO:0010452	adenosine diphosphate measurement
EFO:0005091	monocyte count
EFO:0007985	platelet crit
EFO:0004309	platelet count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D001168	Arthritis	C05.550.114
D003092	Colitis	C06.405.205.265; C06.405.469.158.188
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2599 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

54 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 389,119 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	285
CHEMBL1852688	INFIGRATINIB	4	2,209
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2103830	FOSTAMATINIB	4	3,841
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL3989516	FOSTAMATINIB DISODIUM	4	62
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL941	IMATINIB	4	111,611
CHEMBL3265032	ENTOSPLETINIB	3	1,628
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL50	QUERCETIN	3	74,559
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2
CHEMBL151	LUTEOLIN	2
CHEMBL1738757	REBASTINIB	2
CHEMBL1922094	APITOLISIB	2
CHEMBL1967878	CENISERTIB	2
CHEMBL1976040	ADAVOSERTIB	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL2170582	R-343	2
CHEMBL31574	FISETIN	2
CHEMBL3681949	TOP-1288	2

Clinical evidence (CIViC)

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

Variant	Therapy	Indication	Effect	Level	CIViC
SYK OVEREXPRESSION	Paclitaxel	Ovarian Cancer	Resistance	CIViC D	EID752

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Syk family

Most potent curated ligand interactions (20 total), top 20:

Ligand	Action	Affinity	Parameter
TAS05567	Inhibition	9.43	pIC50
sovleplenib	Inhibition	9.0	pIC50
P505-15	Inhibition	9.0	pIC50
compound 23 [PMID: 17600705]	Inhibition	8.4	pIC50
GSK143	Inhibition	8.12	pIC50
entospletinib	Inhibition	8.11	pIC50
mivavotinib	Inhibition	8.01	pEC50
gusacitinib	Inhibition	8.0	pIC50
lanraplenib	Inhibition	7.87	pIC50
Syk inhibitor	Inhibition	7.85	pIC50
tamatinib	Inhibition	7.72	pKd
BAY 61-3606	Inhibition	7.59	pIC50
cerdulatinib	Inhibition	7.49	pIC50
Syk inhibitor II	Inhibition	7.39	pIC50
GSK2646264	Inhibition	7.1	pIC50
apitolisib	Inhibition	6.87	pIC50
lazertinib	Inhibition	6.7	pIC50
compound 7 [PMID: 22464456]	Inhibition	6.45	pIC50
Syk inhibitor III	Inhibition	5.55	pIC50
ER-27319	Inhibition	5.0	pIC50

Binding affinities (BindingDB)

4194 measured of 4778 human assays (4778 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
cis-(1S,4R)-4-[5-[4-amino-6-[[4-(trifluoromethyl)-2-pyridinyl]amino]-2-pyridinyl]-1,3-thiazol-2-yl]-4-hydroxy-2,2-dimethylcyclohexane-1-carboxylic acid	IC50	0.071 nM	US-9598405: Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
4-hydroxy-4-[5-[4-methyl-6-[[4-(triazolidin-4-yl)-2-pyridinyl]amino]-2-pyridinyl]-1,3-thiazol-2-yl]cyclohexane-1-carboxylic acid	IC50	0.072 nM	US-9598405: Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
cis-(1R,4S)-4-hydroxy-2,2-dimethyl-4-[5-[4-methyl-6-[[4-(trifluoromethyl)-2-pyridinyl]amino]-2-pyridinyl]-1,3-thiazol-2-yl]cyclohexane-1-carboxylic acid	IC50	0.073 nM	US-9598405: Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
BDBM302035	IC50	0.086 nM	US-9598405: Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
cis-(1S,4R)-4-hydroxy-2,2-dimethyl-4-[5-[6-[[4-(trifluoromethyl)-2-pyridinyl]amino]-2-pyridinyl]-1,3-thiazol-2-yl]cyclohexane-1-carboxylic acid	IC50	0.092 nM	US-9598405: Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
cis-(1S,4R)-4-[5-[6-[(5-chloro-4-methyl-2-pyridinyl)amino]-4-methyl-2-pyridinyl]-1,3-thiazol-2-yl]-4-hydroxy-2,2-dimethylcyclohexane-1-carboxylic acid	IC50	0.097 nM	US-9598405: Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
cyclopropyl-[5-[[4-[4-[[(3R)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone	IC50	0.1 nM	US-8871778: Substituted pyrimidine compounds and their use as SYK inhibitors
2,2,2-trifluoro-1-[5-[[6-[4-[[(3R)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]-2-pyridinyl]amino]-1-methylindol-3-yl]ethanone	IC50	0.1 nM	US-8871778: Substituted pyrimidine compounds and their use as SYK inhibitors
(4R)-4-[(1R)-1-[7-(6-morpholin-4-yl-3-pyridinyl)quinolin-5-yl]oxyethyl]pyrrolidin-2-one	IC50	0.1 nM	US-8912173: Substituted quinolines and their use as medicaments
6-[5-[(1R)-1-[(3R)-5-oxopyrrolidin-3-yl]ethoxy]quinolin-7-yl]-1,4-dihydro-3,1-benzoxazin-2-one	IC50	0.1 nM	US-8912173: Substituted quinolines and their use as medicaments
(4R)-4-[(1R)-1-[7-[1-(2-hydroxyethyl)pyrazol-4-yl]quinolin-5-yl]oxyethyl]pyrrolidin-2-one	IC50	0.1 nM	US-8912173: Substituted quinolines and their use as medicaments
2-[4-[5-[(1R)-1-[(3R)-5-oxopyrrolidin-3-yl]ethoxy]quinolin-7-yl]pyrazol-1-yl]ethyl acetate	IC50	0.1 nM	US-8912173: Substituted quinolines and their use as medicaments
(4R)-4-[(1R)-1-[[7-(6-morpholin-4-yl-3-pyridinyl)-1,6-naphthyridin-5-yl]oxy]ethyl]pyrrolidin-2-one	IC50	0.1 nM	US-8969568: Substituted naphthyridines and their use as medicaments
(4R)-4-[(1R)-1-[[7-[3-methoxy-4-(oxan-4-yloxy)phenyl]-1,6-naphthyridin-5-yl]oxy]propyl]pyrrolidin-2-one	IC50	0.1 nM	US-8969568: Substituted naphthyridines and their use as medicaments
(4R)-4-[1-[[7-(3,4-dimethoxyphenyl)-1,6-naphthyridin-5-yl]oxy]-2,2,2-trifluoroethyl]pyrrolidin-2-one	IC50	0.1 nM	US-8969568: Substituted naphthyridines and their use as medicaments
(4R)-4-[(1R)-1-[[7-(3,4-dimethoxyphenyl)-1,6-naphthyridin-5-yl]oxy]ethyl]pyrrolidin-2-one	IC50	0.1 nM	US-8969568: Substituted naphthyridines and their use as medicaments
(4R)-4-[(1R)-1-[[7-(3,4-dimethoxyphenyl)-1,6-naphthyridin-5-yl]oxy]propyl]pyrrolidin-2-one	IC50	0.1 nM	US-8969568: Substituted naphthyridines and their use as medicaments
(4R)-4-[(1R)-1-[[7-(3,4-dimethoxy-5-methylphenyl)-1,6-naphthyridin-5-yl]oxy]ethyl]pyrrolidin-2-one	IC50	0.1 nM	US-8969568: Substituted naphthyridines and their use as medicaments
(4R)-4-[(1R)-1-[[7-(3-methoxy-4-propan-2-yloxyphenyl)-1,6-naphthyridin-5-yl]oxy]ethyl]pyrrolidin-2-one	IC50	0.1 nM	US-8969568: Substituted naphthyridines and their use as medicaments
(4R)-4-[(1R)-1-[[7-(3-methoxy-4-propan-2-yloxyphenyl)-1,6-naphthyridin-5-yl]oxy]propyl]pyrrolidin-2-one	IC50	0.1 nM	US-8969568: Substituted naphthyridines and their use as medicaments
4-[1-[5-[6-[(5-fluoro-4-methyl-2-pyridinyl)amino]-4-methyl-2-pyridinyl]-1,3-thiazol-2-yl]-1-hydroxyethyl]cyclohexane-1-carboxylic acid	IC50	0.1 nM	US-9120785: Pyridyl aminopyridines as Syk inhibitors
BDBM301994	IC50	0.103 nM	US-9598405: Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
cis-(1S,4R)-4-hydroxy-4-[5-[6-[(4-methoxy-2-pyridinyl)amino]-4-methyl-2-pyridinyl]-1,3-thiazol-2-yl]-2,2-dimethylcyclohexane-1-carboxylic acid	IC50	0.104 nM	US-9598405: Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
cis-(1S,4R)-4-hydroxy-2,2-dimethyl-4-[5-[4-methyl-6-[(4-methyl-2-pyridinyl)amino]-2-pyridinyl]-1,3-thiazol-2-yl]cyclohexane-1-carboxylic acid	IC50	0.113 nM	US-9598405: Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
4-[5-[4-amino-6-[[4-(trifluoromethyl)-2-pyridinyl]amino]-2-pyridinyl]-1,3-thiazol-2-yl]-4-hydroxy-2,2-dimethylcyclohexane-1-carboxylic acid	IC50	0.119 nM	US-9598405: Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
cis-(1S,4R)-4-[5-[6-[(5-fluoro-4-methyl-2-pyridinyl)amino]-4-methyl-2-pyridinyl]-1,3-thiazol-2-yl]-4-hydroxy-2,2-dimethylcyclohexane-1-carboxylic acid	IC50	0.127 nM	US-9598405: Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
(5R)-5-hydroxy-5-[5-[3-methyl-5-([1,2,4]triazolo[1,5-a]pyridin-2-ylamino)phenyl]-1,3-thiazol-2-yl]-7,8-dihydro-6H-naphthalene-2-carboxylic acid	IC50	0.129 nM	US-9670196: Thiazole-substituted aminoheteroaryls as Spleen Tyrosine Kinase inhibitors
4-hydroxy-4-[5-[4-methyl-6-[(4-piperidin-4-yloxy-2-pyridinyl)amino]-2-pyridinyl]-1,3-thiazol-2-yl]cyclohexane-1-carboxylic acid	IC50	0.152 nM	US-9598405: Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
cis-(1S,4R)-4-[5-[6-[(4-tert-butyl-2-pyridinyl)amino]-2-pyridinyl]-1,3-thiazol-2-yl]-4-hydroxy-2,2-dimethylcyclohexane-1-carboxylic acid	IC50	0.158 nM	US-9598405: Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
cis-(1S,4R)-4-hydroxy-2,2-dimethyl-4-[5-[4-methyl-6-[[4-(trifluoromethyl)-2-pyridinyl]amino]-2-pyridinyl]-1,3-thiazol-2-yl]cyclohexane-1-carboxylic acid	IC50	0.16 nM	US-9598405: Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
(1S,2R,4R)-4-[5-[6-[(5-fluoro-4-methyl-2-pyridinyl)amino]-4-methyl-2-pyridinyl]-1,3-thiazol-2-yl]-4-hydroxy-2-methylcyclohexane-1-carboxylic acid	IC50	0.161 nM	US-9598405: Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
4-hydroxy-2,2-dimethyl-4-[5-[4-methyl-6-[[4-(trifluoromethyl)-2-pyridinyl]amino]-2-pyridinyl]-1,3-thiazol-2-yl]cyclohexane-1-carboxylic acid	IC50	0.164 nM	US-9598405: Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
(4R)-4-[(1R)-1-[7-(1-methylpyrazol-4-yl)quinolin-5-yl]oxyethyl]pyrrolidin-2-one	IC50	0.2 nM	US-8912173: Substituted quinolines and their use as medicaments
N-ethyl-N-[[4-[5-[(1R)-1-[(3R)-5-oxopyrrolidin-3-yl]ethoxy]quinolin-7-yl]phenyl]methyl]acetamide	IC50	0.2 nM	US-8912173: Substituted quinolines and their use as medicaments
(4R)-4-[(1R)-1-[7-(1-ethylpyrazol-4-yl)quinolin-5-yl]oxyethyl]pyrrolidin-2-one	IC50	0.2 nM	US-8912173: Substituted quinolines and their use as medicaments
(4R)-4-[(1R)-1-[7-[4-(1-aminocyclopropyl)-3-chlorophenyl]quinolin-5-yl]oxyethyl]pyrrolidin-2-one	IC50	0.2 nM	US-8912173: Substituted quinolines and their use as medicaments
(4R)-4-[(1R)-1-[[7-(3,4,5-trimethoxyphenyl)-1,6-naphthyridin-5-yl]oxy]ethyl]pyrrolidin-2-one	IC50	0.2 nM	US-8969568: Substituted naphthyridines and their use as medicaments
(4R)-4-[(1S)-1-[[7-(3,4-dimethoxyphenyl)-1,6-naphthyridin-5-yl]oxy]-2,2,2-trifluoroethyl]pyrrolidin-2-one	IC50	0.2 nM	US-8969568: Substituted naphthyridines and their use as medicaments
(4R)-4-[(1R)-1-[[7-(3,4-dimethoxyphenyl)-1,6-naphthyridin-5-yl]oxy]-3-methoxypropyl]pyrrolidin-2-one	IC50	0.2 nM	US-8969568: Substituted naphthyridines and their use as medicaments
(4R)-4-[(1R)-1-[(7-phenyl-1,6-naphthyridin-5-yl)oxy]ethyl]pyrrolidin-2-one	IC50	0.2 nM	US-8969568: Substituted naphthyridines and their use as medicaments
5-{[(1R,2S)-2-aminocyclohexyl]amino}-3-(5-chloro-1H-indol-2-yl)pyrazine-2-carboxamide	IC50	0.2 nM	US-9775839: 2-pyrazine carboxamides as spleen tyrosine kinase inhibitors
5-{[(3R,4R)-3- aminotetrahydro-2H-pyran-4- yl]amino}-3-(5-ethyl-1H- indol-2-yl)pyrazine-2- carboxamide	IC50	0.2 nM	US-9775839: 2-pyrazine carboxamides as spleen tyrosine kinase inhibitors
cis-(1S,4R)-4-[5-[6-[(5-chloro-4-methyl-2-pyridinyl)amino]-2-pyridinyl]-1,3-thiazol-2-yl]-4-hydroxy-2,2-dimethylcyclohexane-1-carboxylic acid	IC50	0.208 nM	US-9598405: Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
3-[[(1R,2S)-2-aminocyclohexyl]amino]-5-[(1-ethylindol-4-yl)amino]-1,2,4-triazine-6-carboxamide	IC50	0.21 nM	US-9145414: 1,2,4-triazine-6-carboxamide derivative
3-[[(1R,2S)-2-aminocyclohexyl]amino]-5-[[1-(difluoromethyl)indol-4-yl]amino]-1,2,4-triazine-6-carboxamide	IC50	0.22 nM	US-9145414: 1,2,4-triazine-6-carboxamide derivative
BDBM302037	IC50	0.228 nM	US-9598405: Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
3-[[(1R,2S)-2-aminocyclohexyl]amino]-5-[(2-methyl-7-phenylindazol-5-yl)amino]-1,2,4-triazine-6-carboxamide	IC50	0.23 nM	US-9145414: 1,2,4-triazine-6-carboxamide derivative
3-[[(1R,2S)-2-aminocyclohexyl]amino]-5-[[1-(1-methylpyrazol-4-yl)indol-4-yl]amino]-1,2,4-triazine-6-carboxamide	IC50	0.26 nM	US-9145414: 1,2,4-triazine-6-carboxamide derivative
3-[[(1R,2S)-2-aminocyclohexyl]amino]-5-[(2,4-dimethylindazol-6-yl)amino]-1,2,4-triazine-6-carboxamide	IC50	0.26 nM	US-9145414: 1,2,4-triazine-6-carboxamide derivative
3-[[(1R,2S)-2-aminocyclohexyl]amino]-5-(1-benzothiophen-5-ylamino)-1,2,4-triazine-6-carboxamide	IC50	0.26 nM	US-9145414: 1,2,4-triazine-6-carboxamide derivative

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL3415598
10.52	IC50	0.03	nM	CHEMBL3622956
10.52	IC50	0.03	nM	CHEMBL4744190
10.34	IC50	0.046	nM	CHEMBL5425739
10.22	IC50	0.06	nM	CHEMBL3415583
10.22	IC50	0.06	nM	CHEMBL4780257
10.17	IC50	0.067	nM	CHEMBL5435311
10.15	IC50	0.071	nM	CHEMBL5775813
10.14	IC50	0.072	nM	CHEMBL5748905
10.14	IC50	0.073	nM	CHEMBL5788352
10.11	IC50	0.077	nM	CHEMBL4776352
10.10	IC50	0.08	nM	CHEMBL5410717
10.07	IC50	0.086	nM	CHEMBL5739861
10.05	IC50	0.09	nM	CHEMBL4753469
10.04	IC50	0.092	nM	CHEMBL5868234
10.01	IC50	0.098	nM	CHEMBL4762995
10.01	IC50	0.097	nM	CHEMBL5831684
10.00	IC50	0.1	nM	CHEMBL3415589
10.00	IC50	0.1	nM	CHEMBL3415594
10.00	IC50	0.1	nM	CHEMBL3415606
10.00	IC50	0.1	nM	CHEMBL3657551
10.00	IC50	0.1	nM	CHEMBL3657550
10.00	IC50	0.1	nM	CHEMBL3653791
10.00	IC50	0.1	nM	CHEMBL3653846
10.00	IC50	0.1	nM	CHEMBL3653847
10.00	IC50	0.1	nM	CHEMBL3653776
10.00	IC50	0.1	nM	CHEMBL3695989
10.00	IC50	0.1	nM	CHEMBL3696007
10.00	IC50	0.1	nM	CHEMBL3696011
10.00	IC50	0.1	nM	CHEMBL3696026
10.00	IC50	0.1	nM	CHEMBL3696035
10.00	IC50	0.1	nM	CHEMBL3696044
10.00	IC50	0.1	nM	CHEMBL3696046
10.00	IC50	0.1	nM	CHEMBL3696047
10.00	IC50	0.1	nM	CHEMBL3898524
10.00	IC50	0.1	nM	CHEMBL5985551
9.99	IC50	0.103	nM	CHEMBL5961927
9.98	IC50	0.104	nM	CHEMBL5925558
9.96	IC50	0.11	nM	CHEMBL4753141
9.95	IC50	0.113	nM	CHEMBL5795831
9.92	IC50	0.119	nM	CHEMBL5952385
9.90	IC50	0.127	nM	CHEMBL5773271
9.89	IC50	0.13	nM	CHEMBL4784088
9.89	IC50	0.13	nM	CHEMBL5434339
9.89	IC50	0.129	nM	CHEMBL5921266
9.88	IC50	0.133	nM	STAUROSPORINE
9.85	IC50	0.14	nM	CHEMBL4752008
9.82	IC50	0.15	nM	CHEMBL4754597
9.82	IC50	0.152	nM	CHEMBL5923968
9.80	IC50	0.158	nM	CHEMBL5911374

PubChem BioAssay actives

1710 with measured affinity, of 4224 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
5-[[(1R,2S)-2-aminocyclohexyl]amino]-3-[[6-methyl-2-(triazol-2-yl)pyrimidin-4-yl]amino]pyridine-2-carboxamide	1199532: Inhibition of full-length GST-tagged human Syk preincubated for 10 mins followed by peptide substrate/ATP addition measured after 45 mins by TR-FRET assay	ic50	<0.0001	uM
methyl 5-[[4-[5-[(dimethylamino)methyl]-1-methylpyrazol-3-yl]pyrimidin-2-yl]amino]-1,7-dimethylindazole-3-carboxylate	1681023: Inhibition of recombinant full length SYK (unknown origin) by biochemical Omnia assay	ic50	<0.0001	uM
17-hydroxy-10,13,24-trimethyl-2,4,8,9,13,14,20,23,24,33-decazahexacyclo[20.5.2.214,17.13,7.18,11.025,29]tritriaconta-1(28),3,5,7(33),9,11(32),22,25(29),26-nonaen-21-one	2011922: Inhibition of full length recombinant human SYK	ic50	<0.0001	uM
1-[[1-[2-[(3-chloro-1,2-dimethylindol-5-yl)amino]pyrimidin-4-yl]-3-methylpyrazol-4-yl]methyl]azetidin-3-ol	1681023: Inhibition of recombinant full length SYK (unknown origin) by biochemical Omnia assay	ic50	<0.0001	uM
5-[[(1R,2S)-2-aminocyclohexyl]amino]-3-[[4,6-dimethyl-5-(1-methylpyrazol-4-yl)-2-pyridinyl]amino]pyridine-2-carboxamide	1199532: Inhibition of full-length GST-tagged human Syk preincubated for 10 mins followed by peptide substrate/ATP addition measured after 45 mins by TR-FRET assay	ic50	0.0001	uM
N,N-dimethyl-1-[1-[2-(1-methyl-5-methylsulfonylindol-3-yl)-1H-imidazo[4,5-b]pyridin-7-yl]pyrazol-4-yl]methanamine	1674803: Inhibition of SYK (unknown origin)	ic50	0.0001	uM
5-[[4-[4-[(dimethylamino)methyl]-3-fluoropyrazol-1-yl]pyrimidin-2-yl]amino]-N,1-dimethylindazole-3-carboxamide	1681023: Inhibition of recombinant full length SYK (unknown origin) by biochemical Omnia assay	ic50	0.0001	uM
5-[[4-[4-[(dimethylamino)methyl]-3-methoxypyrazol-1-yl]pyrimidin-2-yl]amino]-N,1-dimethylindazole-3-carboxamide	1681023: Inhibition of recombinant full length SYK (unknown origin) by biochemical Omnia assay	ic50	0.0001	uM
7-[[4-[4-[(dimethylamino)methyl]pyrazol-1-yl]pyrimidin-2-yl]amino]-N-methylimidazo[1,5-a]pyridine-1-carboxamide	1681023: Inhibition of recombinant full length SYK (unknown origin) by biochemical Omnia assay	ic50	0.0001	uM
3-[7-[4-[(dimethylamino)methyl]pyrazol-1-yl]-1H-imidazo[4,5-b]pyridin-2-yl]-N,1-dimethylindole-5-carboxamide	1674803: Inhibition of SYK (unknown origin)	ic50	0.0001	uM
N,N-dimethyl-1-[3-methyl-1-[2-[1-methyl-5-(5-methyl-1,3,4-oxadiazol-2-yl)indol-3-yl]-1H-imidazo[4,5-b]pyridin-7-yl]pyrazol-4-yl]methanamine	1674803: Inhibition of SYK (unknown origin)	ic50	0.0001	uM
5-[[4-[4-[(3-hydroxyazetidin-1-yl)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-N,1-dimethylindazole-3-carboxamide	1681023: Inhibition of recombinant full length SYK (unknown origin) by biochemical Omnia assay	ic50	0.0001	uM
N-[4-[5-[(dimethylamino)methyl]-1-methylpyrazol-3-yl]pyrimidin-2-yl]-1-methyl-3-(5-methyl-1,3,4-oxadiazol-2-yl)indazol-5-amine	1681023: Inhibition of recombinant full length SYK (unknown origin) by biochemical Omnia assay	ic50	0.0001	uM
23-[(2R)-2-hydroxypropyl]-10,13-dimethyl-16-oxa-2,4,8,9,13,19,22,23,30-nonazapentacyclo[19.5.2.13,7.18,11.024,28]triaconta-1(27),3,5,7(30),9,11(29),21,24(28),25-nonaen-20-one	2011922: Inhibition of full length recombinant human SYK	ic50	0.0001	uM
10,13,24-trimethyl-2,4,8,9,13,14,20,23,24,33-decazahexacyclo[20.5.2.214,17.13,7.18,11.025,29]tritriaconta-1(28),3,5,7(33),9,11(32),22,25(29),26-nonaen-21-one	2011922: Inhibition of full length recombinant human SYK	ic50	0.0001	uM
10,13,23-trimethyl-16-oxa-2,4,8,9,13,19,22,23,30-nonazapentacyclo[19.5.2.13,7.18,11.024,28]triaconta-1(27),3,5,7(30),9,11(29),21,24(28),25-nonaen-20-one	2011922: Inhibition of full length recombinant human SYK	ic50	0.0001	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1715153: Inhibition of human SYK using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay	ic50	0.0001	uM
5-[[(1R,2S)-2-aminocyclohexyl]amino]-3-[(4,6-dimethyl-2-pyridinyl)amino]pyridine-2-carboxamide	1199532: Inhibition of full-length GST-tagged human Syk preincubated for 10 mins followed by peptide substrate/ATP addition measured after 45 mins by TR-FRET assay	ic50	0.0001	uM
5-[[(3S,4S)-4-amino-1,1-dioxothian-3-yl]amino]-3-[(4,6-dimethyl-2-pyridinyl)amino]pyridine-2-carboxamide	1199532: Inhibition of full-length GST-tagged human Syk preincubated for 10 mins followed by peptide substrate/ATP addition measured after 45 mins by TR-FRET assay	ic50	0.0001	uM
5-[[(1R,2S)-2-aminocyclohexyl]amino]-3-[[6-(triazol-2-yl)-2-pyridinyl]amino]pyridine-2-carboxamide	1199532: Inhibition of full-length GST-tagged human Syk preincubated for 10 mins followed by peptide substrate/ATP addition measured after 45 mins by TR-FRET assay	ic50	0.0001	uM
5-[[(1R,2S)-2-aminocyclohexyl]amino]-3-[[6-(2-hydroxy-2-methylpropoxy)-2-methylpyrimidin-4-yl]amino]pyridine-2-carboxamide	1199532: Inhibition of full-length GST-tagged human Syk preincubated for 10 mins followed by peptide substrate/ATP addition measured after 45 mins by TR-FRET assay	ic50	0.0002	uM
N-[4-[5-[(dimethylamino)methyl]-1-methylpyrazol-3-yl]pyrimidin-2-yl]-3-methyl-1-(5-methyl-1,3,4-oxadiazol-2-yl)imidazo[1,5-a]pyridin-7-amine	1681023: Inhibition of recombinant full length SYK (unknown origin) by biochemical Omnia assay	ic50	0.0002	uM
7-[[4-[4-[(dimethylamino)methyl]pyrazol-1-yl]pyrimidin-2-yl]amino]-N,3-dimethylimidazo[1,5-a]pyridine-1-carboxamide	1696665: Inhibition of SYK (unknown origin)	ic50	0.0002	uM
(3R,4R)-4-N-[1-[2-(1-methylindol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl]pyrazol-4-yl]oxane-3,4-diamine	1674803: Inhibition of SYK (unknown origin)	ic50	0.0002	uM
N-[3-[7-[4-[(dimethylamino)methyl]-3-methylpyrazol-1-yl]-1H-imidazo[4,5-b]pyridin-2-yl]-1-methylindol-5-yl]acetamide	1674803: Inhibition of SYK (unknown origin)	ic50	0.0002	uM
(3R,4R)-4-N-[3-methyl-1-[2-[[1-methyl-3-(5-methyl-1,3,4-oxadiazol-2-yl)indazol-5-yl]amino]pyrimidin-4-yl]pyrazol-4-yl]oxane-3,4-diamine	1696665: Inhibition of SYK (unknown origin)	ic50	0.0002	uM
3-[7-[4-[(dimethylamino)methyl]pyrazol-1-yl]-1H-imidazo[4,5-b]pyridin-2-yl]-N,1-dimethylpyrrolo[2,3-c]pyridine-5-carboxamide	1674803: Inhibition of SYK (unknown origin)	ic50	0.0002	uM
N,1-dimethyl-5-[[4-[3-methyl-4-[(3R)-piperidin-3-yl]oxypyrazol-1-yl]pyrimidin-2-yl]amino]indazole-3-carboxamide	1696665: Inhibition of SYK (unknown origin)	ic50	0.0002	uM
N-[4-[5-[(dimethylamino)methyl]-1-methylpyrazol-3-yl]pyrimidin-2-yl]-1-(5-methyl-1,3,4-oxadiazol-2-yl)imidazo[1,5-a]pyridin-7-amine	1674803: Inhibition of SYK (unknown origin)	ic50	0.0002	uM
5-[[4-[4-[(dimethylamino)methyl]pyrazol-1-yl]pyrimidin-2-yl]amino]-N,1,7-trimethylindazole-3-carboxamide	1681023: Inhibition of recombinant full length SYK (unknown origin) by biochemical Omnia assay	ic50	0.0002	uM
7-[[4-[4-(2-aminoethylamino)pyrazol-1-yl]pyrimidin-2-yl]amino]-N,3-dimethylimidazo[1,5-a]pyridine-1-carboxamide	1696665: Inhibition of SYK (unknown origin)	ic50	0.0002	uM
7-[[4-[4-[(2S,4S)-4-hydroxy-1-methylpyrrolidin-2-yl]pyrazol-1-yl]pyrimidin-2-yl]amino]-N,3-dimethylimidazo[1,5-a]pyridine-1-carboxamide	1681023: Inhibition of recombinant full length SYK (unknown origin) by biochemical Omnia assay	ic50	0.0002	uM
5-[[4-[4-[(dimethylamino)methyl]pyrazol-1-yl]pyrimidin-2-yl]amino]-N,1-dimethylindazole-3-carboxamide	1681023: Inhibition of recombinant full length SYK (unknown origin) by biochemical Omnia assay	ic50	0.0002	uM
7-[[4-[4-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]pyrazol-1-yl]pyrimidin-2-yl]amino]-N,3-dimethylimidazo[1,5-a]pyridine-1-carboxamide	1681023: Inhibition of recombinant full length SYK (unknown origin) by biochemical Omnia assay	ic50	0.0002	uM
1-[5-[[4-[4-[[(3R,4R)-3-aminooxan-4-yl]amino]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]-2,2,2-trifluoroethanone	1696665: Inhibition of SYK (unknown origin)	ic50	0.0002	uM
10,13-dimethyl-23-(oxetan-3-yl)-16-oxa-2,4,8,9,13,19,22,23,30-nonazapentacyclo[19.5.2.13,7.18,11.024,28]triaconta-1(27),3,5,7(30),9,11(29),21,24(28),25-nonaen-20-one	2011922: Inhibition of full length recombinant human SYK	ic50	0.0002	uM
23-[(2S)-2-hydroxypropyl]-10,13-dimethyl-16-oxa-2,4,8,9,13,19,22,23,30-nonazapentacyclo[19.5.2.13,7.18,11.024,28]triaconta-1(27),3,5,7(30),9,11(29),21,24(28),25-nonaen-20-one	2011922: Inhibition of full length recombinant human SYK	ic50	0.0002	uM
5-[[4-[4-[(dimethylamino)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-N,1-dimethylindazole-3-carboxamide	1674803: Inhibition of SYK (unknown origin)	ic50	0.0003	uM
5-[[4-[4-[[(3S,4S)-4-fluoropyrrolidin-3-yl]amino]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-N,1-dimethylindazole-3-carboxamide	1696665: Inhibition of SYK (unknown origin)	ic50	0.0003	uM
5-[[4-[4-[[(3R,4R)-3-aminooxan-4-yl]amino]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-N,1-dimethylindazole-3-carboxamide	1696665: Inhibition of SYK (unknown origin)	ic50	0.0003	uM
5-[[4-[4-[(1-aminocyclopropyl)methylamino]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-N,1-dimethylindazole-3-carboxamide	1696665: Inhibition of SYK (unknown origin)	ic50	0.0003	uM
5-[[4-[4-[[(3R,4R)-3-aminooxan-4-yl]amino]pyrazol-1-yl]pyrimidin-2-yl]amino]-N,1-dimethylindazole-3-carboxamide	1696665: Inhibition of SYK (unknown origin)	ic50	0.0003	uM
5-[[4-[5-[(dimethylamino)methyl]-1-methylpyrazol-3-yl]pyrimidin-2-yl]amino]-N,1,7-trimethylindazole-3-carboxamide	1681023: Inhibition of recombinant full length SYK (unknown origin) by biochemical Omnia assay	ic50	0.0003	uM
5-[[(1R,2S)-2-aminocyclohexyl]amino]-3-[[4-(3-hydroxy-3-methylbutyl)-6-methyl-2-pyridinyl]amino]pyridine-2-carboxamide	1199532: Inhibition of full-length GST-tagged human Syk preincubated for 10 mins followed by peptide substrate/ATP addition measured after 45 mins by TR-FRET assay	ic50	0.0004	uM
7-[[4-[4-[[(3R,4R)-3-aminooxan-4-yl]amino]pyrazol-1-yl]pyrimidin-2-yl]amino]-N,3-dimethylimidazo[1,5-a]pyridine-1-carboxamide	1696665: Inhibition of SYK (unknown origin)	ic50	0.0004	uM
5-[[4-[4-[(3S,4R)-4-fluoropyrrolidin-3-yl]oxy-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-N,1-dimethylindazole-3-carboxamide	1696665: Inhibition of SYK (unknown origin)	ic50	0.0004	uM
23-(2-hydroxy-2-methylpropyl)-10,13-dimethyl-16-oxa-2,4,8,9,13,19,22,23,30-nonazapentacyclo[19.5.2.13,7.18,11.024,28]triaconta-1(27),3,5,7(30),9,11(29),21,24(28),25-nonaen-20-one	2011922: Inhibition of full length recombinant human SYK	ic50	0.0004	uM
23-(2-hydroxyethyl)-10,13-dimethyl-16-oxa-2,4,8,9,13,19,22,23,30-nonazapentacyclo[19.5.2.13,7.18,11.024,28]triaconta-1(27),3,5,7(30),9,11(29),21,24(28),25-nonaen-20-one	2011922: Inhibition of full length recombinant human SYK	ic50	0.0004	uM
6-(1H-indazol-6-yl)-N-(3-methoxy-4-morpholin-4-ylphenyl)imidazo[1,2-a]pyrazin-8-amine	1142338: Inhibition of full length Syk (unknown origin) using biotinylated peptide substrate	ic50	0.0004	uM
5-[[(1R,2S)-2-aminocyclohexyl]amino]-3-(1H-indol-2-yl)pyrazine-2-carboxamide	1199532: Inhibition of full-length GST-tagged human Syk preincubated for 10 mins followed by peptide substrate/ATP addition measured after 45 mins by TR-FRET assay	ic50	0.0005	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
bisphenol A	decreases reaction, increases phosphorylation, decreases expression, decreases methylation	5
(+)-JQ1 compound	decreases expression	3
Resveratrol	increases expression, affects binding, decreases reaction, increases reaction, increases phosphorylation (+2 more)	3
Plant Extracts	affects cotreatment, increases expression, decreases phosphorylation, decreases expression, increases abundance	3
3,3’,4,5’-tetrahydroxystilbene	decreases reaction, increases phosphorylation, decreases abundance, decreases activity	2
entinostat	increases expression, affects cotreatment	2
Arsenic Trioxide	increases phosphorylation, increases expression, decreases reaction	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Nickel	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression	2
Tretinoin	decreases expression, increases expression	2
bisphenol F	decreases methylation	1
biochanin A	increases phosphorylation, decreases reaction	1
triphenyl phosphate	affects expression	1
bis(tri-n-butyltin)oxide	increases expression	1
decabromobiphenyl ether	decreases expression	1
tributyltin	increases expression	1
beta-lapachone	decreases expression	1
cobaltous chloride	increases expression	1
ochratoxin A	increases expression	1
3,4,3’,4’-tetrachlorobiphenyl	affects expression	1
convulxin	decreases reaction, increases reaction, affects reaction, increases phosphorylation, affects binding	1
methacrylaldehyde	affects cotreatment, decreases expression	1
phosphatidylinositol 3,4,5-triphosphate	decreases abundance, decreases activity	1
spiraeoside	decreases phosphorylation	1
2-propylthio-D-beta,gamma-difluoromethylene ATP	affects reaction, increases phosphorylation	1
2-palmitoylglycerol	increases expression	1

ChEMBL screening assays

873 unique, capped per target: 863 binding, 10 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1019643	Binding	Inhibition of SYK at 1 uM	Pyranonaphthoquinone lactones: a new class of AKT selective kinase inhibitors alkylate a regulatory loop cysteine. — J Med Chem
CHEMBL1963712	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: SYK	PubChem BioAssay data set

Cellosaurus cell lines

92 cell lines: 89 cancer cell line, 2 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0354	J.CaM1.6	Cancer cell line	Male
CVCL_0367	Jurkat E6.1	Cancer cell line	Male
CVCL_1316	J.RT3-T3.5	Cancer cell line	Male
CVCL_2530	J45.01	Cancer cell line	Male
CVCL_6410	J.gamma1	Cancer cell line	Male
CVCL_6411	J.gamma1.WT	Cancer cell line	Male
CVCL_6429	P116	Cancer cell line	Male
CVCL_6430	P116.cl39	Cancer cell line	Male
CVCL_6819	10B10	Cancer cell line	Male
CVCL_A9P4	BPS Bioscience Jurkat E6.1 NF-kappaB-driven luciferase reporter	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT02687724	PHASE4	UNKNOWN	Golimumab (GLM) Dose Optimisation to Adequate Levels to Achieve Response in Colitis
NCT00180206	PHASE4	UNKNOWN	Birmingham Hip Resurfacing (BHR) Study: Implantation of a Hip Resurfacing Endoprosthesis
NCT00236366	PHASE4	COMPLETED	A Study of the Effect on Pain Control of Treatment With Fentanyl, Administered Through the Skin, Compared With Placebo in Patients With Osteoarthritis
NCT00291915	PHASE4	UNKNOWN	Multicenter Randomized Prospective Trial Comparing Methotrexate Alone or in Combination With Adalimumab in Early Arthritis
NCT00510536	PHASE4	COMPLETED	Treatment of Mild to Moderate Joint Pain in Patients With Chronic Plaque Psoriasis Receiving Efalizumab
NCT00524160	PHASE4	COMPLETED	A Study of the Effect on Pain Control of Treatment With Fentanyl, Administered Through the Skin, in Patients With Rheumatoid Arthritis or Osteoarthritis
NCT00696059	PHASE4	COMPLETED	Humira in Rheumatoid Arthritis - Do Bone Erosions Heal?
NCT01027286	PHASE4	COMPLETED	Prospective Evaluation of Vitagel for Reduction in Blood Loss and Pain Following Unilateral Total Knee Arthroplasty
NCT01264965	PHASE4	TERMINATED	Non-cancer Pain and Cognitive Impairment: A Disabling Relationship
NCT01270620	PHASE4	COMPLETED	Desflurane or Propofol Anesthesia in Elderly Obese Patients Undergoing Total Knee Replacement
NCT01275014	PHASE4	UNKNOWN	Corticosteroids as Additive in Temporomandibular Joint (TMJ) Arthrocentesis
NCT01414569	PHASE4	COMPLETED	Dexamethasone for Pain After Shoulder Surgery
NCT02011464	PHASE4	COMPLETED	Evaluation Exparel Delivered in Knee Replacement
NCT02697955	PHASE4	COMPLETED	The Effect of Subsartorial Saphenous Block on Postoperative Pain Following Major Ankle and Hind Foot Surgery
NCT02926651	PHASE4	WITHDRAWN	Single Versus Multi-Dose Oral Tranexamic Acid in Patients at High Risk for Blood Transfusion After Total Joint Arthroplasty
NCT03659318	PHASE4	COMPLETED	Robotic-Assisted Versus Conventional Total Knee Arthroplasty(TKA)
NCT01369329	PHASE3	COMPLETED	A Study to Evaluate the Safety and Efficacy of Ustekinumab in Patients With Moderately to Severely Active Crohn’s Disease Who Have Failed or Are Intolerant to Tumor Necrosis Factor (TNF) Antagonist Therapy (UNITI-1)
NCT01369342	PHASE3	COMPLETED	A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction Therapy in Patients With Moderately to Severely Active Crohn’s Disease (UNITI-2)
NCT01369355	PHASE3	COMPLETED	A Study to Evaluate the Safety and Efficacy of Ustekinumab Maintenance Therapy in Patients With Moderately to Severely Active Crohn’s Disease (IM-UNITI)
NCT05947669	PHASE3	RECRUITING	Efficacy and Safety of Infliximab for Immune Checkpoint Inhibitor Induced Colitis
NCT00153660	PHASE3	COMPLETED	Celecoxib Versus Naproxen for Prevention of Recurrent Ulcer Bleeding in Arthritis Patients
NCT00153673	PHASE3	COMPLETED	Effect of Selective COX-2 Inhibition on Ulcer Healing
NCT00211718	PHASE3	UNKNOWN	Intra-Articular Injection of Botulinum Toxin Type A for Shoulder Pain
NCT00313365	PHASE3	WITHDRAWN	Surgical Lavage vs Serial Needle Aspiration for Infected Joints
NCT00365313	PHASE3	COMPLETED	Preventing Recurrent Ulcer Bleeding in Arthritis Patients Using Esomeprazole Plus Celecoxib
NCT00526201	PHASE3	COMPLETED	Help Arthritis With Exercise in West Virginia
NCT00526435	PHASE3	COMPLETED	Evaluation of Walk With Ease in Arthritis
NCT00646178	PHASE3	COMPLETED	Study of the Safety and Efficacy of Adalimumab in Subjects With Moderate to Severely Active Psoriatic Arthritis Subjects With Inadequate Response to Disease Modifying Anti-Rheumatic Drug Therapy
NCT00733902	PHASE3	COMPLETED	Tanezumab in Osteoarthritis of the Knee
NCT00744471	PHASE3	COMPLETED	Tanezumab in Osteoarthritis Of The Hip
NCT00765362	PHASE3	COMPLETED	Mobile - Bearing Knee Study
NCT00784277	PHASE3	COMPLETED	A Study to Compare the Frequency of Constipation Symptoms With Tapentadol Immediate Release (IR) Treatment Versus Oxycodone IR Treatment in Patients With End-stage Joint Disease
NCT00809354	PHASE3	TERMINATED	Long-Term Analgesic Efficacy And Safety Of Tanezumab Alone Or In Combination With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Versus NSAIDs Alone In Patients With Osteoarthritis Of The Knee Or Hip
NCT00830063	PHASE3	COMPLETED	Tanezumab In Osteoarthritis Of The Knee (2)
NCT01004432	PHASE3	COMPLETED	Golimumab in Rheumatoid Arthritis Participants With an Inadequate Response to Etanercept (ENBREL) or Adalimumab (HUMIRA)
NCT01089725	PHASE3	TERMINATED	Efficacy And Safety Study Of Tanezumab Subcutaneous Administration In Osteoarthritis - A Subcutaneous/Intravenous Bridging Study