{"entity":{"id":"syk","kind":"target","name":"SYK","aka":["spleen associated tyrosine kinase","Tyrosine-protein kinase SYK"],"tldr":"SYK (Tyrosine-protein kinase SYK) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target and a biomarker, and an approved or late-stage drug is recorded against it. Tied to Ovarian cancer, Skin cancer, Lung cancer and 4 more.","summary":"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 signalling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains.\n\nCIViC holds 1 clinical evidence item and 0 assertions across 1 variant, naming Paclitaxel. Open Targets scores its association with cancer at 0.72 (direct and indirect evidence; datatypes clinical 0.50, literature 0.99, genetic association 0.38, somatic mutation 0.98, animal model 0.51). In OnCo, 1 product record names it (Fostamatinib).","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:11491","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11491"},{"label":"UniProt P43405","url":"https://www.uniprot.org/uniprotkb/P43405/entry"},{"label":"NCBI Gene 6850","url":"https://www.ncbi.nlm.nih.gov/gene/6850"},{"label":"Ensembl ENSG00000165025","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000165025"},{"label":"Davis et al., Nature 2010: chronic active B-cell receptor signalling in diffuse large B-cell lymphoma","url":"https://doi.org/10.1038/nature08638"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets"],"cancers":["ovarian","skin-cancer","lung-cancer","breast-cancer","colorectal","leukaemia","melanoma","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["fostamatinib"],"companies":[],"institutions":[],"pathways":["bcr-signalling","inflammation-nfkb"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: Open Targets known-drug datatype score 0.50; CIViC holds 1 clinical evidence items on its variants. Evidence tier \"approved-drug\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Lymphoma, Chronic active B-cell receptor signalling, and BTK: The B-cell receptor normally signals only when it meets antigen. In activated B-cell-like lymphoma it signals continuously: the receptors cluster in the membrane and diffuse slowly, exactly as they do in an antigen-stimulated normal B cell, and knocking down IgM, Ig-kappa, CD79A, CD79B or BTK kills the cell. The signal runs CD79a/b to SYK to BTK to PLC-gamma-2 to protein kinase C beta to the CARD11-BCL10-MALT1 complex and into NF-kB. Mutations of the ITAM module of CD79B raise surface receptor expression and blunt LYN, the feedback brake (Davis 2010). Frequency: Mutations of the first ITAM tyrosine of CD79B in 18% of activated B-cell-like cases, frequent in that subtype and rare in other diffuse large B-cell lymphomas, absent from Burkitt and MALT lymphoma; activating CARD11 mutations in roughly 10% of activated B-cell-like cases (Davis 2010). What it changes about treatment: This is the one pathway in lymphoma where the biology picks the drug today. BTK inhibitors are standard in mantle cell lymphoma and Waldenstrom macroglobulinaemia and have activity in primary CNS lymphoma and in the MCD genetic subtype of diffuse large B-cell lymphoma; they do little in germinal-centre disease."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"SYK","role":["drug-target","biomarker"],"evidenceTier":"approved-drug","sources":[{"label":"HGNC HGNC:11491","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11491","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P43405","url":"https://www.uniprot.org/uniprotkb/P43405/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene SYK","url":"https://civicdb.org/features/5572","note":"1 evidence items, 0 assertions, 1 variants; diseases: Ovarian Cancer (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000165025","url":"https://platform.opentargets.org/target/ENSG00000165025/associations","note":"association with cancer (MONDO_0004992) 0.72; per-cancer scores at or above 0.5: colorectal cancer 0.54, melanoma 0.56, skin cancer 0.58, breast cancer 0.54, lung cancer 0.55, leukaemia 0.50 (GraphQL API, CC0)"}],"specificity":"tumour-associated","distribution":"many-types","specificityNote":"Tumour-associated overexpression: HPA finds the RNA tissue enhanced in normal lymphoid tissue, parathyroid gland, so the tumour and the normal tissue it comes from share the target and the medicine relies on the difference in level. HPA SYK: RNA tissue enhanced (lymphoid tissue 69 nTPM, parathyroid gland 82 nTPM); high antibody staining in 13 normal tissues; highest cancer staining lymphoma (8 of 11 high). Distribution: 6 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Ovarian cancer, Skin cancer (all types), Lung cancer (all types), Breast cancer (all types), Colorectal cancer, Leukaemia); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas SYK tissue","url":"https://www.proteinatlas.org/ENSG00000165025-SYK/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas SYK pathology","url":"https://www.proteinatlas.org/ENSG00000165025-SYK/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000165025 associations","url":"https://platform.opentargets.org/target/ENSG00000165025/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:11491","ensembl":"ENSG00000165025","uniprot":"P43405","entrez":"6850","firstDescribed":1994,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Yagi et al, Biochem. Biophys. Res. Commun, 1994, \"Cloning of the cDNA for the deleted syk kinase homologous to ZAP-70 from human basophilic leukemia cell line (KU812)\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/7513161/","biology":"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 signalling 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. Location: Cell membrane; Cytoplasm, cytosol (UniProt). Locus 9q22.2 (HGNC).","whereFound":["Ovarian cancer: CIViC evidence names this disease","Skin cancer: Open Targets association 0.58 with skin cancer (MONDO_0002898)","Lung cancer: Open Targets association 0.55 with lung cancer (MONDO_0008903)","Breast cancer: Open Targets association 0.54 with breast cancer (MONDO_0007254)","Colorectal cancer: Open Targets association 0.54 with colorectal cancer (MONDO_0005575)","Leukaemia: Open Targets association 0.50 with leukaemia (MONDO_0005059)"],"targetClass":"kinase","prevalence":[]},"route":"/targets/syk/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"drug":[{"id":"fostamatinib","kind":"drug","name":"Fostamatinib","route":"/drugs/fostamatinib/"}],"pathway":[{"id":"bcr-signalling","kind":"pathway","name":"B-cell receptor / BTK signalling (to NF-κB)","route":"/pathways/bcr-signalling/"},{"id":"inflammation-nfkb","kind":"pathway","name":"Inflammation & NF-κB","route":"/pathways/inflammation-nfkb/"}]}}