{"entity":{"id":"jak3","kind":"target","name":"JAK3","aka":["Janus kinase 3","Tyrosine-protein kinase JAK3","L-JAK","JAK3_HUMAN","JAK-3"],"tldr":"JAK3 (Tyrosine-protein kinase JAK3) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver and a biomarker, and an approved or late-stage drug is recorded against it. Tied to Myeloproliferative neoplasms, Leukaemia, Non-Hodgkin lymphoma and 5 more.","summary":"Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signalling events in both innate and adaptive immunity and plays a crucial role in haematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R.\n\nCIViC holds 3 clinical evidence items and 0 assertions across 8 variants, naming Atezolizumab and Tofacitinib. Open Targets scores its association with cancer at 0.77 (direct and indirect evidence; datatypes clinical 0.96, affected pathway 0.61, literature 0.95, genetic association 0.18, somatic mutation 0.97, animal model 0.53). IntOGen calls it a driver in 1 cohort (1 activating, 0 loss-of-function), covering Acute Lymphoblastic Leukaemia.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:6193","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6193"},{"label":"UniProt P52333","url":"https://www.uniprot.org/uniprotkb/P52333/entry"},{"label":"NCBI Gene 3718","url":"https://www.ncbi.nlm.nih.gov/gene/3718"},{"label":"Ensembl ENSG00000105639","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000105639"},{"label":"Kucuk et al., Nat Commun 2015: activating STAT3 and STAT5B mutations in lymphomas derived from NK or gamma-delta T cells","url":"https://doi.org/10.1038/ncomms7025"},{"label":"Green et al., Blood 2010: selective 9p24.1 amplification and PD-1 ligand induction through JAK2 in Hodgkin lymphoma and mediastinal large B-cell lymphoma","url":"https://doi.org/10.1182/blood-2010-05-282780"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["myeloproliferative-neoplasms","leukaemia","non-hodgkin-lymphoma","skin-cancer","lung-cancer","colorectal","all-leukemia","nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["jak-stat"],"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 0.96; IntOGen calls it an activating (Act) driver in 1 cohort; CIViC holds 3 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.","Diseases the sources name that have no OnCo cancer page yet, so they are not linked: T-cell Acute Lymphoblastic Leukaemia.","Lymphoma, JAK-STAT, in NK/T-cell lymphoma and in Hodgkin lymphoma: STAT3 and STAT5B mutations lock the transcription factor in its phosphorylated form. The STAT5B N642H substitution increases the binding affinity of the phosphotyrosine for the mutant histidine, so the phosphorylated protein persists and binds its target sites far more, and the growth advantage it gives can be partly reversed by a JAK1/2 inhibitor in the laboratory (Kucuk 2015). In Hodgkin lymphoma and primary mediastinal B-cell lymphoma the pathway is switched on from the other end, by amplification of JAK2 inside the 9p24.1 amplicon and by loss of the brakes SOCS1 and PTPN1. Frequency: Activating STAT3 and STAT5B mutations across 51 NK/T-cell lymphomas and 43 gamma-delta T-cell lymphomas, with STAT5B N642H particularly frequent in the gamma-delta group (Kucuk 2015). JAK2 sits in the 9p24.1 amplicon in Hodgkin lymphoma and mediastinal large B-cell lymphoma, and its amplification raises both protein and activity and specifically induces PD-1 ligand transcription (Green 2010). What it changes about treatment: Not through an approved drug. JAK inhibitors have been tested in both settings without becoming standard; the practical consequence of the Hodgkin and mediastinal finding is that it explains why checkpoint blockade works there."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"JAK3","role":["drug-target","oncogene-driver","biomarker"],"evidenceTier":"approved-drug","sources":[{"label":"HGNC HGNC:6193","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6193","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P52333","url":"https://www.uniprot.org/uniprotkb/P52333/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene JAK3","url":"https://civicdb.org/features/3091","note":"3 evidence items, 0 assertions, 8 variants; diseases: Lung Adenocarcinoma, T-cell Acute Lymphoblastic Leukaemia (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000105639","url":"https://platform.opentargets.org/target/ENSG00000105639/associations","note":"association with cancer (MONDO_0004992) 0.77; per-cancer scores at or above 0.5: colorectal cancer 0.52, acute lymphoblastic leukaemia 0.62, non-Hodgkin lymphoma 0.65, skin cancer 0.58, myeloproliferative neoplasm 0.73, acquired polycythemia vera 0.55 (GraphQL API, CC0)"},{"label":"IntOGen JAK3","url":"https://www.intogen.org/search?gene=JAK3","note":"driver in 1 cohort (Act 1, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance); what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA JAK3: RNA tissue enhanced (lymphoid tissue 53 nTPM); no normal tissue stained high. Distribution: 6 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Myeloid neoplasms, Leukaemia, Lymphoma, Skin cancer (all types), Lung cancer (all types), Colorectal cancer); Open Targets associates it with 3 specific cancer types at or above 0.5 (myelofibrosis, acquired polycythemia vera, essential thrombocythemia). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P52333","url":"https://www.uniprot.org/uniprotkb/P52333/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene JAK3","url":"https://civicdb.org/features/3091","note":"3 evidence items, 0 assertions, 8 variants; diseases: Lung Adenocarcinoma, T-cell Acute Lymphoblastic Leukaemia (GraphQL API, CC0)"},{"label":"IntOGen JAK3","url":"https://www.intogen.org/search?gene=JAK3","note":"driver in 1 cohort (Act 1, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas JAK3 tissue","url":"https://www.proteinatlas.org/ENSG00000105639-JAK3/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000105639 associations","url":"https://platform.opentargets.org/target/ENSG00000105639/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:6193","ensembl":"ENSG00000105639","uniprot":"P52333","entrez":"3718","firstDescribed":1994,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Kawamura et al, Proc. Natl. Acad. Sci. U.S.A, 1994, \"Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8022790/","biology":"Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signalling events in both innate and adaptive immunity and plays a crucial role in haematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. Location: Endomembrane system; Cytoplasm (UniProt). Locus 19p13.11 (HGNC).","whereFound":["Myeloproliferative neoplasms: Open Targets association 0.73 with myeloproliferative neoplasm (MONDO_0020076)","Leukaemia: Open Targets association 0.67 with leukaemia (MONDO_0005059)","Non-Hodgkin lymphoma: Open Targets association 0.65 with non-Hodgkin lymphoma (MONDO_0018908)","Skin cancer: Open Targets association 0.58 with skin cancer (MONDO_0002898)","Lung cancer: Open Targets association 0.55 with lung cancer (MONDO_0008903)","Colorectal cancer: Open Targets association 0.52 with colorectal cancer (MONDO_0005575)"],"targetClass":"kinase","prevalence":[]},"route":"/targets/jak3/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"cutaneous-t-cell-lymphoma","kind":"cancer","name":"Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome)","route":"/cancers/cutaneous-t-cell-lymphoma/"},{"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":"myeloproliferative-neoplasms","kind":"cancer","name":"Myeloproliferative neoplasms (PV, ET, myelofibrosis)","route":"/cancers/myeloproliferative-neoplasms/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"},{"id":"sezary-syndrome","kind":"cancer","name":"Sezary syndrome","route":"/cancers/sezary-syndrome/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"pathway":[{"id":"jak-stat","kind":"pathway","name":"JAK-STAT signalling","route":"/pathways/jak-stat/"}]}}