{"entity":{"id":"map2k4","kind":"target","name":"MAP2K4","aka":["mitogen-activated protein kinase kinase 4","Dual specificity mitogen-activated protein kinase kinase 4","MEK4","JNKK1","PRKMK4","MKK4","MAPKK4","SAPKK1","SKK1","SEK1","SERK1"],"tldr":"MAP2K4 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, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response.","summary":"Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signalling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3.\n\nCIViC holds 2 clinical evidence items and 0 assertions across 2 variants, naming Selumetinib and PLX8725. Open Targets scores its association with cancer at 0.77 (direct and indirect evidence; datatypes literature 0.95, animal model 0.27, genetic association 0.29, somatic mutation 0.97). IntOGen calls it a driver in 15 cohorts (4 activating, 11 loss-of-function), covering Invasive Breast Carcinoma, Cholangiocarcinoma, Colorectal Adenocarcinoma, Oesophagogastric Adenocarcinoma, Oesophageal Squamous Cell Carcinoma, Hepatocellular Carcinoma and others.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:6844","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6844"},{"label":"UniProt P45985","url":"https://www.uniprot.org/uniprotkb/P45985/entry"},{"label":"NCBI Gene 6416","url":"https://www.ncbi.nlm.nih.gov/gene/6416"},{"label":"Ensembl ENSG00000065559","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000065559"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["breast-cancer","colorectal","pancreatic","gastric","esophageal","hcc","skin-cancer","biliary-tract-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"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: CIViC lists 2 therapies; IntOGen calls it an activating (Act) driver in 4 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 11 cohorts; CIViC holds 2 clinical evidence items on its variants. Evidence tier \"clinical-evidence\" 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: Uterus Leiomyosarcoma."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"MAP2K4","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:6844","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6844","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P45985","url":"https://www.uniprot.org/uniprotkb/P45985/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene MAP2K4","url":"https://civicdb.org/features/5200","note":"2 evidence items, 0 assertions, 2 variants; diseases: Cancer, Uterus Leiomyosarcoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000065559","url":"https://platform.opentargets.org/target/ENSG00000065559/associations","note":"association with cancer (MONDO_0004992) 0.77; per-cancer scores at or above 0.5: melanoma 0.51, skin cancer 0.52, breast cancer 0.72, biliary tract cancer 0.50 (GraphQL API, CC0)"},{"label":"IntOGen MAP2K4","url":"https://www.intogen.org/search?gene=MAP2K4","note":"driver in 15 cohorts (Act 4, LoF 11); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:6844","ensembl":"ENSG00000065559","uniprot":"P45985","entrez":"6416","biology":"Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signalling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to pro-inflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. Location: Cytoplasm; Nucleus (UniProt). Locus 17p12 (HGNC).","whereFound":["Breast cancer: Open Targets association 0.72 with breast cancer (MONDO_0007254); IntOGen driver in 6 cohorts (BRCA)","Colorectal cancer: IntOGen driver in 3 cohorts (COADREAD)","Pancreatic ductal adenocarcinoma: IntOGen driver in 2 cohorts (PAAD, PANCREAS)","Gastric & gastro-oesophageal junction cancer: IntOGen driver in 1 cohort (EGC)","Oesophageal cancer: IntOGen driver in 1 cohort (ESCC)","Hepatocellular carcinoma: IntOGen driver in 1 cohort (HCC)"],"targetClass":"kinase","prevalence":[]},"route":"/targets/map2k4/","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":"biliary-tract-cancer","kind":"cancer","name":"Biliary tract cancer (all types)","route":"/cancers/biliary-tract-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":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}]}}