# MAP2K4

Source: https://onco.cc/targets/map2k4/  
OnCo record `map2k4` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

CIViC 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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: mitogen-activated protein kinase kinase 4; Dual specificity mitogen-activated protein kinase kinase 4; MEK4; JNKK1; PRKMK4; MKK4; MAPKK4; SAPKK1; SKK1; SEK1; SERK1
- Tags: cancer-genes-wave
- Symbol: MAP2K4
- Class: kinase
- 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).
- Where found: 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)

## 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.

## Sources

- HGNC HGNC:6844: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6844
- UniProt P45985: https://www.uniprot.org/uniprotkb/P45985/entry
- NCBI Gene 6416: https://www.ncbi.nlm.nih.gov/gene/6416
- Ensembl ENSG00000065559: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000065559

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Biliary tract cancer (all types)](https://onco.cc/cancers/biliary-tract-cancer/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)

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JSON: https://onco.cc/api/v1/entities/map2k4.json