MAP3K4

Mitogen-activated protein kinase kinase kinase 4 Q9Y6R4 M3K4_HUMAN
Protein Coding Chr 6 6q26 Swiss-Prot reviewed Entrez 4216
Mutations
3,100
CL 375 · Tissue 2,694
Samples
779
CL 142 · Tissue 627
Peptides
620
unique mutant peptides
Transcripts
4
isoforms mutated

Stats by Source

Total, split by cell line (COSMIC CL / DepMap / PubMed) vs tissue (COSMIC primary tissue)

How the counts split by source
Stats by Source

Total = all mutations for this gene across every source.

Cell line = COSMIC Cell Lines Project + DepMap + PubMed.

Tissue = COSMIC primary-tissue (patient tumour) samples.

Total can exceed cell line + tissue: COSMIC tissue-derived models sit only in global, and a peptide can be shared across both.

TotalCell lineTissue
Mutations3,1003752,694
Samples779142627
Peptides62094533

Function

MAP3K4 · Mitogen-activated protein kinase kinase kinase 4

The central core of each mitogen-activated protein kinase (MAPK) pathway is a conserved cascade of 3 protein kinases: an activated MAPK kinase kinase (MAPKKK) phosphorylates and activates a specific MAPK kinase (MAPKK), which then activates a specific MAPK. While the ERK MAPKs are activated by mitogenic stimulation, the CSBP2 and JNK MAPKs are activated by environmental stresses such as osmotic shock, UV irradiation, wound stress, and inflammatory factors. This gene encodes a MAPKKK, the MEKK4 protein, also called MTK1. This protein contains a protein kinase catalytic domain at the C terminus. The N-terminal nonkinase domain may contain a regulatory domain. Expression of MEKK4 in mammalian cells activated the CSBP2 and JNK MAPK pathways, but not the ERK pathway. In vitro kinase studies indicated that recombinant MEKK4 can specifically phosphorylate and activate PRKMK6 and SERK1, MAPKKs that activate CSBP2 and JNK, respectively but cannot phosphorylate PRKMK1, an MAPKK that activates ERKs. MEKK4 is a major mediator of environmental stresses that activate the CSBP2 MAPK pathway, and a minor mediator of the JNK pathway. Several alternatively spliced transcripts encoding distinct isoforms have been described. [provided by RefSeq, May 2014].

Isoforms & Proteins

4 transcripts · UniProt mapping is sequence-verified (AA-safe)

About the isoform mapping
Isoforms & Proteins

Each Ensembl transcript (ENST) this gene is mutated on, with its matched UniProt accession.

The mapping is sequence-verified: the UniProt sequence is identical to the transcript translation, so amino-acid positions line up exactly. A * marks an unreviewed (TrEMBL) entry.

Counts are mutations and unique mutant peptides on each transcript.

TranscriptUniProtMutationsPeptides
ENST00000392142 Q9Y6R4 862 600
ENST00000366920 F5H538* 779 563
ENST00000366919 Q9Y6R4-2 731 537
ENST00000348824 J3KNB8* 728 535

Gene Properties

Type
Protein Coding
Chromosome
6
Cytoband
6q26
Entrez ID
Aliases
MAPKKK4MEKK 4MEKK4MTK1PRO0412

Recurrent Mutations

All 600 amino-acid changes on canonical ENST00000392142 · needle height = samples · drag the mini-map to zoom

What this lollipop shows
Recurrent Mutations

A lollipop / needle plot – the standard way to show recurrent mutations along a protein (as used by cBioPortal and MutationMapper).

X-axis = amino-acid position in the protein.

Needle height & head size = how often that exact amino-acid change was observed (its recurrence). Tall/large heads are mutational hotspots.

The most recurrent changes are labelled; hover any needle for the change, position and counts.

Mutation frequency across cancer types

% of samples with a missense/complex mutation in MAP3K4 · cell line vs tissue

How this frequency is counted
Cancer-type mutation frequency

For each cancer type, the fraction of samples that carry at least one missense/complex mutation anywhere in MAP3K4 – counted as distinct samples (a sample counts once no matter how many mutations it has).

Split into cell line and tissue; each cell shows mutated / total and the percentage. Cohorts with <20 samples are omitted. Ordered by combined frequency.

Cancer typeCell linesTissue samples
T-Lymphoblastic Leukemia
12/40 30%
0/0 0%
Endometrial Carcinoma
7/42 17%
45/612 7%
Gastrointestinal Stromal Tumour
0/0 0%
6/133 5%
Melanoma
12/210 6%
79/1899 4%
Chronic Myelogenous Leukemia
1/25 4%
0/0 0%
Non-Small Cell Lung Carcinoma
17/304 6%
42/1390 3%
Colorectal Carcinoma
20/143 14%
97/3239 3%
Gastric Carcinoma
4/74 5%
47/1809 3%
Neuroendocrine Tumour
10/154 6%
9/577 2%
Bladder Carcinoma
2/58 3%
24/956 3%
Biliary Tract Carcinoma
2/54 4%
18/950 2%
Cervical Carcinoma
0/35 0%
9/422 2%
Oral Cavity Carcinoma
1/54 2%
0/0 0%
Other Solid Cancers
4/94 4%
22/1515 1%
Small Cell Lung Carcinoma
0/9 0%
12/752 2%
Hepatocellular Carcinoma
5/46 11%
30/2210 1%
Ewings Sarcoma
2/63 3%
3/262 1%
Wilms Tumour
0/5 0%
7/474 1%
Pheochromocytoma and Paraganglioma
0/0 0%
1/71 1%
Esophageal Carcinoma
1/23 4%
9/769 1%
Other Sarcomas
0/69 0%
9/699 1%
Thyroid Gland Carcinoma
2/45 4%
17/1592 1%
Squamous Cell Lung Carcinoma
1/57 2%
9/810 1%
Glioma
1/52 2%
22/2127 1%
Head and Neck Carcinoma
1/85 1%
16/1574 1%
Glioblastoma
1/98 1%
0/0 0%
Ovarian Carcinoma
4/109 4%
7/998 1%
Breast Carcinoma
6/144 4%
22/3264 1%
Esophageal Squamous Cell Carcinoma
3/51 6%
17/2550 1%
Non-Cancerous
1/104 1%
6/830 1%

Mutation Distribution

Where MAP3K4 is mutated · all tissues, split by cell line vs tissue

Mutation counts by tissue
Mutation Distribution

How many mutations in MAP3K4 were found in each tissue, across the whole database.

Each bar is a tissue (cell-line and tissue names are merged to the standard tissue), split into cell line and tissue (patient tumour) contributions.

This shows the cancer-context where this gene is recurrently altered.

GTEx Expression

Median TPM across 54 healthy tissues

GTEx Portal ↗
About the expression data
GTEx Expression

Median gene expression (TPM) in normal, non-cancer human tissues from the GTEx project.

Useful for judging tumour specificity – a strong neoantigen target ideally comes from a gene with low expression in healthy tissues.

Scroll or drag the mini-axis below the chart to browse all tissues.

Mutations

All 3,100 mutations in MAP3K4

About the mutation list
Mutations

Every mutation record for this gene, across all samples and sources.

The Sample column links to the cell line (cell-line samples) or the tissue type (tissue samples).

Use the Type / Source filters, the search box, and column sorting to explore; each CAN-IMMUNE ID opens the full mutation & peptide view.

IDSampleTranscriptAA Change CDSTypeSourceMutant PeptideWild-type Peptide