MAP3K9
protein-codingmitogen-activated protein kinase kinase kinase 9, the group of Mitogen-activated protein kinase kinase kinases
Gene summary
Enables molecular function activator activity and protein serine/threonine kinase activity. Involved in protein autophosphorylation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]
- MLK1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~87.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MAP3K9 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001284230.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 4 | 6 | |||
| missense | 168 | 168 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 173 | 4 | 0 | 177 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001271159.1 | 12 | MANE Select | |
| Ensembl | ENSP00000451612.2 | 12 | MANE Select | |
| RefSeq | NP_001271160.1 | 11 | Standard | |
| RefSeq | NP_001271161.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- EGF-Core
- Angiopoietin Like Protein 8 Regulatory Pathway
- Oxidative Damage
- p38 MAPK Signaling Pathway
- Insulin Signaling
Biological Process
- MAPK cascade
- protein phosphorylation
- apoptotic process
- activation of JNKK activity
- activation of JUN kinase activity
Molecular Function
- protein serine/threonine kinase activity
- JUN kinase kinase kinase activity
- MAP kinase kinase activity
- protein binding
- ATP binding
Cellular Component
- cellular_component
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000555993
- Coding exons
- 13
- Length
- 87009
- Individuals with no LoFs
- 125717
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 31
- Defined
- 125748
- p
- 0.000123
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.27 | 575 | 667 | 0.862 | 0.0000413 | 7241 |
| Missense (PolyPhen) | 223 | 285.52 | 0.78102 | 2923 | ||
| Synonymous | 1.65 | 231 | 265 | 0.871 | 0.0000153 | 2323 |
| Loss of Function | 4.67 | 11 | 44.7 | 0.246 | 0.00000258 | 483 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00012 | 0.00011 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00016 | 0.00016 | rare |
| South Asian | 0.000099 | 0.000098 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade through the phosphorylation of MAP2K4/MKK4 and MAP2K7/MKK7 which in turn activate the JNKs. The MKK/JNK signaling pathway regulates stress response via activator protein-1 (JUN) and GATA4 transcription factors. Plays also a role in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. {ECO:0000269|PubMed:11416147, ECO:0000269|PubMed:15610029}.;
- Disease
- DISEASE: Note=May play a role in esophageal cancer susceptibility and/or development.;
Recessive Scores
- pRec
- 0.131
Intolerance Scores
- LoFtool
- 0.264
- RVIS EVS
- -1.55
- RVIS percentile EVS
- 3.31
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.738
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |