MAP3K11
protein-codingmitogen-activated protein kinase kinase kinase 11, the group of Mitogen-activated protein kinase kinase kinases
Gene summary
The protein encoded by this gene is a member of the serine/threonine kinase family. This kinase contains a SH3 domain and a leucine zipper-basic motif. This kinase preferentially activates MAPK8/JNK kinase, and functions as a positive regulator of JNK signaling pathway. This kinase can directly phosphorylate, and activates IkappaB kinase alpha and beta, and is found to be involved in the transcription activity of NF-kappaB mediated by Rho family GTPases and CDC42. [provided by RefSeq, Jul 2008]
- MLK3
- PTK1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~17.6 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 MAP3K11 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002419.4. 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 | 1 | 2 | 3 | |||
| missense | 1 | 115 | 2 | 118 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 1 | 117 | 4 | 0 | 122 |
Highest pathogenic variant AF is 0.000006840516
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002410.1 | 10 | MANE Select | |
| Ensembl | ENSP00000309597.3 | 10 | MANE Select | |
| Ensembl | ENSP00000431506.1 | 5 | Standard | |
| Ensembl | ENSP00000435970.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
- MAPK signaling pathway - Homo sapiens (human)
- Tacrolimus/Cyclosporine Pathway, Pharmacodynamics
- EGF-Core
- MAPK Signaling Pathway
Biological Process
- MAPK cascade
- activation of MAPK activity
- protein phosphorylation
- microtubule-based process
- JNK cascade
Molecular Function
- protein kinase activity
- protein serine/threonine kinase activity
- JUN kinase kinase kinase activity
- protein binding
- ATP binding
Cellular Component
- cytoplasm
- centrosome
- microtubule
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000309100
- Coding exons
- 10
- Length
- 17628
- Individuals with no LoFs
- 125723
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 23
- Defined
- 125746
- p
- 0.0000915
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.90 | 401 | 524 | 0.766 | 0.0000347 | 5291 |
| Missense (PolyPhen) | 155 | 231.25 | 0.67028 | 2269 | ||
| Synonymous | -0.832 | 243 | 227 | 1.07 | 0.0000152 | 1869 |
| Loss of Function | 4.06 | 11 | 38.0 | 0.290 | 0.00000239 | 353 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000062 | rare |
| Latino/Admixed American | 0.000035 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000061 | 0.000054 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00013 | 0.00012 | rare |
| South Asian | 0.000099 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Activates the JUN N-terminal pathway. Required for serum-stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen-stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle. {ECO:0000269|PubMed:12529434, ECO:0000269|PubMed:15258589, ECO:0000269|PubMed:8195146, ECO:0000269|PubMed:9003778}.;
Recessive Scores
- pRec
- 0.248
Intolerance Scores
- LoFtool
- 0.273
- RVIS EVS
- -0.71
- RVIS percentile EVS
- 14.71
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.996
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |