MAP3K2
protein-codingmitogen-activated protein kinase kinase kinase 2, the group of Mitogen-activated protein kinase kinase kinases
Gene summary
The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase preferentially activates other kinases involved in the MAP kinase signaling pathway. This kinase has been shown to directly phosphorylate and activate Ikappa B kinases, and thus plays a role in NF-kappa B signaling pathway. This kinase has also been found to bind and activate protein kinase C-related kinase 2, which suggests its involvement in a regulated signaling process. [provided by RefSeq, Jul 2008]
- MEKK2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~89.8 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 MAP3K2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001371910.2. 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 | 2 | 4 | |||
| missense | 54 | 54 | ||||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 62 | 0 | 2 | 64 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001358839.1 | 16 | MANE Select | |
| Ensembl | ENSP00000507315.1 | 16 | MANE Select | |
| RefSeq | NP_001358840.1 | 16 | Standard | |
| RefSeq | NP_006600.3 | 16 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- GnRH signaling pathway - Homo sapiens (human)
- Gap junction - Homo sapiens (human)
- MAPK signaling pathway - Homo sapiens (human)
- EGF-Core
- IL-1 signaling pathway
Biological Process
- activation of MAPKK activity
- activation of MAPK activity
- protein phosphorylation
- activation of JUN kinase activity
- signal transduction by protein phosphorylation
Molecular Function
- protein kinase activity
- protein serine/threonine kinase activity
- MAP kinase kinase kinase activity
- protein binding
- ATP binding
Cellular Component
- nucleoplasm
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000409947
- Coding exons
- 16
- Length
- 89736
- Individuals with no LoFs
- 124638
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 124641
- p
- 0.0000120
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.31 | 198 | 313 | 0.633 | 0.0000159 | 4011 |
| Missense (PolyPhen) | 67 | 134.69 | 0.49744 | 1720 | ||
| Synonymous | 0.190 | 104 | 106 | 0.977 | 0.00000518 | 1137 |
| Loss of Function | 5.31 | 0 | 32.9 | 0.00 | 0.00000188 | 436 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000029 | 0.000027 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7 (By similarity). Plays a role in caveolae kiss-and-run dynamics. {ECO:0000250, ECO:0000269|PubMed:10713157, ECO:0000269|PubMed:16001074}.;
Recessive Scores
- pRec
- 0.170
Intolerance Scores
- RVIS EVS
- -0.29
- RVIS percentile EVS
- 33.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.941
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |