MAP3K12
protein-codingmitogen-activated protein kinase kinase kinase 12, the group of Mitogen-activated protein kinase kinase kinases
Gene summary
This gene encodes a member of the serine/threonine protein kinase family. This kinase contains a leucine-zipper domain and is predominately expressed in neuronal cells. The phosphorylation state of this kinase in synaptic terminals was shown to be regulated by membrane depolarization via calcineurin. This kinase forms heterodimers with leucine zipper containing transcription factors, such as cAMP responsive element binding protein (CREB) and MYC, and thus may play a regulatory role in PKA or retinoic acid induced neuronal differentiation. Alternatively spliced transcript variants encoding different proteins have been described.[provided by RefSeq, Jul 2010]
- ZPK
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~20.4 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 MAP3K12 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001193511.2. 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 | 0 | |||||
| missense | 65 | 1 | 66 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 4 | 4 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 72 | 0 | 1 | 73 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001180440.1 | 13 | MANE Select | |
| Ensembl | ENSP00000449038.1 | 13 | MANE Select | |
| RefSeq | NP_006292.3 | 14 | Standard | |
| Ensembl | ENSP00000267079.2 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- MAPK signaling pathway - Homo sapiens (human)
- EGF-Core
- MAPK Signaling Pathway
- Angiopoietin Like Protein 8 Regulatory Pathway
- MAPK Cascade
Biological Process
- MAPK cascade
- protein phosphorylation
- JNK cascade
- activation of JNKK activity
- activation of JUN kinase activity
Molecular Function
- protein kinase activity
- protein serine/threonine kinase activity
- JUN kinase kinase kinase activity
- protein binding
- ATP binding
Cellular Component
- cytoplasm
- cytosol
- plasma membrane
- membrane
- growth cone
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000547035
- Coding exons
- 13
- Length
- 19574
- Individuals with no LoFs
- 125742
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125748
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.99 | 332 | 525 | 0.633 | 0.0000306 | 5687 |
| Missense (PolyPhen) | 60 | 172.71 | 0.3474 | 1939 | ||
| Synonymous | -1.43 | 234 | 208 | 1.13 | 0.0000111 | 1947 |
| Loss of Function | 5.96 | 0 | 41.3 | 0.00 | 0.00000254 | 441 |
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 | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be an activator of the JNK/SAPK pathway. Phosphorylates beta-casein, histone 1 and myelin basic protein in vitro.;
Recessive Scores
- pRec
- 0.123
Intolerance Scores
- LoFtool
- 0.0529
- RVIS EVS
- -0.58
- RVIS percentile EVS
- 18.72
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.957
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |