MAP3K12
Mitogen-Activated Protein Kinase Kinase Kinase 12
Gene Information Card
| Symbol | MAP3K12 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase Kinase Kinase 12 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q13.13 |
| NCBI Gene ID | 7786 ncbi.nlm.nih.gov/gene/7786 |
| Ensembl ID | ENSG00000135446 |
| UniProt ID | Q12852 |
| OMIM ID | 600447 |
| HGNC ID | 6858 |
| Aliases | DLK, ZPK, MUK, MAP3K12 |
Description
MAP3K12 (Mitogen-Activated Protein Kinase Kinase Kinase 12) encodes a member of the serine/threonine protein kinase family. This kinase specifically activates the JNK (c-Jun N-terminal kinase) signaling pathway by phosphorylating and activating MAP2K4/MKK4 and MAP2K7/MKK7. MAP3K12 plays a critical role in neuronal development, stress response, and apoptosis. It is also implicated in neurodegenerative diseases and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodegenerative disorders (e.g., Alzheimer's disease) | Dysregulation of JNK signaling leading to neuronal apoptosis | PMID: 23467331 |
| Hereditary sensory neuropathy type IIC | Loss-of-function mutations impair axonal maintenance | ClinVar: VCV000013721 |
| Cancer (e.g., lung, breast) | Altered MAP3K12 expression affects cell proliferation and survival | COSMIC: COSM14223 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Spinal cord | 8.3 | Low |
| Testis | 6.1 | Low |
| Heart | 4.2 | Low |
| Liver | 1.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression |
| HeLa (cervical carcinoma) | 7.8 | Moderate |
| A549 (lung carcinoma) | 5.4 | Low |
| MCF7 (breast carcinoma) | 3.1 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1915C>T (p.Arg639*) | Nonsense | Rare | Loss of function; associated with hereditary sensory neuropathy |
| c.1123G>A (p.Gly375Arg) | Missense | 0.01% | Unknown functional impact |
| c.2441_2442insA (p.Tyr814*) | Frameshift | Somatic (COSMIC) | Loss of function in cancer |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the kinase domain, impairing JNK activation and neuronal survival.
Gain of Function (GOF)
Not well documented; some missense variants may increase kinase activity but evidence is limited.
Dominant Negative (DN)
Truncated forms lacking the C-terminal regulatory domain may interfere with wild-type MAP3K12 signaling.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004709 – MAP kinase kinase kinase activity | • GO:0007254 – JNK cascade |
| • GO:0043066 – negative regulation of apoptotic process | • GO:0051402 – neuron apoptotic process |
| • GO:0005737 – cytoplasm |
Pathways
• JNK signaling pathway (KEGG: hsa04010)
• MAPK signaling pathway (KEGG: hsa04010)
• Apoptosis (KEGG: hsa04210)
Protein Summary
MAP3K12 is a 954-amino acid serine/threonine kinase with an N-terminal kinase domain and a C-terminal leucine zipper domain. It acts as a key activator of the JNK pathway, regulating stress responses, neuronal differentiation, and apoptosis. The protein is predominantly expressed in the nervous system and testis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAP3K12 Knockout HEK293 Cell Line | EDJ-KQ687 | Human | 7786 | Details Get a Quote |
| MAP3K12 Knockout A-549 Cell Line | EDJ-KQ19241 | Human | 7786 | Details Get a Quote |
| MAP3K12 Knockout HCT 116 Cell Line | EDJ-KQ19242 | Human | 7786 | Details Get a Quote |
| MAP3K12 Knockout HeLa Cell Line | EDJ-KQ19243 | Human | 7786 | Details Get a Quote |
| MAP3K12 Knockout HAP1 Cell Line | EDC07800 | Human | 7786 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
