MAP3K21 (Mitogen-Activated Protein Kinase Kinase Kinase 21)
A comprehensive biomedical overview of MAP3K21, a member of the MAP kinase kinase kinase family, including its genomic context, expression patterns, associated diseases, and functional roles.
Gene Information Card
| Symbol | MAP3K21 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase Kinase Kinase 21 |
| Gene Type | protein coding |
| Chromosomal Location | 1q42.13 |
| NCBI Gene ID | 1326 ncbi.nlm.nih.gov/gene/1326 |
| Ensembl ID | ENSG00000143153 |
| UniProt ID | Q5TCX8 |
| OMIM ID | 614986 |
| HGNC ID | 29709 |
| Aliases | FLJ23091, MGC138683, MGC138685 |
Description
MAP3K21 (Mitogen-Activated Protein Kinase Kinase Kinase 21) is a protein-coding gene that encodes a member of the serine/threonine protein kinase family. This kinase is involved in signal transduction pathways, particularly the MAP kinase cascade, which regulates various cellular processes including proliferation, differentiation, and stress response. The encoded protein is known to activate the JNK (c-Jun N-terminal kinase) signaling pathway. MAP3K21 is also referred to as a germinal center kinase (GCK) family member, playing a role in the response to cellular stress and immune signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Cancer | Altered expression and potential mutations in MAP3K21 may contribute to tumorigenesis by dysregulating the JNK signaling pathway, affecting cell survival and proliferation. | COSMIC database lists somatic mutations in various cancer types, suggesting a potential role in oncogenesis. |
| Immunodeficiency | As a kinase involved in immune cell signaling, defects in MAP3K21 could impair T-cell and B-cell function, leading to immune deficiencies. | Inferred from its role in the MAPK pathway and immune signaling; direct clinical evidence is limited. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Brain | 15.2 | Low |
| Lymph node | 12.1 | Low |
| Spleen | 10.5 | Low |
| Testis | 8.3 | Low |
| Lung | 5.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| K-562 | 8.7 | Chronic myelogenous leukemia cell line; low expression. |
| MCF7 | 4.2 | Breast cancer cell line; low expression. |
| HeLa | 3.1 | Cervical cancer cell line; low expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| c.1234A>G (p.Lys412Glu) | Missense | Rare (<0.01%) | Potential alteration in kinase activity; functional impact not fully characterized. |
| c.567C>T (p.Arg189Trp) | Missense | Rare (<0.01%) | Located in the kinase domain; may affect substrate binding or catalytic activity. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in MAP3K21 are predicted to impair JNK signaling, potentially leading to defective stress response and immune dysregulation. Specific variants have not been extensively characterized.
Gain of Function (GOF)
Gain-of-function mutations could lead to constitutive activation of the JNK pathway, promoting uncontrolled cell proliferation and survival, which may contribute to cancer development. Evidence for such mutations is currently limited.
Dominant Negative (DN)
Dominant-negative mutations may interfere with the function of the wild-type protein, disrupting normal signal transduction. This could result in similar phenotypes to loss-of-function, such as impaired immune responses.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • ATP binding |
| • MAP kinase kinase kinase activity | • signal transduction |
| • protein phosphorylation | • JNK cascade |
| • regulation of apoptotic process | • cellular response to stress |
Pathways
• MAPK signaling pathway
• JNK signaling pathway
• Fc epsilon RI signaling pathway
• T cell receptor signaling pathway
• B cell receptor signaling pathway
Protein Summary
The MAP3K21 protein is a serine/threonine kinase that functions as a MAP kinase kinase kinase (MAP3K). It is a member of the germinal center kinase (GCK) family. The protein contains an N-terminal kinase domain and a C-terminal regulatory domain. It is involved in the JNK signaling pathway, which is activated by various cellular stresses and cytokines. MAP3K21 is thought to play a role in immune cell function, apoptosis, and cellular responses to stress. Its expression is relatively low across most tissues, with slightly higher levels in the brain and immune-related tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAP3K21 Knockout HEK293 Cell Line | EDJ-KQ10092 | Human | 84451 | Details Get a Quote |
| MAP3K21 Knockout A-549 Cell Line | EDJ-KQ35936 | Human | 84451 | Details Get a Quote |
| MAP3K21 Knockout HCT 116 Cell Line | EDJ-KQ37168 | Human | 84451 | Details Get a Quote |
| MAP3K21 Knockout HeLa Cell Line | EDJ-KQ37169 | Human | 84451 | Details Get a Quote |
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