MAP3K14 (NF-κB-Inducing Kinase) Gene
A key regulator of the noncanonical NF-κB pathway, involved in immune responses, lymphoid organogenesis, and cancer.
Gene Information Card
| Symbol | MAP3K14 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase Kinase Kinase 14 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.31 |
| NCBI Gene ID | 9020 ncbi.nlm.nih.gov/gene/9020 |
| Ensembl ID | ENSG00000006062 |
| UniProt ID | Q99558 |
| OMIM ID | 604655 |
| HGNC ID | 6853 |
| Aliases | NIK, HS, FTDCR1B |
Description
MAP3K14 encodes the NF-κB-inducing kinase (NIK), a serine/threonine kinase that is a central component of the noncanonical NF-κB signaling pathway. NIK is activated by upstream signals from TNF receptor superfamily members (e.g., CD40, BAFF-R, LTβR) and phosphorylates IKKα, leading to p100 processing to p52 and subsequent nuclear translocation of p52/RelB complexes. This pathway regulates genes involved in immune responses, lymphoid organogenesis, and cell survival. Mutations in MAP3K14 can cause immunodeficiency and have been implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency, developmental delay, and hypohidrosis (IDDH) | Loss-of-function mutations in MAP3K14 impair noncanonical NF-κB signaling, leading to defective B-cell and T-cell responses and ectodermal defects. | ClinVar, OMIM |
| Multiple myeloma | Overexpression or constitutive activation of NIK (due to mutations in downstream regulators like TRAF3) drives tumor cell survival and proliferation via noncanonical NF-κB. | COSMIC, literature |
| Breast cancer | Elevated NIK expression correlates with poor prognosis and promotes epithelial-mesenchymal transition and metastasis. | COSMIC, literature |
| Hodgkin lymphoma | Aberrant NIK activation contributes to constitutive NF-κB activity in Hodgkin/Reed-Sternberg cells. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | High | High expression in immune tissues |
| Spleen | High | High expression in immune tissues |
| Bone marrow | Medium | Moderate expression |
| Thymus | Medium | Moderate expression |
| Lung | Low | Low expression |
| Liver | Low | Low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| B cells (e.g., Ramos) | High | Key role in B-cell activation |
| T cells (e.g., Jurkat) | Medium | Involved in T-cell responses |
| Endothelial cells (e.g., HUVEC) | Medium | Regulates adhesion molecule expression |
| Epithelial cells (e.g., HeLa) | Low | Basal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.193C>T (p.Arg65*) | Nonsense | Rare | Loss of function; causes immunodeficiency (IDDH) |
| c.1025G>A (p.Arg342Gln) | Missense | Rare | Loss of function; impairs kinase activity |
| Amplification of 17q21.31 | Copy number gain | Frequent in multiple myeloma | Gain of function; increases NIK expression |
| Deletion of TRAF3 (upstream regulator) | Somatic mutation | Frequent in multiple myeloma | Gain of function; stabilizes NIK protein |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., nonsense, missense) impair NIK kinase activity or protein stability, leading to defective noncanonical NF-κB signaling and immunodeficiency.
Gain of Function (GOF)
Gain-of-function alterations (e.g., gene amplification, stabilizing mutations) increase NIK expression or activity, driving oncogenic NF-κB signaling in cancers.
Dominant Negative (DN)
Dominant-negative mutations are rare but may interfere with NIK oligomerization or substrate binding, reducing pathway activity.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • ATP binding |
| • NF-kappaB-inducing kinase activity | • signal transduction |
| • positive regulation of NF-kappaB transcription factor activity | • lymph node development |
| • B cell activation | • T cell activation |
| • cellular response to cytokine stimulus |
Pathways
• Noncanonical NF-kappaB signaling
• TNF receptor superfamily signaling
• BAFF signaling in B cells
• Lymphotoxin beta receptor signaling
Protein Summary
The NF-κB-inducing kinase (NIK) is a 947-amino acid protein with an N-terminal kinase domain, a central region, and a C-terminal non-catalytic domain. It is normally degraded by a TRAF2/TRAF3/cIAP complex, but upon receptor stimulation, NIK is stabilized and accumulates, then phosphorylates IKKα. This leads to p100 processing and activation of the noncanonical NF-κB pathway. NIK is critical for secondary lymphoid organ development, B-cell survival, and immune responses. Dysregulation of NIK is linked to immunodeficiency and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAP3K14 Knockout HEK293 Cell Line | EDJ-KQ577 | Human | 9020 | Details Get a Quote |
| MAP3K14 Knockout A-549 Cell Line | EDJ-KQ18975 | Human | 9020 | Details Get a Quote |
| MAP3K14 Knockout HCT 116 Cell Line | EDJ-KQ18976 | Human | 9020 | Details Get a Quote |
| MAP3K14 Knockout HeLa Cell Line | EDJ-KQ18977 | Human | 9020 | Details Get a Quote |
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