CAMKK2 (Calcium/Calmodulin Dependent Protein Kinase Kinase 2): Gene, Function, and Disease Relevance
A comprehensive biomedical overview of CAMKK2, including gene structure, expression, mutations, pathways, and clinical significance.
Gene Information Card
| Symbol | CAMKK2 |
|---|---|
| Full Name | Calcium/calmodulin dependent protein kinase kinase 2 |
| Gene Type | protein coding |
| Chromosomal Location | 12q24.31 |
| NCBI Gene ID | 10645 ncbi.nlm.nih.gov/gene/10645 |
| Ensembl ID | ENSG00000110931 |
| UniProt ID | Q96RR4 |
| OMIM ID | 615002 |
| HGNC ID | 1470 |
| Aliases | CAMKKB, CAMKK beta |
Description
CAMKK2 (calcium/calmodulin dependent protein kinase kinase 2) encodes a serine/threonine kinase that is activated by calcium-bound calmodulin. It phosphorylates downstream kinases such as AMPK (PRKAA1) and CAMKI/CAMKIV, thereby regulating cellular energy homeostasis, autophagy, and cell proliferation. CAMKK2 is implicated in various cancers, metabolic disorders, and neurological conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (prostate, breast, liver, etc.) | CAMKK2 promotes tumor growth and survival via AMPK and AKT signaling; overexpression enhances cell proliferation and metastasis. | COSMIC; multiple studies (e.g., PMID: 25944712, 27630125) |
| Obesity and type 2 diabetes | CAMKK2 regulates hypothalamic AMPK activity, influencing food intake and glucose metabolism; genetic variants may affect susceptibility. | ClinVar; OMIM #615002; studies (PMID: 21712999) |
| Neurological disorders (e.g., schizophrenia, bipolar disorder) | CAMKK2 modulates neuronal calcium signaling and synaptic plasticity; altered expression linked to psychiatric conditions. | OMIM; GWAS studies (PMID: 21926972) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Heart | 5.2 | Low |
| Liver | 3.1 | Low |
| Kidney | 4.8 | Low |
| Testis | 8.7 | Medium |
| Skeletal muscle | 2.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 15.2 | High expression; used in functional studies |
| MCF7 (breast cancer) | 9.8 | Moderate; associated with estrogen signaling |
| HepG2 (liver cancer) | 6.4 | Low; role in metabolic regulation |
| SH-SY5Y (neuroblastoma) | 18.5 | High; neuronal model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1345C>T (p.Arg449Trp) | Missense | 0.01% (gnomAD) | Potential loss of kinase activity; reported in ClinVar as uncertain significance |
| c.1003G>A (p.Gly335Ser) | Missense | 0.005% | Unknown; not characterized |
| c.1567A>G (p.Ile523Val) | Missense | 0.02% | Benign; common polymorphism |
| c.1129C>T (p.Arg377Cys) | Missense | 0.001% | Reported in COSMIC in cancer samples; functional impact unknown |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce kinase activity or protein stability, leading to impaired AMPK signaling and altered metabolism.
Gain of Function (GOF)
Amplification or overexpression of CAMKK2 in cancers, enhancing oncogenic signaling.
Dominant Negative (DN)
Not well documented; some truncating mutations may interfere with dimerization.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • calmodulin binding |
| • calcium ion binding | • ATP binding |
| • signal transduction | • regulation of AMPK activity |
| • autophagy | • cell proliferation |
Pathways
• Calcium signaling pathway
• AMPK signaling pathway
• Insulin signaling pathway
• Autophagy pathway
• Neurotrophin signaling pathway
Protein Summary
CAMKK2 is a 588-amino acid protein with a molecular weight of approximately 65 kDa. It contains an N-terminal calmodulin-binding domain and a C-terminal kinase domain. Upon calcium influx, calmodulin binds to CAMKK2, inducing a conformational change that activates its kinase activity. CAMKK2 then phosphorylates AMPK at Thr172, leading to AMPK activation, which regulates energy balance. It also phosphorylates CAMKI and CAMKIV, affecting transcription factors such as CREB. CAMKK2 is expressed in multiple tissues, with highest levels in the brain and testis. Its dysregulation is linked to cancer, metabolic diseases, and neurological disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CAMKK2 Knockout HEK293 Cell Line | EDJ-KQ1857 | Human | 10645 | Details Get a Quote |
| CAMKK2 Knockout HeLa Cell Line | EDJ-KQ20418 | Human | 10645 | Details Get a Quote |
| CAMKK2 Knockout A-549 Cell Line | EDJ-KQ21722 | Human | 10645 | Details Get a Quote |
| CAMKK2 Knockout HCT 116 Cell Line | EDJ-KQ21723 | Human | 10645 | Details Get a Quote |
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