CAMK2A: Calcium/Calmodulin-Dependent Protein Kinase II Alpha
A central regulator of neuronal signaling, synaptic plasticity, and learning; mutations cause neurodevelopmental disorders.
Gene Information Card
| Symbol | CAMK2A |
|---|---|
| Full Name | Calcium/calmodulin dependent protein kinase II alpha |
| Gene Type | protein coding |
| Chromosomal Location | 5q32 |
| NCBI Gene ID | 815 ncbi.nlm.nih.gov/gene/815 |
| Ensembl ID | ENSG00000070808 |
| UniProt ID | Q9UQM7 |
| OMIM ID | 114078 |
| HGNC ID | 1460 |
| Aliases | CAMKA, KIAA0968 |
Description
The CAMK2A gene encodes the alpha subunit of calcium/calmodulin-dependent protein kinase II (CaMKII), a serine/threonine kinase highly abundant in the brain, particularly in the postsynaptic density of excitatory synapses. CaMKII alpha is a central mediator of calcium signaling, playing a critical role in synaptic plasticity, learning, and memory. Upon binding calcium/calmodulin, the kinase undergoes autophosphorylation, leading to a calcium-independent (autonomous) activity that is essential for long-term potentiation (LTP). Mutations in CAMK2A are associated with a neurodevelopmental disorder characterized by intellectual disability, speech delay, and behavioral abnormalities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual developmental disorder, autosomal dominant 53 (MRD53) | Heterozygous de novo missense mutations in CAMK2A lead to altered kinase activity (both loss and gain of function), disrupting synaptic plasticity and neuronal signaling. | ClinVar, OMIM (OMIM: 114078, 617798) |
| Neurodevelopmental disorder with speech delay and behavioral abnormalities | Pathogenic variants impair CaMKII function, affecting dendritic spine maturation and synaptic transmission. | ClinVar, PubMed (PMID: 28191889) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain - Cerebral Cortex | 111.2 | High |
| Brain - Cerebellum | 95.8 | High |
| Brain - Hippocampus | 120.5 | High |
| Brain - Basal Ganglia | 88.3 | High |
| Testis | 5.1 | Low |
| Other Tissues | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (Neuroblastoma) | 45.3 | High expression; used as a neuronal model. |
| U-87 MG (Glioblastoma) | 12.1 | Moderate expression. |
| HeLa (Cervical Carcinoma) | 0.2 | Very low expression. |
| HepG2 (Hepatocellular Carcinoma) | 0.1 | Not expressed. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Pro212Leu (c.635C>T) | Missense | De novo | Reduced kinase activity; associated with MRD53. |
| p.Thr286Ala (c.856A>G) | Missense | Somatic | Prevents autophosphorylation, abolishing autonomous activity; dominant-negative effect. |
| p.Arg312Gln (c.935G>A) | Missense | De novo | Gain-of-function; increased autonomous activity; associated with MRD53. |
| p.Val369Met (c.1105G>A) | Missense | De novo | Impaired kinase activity; associated with neurodevelopmental disorder. |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Pro212Leu and p.Val369Met reduce or abolish the kinase's ability to phosphorylate substrates, impairing downstream signaling pathways critical for synaptic plasticity.
Gain of Function (GOF)
Mutations like p.Arg312Gln increase the kinase's autonomous activity, leading to excessive phosphorylation and disruption of normal synaptic signaling.
Dominant Negative (DN)
The p.Thr286Ala mutation acts in a dominant-negative manner by preventing autophosphorylation, which is required for the sustained activity of the kinase, thereby interfering with the function of the wild-type enzyme.
View complete mutation data：
Gene Ontology (GO)
| • calmodulin binding | • calcium ion binding |
| • ATP binding | • protein serine/threonine kinase activity |
| • calmodulin-dependent protein kinase activity | • protein kinase activity |
| • signal transduction | • synaptic plasticity |
| • long-term potentiation | • dendritic spine development |
| • regulation of neurotransmitter secretion |
Pathways
• Calcium signaling pathway
• Long-term potentiation (LTP)
• Neurotrophin signaling pathway
• Glutamatergic synapse
• Dopaminergic synapse
Protein Summary
The CAMK2A protein is a 478-amino acid serine/threonine kinase that forms a dodecameric holoenzyme. It consists of an N-terminal catalytic domain, a central regulatory domain containing the calmodulin-binding site and the critical autophosphorylation site (Thr286), and a C-terminal association domain responsible for holoenzyme assembly. Upon calcium/calmodulin binding, the kinase is activated and autophosphorylates at Thr286, which makes the enzyme active even after calcium levels drop. This property is essential for the induction and maintenance of long-term potentiation (LTP), a cellular correlate of learning and memory. The protein is highly expressed in the postsynaptic density, where it interacts with NMDA receptors and other scaffolding proteins to modulate synaptic strength.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CAMK2A Knockout HEK293 Cell Line | EDJ-KQ282 | Human | 815 | Details Get a Quote |
| CAMK2A Knockout HeLa Cell Line | EDJ-KQ52784 | Human | 815 | Details Get a Quote |
| CAMK2A Knockout A-549 Cell Line | EDJ-KQ61253 | Human | 815 | Details Get a Quote |
| CAMK2A Knockout HCT 116 Cell Line | EDJ-KQ69749 | Human | 815 | Details Get a Quote |
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