CAMK2A

calcium/calmodulin dependent protein kinase II alpha, the group of Calmodulin dependent protein kinases

Basic information

Region (hg38): 5:150219490-150290093

Previous symbols: [ "CAMKA" ]

Links

ENSG00000070808 ∙ NCBI:815 ∙ OMIM:114078 ∙ HGNC:1460 ∙ Uniprot:Q9UQM7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
• intellectual disability, autosomal dominant 53 (Strong), mode of inheritance: AD
• intellectual disability, autosomal recessive 63 (Limited), mode of inheritance: AR
• intellectual disability, autosomal dominant 40 (Strong), mode of inheritance: AD
• intellectual disability, autosomal recessive 63 (Limited), mode of inheritance: AR
• intellectual disability, autosomal dominant 53 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mental retardation, autosomal dominant, 53; Mental retardation, autosomal recessive, 63	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	28130356; 29100089; 29784083

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CAMK2A gene.

• not provided (61 variants)
• Intellectual disability, autosomal dominant 53 (20 variants)
• Inborn genetic diseases (7 variants)
• Intellectual disability, autosomal recessive 63 (6 variants)
• not specified (4 variants)
• Intellectual disability (2 variants)
• Global developmental delay (1 variants)
• Neurodevelopmental disorder (1 variants)
• Autism spectrum disorder (1 variants)
• Intellectual disability, autosomal dominant 53;Intellectual disability, autosomal recessive 63 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CAMK2A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				12	2	14
missense	2	7	28	3		40
nonsense	2	1	2			5
start loss						0
frameshift		1	1			2
inframe indel		1				1
splice donor/acceptor (+/-2bp)			4			4
splice region			8	1	2	11
non coding			1	5	3	9
Total	4	10	36	20	5

Variants in CAMK2A

This is a list of pathogenic ClinVar variants found in the CAMK2A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-150222414-C-G			Likely benign (Oct 01, 2022)
5-150222483-A-T			Likely benign (Sep 01, 2023)
5-150222520-C-T			Uncertain significance (Sep 01, 2022)
5-150222566-C-G			Likely benign (Jan 01, 2024)
5-150222666-T-C			Likely benign (Nov 01, 2023)
5-150222693-G-A			Likely benign (Aug 01, 2023)
5-150222717-T-C		Intellectual disability, autosomal recessive 63 • Intellectual disability, autosomal dominant 53	Benign (Jul 14, 2021)
5-150222720-G-C		not specified	Uncertain significance (Jan 23, 2024)
5-150222800-T-A		Intellectual disability, autosomal recessive 63 • Intellectual disability, autosomal dominant 53	Benign (Jul 14, 2021)
5-150223013-G-C			Uncertain significance (Jul 14, 2022)
5-150223026-G-A		Intellectual disability, autosomal recessive 63	Pathogenic (Apr 11, 2022)
5-150223029-C-A			Uncertain significance (Sep 14, 2022)
5-150223036-C-T		Intellectual disability, autosomal dominant 53	Uncertain significance (Jun 30, 2023)
5-150223045-A-G		Intellectual disability, autosomal dominant 53 • Intellectual disability, autosomal recessive 63	Benign (Jul 14, 2021)
5-150223046-T-C		Neurodevelopmental disorder	Uncertain significance (Aug 08, 2023)
5-150223049-C-G			Uncertain significance (May 10, 2022)
5-150223049-C-T			Uncertain significance (Oct 14, 2022)
5-150223076-G-A		Inborn genetic diseases	Uncertain significance (Dec 01, 2021)
5-150223092-G-T		Inborn genetic diseases	Uncertain significance (Jan 15, 2018)
5-150223104-C-T			Uncertain significance (Sep 01, 2023)
5-150223122-T-C		Inborn genetic diseases	Uncertain significance (Dec 07, 2022)
5-150223124-C-T			Uncertain significance (Nov 01, 2022)
5-150223125-G-A		Inborn genetic diseases	Uncertain significance (Sep 22, 2023)
5-150223135-G-A		CAMK2A-related disorder	Likely benign (Nov 01, 2023)
5-150223149-C-T			Likely benign (Nov 01, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CAMK2A	protein_coding	protein_coding	ENST00000398376	19	70801

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00155	125689	0	3	125692	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.68	72	300	0.240	0.0000187	3181
Missense in Polyphen		27	154.3	0.17499		1622
Synonymous	0.823	113	125	0.906	0.00000839	933
Loss of Function	4.98	4	36.5	0.110	0.00000198	389

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in synaptic plasticity, neurotransmitter release and long-term potentiation. Member of the NMDAR signaling complex in excitatory synapses, it regulates NMDAR-dependent potentiation of the AMPAR and therefore excitatory synaptic transmission (By similarity). Regulates dendritic spine development (PubMed:28130356). Also regulates the migration of developing neurons (PubMed:29100089). Phosphorylates the transcription factor FOXO3 to activate its transcriptional activity (PubMed:23805378). {ECO:0000250|UniProtKB:P11275, ECO:0000269|PubMed:23805378, ECO:0000269|PubMed:28130356, ECO:0000269|PubMed:29100089}.
• Disease: DISEASE: Mental retardation, autosomal dominant 53 (MRD53) [MIM:617798]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:25533962, ECO:0000269|PubMed:28130356, ECO:0000269|PubMed:29100089}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Long-term potentiation - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Axon guidance - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Glioma - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Necroptosis - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Amphetamine addiction - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Olfactory transduction - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Melanogenesis - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;B Cell Receptor Signaling Pathway;Corticotropin-releasing hormone signaling pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Common Pathways Underlying Drug Addiction;Myometrial Relaxation and Contraction Pathways;Melatonin metabolism and effects;MECP2 and Associated Rett Syndrome;NO-cGMP-PKG mediated Neuroprotection;Wnt Signaling Pathway;EGF-EGFR Signaling Pathway;Calcium Regulation in the Cardiac Cell;ErbB Signaling Pathway;Signaling by WNT;Signal Transduction;HSF1-dependent transactivation;bioactive peptide induced signaling pathway;regulation of pgc-1a;transcription factor creb and its extracellular signals;stathmin and breast cancer resistance to antimicrotubule agents;Ion channel transport;Cytokine Signaling in Immune system;Cellular responses to stress;Immune System;Ion homeostasis;Transport of small molecules;Neuronal System;Phase 0 - rapid depolarisation;Cardiac conduction;Muscle contraction;Cellular responses to external stimuli;IL-7 signaling;Ion transport by P-type ATPases;Ca2+ pathway;Beta-catenin independent WNT signaling;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;JAK STAT pathway and regulation;Noncanonical Wnt signaling pathway;Cellular response to heat stress;EPO signaling;Trafficking of AMPA receptors;Interferon gamma signaling;IFN-gamma pathway;Glutamate binding, activation of AMPA receptors and synaptic plasticity;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Ras activation upon Ca2+ influx through NMDA receptor;CREB phosphorylation through the activation of Ras;Unblocking of NMDA receptor, glutamate binding and activation;CREB phosphorylation through the activation of CaMKII;Post NMDA receptor activation events;Activation of NMDA receptor and postsynaptic events;VEGF;ca-calmodulin-dependent protein kinase activation;Netrin-mediated signaling events;Interferon Signaling;Trk receptor signaling mediated by PI3K and PLC-gamma;FGF signaling pathway;TGF-beta receptor signaling (Consensus)

Recessive Scores

• pRec: 0.388

Intolerance Scores

• loftool: 0.165
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.26

Haploinsufficiency Scores

• pHI: 0.696
• hipred: Y
• hipred_score: 0.853
• ghis: 0.650

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.977

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low

Mouse Genome Informatics

• Gene name: Camk2a
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: camk2a
• Affected structure: Mauthner neuron
• Phenotype tag: abnormal
• Phenotype quality: process quality

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;MAPK cascade;response to ischemia;protein phosphorylation;calcium ion transport;Wnt signaling pathway, calcium modulating pathway;positive regulation of cardiac muscle cell apoptotic process;peptidyl-serine phosphorylation;angiotensin-activated signaling pathway;protein autophosphorylation;regulation of neurotransmitter secretion;regulation of neuronal synaptic plasticity;dendrite morphogenesis;positive regulation of NF-kappaB transcription factor activity;positive regulation of calcium ion transport;interferon-gamma-mediated signaling pathway;dendritic spine development;regulation of synaptic vesicle docking;regulation of mitochondrial membrane permeability involved in apoptotic process;peptidyl-threonine autophosphorylation;regulation of neuron migration
• Cellular component: nucleus;nucleoplasm;cytoplasm;mitochondrion;cytosol;plasma membrane;calcium- and calmodulin-dependent protein kinase complex;postsynaptic density;cell junction;endocytic vesicle membrane;neuron projection;dendritic spine;postsynaptic membrane;Schaffer collateral - CA1 synapse
• Molecular function: protein serine/threonine kinase activity;calmodulin-dependent protein kinase activity;Ras guanyl-nucleotide exchange factor activity;protein binding;calmodulin binding;ATP binding;calcium-dependent protein serine/threonine kinase activity;kinase activity;glutamate receptor binding;identical protein binding;protein homodimerization activity;metal ion binding