CAMK2B

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

Basic information

Region (hg38): 7:44210018-44334577

Previous symbols: [ "CAMKB" ]

Links

ENSG00000058404 ∙ NCBI:816 ∙ OMIM:607707 ∙ HGNC:1461 ∙ Uniprot:Q13554 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Strong), mode of inheritance: AD
• autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
• intellectual disability, autosomal dominant 40 (Definitive), mode of inheritance: AD
• intellectual disability, autosomal dominant 54 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 54	AD	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

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CAMK2B gene.

• not provided (508 variants)
• Intellectual disability, autosomal dominant 54 (39 variants)
• Inborn genetic diseases (25 variants)
• Intellectual disability (8 variants)
• not specified (6 variants)
• CAMK2B-related condition (3 variants)
• Autism spectrum disorder (2 variants)
• 6 conditions (1 variants)
• Abnormality of the nervous system (1 variants)
• Developmental disorder (1 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CAMK2B 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			4	120	16	140
missense	3	4	134	31	14	186
nonsense	1		2			3
start loss						0
frameshift			13	3		16
inframe indel		1	2			3
splice donor/acceptor (+/-2bp)	1	3	11	3		18
splice region			17	35	6	58
non coding			6	97	14	117
Total	5	8	172	254	44

Variants in CAMK2B

This is a list of pathogenic ClinVar variants found in the CAMK2B region.

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

Position	Type	Phenotype	Significance	ClinVar
7-44211027-A-C		not specified	Uncertain significance (Jul 13, 2021)
7-44211086-G-A		not specified	Uncertain significance (Dec 05, 2022)
7-44219955-T-TG		Intellectual disability, autosomal dominant 54	Benign (Jul 14, 2021)
7-44219962-G-GC		Intellectual disability, autosomal dominant 54	Benign (Jul 14, 2021)
7-44220065-C-T			Likely benign (Nov 28, 2022)
7-44220069-A-G		Inborn genetic diseases	Likely benign (Jan 02, 2024)
7-44220071-C-T			Likely benign (Mar 23, 2023)
7-44220072-G-A		Intellectual disability, autosomal dominant 54	Conflicting classifications of pathogenicity (Mar 26, 2024)
7-44220077-C-T			Likely benign (Apr 26, 2023)
7-44220083-C-A			Likely benign (Sep 01, 2022)
7-44220083-C-T			Likely benign (Nov 13, 2023)
7-44220084-G-A			Likely benign (Sep 10, 2023)
7-44220085-C-A			Uncertain significance (Jul 26, 2022)
7-44220085-C-T		CAMK2B-related disorder • Inborn genetic diseases	Likely benign (Feb 01, 2024)
7-44220086-G-A		CAMK2B-related disorder	Benign (Jan 30, 2024)
7-44220089-C-T			Likely benign (Apr 26, 2023)
7-44220101-G-A			Likely benign (Aug 17, 2023)
7-44220104-C-G			Likely benign (Aug 31, 2023)
7-44220106-C-T			Uncertain significance (Aug 07, 2023)
7-44220107-G-A		Intellectual disability, autosomal dominant 54	Benign (Feb 01, 2024)
7-44220116-C-T			Likely benign (Apr 13, 2023)
7-44220121-C-T			Uncertain significance (Sep 12, 2023)
7-44220122-G-A		CAMK2B-related disorder	Likely benign (Dec 18, 2023)
7-44220124-C-T		Inborn genetic diseases	Uncertain significance (Dec 11, 2023)
7-44220125-G-A			Likely benign (Dec 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CAMK2B	protein_coding	protein_coding	ENST00000395749	23	117428

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.739	0.261	125647	0	29	125676	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.07	166	393	0.422	0.0000244	4277
Missense in Polyphen		40	158.73	0.25201		1627
Synonymous	0.219	160	164	0.978	0.0000114	1318
Loss of Function	4.65	8	39.6	0.202	0.00000207	453

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00163	0.00151
Ashkenazi Jewish	0.000102	0.0000993
East Asian	0.00	0.00
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000184	0.0000176
Middle Eastern	0.00	0.00
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 dendritic spine and synapse formation, neuronal plasticity and regulation of sarcoplasmic reticulum Ca(2+) transport in skeletal muscle. In neurons, plays an essential structural role in the reorganization of the actin cytoskeleton during plasticity by binding and bundling actin filaments in a kinase-independent manner. This structural function is required for correct targeting of CaMK2A, which acts downstream of NMDAR to promote dendritic spine and synapse formation and maintain synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In developing hippocampal neurons, promotes arborization of the dendritic tree and in mature neurons, promotes dendritic remodeling. Also regulates the migration of developing neurons (PubMed:29100089). Participates in the modulation of skeletal muscle function in response to exercise. In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of triadin, a ryanodine receptor-coupling factor, and phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2. {ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:29100089}.
• Disease: DISEASE: Mental retardation, autosomal dominant 54 (MRD54) [MIM:617799]: 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: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;Primary Focal Segmental Glomerulosclerosis FSGS;Serotonin and anxiety;Myometrial Relaxation and Contraction Pathways;NO-cGMP-PKG mediated Neuroprotection;Wnt Signaling Pathway;Calcium Regulation in the Cardiac Cell;Regulation of Ras family activation;Signal Transduction;HSF1-dependent transactivation;bioactive peptide induced signaling pathway;links between pyk2 and map kinases;regulation of pgc-1a;transcription factor creb and its extracellular signals;regulation of ck1/cdk5 by type 1 glutamate receptors;nitric oxide signaling pathway;angiotensin ii mediated activation of jnk pathway via pyk2 dependent signaling;stathmin and breast cancer resistance to antimicrotubule agents;endocytotic role of ndk phosphins and dynamin;corticosteroids and cardioprotection;role of mef2d in t-cell apoptosis;ion channels and their functional role in vascular endothelium;signal dependent regulation of myogenesis by corepressor mitr;vegf hypoxia and angiogenesis;pkc-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase;effects of calcineurin in keratinocyte differentiation;nfat and hypertrophy of the heart ;signaling pathway from g-protein families;t cell receptor signaling pathway;bcr signaling pathway;calcium signaling by hbx of hepatitis b virus;Ion channel transport;Cytokine Signaling in Immune system;Cellular responses to stress;Immune System;Ion homeostasis;Transport of small molecules;Neuronal System;actions of nitric oxide in the heart;Phase 0 - rapid depolarisation;Cardiac conduction;Muscle contraction;Cellular responses to external stimuli;IL-7 signaling;control of skeletal myogenesis by hdac and calcium/calmodulin-dependent kinase (camk);Ion transport by P-type ATPases;fmlp induced chemokine gene expression in hmc-1 cells;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;JAK STAT pathway and regulation;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;Interferon Signaling;p38 MAPK signaling pathway (Consensus)

Recessive Scores

• pRec: 0.299

Intolerance Scores

• loftool: 0.575
• rvis_EVS: -0.62
• rvis_percentile_EVS: 17.16

Haploinsufficiency Scores

• pHI: 0.304
• hipred: Y
• hipred_score: 0.736
• ghis: 0.674

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.942

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Camk2b
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: camk2b2
• Affected structure: pectoral fin
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: MAPK cascade;protein phosphorylation;signal transduction;positive regulation of neuron projection development;regulation of skeletal muscle adaptation;protein autophosphorylation;regulation of long-term neuronal synaptic plasticity;regulation of synapse structural plasticity;regulation of calcium ion transport;interferon-gamma-mediated signaling pathway;regulation of dendritic spine development;positive regulation of dendritic spine morphogenesis;positive regulation of synapse maturation;regulation of neuron migration
• Cellular component: nucleoplasm;cytoplasm;microtubule organizing center;cytosol;plasma membrane;cell junction;endocytic vesicle membrane;sarcoplasmic reticulum membrane;neuron projection;synapse
• Molecular function: actin binding;protein serine/threonine kinase activity;calmodulin-dependent protein kinase activity;Ras guanyl-nucleotide exchange factor activity;protein binding;calmodulin binding;ATP binding;identical protein binding;protein homodimerization activity