CAMK2G

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

Basic information

Region (hg38): 10:73812500-73874591

Previous symbols: [ "CAMKG" ]

Links

ENSG00000148660 ∙ NCBI:818 ∙ OMIM:602123 ∙ HGNC:1463 ∙ Uniprot:Q13555 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder 59 (Strong), mode of inheritance: AD
• intellectual developmental disorder 59 (Limited), mode of inheritance: AD
• intellectual developmental disorder 59 (Strong), mode of inheritance: AD
• intellectual developmental disorder 59 (Limited), mode of inheritance: AD
• developmental and epileptic encephalopathy (Limited), mode of inheritance: AD
• intellectual developmental disorder 59 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 59	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; Musculoskeletal; Neurologic	23033978; 30184290

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CAMK2G gene.

• not provided (26 variants)
• Inborn genetic diseases (10 variants)
• Intellectual developmental disorder 59 (9 variants)
• not specified (2 variants)
• Global developmental delay;Intellectual disability, severe;Generalized hypotonia;Autism (1 variants)
• Intellectual disability, severe (1 variants)
• CAMK2G-related syndromic intellectual disability (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 CAMK2G 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				2	2	4
missense		2	26	1		29
nonsense			1			1
start loss						0
frameshift		1	1			2
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding			7		4	11
Total	0	3	36	3	6

Variants in CAMK2G

This is a list of pathogenic ClinVar variants found in the CAMK2G region.

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

Position	Type	Phenotype	Significance	ClinVar
10-73815025-G-A		Intellectual developmental disorder 59	Uncertain significance (Mar 25, 2024)
10-73815047-A-T		not specified	Uncertain significance (May 04, 2022)
10-73815095-G-A			Uncertain significance (Mar 14, 2022)
10-73815144-C-T			Benign (Oct 01, 2022)
10-73815191-C-T		not specified	Uncertain significance (Dec 27, 2023)
10-73815218-T-C			Uncertain significance (Dec 22, 2022)
10-73816870-C-T		CAMK2G-related syndromic intellectual disability	Uncertain significance (Jan 30, 2020)
10-73816874-G-T		Intellectual developmental disorder 59	Uncertain significance (Jan 06, 2021)
10-73817022-C-T			Uncertain significance (Jun 13, 2023)
10-73817099-G-A		CAMK2G-related disorder	Benign (Feb 22, 2019)
10-73817113-T-C			Uncertain significance (Nov 09, 2022)
10-73817479-G-A			Likely benign (Oct 01, 2023)
10-73817489-CA-C			Uncertain significance (Oct 14, 2019)
10-73817509-G-T		CAMK2G-related disorder • not specified	Conflicting classifications of pathogenicity (Oct 05, 2022)
10-73817537-T-A			Uncertain significance (Oct 01, 2023)
10-73819534-G-C		not specified	Uncertain significance (Aug 02, 2021)
10-73819577-G-A		not specified	Uncertain significance (Feb 03, 2022)
10-73819600-C-T		not specified	Uncertain significance (Nov 06, 2023)
10-73819633-C-T		not specified	Uncertain significance (Dec 31, 2023)
10-73819637-G-A			Uncertain significance (Apr 25, 2022)
10-73819639-G-A		Intellectual developmental disorder 59	Uncertain significance (-)
10-73821694-C-T			Uncertain significance (Aug 15, 2022)
10-73821695-A-T		Intellectual developmental disorder 59	Likely pathogenic (Apr 04, 2024)
10-73821698-T-A		not specified	Uncertain significance (Feb 16, 2023)
10-73821708-G-A			Uncertain significance (Jan 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CAMK2G	protein_coding	protein_coding	ENST00000322680	20	62085

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000900	125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.80	145	343	0.422	0.0000211	3646
Missense in Polyphen		67	216.98	0.30878		2303
Synonymous	0.923	118	131	0.898	0.00000827	1054
Loss of Function	5.11	4	37.9	0.105	0.00000207	408

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000185	0.000185
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000441	0.0000439
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 sarcoplasmic reticulum Ca(2+) transport in skeletal muscle and may function in dendritic spine and synapse formation and neuronal plasticity. 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 the ryanodine receptor-coupling factor triadin. In neurons, may participate in the promotion of dendritic spine and synapse formation and maintenance of synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. {ECO:0000269|PubMed:16690701}.
• 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;Energy Metabolism;Myometrial Relaxation and Contraction Pathways;NO-cGMP-PKG mediated Neuroprotection;Splicing factor NOVA regulated synaptic proteins;Wnt Signaling Pathway;Calcium Regulation in the Cardiac Cell;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;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;BCR signaling pathway;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;N-cadherin signaling events;Interferon Signaling (Consensus)

Recessive Scores

• pRec: 0.609

Intolerance Scores

• loftool: 0.466
• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.31

Haploinsufficiency Scores

• pHI: 0.543
• hipred: Y
• hipred_score: 0.689
• ghis: 0.567

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.921

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Camk2g
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; hematopoietic system phenotype; reproductive system 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); digestive/alimentary phenotype; immune system phenotype; neoplasm

Zebrafish Information Network

• Gene name: camk2g2
• Affected structure: calmodulin-dependent protein kinase activity
• Phenotype tag: abnormal
• Phenotype quality: decreased rate

Gene ontology

• Biological process: MAPK cascade;protein dephosphorylation;nervous system development;regulation of skeletal muscle adaptation;insulin secretion;cell differentiation;protein complex oligomerization;regulation of calcium ion transport;interferon-gamma-mediated signaling pathway
• Cellular component: nucleoplasm;cytoplasm;cytosol;plasma membrane;membrane;endocytic vesicle membrane;sarcoplasmic reticulum membrane;neuron projection
• Molecular function: protein serine/threonine kinase activity;calmodulin-dependent protein kinase activity;calcium-dependent protein serine/threonine phosphatase activity;Ras guanyl-nucleotide exchange factor activity;protein binding;calmodulin binding;ATP binding;identical protein binding;protein homodimerization activity