CALM2

calmodulin 2, the group of Phosphorylase kinase subunits|EF-hand domain containing|Receptor ligands

Basic information

Region (hg38): 2:47160083-47176921

Links

ENSG00000143933 ∙ NCBI:805 ∙ OMIM:114182 ∙ HGNC:1445 ∙ Uniprot:P0DP24 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• catecholaminergic polymorphic ventricular tachycardia (Strong), mode of inheritance: AD
• catecholaminergic polymorphic ventricular tachycardia (Strong), mode of inheritance: AD
• long QT syndrome 15 (Definitive), mode of inheritance: AD
• long QT syndrome 15 (Strong), mode of inheritance: AD
• catecholaminergic polymorphic ventricular tachycardia (Moderate), mode of inheritance: AD
• long QT syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Long QT syndrome 15	AD	Cardiovascular	Individuals may suffer from early-onset severe and potentially lethal arrhythmias, and awareness may allow preventive treatment (eg, with beta-blocking medications and ICD placement) and rapid medical response, which may potentially ameliorate morbidity and mortality	Cardiovascular; Neurologic	23388215; 24917665

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CALM2 gene.

• Long QT syndrome 1 (100 variants)
• not provided (35 variants)
• Cardiovascular phenotype (19 variants)
• not specified (14 variants)
• Long QT syndrome 15 (14 variants)
• Inborn genetic diseases (3 variants)
• Long QT syndrome (2 variants)
• CALM2-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CALM2 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	17	1	20
missense	9	6	20			35
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			6	6		12
non coding			6	61	12	79
Total	9	6	29	78	13

Variants in CALM2

This is a list of pathogenic ClinVar variants found in the CALM2 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-47160771-GGTCTTCACTTTGCT-G		Long QT syndrome 1	Uncertain significance (Jan 31, 2024)
2-47160782-T-C		Cardiovascular phenotype	Likely benign (Feb 09, 2020)
2-47160792-A-C		Long QT syndrome 1	Likely pathogenic (Jun 04, 2018)
2-47160797-T-C		Long QT syndrome 1	Likely benign (Jun 30, 2020)
2-47160803-C-G		Long QT syndrome 1	Likely pathogenic (Oct 03, 2022)
2-47160810-AAAG-A		Long QT syndrome 1	Likely benign (Jan 31, 2024)
2-47160813-G-A		Long QT syndrome 1	Likely benign (Nov 04, 2023)
2-47160815-A-AG		Long QT syndrome 1	Likely benign (Feb 24, 2022)
2-47160816-G-A		Long QT syndrome 1	Likely benign (Nov 01, 2023)
2-47160816-GA-G		Long QT syndrome 1	Likely benign (Oct 08, 2021)
2-47160819-G-A		Long QT syndrome 1	Likely benign (Nov 05, 2022)
2-47160847-G-A			Likely benign (Nov 20, 2019)
2-47161577-T-C			Likely benign (Jul 17, 2018)
2-47161625-TCA-T			Benign (Jun 19, 2018)
2-47161626-C-G		Long QT syndrome 15	Benign (Jul 14, 2021)
2-47161627-A-G		Long QT syndrome 15	Benign (Jul 14, 2021)
2-47161627-A-AGGG			Benign (Jan 06, 2019)
2-47161648-G-C			Likely benign (Jun 28, 2018)
2-47161704-G-A		Long QT syndrome 1	Likely benign (Dec 20, 2023)
2-47161705-T-C		not specified • Long QT syndrome 1	Benign (Feb 01, 2024)
2-47161710-C-T		Long QT syndrome 1	Likely benign (Aug 01, 2023)
2-47161712-G-A		Long QT syndrome 1	Likely benign (Jan 25, 2024)
2-47161713-A-C		Long QT syndrome 1	Likely benign (Aug 30, 2023)
2-47161715-A-G		Long QT syndrome 1	Likely benign (Dec 14, 2023)
2-47161719-T-G		Long QT syndrome 1	Uncertain significance (Dec 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CALM2	protein_coding	protein_coding	ENST00000272298	6	16520

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.921	0.0787	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.79	8	76.9	0.104	0.00000350	1015
Missense in Polyphen		0	16.346	0		252
Synonymous	0.264	21	22.6	0.929	9.69e-7	245
Loss of Function	2.64	0	8.13	0.00	3.41e-7	109

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696). {ECO:0000269|PubMed:16760425, ECO:0000269|PubMed:26969752, ECO:0000269|PubMed:27165696}.
• Disease: DISEASE: Long QT syndrome 15 (LQT15) [MIM:616249]: A form of long QT syndrome, a heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. {ECO:0000269|PubMed:23388215, ECO:0000269|PubMed:24917665, ECO:0000269|PubMed:26164367, ECO:0000269|PubMed:26969752, ECO:0000269|PubMed:27165696, ECO:0000269|PubMed:27516456}. Note=The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM2 are the cause of LQT15.
• Pathway: Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Pertussis - Homo sapiens (human);Long-term potentiation - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Glioma - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Renin secretion - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Amphetamine addiction - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Olfactory transduction - Homo sapiens (human);Phototransduction - Homo sapiens (human);Alcoholism - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Muscle/Heart Contraction;Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Bupranolol Action Pathway;Nebivolol Action Pathway;Amlodipine Action Pathway;Verapamil Action Pathway;Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;Alzheimers Disease;Myometrial Relaxation and Contraction Pathways;Ras Signaling;Glycogen Metabolism;Calcium Regulation in the Cardiac Cell;Regulation of Ras family activation;TCR;EGFR1;ErbB1 downstream signaling;BCR signaling pathway;IFN-gamma pathway;Insulin-mediated glucose transport;Downstream signaling in naïve CD8+ T cells;N-cadherin signaling events;Calcineurin-regulated NFAT-dependent transcription in lymphocytes;IL2 signaling events mediated by PI3K;Regulation of cytoplasmic and nuclear SMAD2/3 signaling;p38 MAPK signaling pathway;Role of Calcineurin-dependent NFAT signaling in lymphocytes;Lissencephaly gene (LIS1) in neuronal migration and development;Signaling events mediated by VEGFR1 and VEGFR2;Calcium signaling in the CD4+ TCR pathway;Cellular roles of Anthrax toxin;VEGFR1 specific signals;CD4 T cell receptor signaling-JNK cascade;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.322

Intolerance Scores

• loftool: 0.124
• rvis_EVS: 0.12
• rvis_percentile_EVS: 62.38

Haploinsufficiency Scores

• pHI: 0.697
• hipred: Y
• hipred_score: 0.825
• ghis: 0.550

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.824

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Calm2

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;regulation of heart rate;detection of calcium ion;G protein-coupled receptor signaling pathway;positive regulation of peptidyl-threonine phosphorylation;negative regulation of peptidyl-threonine phosphorylation;regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum;regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion;substantia nigra development;positive regulation of protein autophosphorylation;regulation of cytokinesis;positive regulation of phosphoprotein phosphatase activity;positive regulation of protein dephosphorylation;positive regulation of DNA binding;positive regulation of cyclic-nucleotide phosphodiesterase activity;response to calcium ion;regulation of cardiac muscle contraction;negative regulation of ryanodine-sensitive calcium-release channel activity;positive regulation of ryanodine-sensitive calcium-release channel activity;positive regulation of protein serine/threonine kinase activity;positive regulation by host of symbiont cAMP-mediated signal transduction;regulation of cell communication by electrical coupling involved in cardiac conduction
• Cellular component: spindle pole;nucleus;cytoplasm;centrosome;spindle microtubule;plasma membrane;voltage-gated potassium channel complex;sarcomere;vesicle;protein-containing complex;calcium channel complex;myelin sheath;catalytic complex
• Molecular function: calcium ion binding;protein binding;adenylate cyclase binding;adenylate cyclase activator activity;calcium channel inhibitor activity;protein kinase binding;protein domain specific binding;titin binding;N-terminal myristoylation domain binding;protein serine/threonine kinase activator activity;ion channel binding;protein phosphatase activator activity;disordered domain specific binding