CALM1
calmodulin 1, the group of EF-hand domain containing|Receptor ligands|Phosphorylase kinase subunits
Basic information
Region (hg38): 14:90396502-90408268
Previous symbols: [ "CALML2" ]
Links
Phenotypes
GenCC
Source:
- catecholaminergic polymorphic ventricular tachycardia 4 (Strong), mode of inheritance: AD
- long QT syndrome 14 (Strong), mode of inheritance: AD
- catecholaminergic polymorphic ventricular tachycardia (Supportive), mode of inheritance: AD
- catecholaminergic polymorphic ventricular tachycardia 4 (Strong), mode of inheritance: AD
- long QT syndrome 14 (Definitive), mode of inheritance: AD
- catecholaminergic polymorphic ventricular tachycardia 4 (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:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Long QT syndrome 14; Ventricular tachycardia, catecholaminergic polymorphic, 4 | AD | Cardiovascular | Individuals may present with severe cardiac manifestations, including arrhythmias, syncope, and sudden death, and surveillance, preventive measures (eg, including avoidance of dangerous or excacerbating factors), and treatment (eg, including medical treatment with beta-blockers or ICD placement, which have both been described as beneficial in affected individuals) may allow early and beneficial management | Cardiovascular; Neurologic | 23040497; 23388215; 24076290 |
ClinVar
This is a list of variants' phenotypes submitted to
- Long QT syndrome 14;Catecholaminergic polymorphic ventricular tachycardia 4 (4 variants)
- Long QT syndrome 14 (3 variants)
- Catecholaminergic polymorphic ventricular tachycardia 4;Long QT syndrome 14 (2 variants)
- not provided (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CALM1 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 | 33 | 34 | ||||
| missense | 18 | 35 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 1 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 3 | 6 | 1 | 10 | ||
| non coding | 42 | 11 | 53 | |||
| Total | 9 | 8 | 20 | 75 | 11 |
Variants in CALM1
This is a list of pathogenic ClinVar variants found in the CALM1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 14-90396691-G-T | Benign (Jun 16, 2018) | |||
| 14-90396841-C-T | Benign (Jun 14, 2018) | |||
| 14-90396859-G-T | Benign (Jun 19, 2018) | |||
| 14-90396869-G-C | Likely benign (Sep 22, 2018) | |||
| 14-90397013-C-T | Long QT syndrome 14;Catecholaminergic polymorphic ventricular tachycardia 4 | Benign (Jan 22, 2024) | ||
| 14-90397063-C-T | Likely benign (Jun 14, 2018) | |||
| 14-90397070-C-T | Likely benign (Jul 15, 2018) | |||
| 14-90397108-G-T | Likely benign (Oct 22, 2019) | |||
| 14-90397145-G-A | Catecholaminergic polymorphic ventricular tachycardia 4 | Benign (Jul 14, 2021) | ||
| 14-90397192-A-ACC | not specified | Likely benign (Jun 15, 2017) | ||
| 14-90397199-C-T | not specified | Likely benign (May 19, 2017) | ||
| 14-90397243-G-C | Catecholaminergic polymorphic ventricular tachycardia 4;Long QT syndrome 14 | Likely benign (Apr 12, 2022) | ||
| 14-90397246-T-C | Catecholaminergic polymorphic ventricular tachycardia 4;Long QT syndrome 14 | Likely benign (Oct 25, 2022) | ||
| 14-90397247-G-T | Long QT syndrome 14;Catecholaminergic polymorphic ventricular tachycardia 4 | Likely benign (Aug 31, 2023) | ||
| 14-90397526-C-T | Benign (Jun 18, 2018) | |||
| 14-90397531-G-T | Benign (Jun 14, 2018) | |||
| 14-90397564-C-A | Likely benign (Oct 31, 2018) | |||
| 14-90399936-A-G | Benign (Jun 14, 2018) | |||
| 14-90400002-C-T | Catecholaminergic polymorphic ventricular tachycardia 4 | Benign (Jul 14, 2021) | ||
| 14-90400055-C-G | Catecholaminergic polymorphic ventricular tachycardia 4;Long QT syndrome 14 • not specified | Benign/Likely benign (Aug 27, 2024) | ||
| 14-90400056-T-A | Catecholaminergic polymorphic ventricular tachycardia 4;Long QT syndrome 14 | Likely benign (Aug 20, 2020) | ||
| 14-90400058-C-T | Catecholaminergic polymorphic ventricular tachycardia 4;Long QT syndrome 14 | Likely benign (Jun 07, 2023) | ||
| 14-90400059-A-T | Long QT syndrome 14;Catecholaminergic polymorphic ventricular tachycardia 4 | Likely benign (Aug 27, 2022) | ||
| 14-90400062-T-C | Cardiovascular phenotype • Long QT syndrome 14;Catecholaminergic polymorphic ventricular tachycardia 4 | Uncertain significance (Nov 24, 2023) | ||
| 14-90400079-C-G | Cardiovascular phenotype | Likely benign (Aug 03, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CALM1 | protein_coding | protein_coding | ENST00000356978 | 6 | 11760 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.945 | 0.0551 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.05 | 6 | 85.3 | 0.0703 | 0.00000457 | 1013 |
| Missense in Polyphen | 0 | 17.503 | 0 | 261 | ||
| Synonymous | 1.10 | 22 | 29.6 | 0.743 | 0.00000179 | 251 |
| Loss of Function | 2.80 | 0 | 9.15 | 0.00 | 4.70e-7 | 106 |
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:
- 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:23893133, ECO:0000269|PubMed:26969752, ECO:0000269|PubMed:27165696}.;
- Disease
- DISEASE: Ventricular tachycardia, catecholaminergic polymorphic, 4 (CPVT4) [MIM:614916]: An arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. Patients present with recurrent syncope, seizures, or sudden death after physical activity or emotional stress. CPVT4 inheritance is autosomal dominant. {ECO:0000269|PubMed:23040497, ECO:0000269|PubMed:26164367, ECO:0000269|PubMed:27165696, ECO:0000269|PubMed:27516456}. Note=The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4.; DISEASE: Long QT syndrome 14 (LQT14) [MIM:616247]: 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:24076290, ECO:0000269|PubMed:26164367, ECO:0000269|PubMed:26969752, ECO:0000269|PubMed:27165696}. Note=The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of LQT14.;
- 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;Physiological and Pathological Hypertrophy of the Heart;MicroRNAs in cardiomyocyte hypertrophy;Alzheimers Disease;Endothelin Pathways;T-Cell Receptor and Co-stimulatory Signaling;Common Pathways Underlying Drug Addiction;Cardiac Hypertrophic Response;Myometrial Relaxation and Contraction Pathways;Melatonin metabolism and effects;G Protein Signaling Pathways;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;NO-cGMP-PKG mediated Neuroprotection;Ras Signaling;Endochondral Ossification;Glycogen Metabolism;G13 Signaling Pathway;Calcium Regulation in the Cardiac Cell;Smooth Muscle Contraction;Signaling by GPCR;Regulation of Ras family activation;Antigen activates B Cell Receptor (BCR) leading to generation of second messengers;Disease;Signaling by WNT;Signal Transduction;Vesicle-mediated transport;VEGFA-VEGFR2 Pathway;Membrane Trafficking;Stimuli-sensing channels;Ion channel transport;Metabolism of carbohydrates;Metabolism of nitric oxide;Post-translational protein modification;Calcineurin activates NFAT;Metabolism of proteins;Signaling by the B Cell Receptor (BCR);CLEC7A (Dectin-1) induces NFAT activation;Activation of Ca-permeable Kainate Receptor;Ionotropic activity of kainate receptors;CLEC7A (Dectin-1) signaling;C-type lectin receptors (CLRs);Uptake and actions of bacterial toxins;FCERI mediated Ca+2 mobilization;Fc epsilon receptor (FCERI) signaling;TCR;Uptake and function of anthrax toxins;Infectious disease;eNOS activation;eNOS activation and regulation;Innate Immune System;Immune System;Metabolism;Adaptive Immune System;Ion homeostasis;PKA activation;PKA-mediated phosphorylation of CREB;CaMK IV-mediated phosphorylation of CREB;Calmodulin induced events;CaM pathway;Activation of kainate receptors upon glutamate binding;Cam-PDE 1 activation;Sodium/Calcium exchangers;Transport of inorganic cations/anions and amino acids/oligopeptides;Downstream signaling events of B Cell Receptor (BCR);SLC-mediated transmembrane transport;Transport of small molecules;Neuronal System;RHO GTPases activate PAKs;Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation;Metabolism of cofactors;Metabolism of vitamins and cofactors;Phase 0 - rapid depolarisation;Cardiac conduction;Muscle contraction;DARPP-32 events;RHO GTPases activate IQGAPs;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;RHO GTPase Effectors;Signaling by Rho GTPases;EGFR1;Synthesis of IP3 and IP4 in the cytosol;Ion transport by P-type ATPases;Ca2+ pathway;Beta-catenin independent WNT signaling;ErbB1 downstream signaling;Hemostasis;DAG and IP3 signaling;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;BCR signaling pathway;Inositol phosphate metabolism;IFN-gamma pathway;Signaling by VEGF;Ca-dependent events;PLC beta mediated events;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;G-protein mediated events;Opioid Signalling;G alpha (i) signalling events;Activation of CaMK IV;CREB phosphorylation through the activation of CaMKK;Protein methylation;Inactivation, recovery and regulation of the phototransduction cascade;The phototransduction cascade;Visual phototransduction;Ras activation upon Ca2+ influx through NMDA receptor;CREB phosphorylation through the activation of Ras;CREB phosphorylation through the activation of CaMKII;Post NMDA receptor activation events;Activation of NMDA receptor and postsynaptic events;Transcriptional activation of mitochondrial biogenesis;Mitochondrial biogenesis;Translocation of GLUT4 to the plasma membrane;Signaling by Receptor Tyrosine Kinases;Reduction of cytosolic Ca++ levels;Platelet calcium homeostasis;Platelet homeostasis;GPCR downstream signalling;Intracellular signaling by second messengers;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;Glycogen breakdown (glycogenolysis);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;VEGFR2 mediated vascular permeability;VEGFR2 mediated cell proliferation;Glycogen metabolism;CD4 T cell receptor signaling;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.363
Intolerance Scores
- loftool
- rvis_EVS
- 0.04
- rvis_percentile_EVS
- 56.25
Haploinsufficiency Scores
- pHI
- hipred
- Y
- hipred_score
- 0.793
- ghis
- 0.713
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.585
Mouse Genome Informatics
- Gene name
- Calm1
- Phenotype
Zebrafish Information Network
- Gene name
- calm1a
- Affected structure
- midbrain hindbrain boundary
- Phenotype tag
- abnormal
- Phenotype quality
- increased angle to
Gene ontology
- Biological process
- MAPK cascade;response to amphetamine;regulation of heart rate;platelet degranulation;detection of calcium ion;muscle contraction;G protein-coupled receptor signaling pathway;activation of adenylate cyclase activity;Wnt signaling pathway, calcium modulating 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;calcium-mediated signaling;substantia nigra development;regulation of rhodopsin mediated signaling pathway;positive regulation of protein autophosphorylation;regulation of cytokinesis;positive regulation of phosphoprotein phosphatase activity;positive regulation of protein dephosphorylation;Fc-epsilon receptor signaling pathway;inositol phosphate metabolic process;regulation of nitric-oxide synthase activity;positive regulation of nitric-oxide synthase activity;cofactor metabolic process;positive regulation of cyclic-nucleotide phosphodiesterase activity;response to corticosterone;response to calcium ion;regulation of cardiac muscle contraction;regulation of ryanodine-sensitive calcium-release channel activity;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;establishment of protein localization to mitochondrial membrane;regulation of synaptic vesicle endocytosis;regulation of calcium ion transmembrane transporter activity;regulation of high voltage-gated calcium channel activity;regulation of cell communication by electrical coupling involved in cardiac conduction;regulation of synaptic vesicle exocytosis
- Cellular component
- spindle pole;extracellular region;nucleus;nucleoplasm;cytoplasm;centrosome;cytosol;spindle microtubule;plasma membrane;sarcomere;growth cone;synaptic vesicle membrane;mitochondrial membrane;vesicle;protein-containing complex;calcium channel complex;myelin sheath;catalytic complex
- Molecular function
- Ras guanyl-nucleotide exchange factor activity;calcium ion binding;protein binding;adenylate cyclase binding;inositol-1,4,5-trisphosphate 3-kinase activity;adenylate cyclase activator activity;calcium channel inhibitor activity;protein kinase binding;protein domain specific binding;nitric-oxide synthase regulator activity;titin binding;type 3 metabotropic glutamate receptor binding;N-terminal myristoylation domain binding;protein serine/threonine kinase activator activity;phosphatidylinositol 3-kinase binding;ion channel binding;calcium-dependent protein binding;nitric-oxide synthase binding;protein phosphatase activator activity;disordered domain specific binding