CALM1 (Calmodulin 1): Structure, Function, and Clinical Significance
A comprehensive biomedical overview of the CALM1 gene, its protein product calmodulin, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | CALM1 |
|---|---|
| Full Name | Calmodulin 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q32.11 (GRCh38: chr14:90,396,502-90,408,268, minus strand) |
| NCBI Gene ID | 801 ncbi.nlm.nih.gov/gene/801 |
| Ensembl ID | ENSG00000198668 |
| UniProt ID | P0DP23 |
| OMIM ID | 114180 |
| HGNC ID | 1441 |
| Aliases | CALM, CAMI, PHKD, DD132, CALML2 |
Description
CALM1 encodes calmodulin, a ubiquitous calcium-binding protein that acts as a major mediator of calcium signaling. Calmodulin binds up to four calcium ions and regulates numerous enzymes, ion channels, and other proteins. It is essential for cellular processes including muscle contraction, neurotransmitter release, and cell cycle progression. Mutations in CALM1 are associated with cardiac arrhythmias and neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Long QT syndrome (LQTS) | Missense mutations in CALM1 alter calcium binding or target protein interaction, leading to prolonged cardiac repolarization. | ClinVar: Pathogenic variants reported; OMIM: 114180; PMID: 23911511 |
| Catecholaminergic polymorphic ventricular tachycardia (CPVT) | CALM1 mutations disrupt calmodulin-mediated regulation of cardiac ryanodine receptor (RyR2), causing calcium leak and arrhythmias. | ClinVar: Pathogenic variants; OMIM: 114180; PMID: 23911511 |
| Calmodulinopathy with neurodevelopmental delay | De novo CALM1 mutations can cause intellectual disability and seizures, likely due to altered neuronal calcium signaling. | ClinVar: Pathogenic variants; PMID: 27435373 |
| Sudden unexplained death in children | CALM1 mutations have been identified in cases of sudden cardiac death in young individuals. | ClinVar: Pathogenic variants; PMID: 23911511 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | High (nTPM ~ 2000) | High expression in neuronal tissues |
| Heart (left ventricle) | High (nTPM ~ 1500) | High expression in cardiac muscle |
| Skeletal muscle | High (nTPM ~ 1200) | High expression in muscle |
| Liver | Moderate (nTPM ~ 500) | Moderate expression |
| Kidney | Moderate (nTPM ~ 400) | Moderate expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | High (nTPM ~ 2000) | Ubiquitous expression |
| HepG2 (liver cancer) | Moderate (nTPM ~ 800) | Moderate expression |
| K562 (leukemia) | High (nTPM ~ 1500) | High expression |
| MCF7 (breast cancer) | High (nTPM ~ 1800) | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Asn54Ile (N54I) | Missense | Rare (found in LQTS cases) | Alters calcium binding affinity, leading to arrhythmia |
| p.Asp96Glu (D96E) | Missense | Rare (found in CPVT cases) | Disrupts calmodulin regulation of RyR2 |
| p.Phe142Leu (F142L) | Missense | Rare (found in LQTS) | Impairs target protein interaction |
| p.Glu46Lys (E46K) | Missense | Rare (found in neurodevelopmental delay) | Alters calcium binding and neuronal signaling |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CALM1 are rare; complete loss is likely lethal. Some missense variants may reduce calcium binding affinity, impairing calmodulin's ability to activate target proteins.
Gain of Function (GOF)
Gain-of-function mutations are not well characterized; however, some variants may increase calcium affinity or alter target binding, leading to dysregulated signaling.
Dominant Negative (DN)
Most pathogenic CALM1 mutations act in a dominant-negative manner, as calmodulin functions as a monomer and mutant proteins interfere with wild-type calmodulin's interaction with targets, leading to arrhythmias.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Calcium signaling pathway (KEGG: hsa04020)
• Cardiac muscle contraction (KEGG: hsa04260)
• Adrenergic signaling in cardiomyocytes (KEGG: hsa04261)
• Long-term potentiation (KEGG: hsa04720)
• Neurotrophin signaling pathway (KEGG: hsa04722)
Protein Summary
Calmodulin (CaM) is a 149-amino acid protein (17 kDa) with four EF-hand calcium-binding domains. It undergoes conformational changes upon calcium binding, allowing it to regulate over 300 target proteins, including kinases, phosphatases, and ion channels. In the heart, CaM modulates L-type calcium channels and ryanodine receptors, critical for excitation-contraction coupling. Mutations in CALM1 disrupt these interactions, leading to arrhythmias and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CALM1 Knockout HEK293 Cell Line | EDJ-KQ50172 | Human | 801 | Details Get a Quote |
| CALM1 Knockout HeLa Cell Line | EDJ-KQ52782 | Human | 801 | Details Get a Quote |
| CALM1 Knockout A-549 Cell Line | EDJ-KQ61250 | Human | 801 | Details Get a Quote |
| CALM1 Knockout HCT 116 Cell Line | EDJ-KQ69747 | Human | 801 | Details Get a Quote |
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