GeneBe

CASQ2

calsequestrin 2, the group of Protein disulfide isomerases

Basic information

Region (hg38): 1:115698038-115837921

Links

ENSG00000118729 ∙ NCBI:845 ∙ OMIM:114251 ∙ HGNC:1513 ∙ Uniprot:O14958 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • catecholaminergic polymorphic ventricular tachycardia 2 (Strong), mode of inheritance: AR
  • catecholaminergic polymorphic ventricular tachycardia 2 (Moderate), mode of inheritance: AR
  • catecholaminergic polymorphic ventricular tachycardia (Supportive), mode of inheritance: AD
  • catecholaminergic polymorphic ventricular tachycardia 2 (Moderate), mode of inheritance: AD
  • catecholaminergic polymorphic ventricular tachycardia 2 (Definitive), mode of inheritance: AR
  • catecholaminergic polymorphic ventricular tachycardia 2 (Strong), mode of inheritance: AR
  • hypertrophic cardiomyopathy (Disputed Evidence), mode of inheritance: AD
  • catecholaminergic polymorphic ventricular tachycardia (Definitive), mode of inheritance: AR
  • catecholaminergic polymorphic ventricular tachycardia (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Ventricular tachycardia, catecholaminergic, polymorphic, 2ARCardiovascularIndividuals may present with sudden cardiac death (eg, in the setting of exercise or excited states), and the overall mortality in untreated individuals is high early in life, such that surveillance and preventive measures/medical management, including ICD treatment, may be helpful to help decrease morbidity (however, storms of ventricular tachycardia have been described as being treated but not terminated through ICD shocks, and did not degenerate to ventricular fibrillation)Cardiovascular11401939; 16908766; 22481011; 22650415

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CASQ2 gene.

  • Catecholaminergic_polymorphic_ventricular_tachycardia_1 (505 variants)
  • Cardiovascular_phenotype (283 variants)
  • Catecholaminergic_polymorphic_ventricular_tachycardia_2 (183 variants)
  • not_provided (130 variants)
  • not_specified (72 variants)
  • Cardiomyopathy (26 variants)
  • Catecholaminergic_polymorphic_ventricular_tachycardia (11 variants)
  • CASQ2-related_disorder (5 variants)
  • Caudal_regression_sequence (2 variants)
  • Long_QT_syndrome (2 variants)
  • Neural_tube_defect (2 variants)
  • Wolff-Parkinson-White_pattern (1 variants)
  • Sudden_unexplained_death (1 variants)
  • Conduction_disorder_of_the_heart (1 variants)
  • Progressive_familial_heart_block (1 variants)
  • Cardiac_arrhythmia (1 variants)
  • Primary_dilated_cardiomyopathy (1 variants)
  • Polymorphic_ventricular_tachycardia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CASQ2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001232.4. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
4
clinvar
153
clinvar
1
clinvar
 159
missense
2
clinvar
10
clinvar
246
clinvar
15
clinvar
1
clinvar
 274
nonsense
13
clinvar
7
clinvar
1
clinvar
 21
start loss
1
2
 3
frameshift
12
clinvar
9
clinvar
1
clinvar
1
clinvar
 23
splice donor/acceptor (+/-2bp)
4
clinvar
21
clinvar
1
clinvar
1
clinvar
 27
Total 32 50 253 170 2

Highest pathogenic variant AF is 0.0000637875

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
CASQ2protein_codingprotein_codingENST00000261448 1168775
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.39e-120.05121257060421257480.000167
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.1952172091.040.00001142701
Missense in Polyphen7178.2890.90691033
Synonymous-0.4708377.71.070.00000455672
Loss of Function0.2621920.30.9379.67e-7259

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0003300.000329
Ashkenazi Jewish0.000.00
East Asian0.0001630.000163
Finnish0.000.00
European (Non-Finnish)0.0001760.000176
Middle Eastern0.0001630.000163
South Asian0.0003600.000359
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle. Calcium ions are bound by clusters of acidic residues at the protein surface, especially at the interface between subunits. Can bind around 60 Ca(2+) ions. Regulates the release of lumenal Ca(2+) via the calcium release channel RYR2; this plays an important role in triggering muscle contraction. Plays a role in excitation-contraction coupling in the heart and in regulating the rate of heart beats. {ECO:0000269|PubMed:16908766, ECO:0000269|PubMed:17881003, ECO:0000269|PubMed:18399795, ECO:0000269|PubMed:21416293}.;
Disease
DISEASE: Ventricular tachycardia, catecholaminergic polymorphic, 2 (CPVT2) [MIM:611938]: 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. CPVT2 inheritance is autosomal recessive. {ECO:0000269|PubMed:11704930, ECO:0000269|PubMed:15485681, ECO:0000269|PubMed:16908766, ECO:0000269|PubMed:17881003, ECO:0000269|PubMed:18399795, ECO:0000269|PubMed:27157848}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Antiarrhythmic Pathway, Pharmacodynamics;Calcium Regulation in the Cardiac Cell (Consensus)

Recessive Scores

pRec
0.153

Intolerance Scores

loftool
0.765
rvis_EVS
-0.16
rvis_percentile_EVS
42.06

Haploinsufficiency Scores

pHI
0.121
hipred
N
hipred_score
0.352
ghis
0.458

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.354

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Casq2
Phenotype
adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; muscle 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; embryo phenotype; immune system phenotype; vision/eye phenotype;

Gene ontology

Biological process
regulation of heart rate;detection of calcium ion;striated muscle contraction;regulation of cell communication by electrical coupling;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;regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion;ion transmembrane transport;negative regulation of potassium ion transport;sarcomere organization;sequestering of calcium ion;protein polymerization;cardiac muscle contraction;regulation of membrane repolarization;negative regulation of ryanodine-sensitive calcium-release channel activity;cellular response to caffeine;Purkinje myocyte to ventricular cardiac muscle cell signaling;negative regulation of potassium ion transmembrane transporter activity;regulation of cardiac conduction
Cellular component
cytoplasm;junctional sarcoplasmic reticulum membrane;sarcoplasmic reticulum;Z disc;junctional membrane complex;sarcoplasmic reticulum membrane;sarcoplasmic reticulum lumen;calcium channel complex
Molecular function
calcium ion binding;protein binding;protein homodimerization activity;calcium-dependent protein binding