GeneBe

CASQ1

calsequestrin 1, the group of Protein disulfide isomerases

Basic information

Region (hg38): 1:160190575-160201886

Previous symbols: [ "CASQ" ]

Links

ENSG00000143318 ∙ NCBI:844 ∙ OMIM:114250 ∙ HGNC:1512 ∙ Uniprot:P31415 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • tubular aggregate myopathy (Supportive), mode of inheritance: AD
  • myopathy due to calsequestrin and SERCA1 protein overload (Supportive), mode of inheritance: AD
  • myopathy due to calsequestrin and SERCA1 protein overload (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Myopathy, vacuolar, with CASQ1 aggregatesADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingMusculoskeletal25116801

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CASQ1 gene.

  • not_provided (316 variants)
  • Inborn_genetic_diseases (88 variants)
  • Myopathy_due_to_calsequestrin_and_SERCA1_protein_overload (30 variants)
  • not_specified (12 variants)
  • CASQ1-related_disorder (7 variants)
  • Myopathy_with_tubular_aggregates (2 variants)
  • Myopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CASQ1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001231.5. 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
3
clinvar
70
clinvar
1
clinvar
 74
missense
2
clinvar
2
clinvar
157
clinvar
9
clinvar
4
clinvar
 174
nonsense
11
clinvar
 11
start loss
1
1
 2
frameshift
1
clinvar
10
clinvar
 11
splice donor/acceptor (+/-2bp)
1
clinvar
9
clinvar
1
clinvar
 11
Total 2 4 191 81 5

Highest pathogenic variant AF is 0.0000371779

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
CASQ1protein_codingprotein_codingENST00000368078 1111392
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
3.86e-180.0014212544023061257480.00123
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.01872262251.000.00001202640
Missense in Polyphen6471.7810.8916895
Synonymous0.9578394.90.8750.00000613710
Loss of Function-0.5702522.11.130.00000112258

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0009020.000901
Ashkenazi Jewish0.0001990.000198
East Asian0.001580.00158
Finnish0.0007860.000786
European (Non-Finnish)0.001840.00183
Middle Eastern0.001580.00158
South Asian0.0008220.000784
Other0.001140.00114

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 (PubMed:28895244). Calcium ions are bound by clusters of acidic residues at the protein surface, often at the interface between subunits. Can bind around 80 Ca(2+) ions (PubMed:28895244). Regulates the release of lumenal Ca(2+) via the calcium release channel RYR1; this plays an important role in triggering muscle contraction. Negatively regulates store-operated Ca(2+) entry (SOCE) activity (PubMed:27185316). {ECO:0000269|PubMed:22337878, ECO:0000269|PubMed:27185316, ECO:0000269|PubMed:28895244, ECO:0000303|PubMed:22337878}.;
Disease
DISEASE: Myopathy, vacuolar, with CASQ1 aggregates (VMCQA) [MIM:616231]: An autosomal dominant mild muscle disorder characterized by adult onset of muscle cramping and weakness as well as increased levels of serum creatine kinase. The disorder is not progressive, and some patients may be asymptomatic. {ECO:0000269|PubMed:25116801, ECO:0000269|PubMed:26136523, ECO:0000269|PubMed:27196359, ECO:0000269|PubMed:28895244}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myopathy, tubular aggregate, 1 (TAM1) [MIM:160565]: A rare congenital myopathy characterized by regular arrays of membrane tubules on muscle biopsies without additional histopathological hallmarks. Tubular aggregates in muscle are structures of variable appearance consisting of an outer tubule containing either one or more microtubule-like structures or amorphous material. They may occur in a variety of circumstances, including inherited myopathies, alcohol- and drug-induced myopathies, exercise-induced cramps or muscle weakness. {ECO:0000269|PubMed:28895244}. 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
0.201

Intolerance Scores

loftool
0.733
rvis_EVS
0.6
rvis_percentile_EVS
82.74

Haploinsufficiency Scores

pHI
0.498
hipred
N
hipred_score
0.167
ghis
0.422

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.598

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Casq1
Phenotype
hematopoietic system phenotype; growth/size/body region phenotype; muscle phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process
endoplasmic reticulum organization;skeletal muscle tissue development;response to heat;response to organic substance;regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion;response to denervation involved in regulation of muscle adaptation;ion transmembrane transport;sarcomere organization;protein polymerization;positive regulation of release of sequestered calcium ion into cytosol;positive regulation of store-operated calcium channel activity;regulation of cardiac conduction;regulation of store-operated calcium entry
Cellular component
mitochondrion;mitochondrial matrix;endoplasmic reticulum;smooth endoplasmic reticulum;Golgi apparatus;terminal cisterna lumen;sarcoplasmic reticulum;Z disc;T-tubule;sarcoplasmic reticulum membrane;sarcoplasmic reticulum lumen
Molecular function
calcium ion binding;protein binding;identical protein binding