CASQ1

Chr 1AD

calsequestrin 1

Also known as: CASQ, CSQ1, PDIB1, VMCQA

This gene encodes the skeletal muscle specific member of the calsequestrin protein family. Calsequestrin functions as a luminal sarcoplasmic reticulum calcium sensor in both cardiac and skeletal muscle cells. This protein, also known as calmitine, functions as a calcium regulator in the mitochondria of skeletal muscle. This protein is absent in patients with Duchenne and Becker types of muscular dystrophy. [provided by RefSeq, Jun 2013]

OMIMResearchGenerating clinical summary…
MultiplemechanismADLOEUF 1.581 OMIM phenotype
Clinical SummaryCASQ1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
5 unique Pathogenic / Likely Pathogenic· 227 VUS of 404 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.58LOEUF
pLI 0.000
Z-score -0.57
OE 1.13 (0.821.58)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.02Z-score
OE missense 1.00 (0.901.12)
226 obs / 225.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?1.13 (0.821.58)
00.351.4
Missense OE?1.00 (0.901.12)
00.61.4
Synonymous OE?0.88
01.21.6
LoF obs/exp: 25 / 22.1Missense obs/exp: 226 / 225.2Syn Z: 0.96

This gene — mechanism propensity

DN
0.6356th %ile
GOF
0.6444th %ile
LOF
0.2775th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

404 submitted variants in ClinVar

Classification Summary

Pathogenic2
Likely Pathogenic3
VUS227
Likely Benign140
Benign15
Conflicting11
2
Pathogenic
3
Likely Pathogenic
227
VUS
140
Likely Benign
15
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
0
0
2
Likely Pathogenic
2
1
0
0
3
VUS
30
179
15
3
227
Likely Benign
0
3
59
78
140
Benign
0
5
9
1
15
Conflicting
11
Total321908382398

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap CASQ1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

CASQ1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →