CASQ1

Chr 1AD

calsequestrin 1

Also known as: CASQ, CSQ1, PDIB1, VMCQA

NCBI Gene: 844 ENSG00000143318 UniProt: P31415 OMIM: 114250

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Myopathy, vacuolar, with CASQ1 aggregatesMIM #616231

UniProtMyopathy, tubular aggregate, 1

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Myopathy, vacuolar, with CASQ1 aggregates; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.58

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.58LOEUF

pLI 0.000

Z-score -0.57

OE 1.13 (0.82–1.58)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.02Z-score

OE missense 1.00 (0.90–1.12)

226 obs / 225.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.13 (0.82–1.58)

0≤0.351.4

Missense OE?1.00 (0.90–1.12)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 25 / 22.1Missense obs/exp: 226 / 225.2Syn Z: 0.96

Background carrier burden — how many people carry a rare variant somewhere in CASQ1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

502 rare PASS variants

Rare truncating (LoF)

1 in 1,100

90 rare PASS variants

Rare synonymous (reference)

1 in 140

189 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CASQ1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 1,800
South Asian	~43k	1 in 56	1 in 720
Remaining (unassigned)	~30k	1 in 79	1 in 1,400
European (Finnish)	~27k	1 in 250	1 in 3,000
Admixed American	~22k	1 in 93	1 in 970
African / African American	~21k	1 in 160	1 in 700
East Asian	~20k	1 in 110	1 in 1,000
Ashkenazi Jewish	~13k	1 in 280	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 120	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 10 of 11 coding exons well covered in gnomAD exomes; exon 9 marginal. Genomes: all 11.? see exons ↓