CASQ1

Summary

CASQ1 (calsequestrin 1, HGNC:1512) is a protein-coding gene on chromosome 1q23.2, encoding Calsequestrin-1 (P31415). Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle.

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.

Source: NCBI Gene 844 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myopathy due to calsequestrin and SERCA1 protein overload (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 404 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 16
• MANE Select transcript: NM_001231

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1512
Approved symbol	CASQ1
Name	calsequestrin 1
Location	1q23.2
Locus type	gene with protein product
Status	Approved
Aliases	PDIB1, CSQ1
Ensembl gene	ENSG00000143318
Ensembl biotype	protein_coding
OMIM	114250
Entrez	844

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000368078, ENST00000467691, ENST00000481081, ENST00000954562, ENST00000954563

RefSeq mRNA: 1 — MANE Select: NM_001231 NM_001231

CCDS: CCDS1198

Canonical transcript exons

ENST00000368078 — 11 exons

Exon	Start	End
ENSE00000959223	160192802	160192886
ENSE00000959231	160199851	160199925
ENSE00001886410	160190575	160191030
ENSE00001940111	160201245	160201886
ENSE00003461137	160195012	160195123
ENSE00003473934	160193747	160193847
ENSE00003508983	160197569	160197614
ENSE00003515805	160198953	160199053
ENSE00003534557	160198677	160198731
ENSE00003587315	160195461	160195534
ENSE00003660165	160195897	160196027

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 99.68.

FANTOM5 (CAGE): breadth broad, TPM avg 6.6111 / max 2023.0878, expressed in 205 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6065	5.1705	84
6068	0.7976	29
6069	0.2017	68
6063	0.1624	57
6066	0.0701	14
6067	0.0690	15
6070	0.0544	32
6062	0.0496	22
6064	0.0356	17

Top tissues by expression

279 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	99.68	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.55	gold quality
gluteal muscle	UBERON:0002000	99.48	gold quality
triceps brachii	UBERON:0001509	99.47	gold quality
vastus lateralis	UBERON:0001379	99.46	gold quality
biceps brachii	UBERON:0001507	99.46	gold quality
quadriceps femoris	UBERON:0001377	99.37	gold quality
gastrocnemius	UBERON:0001388	99.37	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.27	gold quality
skeletal muscle tissue	UBERON:0001134	99.14	gold quality
diaphragm	UBERON:0001103	99.03	gold quality
deltoid	UBERON:0001476	98.36	gold quality
muscle organ	UBERON:0001630	98.24	gold quality
body of tongue	UBERON:0011876	98.24	gold quality
muscle of leg	UBERON:0001383	97.84	gold quality
tibialis anterior	UBERON:0001385	97.74	gold quality
muscle tissue	UBERON:0002385	93.57	gold quality
heart left ventricle	UBERON:0002084	88.82	gold quality
apex of heart	UBERON:0002098	88.75	gold quality
tongue	UBERON:0001723	88.50	gold quality
cardiac ventricle	UBERON:0002082	88.32	gold quality
prefrontal cortex	UBERON:0000451	84.62	gold quality
right atrium auricular region	UBERON:0006631	84.24	gold quality
heart	UBERON:0000948	83.75	gold quality
right frontal lobe	UBERON:0002810	83.11	gold quality
anterior cingulate cortex	UBERON:0009835	82.45	gold quality
cingulate cortex	UBERON:0003027	82.33	gold quality
cardiac atrium	UBERON:0002081	82.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.95	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	79.92	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.81

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1

miRNA regulators (miRDB)

61 targeting CASQ1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-4784	99.15	67.41	1733

Literature-anchored findings (GeneRIF, showing 17)

• Single nucleotide polymorphisms within CASQ1 were genotyped in Amish subjects with type 2 diabetes, glucose intolerance and normals. (PMID:15561962)
• Noncoding single nucleotide polymorphisms in CASQ1 alter diabetes susceptibility, either by a direct effect on CASQ1 gene expression or perhaps by regulating a nearby gene. (PMID:15561963)
• Phospholamban in the human esophagus might be of less importance for regulation of SERCA than in heart. Lower expression of calsequestrin and calreticulin might contribute to increased lower esophageal sphincter pressure in achalasia. (PMID:17009399)
• CASQ1 polymorphism is not associated with type 2 diabetes (PMID:17681849)
• Downregulation of CSQ-1 in diabetic platelets and impairment of CSQ-1 in normal cells leads to disturbed Ca(2+) release, demonstrating a potential role for CSQ-1 in the regulation of the platelet Ca(2+) release process (PMID:22060633)
• a mechanism for the observed in vitro and in vivo dynamic high-capacity and low-affinity Ca(2+)-binding activity of calsequestrin (PMID:22337878)
• CASQ1 is not a major malignant hyperthermia susceptibility locus in the North American population (PMID:23460944)
• a direct interaction of dysferlin with Trim72/MG53, AHNAK, cytoplasmic dynein, myomesin-2 and calsequestrin-1, but not with caveolin-3 or dystrophin, is reported. (PMID:23792176)
• The sarcoplasmic reticulum calcium content in human type II fibres is primarily determined by the CSQ1 abundance, and in type I fibres, by the combined amounts of both CSQ1 and CSQ2. (PMID:24127619)
• There is a significant association between SNP A175G and heat stroke. (PMID:24887214)
• Missense mutation in CASQ1 gene causes the formation of abnormal sarcoplasmic reticulum (SR) vacuoles containing aggregates of CASQ1 results in altered Ca2+ release, and vacuolar myopathy patients phenotype. (PMID:25116801)
• the protein aggregate myopathy with benign evolution and muscle inclusions composed of excess CASQ1 due to the D244G heterozygous missense mutation in the CASQ1 gene (PMID:26136523)
• Equilibrium dialysis and turbidity measurements showed that D244G and, to a lesser extent, M87T partially lose Ca(2+) binding exhibited by wild type calsequestrin 1 at high Ca(2+) concentrations. (PMID:26416891)
• Calsequestrin-1 monomers suppress Store-Operated Ca2+ Entry by interacting with STIM1 and attenuating STIM1 aggregation via its C-terminal amino acid 362-396. (PMID:27185316)
• the p.D244G variant in CASQ1 is associated with a skeletal muscle disease and alters sarcoplasmic calcium release (PMID:27196359)
• These results widen the spectrum of skeletal muscle diseases associated with CASQ1 and indicate that these mutations affect properties critical for correct Ca(2+) handling in skeletal muscle fibers. (PMID:28895244)
• This study showed that twenty-two CASQ1-mutated patients (12 families) were identified, 21 sharing the previously described founder mutation (p.Asp244Gly) and 1 with the p.Gly103Asp mutation. (PMID:30258016)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	casq1b	ENSDARG00000018105
danio_rerio	casq1a	ENSDARG00000038716
mus_musculus	Casq1	ENSMUSG00000007122
rattus_norvegicus	Casq1	ENSRNOG00000006930
caenorhabditis_elegans		WBGENE00000822

Paralogs (1): CASQ2 (ENSG00000118729)

Protein

Protein identifiers

Calsequestrin-1 — P31415 (reviewed: P31415)

Alternative names: Calmitine, Calsequestrin, skeletal muscle isoform

All UniProt accessions (2): P31415, C9JAC8

UniProt curated annotations — full annotation on UniProt →

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, often at the interface between subunits. Can bind around 80 Ca(2+) ions. 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.

Subunit / interactions. Monomer; increases in response to a depletion of intracellular calcium. Homodimer. Homotetramer and homopolymer. Can form linear homooligomers. Ca(2+) ions promote oligomerization. Interacts (via C-terminal end and preferentially with the monomeric form) with STIM1; this interaction increases in response to a depletion of intracellular calcium, decreases both STIM1 aggregation and clustering, interaction of STIM1 with ORAI1 and store-operated Ca(2+) entry (SOCE) activity. Interacts with ASPH and TRDN.

Subcellular location. Endoplasmic reticulum. Sarcoplasmic reticulum. Sarcoplasmic reticulum lumen. Sarcoplasmic reticulum membrane. Mitochondrion matrix.

Tissue specificity. Expressed in myoblasts (at protein level).

Post-translational modifications. N-glycosylated.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the calsequestrin family.

RefSeq proteins (1): NP_001222* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001393	Calsequestrin	Family
IPR018233	Calsequestrin_CS	Conserved_site
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR041858	Calsequestrin_middle_dom	Domain
IPR041859	Calsequestrin_N	Domain
IPR041860	Calsequestrin_C	Domain

Pfam: PF01216

UniProt features (53 total): strand 19, helix 15, turn 6, sequence variant 5, modified residue 4, signal peptide 1, chain 1, sequence conflict 1, glycosylation site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
5CRG	X-RAY DIFFRACTION	1.97
3UOM	X-RAY DIFFRACTION	2.02
5CRH	X-RAY DIFFRACTION	2.03
5CRD	X-RAY DIFFRACTION	2.08
8F48	X-RAY DIFFRACTION	2.9
5CRE	X-RAY DIFFRACTION	3.31

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31415-F1	90.51	0.83

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 43, 81, 124, 216

Glycosylation sites (1): 350

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-2672351	Stimuli-sensing channels
R-HSA-5578775	Ion homeostasis
R-HSA-382551	Transport of small molecules
R-HSA-397014	Muscle contraction
R-HSA-5576891	Cardiac conduction
R-HSA-983712	Ion channel transport

MSigDB gene sets: 229 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, MYOGENIN_Q6, GOBP_POSITIVE_REGULATION_OF_CATION_CHANNEL_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, MAZ_Q6, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_MULTICELLULAR_ORGANISMAL_MOVEMENT, MEF2_02, GOBP_SARCOMERE_ORGANIZATION, GOBP_SKELETAL_MUSCLE_CONTRACTION, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, CEBPB_01, GOBP_MONOATOMIC_CATION_TRANSPORT, SRF_Q5_01

GO Biological Process (14): endoplasmic reticulum organization (GO:0007029), skeletal muscle tissue development (GO:0007519), response to heat (GO:0009408), regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion (GO:0014809), response to denervation involved in regulation of muscle adaptation (GO:0014894), sarcomere organization (GO:0045214), protein polymerization (GO:0051258), positive regulation of release of sequestered calcium ion into cytosol (GO:0051281), positive regulation of store-operated calcium channel activity (GO:1901341), regulation of store-operated calcium entry (GO:2001256), regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum (GO:0010880), response to muscle inactivity (GO:0014870), regulation of release of sequestered calcium ion into cytosol (GO:0051279), obsolete regulation of sequestering of calcium ion (GO:0051282)

GO Molecular Function (4): calcium ion binding (GO:0005509), identical protein binding (GO:0042802), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (15): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), endoplasmic reticulum (GO:0005783), smooth endoplasmic reticulum (GO:0005790), terminal cisterna lumen (GO:0014804), sarcoplasmic reticulum (GO:0016529), Z disc (GO:0030018), T-tubule (GO:0030315), sarcoplasmic reticulum membrane (GO:0033017), sarcoplasmic reticulum lumen (GO:0033018), terminal cisterna (GO:0014802), membrane (GO:0016020), myofibril (GO:0030016), I band (GO:0031674), sarcolemma (GO:0042383)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Ion channel transport	1
Cardiac conduction	1
Muscle contraction	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
sarcoplasmic reticulum	3
release of sequestered calcium ion into cytosol	2
regulation of release of sequestered calcium ion into cytosol	2
cytoplasm	2
intracellular membrane-bounded organelle	2
endoplasmic reticulum	2
organelle organization	1
endomembrane system organization	1
striated muscle tissue development	1
skeletal muscle organ development	1
response to stress	1
response to temperature stimulus	1
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of skeletal muscle contraction by calcium ion signaling	1
response to muscle inactivity	1
regulation of muscle adaptation	1
myofibril assembly	1
actomyosin structure organization	1
protein-containing complex assembly	1
positive regulation of calcium ion transmembrane transport	1
store-operated calcium channel activity	1
regulation of store-operated calcium channel activity	1
positive regulation of cation channel activity	1
store-operated calcium entry	1
regulation of calcium ion transport	1
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
response to inactivity	1
regulation of calcium ion transmembrane transport	1
metal ion binding	1
protein binding	1
binding	1
cation binding	1
mitochondrion	1
intracellular organelle lumen	1
endomembrane system	1
terminal cisterna	1
sarcoplasmic reticulum lumen	1
sarcoplasm	1
I band	1

Protein interactions and networks

STRING

1589 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CASQ1	ASPH	Q12797	982
CASQ1	TRDN	Q13061	979
CASQ1	ATP2A1	O14983	752
CASQ1	SRL	Q86TD4	745
CASQ1	JSRP1	Q96MG2	729
CASQ1	RYR1	P21817	726
CASQ1	JPH1	Q9HDC5	693
CASQ1	MYH6	P13533	668
CASQ1	TFAM	Q00059	665
CASQ1	SDF4	Q9BRK5	658
CASQ1	JPH2	Q9BR39	657
CASQ1	APOA2	P02652	654
CASQ1	ATP1A2	P50993	648
CASQ1	RYR2	Q92736	643
CASQ1	STAC3	Q96MF2	623

IntAct

6 interactions, top by confidence:

A	B	Type	Score
GAS2L2	CASQ1	psi-mi:“MI:0915”(physical association)	0.560
CASQ1	GAS2L2	psi-mi:“MI:0915”(physical association)	0.560
CASQ1	PCNA	psi-mi:“MI:0915”(physical association)	0.370
ILKAP	MYO1C	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): CASQ1 (Affinity Capture-MS), CASQ1 (Reconstituted Complex), CASQ1 (Synthetic Lethality), CASQ1 (Affinity Capture-MS), CASQ1 (Affinity Capture-MS), CASQ1 (Affinity Capture-Western)

ESM2 similar proteins: A0A8M1N5Y4, A5PMF7, O09161, O09165, O14958, O18934, O77560, O80977, P07221, P08003, P12637, P13667, P19204, P19633, P20942, P24643, P27824, P31231, P31235, P31415, P35564, P35565, P38659, P51868, P81628, P93026, P93484, Q01H84, Q0JD42, Q14554, Q29RV1, Q2KIL5, Q56ZQ3, Q5FVM7, Q5I0H9, Q5R440, Q5RAN9, Q5RCM7, Q5WA72, Q5ZKZ4

Diamond homologs: O09161, O09165, O14958, O18934, P07221, P12637, P19204, P19633, P31231, P31235, P31236, P31415, P51868, Q5RAN9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

404 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	227
Likely benign	129
Benign	15

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
183021	NM_001231.5(CASQ1):c.731A>G (p.Asp244Gly)	Pathogenic
3233253	NM_001231.5(CASQ1):c.166A>T (p.Asn56Tyr)	Pathogenic
2505628	NM_001231.5(CASQ1):c.1154T>C (p.Ile385Thr)	Likely pathogenic
2687779	NM_001231.5(CASQ1):c.984+1G>A	Likely pathogenic
806251	NM_001231.5(CASQ1):c.790del (p.Thr263_Leu264insTer)	Likely pathogenic

SpliceAI

1260 predictions. Top by Δscore:

Variant	Effect	Δscore
1:160191027:GGAG:G	donor_gain	1.0000
1:160191028:GAG:G	donor_gain	1.0000
1:160191028:GAGG:G	donor_gain	1.0000
1:160191029:AGGTG:A	donor_loss	1.0000
1:160191031:G:GA	donor_loss	1.0000
1:160191031:G:GG	donor_gain	1.0000
1:160191032:T:A	donor_loss	1.0000
1:160192798:CCA:C	acceptor_loss	1.0000
1:160192800:A:AG	acceptor_gain	1.0000
1:160192800:AG:A	acceptor_loss	1.0000
1:160192801:G:GG	acceptor_gain	1.0000
1:160192801:GT:G	acceptor_gain	1.0000
1:160192801:GTT:G	acceptor_gain	1.0000
1:160192801:GTTA:G	acceptor_gain	1.0000
1:160192885:AGG:A	donor_loss	1.0000
1:160192886:GGTAA:G	donor_loss	1.0000
1:160192888:T:A	donor_loss	1.0000
1:160193848:G:GG	donor_gain	1.0000
1:160195078:GA:G	donor_gain	1.0000
1:160195120:GAGC:G	donor_gain	1.0000
1:160195122:GC:G	donor_gain	1.0000
1:160195124:G:GG	donor_gain	1.0000
1:160195550:GCT:G	donor_gain	1.0000
1:160195882:C:G	acceptor_gain	1.0000
1:160195893:AAAG:A	acceptor_gain	1.0000
1:160195894:A:G	acceptor_gain	1.0000
1:160195894:AAGGT:A	acceptor_gain	1.0000
1:160195895:A:AG	acceptor_gain	1.0000
1:160195895:AGGT:A	acceptor_gain	1.0000
1:160195896:G:A	acceptor_gain	1.0000

AlphaMissense

2653 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:160201259:G:C	W358C	1.000
1:160201259:G:T	W358C	1.000
1:160195097:G:A	G184D	0.999
1:160195484:G:C	A201P	0.999
1:160195485:C:A	A201D	0.999
1:160197612:T:A	W276R	0.999
1:160197612:T:C	W276R	0.999
1:160197614:G:C	W276C	0.999
1:160197614:G:T	W276C	0.999
1:160198711:T:C	F288S	0.999
1:160198965:T:C	F299S	0.999
1:160198977:T:A	L303H	0.999
1:160198977:T:C	L303P	0.999
1:160199027:T:A	W320R	0.999
1:160199027:T:C	W320R	0.999
1:160199863:T:A	W333R	0.999
1:160199863:T:C	W333R	0.999
1:160199865:G:C	W333C	0.999
1:160199865:G:T	W333C	0.999
1:160199906:G:A	G347E	0.999
1:160199912:T:A	V349D	0.999
1:160201257:T:A	W358R	0.999
1:160201257:T:C	W358R	0.999
1:160201311:T:A	W376R	0.999
1:160201311:T:C	W376R	0.999
1:160201313:G:C	W376C	0.999
1:160201313:G:T	W376C	0.999
1:160195091:T:C	L182P	0.998
1:160195096:G:C	G184R	0.998
1:160195103:T:C	F186S	0.998

dbSNP variants (sampled 300 via entrez): RS1000186060 (1:160194518 T>G), RS1000329936 (1:160192104 G>A), RS1000354815 (1:160196970 A>G), RS1000502907 (1:160198435 C>A,T), RS1000781728 (1:160193290 G>A,T), RS1001010022 (1:160191117 T>C,G), RS1001038238 (1:160193058 G>A,C), RS1001331553 (1:160190490 G>T), RS1001483583 (1:160196418 C>T), RS1001636032 (1:160194173 CACAT>C), RS1001971577 (1:160192716 A>G), RS1002440800 (1:160197655 GGGT>G), RS1002895962 (1:160200263 C>T), RS1003198953 (1:160189402 C>A,G), RS1003254044 (1:160200442 T>A)

Disease associations

OMIM: gene MIM:114250 | disease phenotypes: MIM:616231, MIM:160565

GenCC curated gene-disease

Disease	Classification	Inheritance
myopathy due to calsequestrin and SERCA1 protein overload	Strong	Autosomal dominant
tubular aggregate myopathy	Supportive	Autosomal dominant

Mondo (3): myopathy due to calsequestrin and SERCA1 protein overload (MONDO:0014546), myopathy (MONDO:0005336), tubular aggregate myopathy (MONDO:0008051)

Orphanet (2): Vacuolar myopathy with sarcoplasmic reticulum protein aggregates (Orphanet:88635), Tubular aggregate myopathy (Orphanet:2593)

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001324	Muscle weakness
HP:0003198	Myopathy
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003326	Myalgia
HP:0003388	Easy fatigability
HP:0003394	Muscle spasm
HP:0003458	EMG: myopathic abnormalities
HP:0003473	Fatigable weakness
HP:0003554	Type 2 muscle fiber atrophy
HP:0003557	Increased variability in muscle fiber diameter
HP:0003687	Centrally nucleated skeletal muscle fibers
HP:0003701	Proximal muscle weakness
HP:0030200	Fatiguable weakness of proximal limb muscles
HP:0034940	Muscle fiber calsequestrin 1-containing inclusion bodies
HP:0100301	Muscle fiber tubular inclusions

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	increases expression	1
Sunitinib	decreases expression	1
Doxorubicin	decreases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

46 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00120055	PHASE4	COMPLETED	Association Between Systemic Exposure of Atorvastatin and Metabolites and Atorvastatin-induced Myotoxicity
NCT03633565	PHASE4	UNKNOWN	Comparative Study of Strategies for Management of Duchenne Myopathy (DM)
NCT01225614	PHASE3	UNKNOWN	Efficacy and Tolerance of Early Launching of Nocturnal Non Invasive
NCT00278564	PHASE1	TERMINATED	Stem Cell Transplantation in Idiopathic Inflammatory Myopathy Diseases
NCT01642056	PHASE1/PHASE2	COMPLETED	EPI-743 for Metabolism or Mitochondrial Disorders
NCT02124070	PHASE1/PHASE2	WITHDRAWN	Therapeutic Effect of Recombinant Human Growth Hormone (rhGH) on the Myopathy of Cystinosis
NCT00549029	Not specified	UNKNOWN	The Association of Genetic Polymorphisms With Statin-Induced Myopathy.
NCT00767130	Not specified	UNKNOWN	DNA Diagnostic System for Statin Safety and Efficacy
NCT00922428	Not specified	COMPLETED	PASCOE-Agil HOM-Injektopas in the Treatment of Rheumatic Disorders
NCT00937001	Not specified	ACTIVE_NOT_RECRUITING	Critical Illness Myopathy as a Cause of Debilitating ICU-Acquired Weakness
NCT00990834	Not specified	WITHDRAWN	Muscle Characteristics Associated With Statin Therapy
NCT01022450	Not specified	UNKNOWN	Study of the Causes of the Breakdown of Muscle Fibers in Hospitalized Patients
NCT01040650	Not specified	TERMINATED	Metabolic Features of Post-Myopathy Patients Associated With Statin Treatment
NCT01047163	Not specified	COMPLETED	Maintenance of Muscle Mass in Older People: the Negative Impact of Statin Therapy
NCT01270269	Not specified	COMPLETED	ACT-ICU Study: Activity and Cognitive Therapy in the Intensive Care Unit
NCT01353430	Not specified	RECRUITING	Characterization of Inclusion Body Myopathy Associated With Paget’s Disease of Bone and Frontotemporal Dementia (IBMPFD)
NCT01395563	Not specified	WITHDRAWN	Strength Training on Pancreatic Cancer
NCT01530841	Not specified	COMPLETED	Efficacy and Tolerance of AVAPS Mode in Myotonic Dystrophy
NCT01547767	Not specified	COMPLETED	Investigations Into ISCU Myopathy or Iron Sulfur Scaffold U Protein Myopathy
NCT01702987	Not specified	COMPLETED	Evaluation of Ubiquinol on Mitochondrial Oxidative Capacity in Statin Patients Using 31PMRS
NCT01790178	Not specified	COMPLETED	Ultrasound in Muscle Biopsy
NCT02011282	Not specified	COMPLETED	Electro-Neuro-Muscular Stimulation in ICU
NCT02104921	Not specified	COMPLETED	Innovative Ultrasound Technology in Neuromuscular Disease
NCT02118805	Not specified	COMPLETED	Innovative Measures of Speech and Swallowing Dysfunction in Neurological Disorders
NCT02235220	Not specified	UNKNOWN	Reduction of Masticatory Muscle Activity by Restoring Canine Guidance
NCT02247895	Not specified	TERMINATED	Treatment of Muscle Weakness in Critically Ill Patients
NCT02315339	Not specified	TERMINATED	European Home Mechanical Ventilation Registry
NCT02442986	Not specified	COMPLETED	Neurological Outcome in Surgical and Non-surgical Septic Patients
NCT02706314	Not specified	COMPLETED	Impact of Human Blood Serum From Critically Ill Patients on Human Colon Neuronal Networks.
NCT02765828	Not specified	COMPLETED	Identification of Tongue Involvement in Late-Onset Pompe Disease
NCT03042286	Not specified	UNKNOWN	SAPhIRE Statin Adverse Drug Reaction
NCT03141749	Not specified	COMPLETED	Venous Thromboembolism in DM1
NCT03660969	Not specified	ACTIVE_NOT_RECRUITING	Reliability of Cardiac Troponins for the Diagnosis of Myocardial Infarction in the Presence of Skeletal Muscle Disease
NCT03749538	Not specified	RECRUITING	Acute Transcranial Direct Current Stimulation in Patients With Systemic Autoimmune Myopathies
NCT03751644	Not specified	COMPLETED	Peripherical Neuromuscular Electrical Stimulation in Systemic Autoimmune Myopathies
NCT03998540	Not specified	UNKNOWN	Improvement of DIAgnostic and Phenotype-genotype Correlation Studies in Patients With MYOpathy Suspected of TITinopathy
NCT04678635	Not specified	RECRUITING	Chronic Transcranial Direct Current Stimulation in Patients With Systemic Autoimmune Myopathies
NCT04881214	Not specified	UNKNOWN	COVID-19 Pneumonia: Pulmonary Physiology, Health-related Quality of Life and Benefit of a Rehabilitation Program
NCT04941079	Not specified	UNKNOWN	Safety and Efficacy of Inactivated SARS-CoV-2 Vaccine in Immune-related Myopathy (Myasthenia Gravis and Inflammatory Myopathy) Patients ：a Prospective Observational Study
NCT05599568	Not specified	RECRUITING	Repeated Bout Effect i Neuromuscular Diseases