CASQ1 (calsequestrin 1)

Gene

• Entrez ID: 844
• Gene name: Calsequestrin 1
• Gene symbol: CASQ1
• Synonyms (NCBI Gene): CASQ, CSQ1, PDIB1, VMCQA
• Chromosome: 1
• Chromosome location: 1q23.2
• Summary: 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, functio

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs150143470	G>T	Conflicting-interpretations-of-pathogenicity	Stop gained, coding sequence variant
rs730882052	A>G	Pathogenic	Coding sequence variant, missense variant
rs749145120	G>A,T	Likely-pathogenic	Coding sequence variant, missense variant
rs773153762	C>-	Likely-pathogenic	Stop gained, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018690	hsa-miR-335-5p	Microarray	18185580
MIRT029942	hsa-miR-26b-5p	Microarray	19088304
MIRT437538	hsa-miR-19b-3p	Immunoprecipitaion	22382630
MIRT864261	hsa-miR-135a	CLIP-seq
MIRT864262	hsa-miR-135b	CLIP-seq
MIRT864263	hsa-miR-3125	CLIP-seq
MIRT864264	hsa-miR-3150b-3p	CLIP-seq
MIRT864265	hsa-miR-3916	CLIP-seq
MIRT864266	hsa-miR-4784	CLIP-seq
MIRT864267	hsa-miR-877	CLIP-seq
MIRT864264	hsa-miR-3150b-3p	CLIP-seq
MIRT1956168	hsa-miR-4457	CLIP-seq
MIRT864266	hsa-miR-4784	CLIP-seq
MIRT1956169	hsa-miR-511	CLIP-seq
MIRT1956170	hsa-miR-513b	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005509	Function	Calcium ion binding	IBA
GO:0005509	Function	Calcium ion binding	IDA	22337878, 28895244
GO:0005509	Function	Calcium ion binding	IEA
GO:0005515	Function	Protein binding	IPI	27185316, 32296183
GO:0005739	Component	Mitochondrion	HDA	20833797
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	ISS
GO:0005759	Component	Mitochondrial matrix	TAS	7945294
GO:0005783	Component	Endoplasmic reticulum	IDA	27185316
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005783	Component	Endoplasmic reticulum	NAS	7945294
GO:0005790	Component	Smooth endoplasmic reticulum	TAS	7945294
GO:0007029	Process	Endoplasmic reticulum organization	IEA
GO:0007519	Process	Skeletal muscle tissue development	IEA
GO:0009408	Process	Response to heat	IEA
GO:0010880	Process	Regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	IEA
GO:0014802	Component	Terminal cisterna	IEA
GO:0014804	Component	Terminal cisterna lumen	IEA
GO:0014809	Process	Regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion	IBA
GO:0014809	Process	Regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion	IEA
GO:0014809	Process	Regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion	ISS
GO:0014870	Process	Response to muscle inactivity	IEA
GO:0014894	Process	Response to denervation involved in regulation of muscle adaptation	IEA
GO:0016020	Component	Membrane	IEA
GO:0016529	Component	Sarcoplasmic reticulum	IEA
GO:0016529	Component	Sarcoplasmic reticulum	ISS
GO:0030016	Component	Myofibril	IEA
GO:0030018	Component	Z disc	IBA
GO:0030315	Component	T-tubule	IEA
GO:0031674	Component	I band	IEA
GO:0033017	Component	Sarcoplasmic reticulum membrane	IEA
GO:0033017	Component	Sarcoplasmic reticulum membrane	TAS
GO:0033018	Component	Sarcoplasmic reticulum lumen	IBA
GO:0033018	Component	Sarcoplasmic reticulum lumen	IEA
GO:0033018	Component	Sarcoplasmic reticulum lumen	ISS
GO:0042383	Component	Sarcolemma	IEA
GO:0042802	Function	Identical protein binding	IDA	27185316, 28895244
GO:0045214	Process	Sarcomere organization	IEA
GO:0045214	Process	Sarcomere organization	ISS
GO:0046872	Function	Metal ion binding	IEA
GO:0051258	Process	Protein polymerization	IDA	22337878
GO:0051258	Process	Protein polymerization	IEA
GO:0051279	Process	Regulation of release of sequestered calcium ion into cytosol	IEA
GO:0051281	Process	Positive regulation of release of sequestered calcium ion into cytosol	IMP	28895244
GO:0051282	Process	Regulation of sequestering of calcium ion	IEA
GO:1901341	Process	Positive regulation of store-operated calcium channel activity	IMP	27185316, 28895244
GO:2001256	Process	Regulation of store-operated calcium entry	IMP	28895244

Other IDs

• MIM: 114250
• HGNC: 1512
• e!Ensembl: ENSG00000143318

Protein

• UniProt ID: P31415
• Protein name: Calsequestrin-1 (Calmitine) (Calsequestrin, skeletal muscle isoform)
• Protein 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 inter
• PDB: 3UOM, 5CRD, 5CRE, 5CRG, 5CRH, 8F48
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01216	Calsequestrin	11 → 396	Calsequestrin	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed in myoblasts (at protein level). {ECO:0000269|PubMed:27196359}.
• Sequence:

  MSATDRMGPRAVPGLRLALLLLLVLGTPKSGVQGQEGLDFPEYDGVDRVINVNAKNYKNV
  FKKYEVLALLYHEPPEDDKASQRQFEMEELILELAAQVLEDKGVGFGLVDSEKDAAVAKK
  LGLTEVDSMYVFKGDEVIEYDGEFSADTIVEFLLDVLEDPVELIEGERELQAFENIEDEI
  KLIGYFKSKDSEHYKAFEDAAEEFHPYIPFFATFDSKVAKKLTLKLNEIDFYEAFMEEPV
  TIPDKPNSEEEIVNFVEEHRRSTLRKLKPESMYETWEDDMDGIHIVAFAEEADPDGFEFL
  ETLKAVAQDNTENPDLSIIWIDPDDFPLLVPYWEKTFDIDLSAPQIGVVNVTDADSVWME
  MDDEEDLPSAEELEDWLEDVLEGEINTEDDDDDDDD

• Sequence length: 396

Pathways

KEGG:

Calcium signaling pathway

Reactome:

Stimuli-sensing channels
Ion homeostasis

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Myopathy due to calsequestrin and SERCA1 protein overload	Pathogenic; Likely pathogenic	rs730882052, rs1422979746	RCV000161143 RCV003485017	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Myopathy with tubular aggregates	Pathogenic	rs2525040830	RCV004587619	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CASQ1-related disorder	Uncertain significance; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETES MELLITUS, NON-INSULIN-DEPENDENT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myopathy	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Ovarian cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TUBULAR AGGREGATE MYOPATHY	—	Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VACUOLAR MYOPATHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VACUOLAR MYOPATHY WITH SARCOPLASMIC RETICULUM PROTEIN AGGREGATES	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Atrophy	Atrophy	Pubtator	30258016	Associate	★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune Diseases	BEFREE	20464711		★☆☆☆☆ Found in Text Mining only
Cardiovascular Abnormalities	Cardiovascular abnormalities	Pubtator	30258016	Associate	★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	BEFREE	19417098, 24887214		★☆☆☆☆ Found in Text Mining only
Common Migraine	Common Migraine	BEFREE	17727731		★☆☆☆☆ Found in Text Mining only
Crisponi syndrome	Crisponi syndrome	Pubtator	25532418	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	15561963, 17681849		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	15561963, 17681849		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	15561962, 15561963, 17681849		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Heart Diseases	Heart disease	Pubtator	24427266, 30258016	Associate	★☆☆☆☆ Found in Text Mining only
Malignant Hyperthermia	Malignant hyperthermia	Pubtator	26416891	Associate	★☆☆☆☆ Found in Text Mining only
Meningioma	Meningioma	Pubtator	30258016	Associate	★☆☆☆☆ Found in Text Mining only
Migraine with Aura	Migraine with Aura	BEFREE	17727731		★☆☆☆☆ Found in Text Mining only
Muscular Dystrophy, Duchenne	Duchenne Muscular Dystrophy	BEFREE	7599203		★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	BEFREE	22130610, 25116801, 26136523, 27196359, 7599203		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Myopathy	Myopathy	HPO_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
MYOPATHY, TUBULAR AGGREGATE, 1	Myopathy	UNIPROT_DG	28895244		★☆☆☆☆ Found in Text Mining only
MYOPATHY, VACUOLAR, WITH CASQ1 AGGREGATES	Myopathy	ORPHANET_DG	25116801		★☆☆☆☆ Found in Text Mining only
MYOPATHY, VACUOLAR, WITH CASQ1 AGGREGATES	Myopathy	GENOMICS_ENGLAND_DG	25116801		★☆☆☆☆ Found in Text Mining only
MYOPATHY, VACUOLAR, WITH CASQ1 AGGREGATES	Myopathy	UNIPROT_DG	25116801, 26136523, 27196359, 28895244		★☆☆☆☆ Found in Text Mining only
MYOPATHY, VACUOLAR, WITH CASQ1 AGGREGATES	Myopathy	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
MYOPATHY, VACUOLAR, WITH CASQ1 AGGREGATES	Myopathy	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Myositis	Myositis	BEFREE	20464711		★☆☆☆☆ Found in Text Mining only
Stormorken Syndrome	Stormorken Syndrome	BEFREE	30243034		★☆☆☆☆ Found in Text Mining only
Tachycardia Ventricular	Ventricular tachycardia	Pubtator	26087026	Associate	★☆☆☆☆ Found in Text Mining only
Thyroid associated opthalmopathies	Thyroid eye disease	BEFREE	20039900, 20464711		★☆☆☆☆ Found in Text Mining only
Tubular Aggregate Myopathy	Tubular Aggregate Myopathy	BEFREE	28895244, 30243034		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Tubular Aggregate Myopathy	Tubular Aggregate Myopathy	ORPHANET_DG	28895244, 29039140		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Tubular aggregate myopathy	Tubular Aggregate Myopathy	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Vacuolar myopathy	Vacuolar Myopathy	BEFREE	25116801		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Vacuolar myopathy	Vacuolar myopathy	Pubtator	26416891	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Vacuolar myopathy with sarcoplasmic reticulum protein aggregates	Vacuolar myopathy with casq1 aggregates	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
X-linked myopathy with excessive autophagy	Myopathy With Excessive Autophagy, X-Linked	BEFREE	25116801		★☆☆☆☆ Found in Text Mining only