CAST

Summary

CAST (calpastatin, HGNC:1515) is a long non-coding RNA gene on chromosome 5q15. Specific inhibition of calpain (calcium-dependent cysteine protease).

The protein encoded by this gene is an endogenous calpain (calcium-dependent cysteine protease) inhibitor. It consists of an N-terminal domain L and four repetitive calpain-inhibition domains (domains 1-4), and it is involved in the proteolysis of amyloid precursor protein. The calpain/calpastatin system is involved in numerous membrane fusion events, such as neural vesicle exocytosis and platelet and red-cell aggregation. The encoded protein is also thought to affect the expression levels of genes encoding structural or regulatory proteins. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 831 — RefSeq curated summary.

At a glance

• Gene type: non-coding (lncRNA) — no protein product; not a drug target. Variant/disease associations are omitted (they would be positional, from an overlapping protein-coding gene).

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1515
Approved symbol	CAST
Name	calpastatin
Location	5q15
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000153113
Ensembl biotype	lncRNA
OMIM	114090
Entrez	831

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 lncRNA

ENST00000502645, ENST00000507997, ENST00000511775, ENST00000513158, ENST00000513926, ENST00000718075, ENST00000718076, ENST00000718077, ENST00000718089, ENST00000718090, ENST00000718092

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000502645 — 6 exons

Exon	Start	End
ENSE00002030802	96379566	96379652
ENSE00002058049	96318473	96318544
ENSE00002082950	95962001	95962036
ENSE00002459286	96308724	96308882
ENSE00004034055	96110934	96111005
ENSE00004034056	96381043	96381384

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.48.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4512 / max 65.3159, expressed in 153 samples.

FANTOM5 promoters (29 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57691	31.0303	1741
57683	21.0097	1716
57685	11.9371	1575
57684	10.1740	1542
57687	7.8136	1367
57692	6.1030	1526
57686	4.1457	1394
57680	2.8925	1240
57678	2.7366	1235
57682	2.4591	1168

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.48	gold quality
bronchial epithelial cell	CL:0002328	99.39	gold quality
colonic epithelium	UBERON:0000397	99.34	gold quality
penis	UBERON:0000989	99.33	gold quality
synovial joint	UBERON:0002217	99.25	gold quality
oral cavity	UBERON:0000167	99.23	gold quality
lower esophagus mucosa	UBERON:0035834	99.23	gold quality
urethra	UBERON:0000057	99.21	gold quality
upper leg skin	UBERON:0004262	99.20	gold quality
epithelium of bronchus	UBERON:0002031	99.12	gold quality
bronchus	UBERON:0002185	99.09	gold quality
pharyngeal mucosa	UBERON:0000355	99.08	gold quality
skin of hip	UBERON:0001554	99.07	gold quality
esophagus mucosa	UBERON:0002469	99.05	gold quality
tongue squamous epithelium	UBERON:0006919	99.04	gold quality
esophagus squamous epithelium	UBERON:0006920	99.03	gold quality
palpebral conjunctiva	UBERON:0001812	99.00	gold quality
upper arm skin	UBERON:0004263	98.98	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.98	gold quality
epithelium of nasopharynx	UBERON:0001951	98.96	gold quality
nasopharynx	UBERON:0001728	98.94	gold quality
myocardium	UBERON:0002349	98.93	gold quality
gingiva	UBERON:0001828	98.92	gold quality
gingival epithelium	UBERON:0001949	98.91	gold quality
epithelium of esophagus	UBERON:0001976	98.89	gold quality
left ventricle myocardium	UBERON:0006566	98.89	gold quality
vagina	UBERON:0000996	98.87	gold quality
squamous epithelium	UBERON:0006914	98.86	gold quality
monocyte	CL:0000576	98.81	gold quality
tendon	UBERON:0000043	98.81	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	23.61
E-MTAB-9388	yes	11.26
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

• involved in the proteolysis of amyloid precursor protein, which is thought to be abnormal in patients with Alzheimer’s disease (PMID:11849768)
• Overexpression of calpastatin reduced muscle atrophy during 10 day unloading period. Overexpression completely prevented shift in myofibrillar myosin content from slow to fast isoforms, which normally occurs in muscle unloading. (PMID:12482888)
• insights into how the calpain/calpastatin network is spatially and temporally regulated in cells binding to the extracellular matrix (PMID:14559243)
• calpastatin and calpain-1 represent critical proximal elements in a cascade of pro-apoptotic events leading to Bax, mitochondria, and caspase-3 activation (PMID:14612448)
• Calpastatin amino acid side chains at leucine-11 and isoleucine-18 interact with hydrophobic pockets in calpain, and each of these interactions is indispensable for effective inhibition of calpain. (PMID:14992597)
• Overexpression of calpastatin in transgenic mice is associated with an increase in GLUT4 protein. (PMID:15014085)
• A complete calpain-calpastatin system is expressed in the human oocyte and may play a role in the various calcium-mediated processes occurring during activation of human oocytes. (PMID:15950654)
• CS(L) modulates Ca2+-channel activity through interacting with the calmodulin-binding site on the C-terminal tail of the Cav1.2 channel. (PMID:17950697)
• The activity of calpain in human peripheral blood lymphocytes, was estimated by assessing the levels of limited proteolysis of calpastatin. (PMID:18165173)
• Results suggest a regulation on the calpain-calpastatin expression response to muscle damaging eccentric exercise, but not concentric exercise. (PMID:18340456)
• genetically determined IL-1alpha levels may modulate transcription of calpain and calpastatin (PMID:18498295)
• NMR data of calapastin tripartite binding mode to capain induced by calcium were presented. (PMID:18519038)
• performed a full NMR assignment of hCSD1 to characterize it in its solution state (PMID:18537264)
• c-Myc regulates calpain activity through calpastatin; apoptosis induced by calpain inhibition is dependent on c-Myc, and calpastatin knockdown promotes transformation in c-Myc-negative cells (PMID:18544539)
• Proof of concept that the calpastatin-based reagents may be useful to selectively detect the active conformation of calpain. (PMID:18793761)
• Role of the calpain-calpastatin system in the density-dependent growth arrest. (PMID:18809371)
• recruitment of calpastatin into aggregates allows translocation and activation of protease to the membranes; on the contrary, the presence of large amounts of calpastatin in the cytosol prevents both processes, protecting the cell from proteolysis (PMID:19103264)
• Overexpression of calpain-2 and low expression of calpastatin may involve in the pathological development of stress urinary incontinence. (PMID:19756344)
• A confirmation study reports that a single nucleotide polymorphism and CAST are associated with Parkinson disease. (PMID:20127884)
• Variations in CAST gene is associated with femoral neck Low bone mineral density. (PMID:21424381)
• The data supports the hypothesis that calpastatin may play a role in regulating the initial metastatic dissemination of breast cancer. (PMID:21531560)
• intervertebral discs at early stages of degeneration expressed low levels of calpastatin, and few cells expressed degenerative enzymes. At more advanced stages of degeneration, expression and number of cells immunopositive for calpastatin were higher (PMID:21839844)
• CSL competes with CaM as a partial agonist for the site in the IQ domain in the C-terminal region of the Cav1.2 channel, which may be involved in activation of the channel. (PMID:21937422)
• calpain basal activity becomes measurable at a significant extent in peripheral blood mononuclear cells from cystic fibrosis patients due to a 40-60% decrease in both calpastatin protein and inhibitory activity (PMID:21983488)
• calpastatin-calpain balance varied during Th-1,2, and -17 development; overexpression of a domain of calpastatin suppressed production of IL-6 and IL-17 by Th cells and of IL-6 by fibroblasts; suppression of IL-6 occurred by reducing NF-kappaB signaling (PMID:22046434)
• Neuronal overexpression of calpastatin modulates amyloid precursor protein processing in brains of transgenic beta-amyloid depositing mice. (PMID:22206846)
• Mycoplasma hyorhinis membrane lipoproteins induce calpastatin upregulation in human cells (PMID:22288381)
• Calpastatin overexpression reduces calpain-mediated proteolysis and behavioral impairment after traumatic brain injury. (PMID:22572592)
• The results suggest that calpain-2 and calpastatin expression is important in pancreatic cancers, influencing disease progression (PMID:23140395)
• Linkage analysis and genetic association support involvement of CAST gene in the genetic susceptibility to keratoconus. (PMID:23449483)
• HER2 inhibited calpain-1 activity through upregulating calpastatin, an endogenous calpain inhibitor. (PMID:23707532)
• Calpastatin gene (CAST) is not associated with late onset sporadic Parkinson’s disease in the Han Chinese population. (PMID:23951044)
• Calpastatin binds with Cav1.2 amino acid motifs in a calcium dependent manner. (PMID:24462690)
• Loss of CAST in angiogenic ECs facilitates mu-calpain-induced SOCS3 degradation, which amplifies pathological angiogenesis through interleukin-6/STAT3/VEGF-C axis. (PMID:25648699)
• We describe PLACK syndrome, as a clinical entity of defective epidermal adhesion, caused by loss-of-function mutations in calpastatin. (PMID:25683118)
• calpains and calpastatin in patients with idiopathic pulmonary arterial hypertension (PAH) and mice with hypoxic or spontaneous (SM22-5HTT(+) strain) PH, were investigated. (PMID:26974350)
• Kaposi sarcoma-associated herpesvirus reduces CAST (calpastatin) and consequently decreases ATG5 expression in both THP-1 monocytoid cells and primary monocytes. (PMID:27715410)
• single nucleotide polymorphisms in CAST gene confer risk for keratoconus susceptibility in Han Chinese population (PMID:29428799)
• Unexpected role of the L-domain of calpastatin during the autoproteolytic activation of human erythrocyte calpain. (PMID:29572388)
• Low CAST expression is associated with ovarian cancer. (PMID:30448882)

Cross-species orthologs

0 orthologs

Protein

Non-coding RNA — no protein product; not a drug target.

Function

No curated pathway, Gene-Ontology, or interaction data.

Disease & clinical

No curated disease, variant, or cancer-driver associations.

Drugs & pharmacology

No drug or pharmacology data — not an established drug target.