CASQ2

Summary

CASQ2 (calsequestrin 2, HGNC:1513) is a protein-coding gene on chromosome 1p13.1, encoding Calsequestrin-2 (O14958). Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle.

The protein encoded by this gene specifies the cardiac muscle family member of the calsequestrin family. Calsequestrin is localized to the sarcoplasmic reticulum in cardiac and slow skeletal muscle cells. The protein is a calcium binding protein that stores calcium for muscle function. Mutations in this gene cause stress-induced polymorphic ventricular tachycardia, also referred to as catecholaminergic polymorphic ventricular tachycardia 2 (CPVT2), a disease characterized by bidirectional ventricular tachycardia that may lead to cardiac arrest.

Source: NCBI Gene 845 — RefSeq curated summary.

At a glance

• Gene–disease (curated): catecholaminergic polymorphic ventricular tachycardia (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 31 (top 4% of genes corpus-wide)
• Clinical variants (ClinVar): 902 total — 34 pathogenic, 27 likely-pathogenic (top 3% of genes corpus-wide)
• GTEx eGene: eQTL in 23 tissues, sQTL in 4 (q < 0.05)
• Phenotypes (HPO): 21
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.32 (unconstrained)
• MANE Select transcript: NM_001232

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1513
Approved symbol	CASQ2
Name	calsequestrin 2
Location	1p13.1
Locus type	gene with protein product
Status	Approved
Aliases	PDIB2
Ensembl gene	ENSG00000118729
Ensembl biotype	protein_coding
OMIM	114251
Entrez	845

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 12 protein_coding, 12 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000261448

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 1

ENST00000261448, ENST00000488931, ENST00000713711, ENST00000713712, ENST00000713713, ENST00000713727, ENST00000713728, ENST00000713729, ENST00000850611, ENST00000850612, ENST00000874188, ENST00000874189, ENST00000975308, ENST00000975309, ENST00000975310, ENST00001054852, ENST00001054853, ENST00001054854, ENST00001054856, ENST00001054860, ENST00001122008, ENST00001122009, ENST00001122010, ENST00001122011, ENST00001145693

RefSeq mRNA: 1 — MANE Select: NM_001232 NM_001232

CCDS: CCDS884

Canonical transcript exons

ENST00000261448 — 11 exons

Exon	Start	End
ENSE00000800544	115738224	115738335
ENSE00000800545	115740728	115740828
ENSE00000800546	115744828	115744912
ENSE00001074019	115732901	115732974
ENSE00001074020	115702921	115702995
ENSE00001074027	115705192	115705292
ENSE00001957067	115768308	115768714
ENSE00003541303	115717840	115717894
ENSE00003569802	115726992	115727122
ENSE00003670364	115725508	115725553
ENSE00004282326	115700021	115701426

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 99.79.

FANTOM5 (CAGE): breadth broad, TPM avg 5.1790 / max 1112.6405, expressed in 185 samples.

Highest expression (Bgee): heart right ventricle, ventricle myocardium, myocardium, cardiac ventricle, heart left ventricle.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CASQ2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 23 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 27 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	2.3e-57	+0.29	1:115767809:C:T
Artery Aorta	eqtl	5.9e-26	+0.95	1:115760460:T:C
Artery Coronary	eqtl	3.8e-11	+0.28	1:115767244:T:C
Colon Sigmoid	eqtl	3.1e-09	+0.22	1:115741981:G:A
Colon Transverse	eqtl	3.1e-08	+0.14	1:115729862:T:C
Testis	sqtl	1.8e-07	-0.51	1:115703278:T:C
Heart Left Ventricle	eqtl	5.5e-07	+0.13	1:115767244:T:C
Adipose Subcutaneous	sqtl	1.1e-06	-0.34	1:115765225:G:A
Heart Atrial Appendage	eqtl	1.2e-06	-0.11	1:115755137:C:A
Esophagus Gastroesophageal Junction	eqtl	1.0e-04	+0.14	1:115720295:T:G
Adipose Visceral Omentum	sqtl	1.3e-04	-0.36	1:115757516:A:G
Adipose Subcutaneous	eqtl	3.6e-04	-0.11	1:115760302:C:T
Muscle Skeletal	eqtl	1.5e-03	+0.11	1:115735882:C:A
Nerve Tibial	eqtl	2.7e-03	+0.11	1:115755443:C:A
Esophagus Muscularis	eqtl	3.3e-03	+0.10	1:115678910:C:A
Brain Nucleus accumbens basal ganglia	eqtl	6.2e-03	-0.33	1:115840712:C:A
Esophagus Mucosa	eqtl	1.1e-02	-0.07	1:115765225:G:A
Colon Transverse	sqtl	1.5e-02	-1.30	1:115316562:C:T
Cells Cultured fibroblasts	eqtl	1.9e-02	+0.31	1:115384943:T:C
Skin Sun Exposed Lower leg	eqtl	2.1e-02	-0.10	1:115796144:C:T

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
13987	3.1087	160
13988	0.8312	106
13989	0.6992	100
13986	0.2441	52
13990	0.1796	54
13983	0.0929	33
13985	0.0233	12

Top tissues by expression

showing 100 of 283 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	99.79	gold quality
left ventricle myocardium	UBERON:0006566	99.59	gold quality
myocardium	UBERON:0002349	99.53	gold quality
cardiac ventricle	UBERON:0002082	99.43	gold quality
heart left ventricle	UBERON:0002084	99.42	gold quality
cardiac atrium	UBERON:0002081	99.29	gold quality
right atrium auricular region	UBERON:0006631	99.29	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.26	gold quality
apex of heart	UBERON:0002098	98.95	gold quality
heart	UBERON:0000948	98.90	gold quality
vena cava	UBERON:0004087	98.70	gold quality
biceps brachii	UBERON:0001507	98.37	gold quality
popliteal artery	UBERON:0002250	98.36	gold quality
tibial artery	UBERON:0007610	98.36	gold quality
gluteal muscle	UBERON:0002000	98.28	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.20	gold quality
right coronary artery	UBERON:0001625	98.14	gold quality
diaphragm	UBERON:0001103	98.13	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.01	gold quality
triceps brachii	UBERON:0001509	97.99	gold quality
blood vessel layer	UBERON:0004797	97.97	gold quality
tibialis anterior	UBERON:0001385	97.91	gold quality
deltoid	UBERON:0001476	97.90	gold quality
saphenous vein	UBERON:0007318	97.90	gold quality
skeletal muscle tissue	UBERON:0001134	97.52	gold quality
quadriceps femoris	UBERON:0001377	97.48	gold quality
vastus lateralis	UBERON:0001379	97.46	gold quality
coronary artery	UBERON:0001621	96.95	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.91	gold quality
left coronary artery	UBERON:0001626	96.90	gold quality
body of tongue	UBERON:0011876	96.74	gold quality
gastrocnemius	UBERON:0001388	96.57	gold quality
muscle tissue	UBERON:0002385	96.55	gold quality
muscle organ	UBERON:0001630	96.53	gold quality
skeletal muscle organ	UBERON:0014892	96.53	gold quality
muscle of leg	UBERON:0001383	96.12	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.96	gold quality
lower esophagus	UBERON:0013473	93.88	gold quality
aorta	UBERON:0000947	93.40	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.35	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.31	gold quality
nipple	UBERON:0002030	91.73	gold quality
superficial temporal artery	UBERON:0001614	90.21	gold quality
mucosa of stomach	UBERON:0001199	89.85	gold quality
tongue	UBERON:0001723	89.20	gold quality
colonic epithelium	UBERON:0000397	87.84	gold quality
thoracic aorta	UBERON:0001515	86.89	gold quality
ascending aorta	UBERON:0001496	86.84	gold quality
descending thoracic aorta	UBERON:0002345	86.47	gold quality
urethra	UBERON:0000057	86.39	gold quality
smooth muscle tissue	UBERON:0001135	86.24	gold quality
endothelial cell	CL:0000115	85.27	silver quality
urinary bladder	UBERON:0001255	85.12	gold quality
left uterine tube	UBERON:0001303	85.10	gold quality
body of uterus	UBERON:0009853	84.28	gold quality
superior surface of tongue	UBERON:0007371	84.03	gold quality
sigmoid colon	UBERON:0001159	84.00	gold quality
esophagus	UBERON:0001043	83.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.79	gold quality
pericardium	UBERON:0002407	80.77	gold quality
rectum	UBERON:0001052	80.74	gold quality
subcutaneous adipose tissue	UBERON:0002190	80.58	gold quality
parietal pleura	UBERON:0002400	80.52	gold quality
fundus of stomach	UBERON:0001160	80.14	gold quality
choroid plexus epithelium	UBERON:0003911	80.08	gold quality
pharyngeal mucosa	UBERON:0000355	79.76	gold quality
adipose tissue	UBERON:0001013	79.35	gold quality
myometrium	UBERON:0001296	79.13	gold quality
colon	UBERON:0001155	79.01	gold quality
large intestine	UBERON:0000059	78.68	gold quality
connective tissue	UBERON:0002384	78.65	gold quality
penis	UBERON:0000989	78.52	gold quality
gall bladder	UBERON:0002110	78.24	gold quality
omental fat pad	UBERON:0010414	78.16	gold quality
peritoneum	UBERON:0002358	78.12	gold quality
adipose tissue of abdominal region	UBERON:0007808	77.75	gold quality
transverse colon	UBERON:0001157	77.69	gold quality
pleura	UBERON:0000977	77.56	gold quality
endocervix	UBERON:0000458	76.70	gold quality
calcaneal tendon	UBERON:0003701	76.53	gold quality
seminal vesicle	UBERON:0000998	76.05	gold quality
tibial nerve	UBERON:0001323	76.04	gold quality
intestine	UBERON:0000160	75.99	gold quality
visceral pleura	UBERON:0002401	75.45	gold quality
vermiform appendix	UBERON:0001154	74.96	gold quality
mucosa of urinary bladder	UBERON:0001259	74.94	silver quality
caecum	UBERON:0001153	74.38	gold quality
trabecular bone tissue	UBERON:0002483	74.29	gold quality
esophagus mucosa	UBERON:0002469	73.98	gold quality
synovial joint	UBERON:0002217	73.96	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	73.76	gold quality
lower esophagus mucosa	UBERON:0035834	73.73	gold quality
body of stomach	UBERON:0001161	73.18	gold quality
stomach	UBERON:0000945	72.75	gold quality
ectocervix	UBERON:0012249	72.63	gold quality
skin of leg	UBERON:0001511	72.47	gold quality
right lung	UBERON:0002167	72.41	gold quality
trachea	UBERON:0003126	72.17	silver quality
tendon	UBERON:0000043	71.67	gold quality
upper lobe of left lung	UBERON:0008952	71.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 75 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Heart muscle	tissue	989.2	high
Skeletal muscle	tissue	170.5	medium
Tongue	tissue	154.2
Urinary bladder	tissue	36.8	not detected
Smooth muscle	tissue	36.5	not detected
Esophagus	tissue	36.1	not detected
Adipose tissue	tissue	29.9	not detected
Seminal vesicle	tissue	19.0	not detected
Colon	tissue	17.6	not detected
Rectum	tissue	16.0	not detected
Prostate	tissue	12.9	not detected
Endometrium 1	tissue	11.5	not detected
Caudate putamen	tissue	7.6
Cervix	tissue	6.2	not detected
Epididymis	tissue	6.2	not detected
Gallbladder	tissue	6.2	not detected
Fallopian tube	tissue	6.2	not detected
Appendix	tissue	6.0	not detected
Vagina	tissue	5.7	not detected
Superior colliculi	tissue	5.4
Lung	tissue	4.5	not detected
Spinal cord	tissue	4.3
Thalamus	tissue	4.1
Small intestine	tissue	4.0	not detected
Midbrain	tissue	3.9
Substantia nigra	tissue	3.3
Kidney	tissue	3.2	not detected
Duodenum	tissue	3.1	not detected
Ovary	tissue	3.0	not detected
Breast	tissue	2.9	not detected
Adrenal gland	tissue	2.9	not detected
Pons	tissue	2.4
Thyroid gland	tissue	2.4	not detected
Cerebral cortex	tissue	2.1	not detected
Putamen	tissue	2.1
Somatosensory cortex	tissue	2.1
Choroid plexus	tissue	1.9
Salivary gland	tissue	1.8	not detected
Frontal cortex	tissue	1.7
Occipital cortex	tissue	1.7
Medulla oblongata	tissue	1.6
Cerebellum	tissue	1.6	not detected
Hippocampal formation	tissue	1.6
Entorhinal cortex	tissue	1.6
Parathyroid gland	tissue	1.5
Placenta	tissue	1.5	not detected
Thymus	tissue	1.5
Temporal cortex	tissue	1.5
Testis	tissue	1.4	not detected
Retrosplenial and cingulate cortex	tissue	1.4
Pancreas	tissue	1.2	not detected
Tonsil	tissue	1.2	not detected
Prefrontal cortex	tissue	1.1
Stomach 1	tissue	1.1	not detected
Basal ganglia	tissue	1.1	not detected
Nucleus accumbens	tissue	1.1
Hippocampus	tissue	1.1	not detected
Locus coeruleus	tissue	1.0
Pituitary gland	tissue	0.9
Motor cortex	tissue	0.9

Brain sub-regions (HPA Brain Atlas): detected in 187; highest nTPM — Blood vessel (174.0), Ventral posteromedial thalamic nucleus (11.8), Pulvinar (11.4), Habenula (11.2), Nucleus rhomboideus (11.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CASQ2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 56 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-8064	99.45	66.92	875
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-4427	99.34	70.33	1854

Functional genomics

gnomAD constraint: pLI 1.18e-10, LOEUF 1.32, missense Z 0.306 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000261448 — one region, missense o/e 1.01. ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in Bedouin families from Israel (PMID:11704930)
• calsequestrin 2 mutations causes severe forms of catecholaminergic polymorphic ventricular tachycardia (PMID:12386154)
• missense mutation in the CASQ2 gene is associated with autosomal-recessive CPVT(catecholamine-induced polymorphic ventricular tachycardia). (PMID:12732448)
• A missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in Bedouin families from Israel. (PMID:12858557)
• Intracellular Ca2+ cycling in normal heart relies on intricate interplay of CASQ2 with proteins of RyR2 channel complex, and disruption of these interactions can lead to cardiac arrhythmia. (PMID:16601229)
• CASQ2 mutations identified in polymorphic ventricular tachycardia create distinct abnormalities that lead to abnormal intracellular calcium regulation, thus facilitating the development of tachyarrhythmias. (PMID:16908766)
• CSQ was a highly phosphorylated protein with a glycan structure predictive of ER-retained proteins. (PMID:17045261)
• A variant was identified in CASQ2. (PMID:17655857)
• Data show that all three CPVT-related missense mutations lead to significant reduction in Ca2+-binding capacity and scattering experiments confirm that the linear polymerization behavior of CSQ is linked directly to its high-capacity Ca2+ binding. (PMID:17881003)
• analysis of how human and rat CASQ2 ventricular tachycardia-related mutations R33Q and L167H alter calcium sensitivity (PMID:18399795)
• study concludes CASQ2 in the sarcoplasmic reticulum (SR )determines magnitude & duration of Ca release from each SR terminal; 2 CPVT-inducing CASQ2 mutations lead to increased diastolic SR Ca release events and exhibit a similar CPVT disease phenotype (PMID:18469084)
• A novel mutation of F189L in the CASQ2 gene was identified in families with catecholaminergic polymorphic ventricular tachycardia. (PMID:18543230)
• REVIEW of Casq2 mutations that cause catecholaminergic polymorphic ventricular tachycardia and their effects on Casq2 function and Ca handling (PMID:18669926)
• Facilitated maturation of Ca2+ handling properties of human embryonic stem cell-derived cardiomyocytes by calsequestrin expression. (PMID:19357236)
• Data suggest that calsequestrin (CSQ)2 facilitates Ca(2+) release through RyR2 during systole, while CSQ1 curtails RyR1 opening to maintain Ca(2+) and allow repeated release/ graded activation with increased stimulation frequency. (PMID:19376574)
• Cardiac and fatal or near-fatal events were not rare in both catecholaminergic polymorphic ventricular tachycardia RYR2 and a CASQ2 mutation probands and affected family members during the long-term follow-up (PMID:19398665)
• up-regulation of casq2 gene in the thyroid of patients with Graves’ Hyperthyroidism may lead to the production of autoantibodies and sensitized T-lymphocytes, which cross-react with calsequestrin of patients who develop ophthalmopathy. (PMID:20039900)
• The human CASQ2 mutation K206N is associated with hyperglycosylation and altered cellular calcium handling. (PMID:20302875)
• A regulatory role of CASQ2 on cytosolic Ca(2+) and hERG channels which may contribute to the etiology of CPVT. (PMID:21063088)
• Catecholaminergic polymorphic ventricular tachycardia (CPTV) mutations modify CASQ2 behaviour, including folding, aggregation/polymerization and selectivity towards Ca2+. (PMID:21265816)
• Studies identified two phosphorylation sites, Ser(385) and Ser(393 in hCASQ2 by mass-spectroscopy. (PMID:21416293)
• Molecular analysis of the CASQ2 gene in 43 probands with Catecholaminergic polymorphic ventricular tachycardia were performed and eight mutations in five patients, were identified. (PMID:21618644)
• Common variations in or near CASQ2, GPD1L, and NOS1AP are associated with increased risk of sudden cardiac death in patients with coronary artery disease (PMID:21685173)
• Two causative genes of CPVT have been identified: RYR2, encoding the cardiac ryanodine receptor (RyR2) Ca(2+) release channel, and CASQ2, encoding cardiac calsequestrin. Their mutation have been found in 60% of patients with CPVT. (PMID:21872879)
• Aspartate to histidine casq2 mutation causes arrhythmia in cardiomyocytes generated from catecholaminergic polymorphic ventricular tachycardia patients. (PMID:22050625)
• Ca(2+) and JNT-dependent disassembly of the CSQ2 polymer (PMID:22123818)
• A review of the physiology of Casq2 in cardiac Ca2+ handling and discuss pathophysiological mechanisms that lead to catecholaminergic polymorphic ventricular tachycardia caused by CASQ2 mutations. (PMID:22421959)
• patients with CASQ2-associated CPVT should be recommended to receive ICDs to prevent sudden death when medical therapy is not effective. (PMID:22481011)
• In a consanguineous family, a novel homozygous CASQ2 mutation (p.L77P) was identified in a child with CPVT who required implantation of a cardioverter defibrillator due to episodes of syncope while on medical therapy (PMID:22650415)
• Genetic background of catecholaminergic polymorphic ventricular tachycardia in Japan. (PMID:23595086)
• 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)
• We observed association between a CASQ2 polymorphism and SCA due to VA in patients with CAD adjusting for CHF and independent associations between CASQ2 SNPs and CHF adjusting for SCA. (PMID:24444446)
• Mutations in the MYBPC3 and CASQ2 genes and six combinations between loci in the MYBPC3, MYH7 and CASQ2 genes were responsible for cardiomyopathy risk in a studied cohort. (PMID:25892673)
• induced Pluripotent Stem Cell-derived cardiomyocytes are useful for investigating the similarities/differences in the pathophysiological consequences of RyR2 versus CASQ2 mutations underlying Catecholaminergic polymorphic ventricular tachycardia. (PMID:26153920)
• We show for the first time a heterozygous CASQ2 variant causing autosomal dominant CPVT in a large family with a severe phenotype. (PMID:27157848)
• a direct interaction exists between RyR2 and CSQ2, is reported. (PMID:27609834)
• CASQ2 variants are associated with catecholaminergic polymorphic ventricular tachycardia. (PMID:31482657)
• Catecholaminergic Polymorphic Ventricular Tachycardia. (PMID:31934898)
• Association of T66A polymorphism in CASQ2 with PR interval in a Chinese population.", trans “Assoziation des T66A-Polymorphismus im CASQ2-Gen mit dem PR-Intervall in einer chinesischen Population. (PMID:32291483)
• An International Multicenter Evaluation of Inheritance Patterns, Arrhythmic Risks, and Underlying Mechanisms of CASQ2-Catecholaminergic Polymorphic Ventricular Tachycardia. (PMID:32693635)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	casq2	ENSDARG00000008982
mus_musculus	Casq2	ENSMUSG00000027861
rattus_norvegicus	Casq2	ENSRNOG00000016243
caenorhabditis_elegans		WBGENE00000822

Paralogs (1): CASQ1 (ENSG00000143318)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1309469) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 24 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal myocardial fiber physiology	4
abnormal myocardial fiber morphology	2
cardiac hypertrophy	2
abnormal sinus arrhythmia	2
decreased heart rate	2
ventricular tachycardia	2
ventricular premature beat	2
decreased heart left ventricle muscle contractility	2
abnormal cardiovascular system physiology	1
edema	1
heart left ventricle hypertrophy	1
increased heart weight	1
thick ventricular wall	1
decreased heart rate variability	1
abnormal cardiac muscle relaxation	1
abnormal sarcoplasmic reticulum morphology	1
increased response of heart to induced stress	1
increased myocardial fiber size	1
decreased cardiac muscle contractility	1
cardiovascular system phenotype	1
increased heart atrium size	1
preweaning lethality, complete penetrance	1
polymorphic ventricular tachycardia	1
bidirectional ventricular tachycardia	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RAN9	98.9%	Diamond
Oryctolagus cuniculus	P31235	95.7%	Diamond
Canis lupus familiaris	P12637	95.2%	Diamond
Sus scrofa	O18934	95.0%	Diamond
Gallus gallus	P19204	81.8%	Diamond
Pelophylax lessonae	P31231	80.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
NHLH2	protein-coding	4808
VANGL1	protein-coding	81839
LINC01649	ncRNA	101928995

Protein

Protein identifiers

Calsequestrin-2 — O14958 (reviewed: O14958)

Alternative names: Calsequestrin, cardiac muscle isoform

All UniProt accessions (9): A0AA34QVH1, A0AAQ5BGQ8, A0AAQ5BGR1, A0AAQ5BGR3, A0AAQ5BGR5, A0AAQ5BGS1, A0AAQ5BGT6, A0ABB0MVM1, O14958

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, especially at the interface between subunits. Can bind around 60 Ca(2+) ions. Regulates the release of lumenal Ca(2+) via the calcium release channel RYR2; this plays an important role in triggering muscle contraction. Plays a role in excitation-contraction coupling in the heart and in regulating the rate of heart beats.

Subunit / interactions. Monomer, homodimer and homooligomer. Mostly monomeric in the absence of calcium. Forms higher oligomers in a calcium-dependent manner. Dimers associate to form tetramers, that then form linear homomer chains. Interacts with ASPH and TRDN.

Subcellular location. Sarcoplasmic reticulum lumen.

Post-translational modifications. Phosphorylation in the C-terminus, probably by CK2, moderately increases calcium buffering capacity. N-glycosylated.

Disease relevance. Ventricular tachycardia, catecholaminergic polymorphic, 2 (CPVT2) [MIM:611938] An arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. Patients present with recurrent syncope, seizures, or sudden death after physical activity or emotional stress. CPVT2 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the calsequestrin family.

Isoforms (2)

UniProt ID	Names	Canonical?
O14958-1	1	yes
O14958-2	2

RefSeq proteins (1): NP_001223* (*=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 (54 total): strand 15, helix 14, sequence variant 8, turn 6, modified residue 3, sequence conflict 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures by resolution:

PDB	Title	Method	Resolution (Å)
6OWV	Crystal structure of a Human Cardiac Calsequestrin Filament	X-RAY DIFFRACTION	1.88
7F05	Crystal structure of human cardiac calsequestrin bound with calcium	X-RAY DIFFRACTION	2.3
2VAF	Crystal structure of Human Cardiac Calsequestrin	X-RAY DIFFRACTION	3.8
6OWW	Crystal structure of a Human Cardiac Calsequestrin Filament Complexed with Ytterbium	X-RAY DIFFRACTION	3.84

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14958-F1	90.63	0.84

Human Protein Atlas

Protein class: Transporters, Accessory Factors Involved in Transport, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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 (3)

Type	Positions
Phosphotyrosine	282
Phosphoserine	385, 393

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	335

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 6; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

6 pathways:

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

MSigDB gene sets: 290 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CIRCULATORY_SYSTEM_PROCESS, LFA1_Q6, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, TGACCTY_ERR1_Q2, MEF2_02, MODULE_329, AAAYRNCTG_UNKNOWN, GNF2_MYL3, GOBP_REGULATION_OF_CARDIAC_MUSCLE_CONTRACTION_BY_REGULATION_OF_THE_RELEASE_OF_SEQUESTERED_CALCIUM_ION, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING

GO Biological Process (16): regulation of heart rate (GO:0002027), detection of calcium ion (GO:0005513), intracellular calcium ion homeostasis (GO:0006874), striated muscle contraction (GO:0006941), regulation of cell communication by electrical coupling (GO:0010649), regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum (GO:0010880), regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion (GO:0010881), negative regulation of potassium ion transport (GO:0043267), protein polymerization (GO:0051258), cardiac muscle contraction (GO:0060048), regulation of membrane repolarization (GO:0060306), cellular response to caffeine (GO:0071313), Purkinje myocyte to ventricular cardiac muscle cell signaling (GO:0086029), regulation of membrane repolarization during ventricular cardiac muscle cell action potential (GO:1905024), sarcomere organization (GO:0045214), regulation of release of sequestered calcium ion into cytosol (GO:0051279)

GO Molecular Function (5): calcium ion binding (GO:0005509), calcium-dependent protein binding (GO:0048306), calcium ion sequestering activity (GO:0140314), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): cytoplasm (GO:0005737), junctional sarcoplasmic reticulum membrane (GO:0014701), sarcoplasmic reticulum (GO:0016529), Z disc (GO:0030018), sarcoplasmic reticulum membrane (GO:0033017), sarcoplasmic reticulum lumen (GO:0033018), calcium channel complex (GO:0034704), junctional membrane complex (GO:0030314)

Reactome top-level categories

4 top-level categories:

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

GO top-level categories

52 GO namespaces:

Category	Terms
calcium ion binding	2
cellular anatomical structure	2
sarcoplasm	2
sarcoplasmic reticulum	2
regulation of heart contraction	1
regulation of biological quality	1
detection of chemical stimulus	1
response to calcium ion	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
muscle contraction	1
cell communication by electrical coupling	1
regulation of cell communication	1
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of release of sequestered calcium ion into cytosol	1
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of cardiac muscle contraction by calcium ion signaling	1
potassium ion transport	1
regulation of potassium ion transport	1
negative regulation of monoatomic ion transport	1
protein-containing complex assembly	1
striated muscle contraction	1
heart contraction	1
regulation of membrane potential	1
regulation of biological process	1
membrane repolarization	1
response to caffeine	1
cellular response to alkaloid	1
cellular response to purine-containing compound	1
cell-cell signaling	1
Purkinje myocyte to ventricular cardiac muscle cell communication	1
regulation of ventricular cardiac muscle cell membrane repolarization	1
membrane repolarization during ventricular cardiac muscle cell action potential	1
regulation of membrane repolarization during cardiac muscle cell action potential	1
myofibril assembly	1
actomyosin structure organization	1
release of sequestered calcium ion into cytosol	1
regulation of calcium ion transmembrane transport	1
metal ion binding	1
protein binding	1
metal ion sequestering activity	1
binding	1
cation binding	1
intracellular anatomical structure	1
sarcoplasmic reticulum membrane	1
endoplasmic reticulum	1
I band	1
endoplasmic reticulum membrane	1
bounding membrane of organelle	1
endoplasmic reticulum lumen	1
cation channel complex	1
protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 29 annotations. The rest are phylogenetic / computational / electronic (IEA).

11 experimentally-supported GO terms:

GO term	NS	Evidence
cardiac muscle contraction	BP	mutant phenotype
cellular response to caffeine	BP	mutant phenotype
intracellular calcium ion homeostasis	BP	mutant phenotype
protein polymerization	BP	direct assay
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	BP	direct assay
regulation of cell communication by electrical coupling	BP	mutant phenotype
regulation of heart rate	BP	mutant phenotype
cytoplasm	CC	direct assay
calcium ion binding	MF	direct assay
calcium ion sequestering activity	MF	direct assay
calcium-dependent protein binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,368 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CASQ2	RYR2	Q92736	949
CASQ2	TRDN	Q13061	936
CASQ2	ASPH	Q12797	874
CASQ2	FKBP1B	P68106	841
CASQ2	SCN5A	Q14524	704
CASQ2	KCNJ2	P48049	701
CASQ2	TECRL	Q5HYJ1	676
CASQ2	NPR1	P16066	660
CASQ2	ATP2A2	P16614	651
CASQ2	KCNH2	Q12809	648
CASQ2	TNNT2	P45379	634
CASQ2	CACNA1C	Q13936	626
CASQ2	JPH2	Q9BR39	620
CASQ2	MYBPC3	Q14896	619
CASQ2	CALR	P27797	618

IntAct

Human interaction partners of CASQ2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

16 partners by confidence:

Partner	Interaction type	MIscore	Records
BYSL	physical association	0.560	3
PES1	association	0.530	1
DNAJC3	physical association	0.400	1
ERI2	physical association	0.400	1
H1-1	physical association	0.400	1
H1-2	physical association	0.400	1
H1-5	physical association	0.400	1
H2BC21	physical association	0.400	1
H2BC9	physical association	0.400	1
H3-4	physical association	0.400	1
MYH9	physical association	0.400	1
PLEC	physical association	0.400	1
RPL10A	physical association	0.400	1
CFTR	physical association	0.370	1
KCNN4	association	0.350	1
TSNARE1	association	0.350	1

BioGRID (134 interactions; top human partners by supporting records): ACTA2 (Affinity Capture-MS; 3 records), ASB1 (Affinity Capture-MS; 3 records), BOP1 (Affinity Capture-MS; 3 records), CCDC8 (Affinity Capture-MS; 3 records), CUL7 (Affinity Capture-MS; 3 records), DAXX (Affinity Capture-MS; 3 records), DDX51 (Affinity Capture-MS; 3 records), EPB41L4B (Affinity Capture-MS; 3 records), EPB41L5 (Affinity Capture-MS; 3 records), FBXW8 (Affinity Capture-MS; 3 records), GLTSCR2 (Affinity Capture-MS; 3 records), GTF3C2 (Affinity Capture-MS; 3 records), GTF3C3 (Affinity Capture-MS; 3 records), KLHL11 (Affinity Capture-MS; 3 records), MARK3 (Affinity Capture-MS; 3 records)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
CSNK2A1	unknown	CASQ2	phosphorylation
CSNK2A2	unknown	CASQ2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 16 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
nucleosome assembly	6	56.2×	8e-08

Disease & clinical

Genetic variants

Variant evidence for CASQ2: 902 ClinVar records (61 pathogenic / likely pathogenic); 31 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	34
Likely pathogenic	27
Uncertain significance	348
Likely benign	349
Benign	51

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 61 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
17611	NM_001232.4(CASQ2):c.339_354del (p.Ser113fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
190758	NM_001232.4(CASQ2):c.1017dup (p.Asp340Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1784131	NM_001232.4(CASQ2):c.199C>T (p.Gln67Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2565185	NM_001232.4(CASQ2):c.1028G>A (p.Trp343Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3236407	NM_001232.4(CASQ2):c.320-2A>G	Pathogenic	criteria provided, multiple submitters, no conflicts	2
228247	NM_001232.4(CASQ2):c.940-1G>T	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
408869	NM_001232.4(CASQ2):c.235-2A>G	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
2089290	NM_001232.4(CASQ2):c.319+2T>G	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2997913	NM_001232.4(CASQ2):c.420+1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3263466	NM_001232.4(CASQ2):c.533-2A>G	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3575248	NM_001232.4(CASQ2):c.738-1G>T	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3575384	NM_001232.4(CASQ2):c.606+2T>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
41042	NM_001232.4(CASQ2):c.62del (p.Glu21fs)	Pathogenic	criteria provided, single submitter	2
190754	NM_001232.4(CASQ2):c.204del (p.Lys68fs)	Pathogenic	criteria provided, single submitter	1
651334	NM_001232.4(CASQ2):c.856G>T (p.Glu286Ter)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CASQ2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 40 predictions of 597):

Position(s)	Effect	Δscore	Sites
1:115701427–115701428	acceptor_loss	1.0000	5
1:115701431–115701432	acceptor_gain	1.0000	2
1:115702996–115702997	acceptor_loss	1.0000	4
1:115703000	acceptor_gain	1.0000
1:115705190–115705191	donor_loss	1.0000	4
1:115705293–115705294	acceptor_loss	1.0000	4
1:115726990–115726991	donor_loss	1.0000	4
1:115732899–115732900	donor_loss	1.0000	5
1:115740726–115740727	donor_loss	1.0000	5
1:115740829–115740830	acceptor_loss	1.0000	6

AlphaMissense

824 missense substitutions predicted likely pathogenic (of 2,713 scored), across 215 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F273	8	0.963	0.995
F322	8	0.937	0.990
F171	8	0.927	0.984
D29	8	0.908	0.971
F284	8	0.906	0.989
F311	8	0.898	0.983
D338	8	0.838	0.926
D307	8	0.825	0.956
D278	8	0.798	0.884
D263	8	0.795	0.916
W343	7	0.985	0.998
W361	7	0.984	0.996
W261	7	0.977	0.997
W318	7	0.976	0.997
F125	7	0.968	0.991
F137	7	0.933	0.989
F195	7	0.931	0.990
F258	7	0.930	0.980
F182	7	0.926	0.978
F220	7	0.925	0.964

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Head and Neck Squamous Cell Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (validation)	favorable	3.14e-07
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	3.87e-06
Head and Neck Squamous Cell Carcinoma (TCGA)	unfavorable	0.000468

Disease associations

OMIM: gene MIM:114251 | disease phenotypes: MIM:611938, MIM:600996, MIM:604772, MIM:194200

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
catecholaminergic polymorphic ventricular tachycardia 2	Definitive	Autosomal recessive	5
catecholaminergic polymorphic ventricular tachycardia	Definitive	Autosomal recessive	2
familial hypertrophic cardiomyopathy	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

3 validity classifications:

Disease	Classification	Inheritance
hypertrophic cardiomyopathy	Disputed	AD
catecholaminergic polymorphic ventricular tachycardia	Definitive	AR
catecholaminergic polymorphic ventricular tachycardia	Moderate	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (4 panels, 4 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

4 panels:

Panel	Rating
Cardiac arrhythmias	green
Catecholaminergic polymorphic VT	green
Sudden unexplained death or survivors of a cardiac event	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (6): catecholaminergic polymorphic ventricular tachycardia 2 (MONDO:0012762), catecholaminergic polymorphic ventricular tachycardia 1 (MONDO:0011484), catecholaminergic polymorphic ventricular tachycardia (MONDO:0017990), long QT syndrome (MONDO:0002442), Wolff-Parkinson-White syndrome (MONDO:0008685), familial hypertrophic cardiomyopathy (MONDO:0024573)

Orphanet (2): Catecholaminergic polymorphic ventricular tachycardia (Orphanet:3286), NON RARE IN EUROPE: Wolff-Parkinson-White syndrome (Orphanet:907)

HPO phenotypes

21 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0001250	Seizure
HP:0001279	Syncope
HP:0001644	Dilated cardiomyopathy
HP:0001645	Sudden cardiac death
HP:0001662	Bradycardia
HP:0001678	Atrioventricular block
HP:0001699	Sudden death
HP:0003621	Juvenile onset
HP:0004756	Ventricular tachycardia
HP:0004757	Paroxysmal atrial fibrillation
HP:0004758	Effort-induced polymorphic ventricular tachycardia
HP:0006673	Reduced systolic function
HP:0011462	Young adult onset
HP:0011463	Childhood onset
HP:0011704	Sick sinus syndrome
HP:0025478	Atrial standstill
HP:0031677	Polymorphic ventricular tachycardia
HP:0034039	Ventricular couplet
HP:0034040	Bidirectional ventricular tachycardia

GWAS associations

showing 30 of 31 associations:

Study	Trait	p-value
GCST010796_1068	Electrocardiogram morphology (amplitude at temporal datapoints)	6e-27
GCST010796_1061	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-26
GCST010796_1062	Electrocardiogram morphology (amplitude at temporal datapoints)	6e-26
GCST010796_1059	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-25
GCST010796_1060	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-25
GCST010796_1063	Electrocardiogram morphology (amplitude at temporal datapoints)	6e-25
GCST010796_1058	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-24
GCST010796_1064	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-23
GCST010796_1057	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-22
GCST010796_1065	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-20
GCST010796_1056	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-20
GCST010796_1055	Electrocardiogram morphology (amplitude at temporal datapoints)	5e-19
GCST007104_2	QRS duration	2e-18
GCST010796_1054	Electrocardiogram morphology (amplitude at temporal datapoints)	5e-18
GCST010796_1053	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-16
GCST006061_126	Atrial fibrillation	5e-16
GCST010796_1066	Electrocardiogram morphology (amplitude at temporal datapoints)	5e-16
GCST010796_1052	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-15
GCST006061_127	Atrial fibrillation	3e-15
GCST006414_13	Atrial fibrillation	5e-13
GCST007269_167	Pulse pressure	2e-12
GCST010796_1067	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-12
GCST010796_1051	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-12
GCST007103_2	QRS duration	2e-11
GCST011216_5	Left ventricular global radial strain	2e-11
GCST010796_1050	Electrocardiogram morphology (amplitude at temporal datapoints)	8e-11
GCST010796_1049	Electrocardiogram morphology (amplitude at temporal datapoints)	7e-10
GCST003844_36	QRS duration	7e-9
GCST003598_19	QRS duration	8e-9
GCST003598_29	QRS duration	3e-8

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0005054	QRS complex
EFO:0005763	pulse pressure measurement
EFO:0004327	electrocardiography
EFO:0008205	left ventricular structural measurement

MeSH disease descriptors

4 disease descriptors:

Descriptor	Name	Tree numbers
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D014927	Wolff-Parkinson-White Syndrome	C14.280.067.780.977; C14.280.123.750.977; C16.131.240.400.980
C563409	Arrhythmogenic Right Ventricular Dysplasia, Familial, 2 *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	4
Doxorubicin	decreases expression	3
Nickel	decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
sodium arsenite	increases expression	1
CGP 52608	affects binding, increases reaction	1
2,7-dihydroxynaphthalene	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
incobotulinumtoxinA	decreases expression	1
Sunitinib	decreases expression	1
Amphotericin B	increases expression	1
Arsenic	affects methylation	1
Bleomycin	increases expression	1
Dexamethasone	affects expression	1
Estradiol	affects binding, increases expression	1
Etoposide	decreases expression	1
Triclosan	decreases expression	1
Cyclosporine	increases methylation	1

Cellosaurus cell lines

3 cell lines: 3 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C6P2	CIAUi003-A-1	Induced pluripotent stem cell	Female
CVCL_E4JF	UMGi158-B	Induced pluripotent stem cell	Female
CVCL_WM06	CIAUi003-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 314 trials:

NCT	Phase	Status	Title
NCT00348530	Phase 4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	Phase 4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	Phase 4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	Phase 4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	Phase 4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	Phase 4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	Phase 4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	Phase 4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	Phase 4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	Phase 4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	Phase 4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	Phase 4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	Phase 4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	Phase 4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	Phase 4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	Phase 4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	Phase 4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05371496	Phase 4	COMPLETED	Cardiac and Metabolic Effects of Semaglutide in Heart Failure With Preserved Ejection Fraction
NCT05718128	Phase 4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	Phase 4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00170183	Phase 3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
NCT00270387	Phase 3	COMPLETED	A Study of Short-Term Outcomes and Economic Impact For Patients With Worsening Congestive Heart Failure When Natrecor (Nesiritide) is Added to Standard-Care Therapy, Compared to Administration of Placebo With Standard-Care Therapy
NCT00321295	Phase 3	COMPLETED	Biventricular Pacing In Patients With Left Ventricular Dysfunction After Cardiovascular Surgery
NCT00483197	Phase 3	UNKNOWN	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Pivotal Trial
NCT00490321	Phase 3	UNKNOWN	VentrAssistTM LVAD for the Treatment of Advanced Heart Failure - Destination Therapy
NCT00626028	Phase 3	COMPLETED	Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing
NCT01013714	Phase 3	UNKNOWN	Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias
NCT01217827	Phase 3	COMPLETED	Implantable Cardioverter-Defibrillator Use in the VA System
NCT01648634	Phase 3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02924285	Phase 3	COMPLETED	Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease
NCT03860935	Phase 3	COMPLETED	Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy
NCT04166331	Phase 3	COMPLETED	Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion
NCT05175066	Phase 3	COMPLETED	Bisoprolol Administration to Prevent Anthracycline-induced Cardiotoxicity
NCT05237323	Phase 3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT06158698	Phase 3	RECRUITING	CMP-MYTHiC Trial and Registry - CardioMyoPathy With MYocarditis THerapy With Colchicine
NCT06563895	Phase 3	RECRUITING	Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
NCT06846086	Phase 3	RECRUITING	Cardioprotective Effects of Melatonin in Patients With Cardiomyopathy
NCT07116473	Phase 3	NOT_YET_RECRUITING	To Evaluate the Long-term Safety and Tolerability of Acoramidis in Participants With Newly Diagnosed ATTR-CM (ACT-EARLY OLE)
NCT06658899	Phase 2	RECRUITING	A Phase 2 Study of CRD-4730 in CPVT
NCT07263139	Phase 2	RECRUITING	Safety, Tolerability, and Exploratory Efficacy of AGP100 in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
NCT05122975	Phase 2	TERMINATED	Treatment of an Inherited Ventricular Arrhythmia
NCT06005428	Phase 2	TERMINATED	Effectiveness of CRD-4730 in Participants With Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
NCT00185250	Phase 2	COMPLETED	Betaferon/ Betaseron (Interferon Beta-1b) in Patients With Chronic Viral Cardiomyopathy
NCT00490347	Phase 2	COMPLETED	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Feasibility Trial
NCT00694161	Phase 2	COMPLETED	The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy
NCT01102140	Phase 2	TERMINATED	The Impact of Pomegranate Extract on Chronic Cardiomyopathy Complicated by Renal Insufficiency (ImPrOVE): a Pilot Study
NCT01442129	Phase 2	COMPLETED	The Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in Patients Undergoing LVAD Implantation
NCT01636570	Phase 2	COMPLETED	Vitamin D3 Supplementation for Heart Failure Patients
NCT01643330	Phase 2	COMPLETED	A Study of Genetically Targeted Enzyme Replacement Therapy for Advanced Heart Failure
NCT02016365	Phase 2	COMPLETED	Safety and Efficacy Study of Doxycycline/UrsoDeoxyCholicAcid on Disease Progression in ATTR Amyloidosis
NCT02362646	Phase 2	COMPLETED	Safety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients
NCT02485938	Phase 2	COMPLETED	HOPE-Duchenne (Halt cardiomyOPathy progrEssion in Duchenne)
NCT02681913	Phase 2	UNKNOWN	Adenosine as an Adjunct to Blood Cardioplegia
NCT04304560	Phase 2	UNKNOWN	Value of SGLT2 Inhibitor (Dapagliflozin) as an Added Therapy in Diabetic Patients With Heart Failure With Reduced Ejection Fraction; Randomized Controlled Clinical Trial
NCT06080074	Phase 2	RECRUITING	Multicenter Trial of ECMO in Children With Severe Cardiac Failure Using the Cardiohelp System
NCT07148089	Phase 1	RECRUITING	A Study of SGT-501 Gene Therapy in Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
NCT00696410	Phase 1	COMPLETED	The Impact of Zinc Supplementation on Left Ventricular Function in Nonischemic Cardiomyopathy
NCT02077010	Phase 1	COMPLETED	Nebulized Inhaled Milrinone in a Hospitalized Advanced Heart Failure Population
NCT02408432	Phase 1	COMPLETED	Bone Marrow Derived Mesenchymal Stem Cells in Improving Heart Function in Patients With Heart Failure Caused by Anthracyclines
NCT02646540	Phase 1	COMPLETED	AiDing Diuresis wIth Tolvaptan (ADD-IT)