CACNA1S

Summary

CACNA1S (calcium voltage-gated channel subunit alpha1 S, HGNC:1397) is a protein-coding gene on chromosome 1q32.1, encoding Voltage-dependent L-type calcium channel subunit alpha-1S (Q13698). Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle.

This gene encodes one of the five subunits of the slowly inactivating L-type voltage-dependent calcium channel in skeletal muscle cells. Mutations in this gene have been associated with hypokalemic periodic paralysis, thyrotoxic periodic paralysis and malignant hyperthermia susceptibility.

Source: NCBI Gene 779 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypokalemic periodic paralysis, type 1 (Strong, GenCC) — +4 more curated relationships
• GWAS associations: 29
• Clinical variants (ClinVar): 3,508 total — 73 pathogenic, 48 likely-pathogenic
• Phenotypes (HPO): 95
• Druggable target: yes — 48 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000069

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1397
Approved symbol	CACNA1S
Name	calcium voltage-gated channel subunit alpha1 S
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	Cav1.1, hypoPP
Ensembl gene	ENSG00000081248
Ensembl biotype	protein_coding
OMIM	114208
Entrez	779

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 nonsense_mediated_decay, 3 protein_coding, 1 retained_intron

ENST00000362061, ENST00000367338, ENST00000679417, ENST00000680051, ENST00000680059, ENST00000681078, ENST00000681190, ENST00000681874, ENST00000713699

RefSeq mRNA: 1 — MANE Select: NM_000069 NM_000069

CCDS: CCDS1407

Canonical transcript exons

ENST00000362061 — 44 exons

Exon	Start	End
ENSE00000522341	201050389	201050516
ENSE00000791228	201044328	201044456
ENSE00000914678	201043281	201043531
ENSE00000914688	201047115	201047239
ENSE00000914730	201050984	201051143
ENSE00001667889	201048582	201048684
ENSE00001724912	201049003	201049099
ENSE00001772983	201047525	201047626
ENSE00004020754	201052557	201052648
ENSE00004020755	201066229	201066316
ENSE00004020756	201112188	201112426
ENSE00004020757	201072755	201072824
ENSE00004020758	201084950	201085031
ENSE00004020759	201040231	201040374
ENSE00004020760	201059189	201059299
ENSE00004020761	201062462	201062514
ENSE00004020762	201070272	201070404
ENSE00004020763	201065838	201065945
ENSE00004020764	201110164	201110269
ENSE00004020765	201089258	201089463
ENSE00004020766	201085436	201085581
ENSE00004020767	201061944	201062090
ENSE00004020768	201091640	201091792
ENSE00004020769	201060658	201060816
ENSE00004020770	201054505	201054561
ENSE00004020771	201053459	201053587
ENSE00004020772	201053209	201053274
ENSE00004020773	201058408	201058491
ENSE00004020774	201061267	201061468
ENSE00004020775	201093882	201094021
ENSE00004020776	201040622	201040713
ENSE00004020777	201069472	201069601
ENSE00004020778	201073549	201073642
ENSE00004020779	201074506	201074620
ENSE00004020780	201039512	201040082
ENSE00004020781	201076920	201077127
ENSE00004020782	201083162	201083322
ENSE00004020783	201069137	201069196
ENSE00004020784	201066887	201066993
ENSE00004020785	201091972	201092114
ENSE00004020786	201041504	201041589
ENSE00004020787	201075495	201075615
ENSE00004020788	201087826	201087929
ENSE00004020789	201077879	201078104

Expression profiles

Bgee: expression breadth ubiquitous, 105 present calls, max score 98.18.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2435 / max 71.8424, expressed in 52 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16602	0.2190	44
16603	0.0244	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gluteal muscle	UBERON:0002000	98.18	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.13	gold quality
triceps brachii	UBERON:0001509	97.94	gold quality
vastus lateralis	UBERON:0001379	97.73	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.51	gold quality
quadriceps femoris	UBERON:0001377	97.37	gold quality
diaphragm	UBERON:0001103	97.33	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.30	gold quality
biceps brachii	UBERON:0001507	97.20	gold quality
skeletal muscle tissue	UBERON:0001134	96.92	gold quality
gastrocnemius	UBERON:0001388	96.07	gold quality
muscle organ	UBERON:0001630	95.09	gold quality
muscle of leg	UBERON:0001383	94.25	gold quality
deltoid	UBERON:0001476	94.18	gold quality
tibialis anterior	UBERON:0001385	93.72	silver quality
muscle tissue	UBERON:0002385	90.46	gold quality
body of tongue	UBERON:0011876	85.68	gold quality
pancreatic ductal cell	CL:0002079	83.95	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.37	gold quality
tongue	UBERON:0001723	79.08	gold quality
type B pancreatic cell	CL:0000169	74.38	gold quality
olfactory bulb	UBERON:0002264	74.28	gold quality
trabecular bone tissue	UBERON:0002483	72.91	gold quality
superior surface of tongue	UBERON:0007371	72.60	gold quality
tendon of biceps brachii	UBERON:0008188	72.23	gold quality
myocardium	UBERON:0002349	70.60	gold quality
cardiac muscle of right atrium	UBERON:0003379	68.16	gold quality
left ventricle myocardium	UBERON:0006566	67.93	gold quality
synovial joint	UBERON:0002217	67.91	gold quality
orbitofrontal cortex	UBERON:0004167	67.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.40

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, GATA2

miRNA regulators (miRDB)

18 targeting CACNA1S, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-6781-3P	97.44	66.85	970
HSA-MIR-3116	97.07	65.78	1324

Literature-anchored findings (GeneRIF, showing 40)

• polymorphisms in the CACNA1S gene is associated with Malignant Hyperthermia (PMID:12636044)
• a mutation of the CACNA1S gene may have a role in hypokalemic periodic paralysis (PMID:15716625)
• a novel Arg528Gly mutation in the CACNA1S gene that causes Hypokalemic periodic paralysis in a Chinese family (PMID:15726306)
• We propose that CACNA1S mutations may comprise a previously unrecognized genetic risk factor in a greater spectrum of motor unit disorders including amyotrophic lateral sclerosis. (PMID:17587224)
• A Polish three-generation family with hypokalemic periodic paralysis and a mutation in CACNA1S is investigated. (PMID:18229654)
• All mutations affected CACNA1S arginine residues, consistent with the gating pore cation leak hypothesis of hypokalemic periodic paralysis. Arginine mutations in S4 segments underlie 90% of hypokalemic periodic paralysis cases. (PMID:19118277)
• Ca(V)1.1 Delta 29 splice variant revealed the structural bases underlying the specific gating properties of skeletal muscle Ca(2+) channels, and suggests the existence of a distinct mode of excitation-contraction coupling in developing muscle (PMID:19134469)
• A novel method to detect autoantibodies to dihydropyridine receptor (DHPR), found increased DHPR antibody in myasthenia gravis patients compared to controls. (PMID:19187971)
• Results identify a new mutation in CACNA1S and expand the spectrum of CACNA1S mutations associated with HypoPP. (PMID:19779499)
• The study identified a single potentially pathogenic change in CACNA1S (p.Arg174Trp), and highlights that the haplotype structure across CACNA1S is diverse, with a high degree of variability (PMID:19825159)
• All individuals in the Italian family with malignant hyperthermia showed cosegregation of informative markers close to the voltage-dependent Ca2+ channel alpha-1S-subunit gene. Sequence analysis showed a c.4060A>T transversion. (PMID:20861472)
• Mutations in the affected genes cause Malignant Hyperthermia. (PMID:21248738)
• Expression of transgenic variants of dihydropyridine receptor (alpha1DHPR) subunit leads to replacement of native channels interacting with ryanodine receptor 1 (RyR1), demonstrating molecular remodelling in adult skeletal muscle fibers. (PMID:21262876)
• Three SNPs of CACNA1S gene exon 11 were found but could not be associated with thyrotoxic hypokalemic periodic paralysis in people of Han Nationality in Sichuan. (PMID:21774221)
• All familial periodic paralysis patients studied have mutations in either CACNA1S or SCN4A, but only 4 sporadic periodic paralysis patients have de novo mutations in CACNA1S (R1239H) and SCN4A (R669x2, R1135H). (PMID:21841462)
• Affected members of a 5-generation Chinese family with hypokalemic periodic paralysis patients had a novel His916Gln mutation in all male HypoPP patients of the family. Penetrance of the mutation was complete in male carriers, but not female carriers. (PMID:21845430)
• A novel mutation in the CACNA1S gene–p.Arg900Gly–is found in a patient with hypokalemic periodic paralysis; this mutation is subsequently found to affect some of the patient’s other family members. (PMID:21855088)
• Misregulated splicing and altered gating of Ca(V)1.1 calcium channel is associated with muscle weakness in myotonic dystrophy. (PMID:22140091)
• Data indicate that the presence of either one of these JP-45 variants decreased the sensitivity of the dihydropyridine receptor DHPR to activation. (PMID:22927026)
• Aberrant splicing of Cav 1.1 may alter intracellular Ca(2+) signalling in myotonic dystrophy 1 and 2 myotubes. The differing dysregulation of intracellular Ca(2+) handling in DM1 and DM2 may explain their distinct sarcolemmal hyperexcitabilities. (PMID:23888875)
• Exome sequencing revealed one rare cacna1s nonsynonymous variant in a family with malignant hyperthermia (PMID:24013571)
• The authors found one and three rare variants of unknown significance in CACNA1S in the Malignant Hyperthermia and Exertional Heat cohorts (PMID:25658027)
• Defects in the genes coding for the skeletal muscle ryanodine receptor and alpha 1 subunit of the dihydropyridine receptor (CACNA1S) have been identified as causative for malignant hyperthermia. (PMID:25735680)
• CACNA1S and SCN4A mutations are relatively rare in patients with hypokalemic periodic paralysis (PMID:26252573)
• whole-exome next-generation sequencing was used to identify a mutation in the CACNA1S gene, R900S, which is a rare mutation associated with hypokalemic periodic paralysis; study provides further evidence for the phenotypic variation and pharmacogenomics of hypokalemic periodic paralysis (PMID:26433613)
• These results provide new insights into the role of muscle-specific proteins on the structural arrangement of alpha1S intracellular loops and point to a new conformational effect of the beta1a subunit in supporting skeletal muscle excitation-contraction coupling. (PMID:27129199)
• he ryanodine receptor 1 (RyR1) is mainly expressed in the sarcoplasmic reticulum (SR) of skeletal muscle and is a calcium release channel which is coupled to the dihydropyridine receptor (CACNA1S) in the T-tubule of the sarcolemma. (PMID:27147545)
• review of the pharmacogenetics and pathophysiology of CACNA1S mutations in malignant hyperthermia susceptibility type 5 (MHS5); several mutations are known to be risk factors for increased susceptibility; at present, one or at most six CACNA1S mutations display significant linkage or association either to clinically diagnosed MH or to MHS (PMID:28011884)
• Study identified by exome sequencing both recessive and dominant CACNA1S mutations as a cause of a congenital myopathy characterized by peculiar morphological hallmarks in a cohort of 11 patients from 7 families. (PMID:28012042)
• Study used structure modeling and MD simulations to predict pathogenic omega-currents in CaV1.1 and CaV1.3 Ca(2+) channels bearing several S4 charge mutations: omega-currents conducted in resting state, but not during voltage-sensing domain activation. Mechanism responsible depends on the number of charges in S4, the position of the mutated S4 charge and countercharges, and the nature of the replacing amino acid. (PMID:28978442)
• V876E mutation generates a gating pore current that carries strong resting Na(+) inward currents in physiological conditions that are likely responsible for the severe hypokalemic periodic paralysis associated with this mutation. (PMID:29114033)
• Cav1.1 is specified for the excitation-contraction coupling of skeletal muscles, and has been a prototype in the structural investigations of Cav channels. This article summarized the recent advances in the structural elucidation of Cav1.1 and the mechanistic insights derived from the 3.6 A structure obtained using single-particle, electron cryomicroscopy. (PMID:29594856)
• Genetic variants within the RYR1 and CACNA1S genes are likely to be a major contributor to the susceptibility to statin-associated muscle symptoms. (PMID:30325262)
• Accumulating evidence supports its possible involvement in linking CaV1.1 and RyR1 in skeletal muscle EC coupling, but also indicates a second, much broader role of STAC proteins in the regulation of calcium/calmodulin-dependent feedback regulation of L-type calcium channels. (PMID:30543836)
• Bayesian statistics predicted CACNA1S variant p.Thr1009Lys and RYR1 variants p.Ser1728Phe and p.Leu4824Pro are likely pathogenic, and novel STAC3 variant p.Met187Thr has uncertain significance. Nearly a third of MHS subjects had only benign variants. Bayesian method provides new approach to predict MH pathogenicity of genetic variants (PMID:31559918)
• PharmGKB summary: very important pharmacogene information for CACNA1S. (PMID:31851124)
• Investigating the genetic susceptibility to exertional heat illness. (PMID:32054689)
• The expanding phenotype of hypokalemic periodic paralysis in a Japanese family with p.Val876Glu mutation in CACNA1S. (PMID:32104981)
• Mutation spectrum and health status in skeletal muscle channelopathies in Japan. (PMID:32660787)
• CACNA1S haploinsufficiency confers resistance to New World arenavirus infection. (PMID:32719120)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cacna1sa	ENSDARG00000029457
danio_rerio	cacna1sb	ENSDARG00000042552
mus_musculus	Cacna1s	ENSMUSG00000026407
rattus_norvegicus	Cacna1s	ENSRNOG00000046231

Paralogs (26): CACNA1G (ENSG00000006283), SCN4A (ENSG00000007314), CACNA1I (ENSG00000100346), CACNA1F (ENSG00000102001), NALCN (ENSG00000102452), SCN2A (ENSG00000136531), SCN7A (ENSG00000136546), CACNA1A (ENSG00000141837), SCN1A (ENSG00000144285), CACNA1B (ENSG00000148408), CACNA1C (ENSG00000151067), CATSPER3 (ENSG00000152705), SCN3A (ENSG00000153253), CACNA1D (ENSG00000157388), TPCN2 (ENSG00000162341), CATSPER2 (ENSG00000166762), SCN11A (ENSG00000168356), SCN9A (ENSG00000169432), CATSPER1 (ENSG00000175294), SCN5A (ENSG00000183873), SCN10A (ENSG00000185313), TPCN1 (ENSG00000186815), CATSPER4 (ENSG00000188782), CACNA1H (ENSG00000196557), SCN8A (ENSG00000196876), CACNA1E (ENSG00000198216)

Protein

Protein identifiers

Voltage-dependent L-type calcium channel subunit alpha-1S — Q13698 (reviewed: Q13698)

Alternative names: Calcium channel, L type, alpha-1 polypeptide, isoform 3, skeletal muscle, Voltage-gated calcium channel subunit alpha Cav1.1

All UniProt accessions (8): Q13698, A0A7P0T8M7, A0A7P0TB53, A0A7P0TBJ5, A0A7P0TBR2, A0A7P0Z433, A0AAQ5BGP9, B1ALM3

UniProt curated annotations — full annotation on UniProt →

Function. Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle via their interaction with RYR1, which triggers Ca(2+) release from the sarcoplasmic reticulum and ultimately results in muscle contraction. Long-lasting (L-type) calcium channels belong to the ‘high-voltage activated’ (HVA) group.

Subunit / interactions. Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or CACNB2, CACNG1 and CACNA2D1. The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains either CACNB1 or CACNB2. CACNA1S channel activity is modulated by the auxiliary subunits (CACNB1 or CACNB2, CACNG1 and CACNA2D1). Interacts with DYSF and JSRP1. Interacts with RYR1. Interacts with STAC, STAC2 and STAC3 (via their SH3 domains). Interacts with CALM.

Subcellular location. Cell membrane. Sarcolemma. T-tubule.

Tissue specificity. Skeletal muscle specific.

Post-translational modifications. The alpha-1S subunit is found in two isoforms in the skeletal muscle: a minor form of 212 kDa containing the complete amino acid sequence, and a major form of 190 kDa derived from the full-length form by post-translational proteolysis close to Phe-1690. Phosphorylated. Phosphorylation by PKA activates the calcium channel. Both the minor and major forms are phosphorylated in vitro by PKA. Phosphorylation at Ser-1575 is involved in beta-adrenergic-mediated regulation of the channel.

Disease relevance. Periodic paralysis hypokalemic 1 (HOKPP1) [MIM:170400] An autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels. The disease is caused by variants affecting the gene represented in this entry. Malignant hyperthermia 5 (MHS5) [MIM:601887] Autosomal dominant disorder that is potentially lethal in susceptible individuals on exposure to commonly used inhalational anesthetics and depolarizing muscle relaxants. Disease susceptibility is associated with variants affecting the gene represented in this entry. Thyrotoxic periodic paralysis 1 (TTPP1) [MIM:188580] A sporadic muscular disorder characterized by episodic weakness and hypokalemia during a thyrotoxic state. It is clinically similar to hereditary hypokalemic periodic paralysis, except for the fact that hyperthyroidism is an absolute requirement for disease manifestation. The disease presents with recurrent episodes of acute muscular weakness of the four extremities that vary in severity from paresis to complete paralysis. Attacks are triggered by ingestion of a high carbohydrate load or strenuous physical activity followed by a period of rest. Thyrotoxic periodic paralysis can occur in association with any cause of hyperthyroidism, but is most commonly associated with Graves disease. Disease susceptibility is associated with variants affecting the gene represented in this entry. Congenital myopathy 18 (CMYO18) [MIM:620246] A congenital myopathy of variable severity, ranging from severe fetal akinesia to milder forms of muscle weakness. Most affected individuals show delayed motor development with generalized hypotonia and progressive axial and limb muscle weakness beginning soon after birth or in infancy. Additional features may include swallowing difficulties, external ophthalmoplegia, ptosis, high-arched palate, and respiratory insufficiency. Muscle biopsy shows variable morphologic abnormalities, including alveolar changes in the intermyofibrillar network, fiber size variability, focal disorganization, internal nuclei, and dilated sarcoplasmic reticulum and T-tubules. CMYO18 inheritance is autosomal dominant or recessive. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Channel activity is blocked by dihydropyridines (DHP), phenylalkylamines, and by benzothiazepines.

Domain organisation. Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position. The loop between repeats II and III interacts with the ryanodine receptor, and is therefore important for calcium release from the endoplasmic reticulum necessary for muscle contraction.

Similarity. Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1S subfamily.

RefSeq proteins (1): NP_000060* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002077	VDCCAlpha1	Family
IPR005446	VDCC_L_a1su	Family
IPR005450	VDCC_L_a1ssu	Family
IPR005821	Ion_trans_dom	Domain
IPR014873	VDCC_a1su_IQ	Domain
IPR027359	Volt_channel_dom_sf	Homologous_superfamily
IPR031649	GPHH_dom	Domain
IPR050599	VDCC_alpha-1_subunit	Family

Pfam: PF00520, PF08763, PF16905

Catalyzed reactions (Rhea), 1 shown:

• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)

UniProt features (133 total): topological domain 29, transmembrane region 24, sequence variant 21, sequence conflict 16, region of interest 10, modified residue 5, intramembrane region 4, repeat 4, short sequence motif 4, disulfide bond 4, compositionally biased region 3, binding site 3, glycosylation site 3, helix 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6B27	X-RAY DIFFRACTION	1.73
2VAY	X-RAY DIFFRACTION	1.94

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13698-F1	72.36	0.23

Functional residue map

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

Ligand- & substrate-binding residues (3): 292; 614; 1014

Post-translational modifications (5): 393, 397, 687, 1575, 1617

Disulfide bonds (4): 226–254, 245–261, 957–968, 1338–1352

Glycosylation sites (3): 79, 257, 1141

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-419037	NCAM1 interactions
R-HSA-1266738	Developmental Biology
R-HSA-375165	NCAM signaling for neurite out-growth
R-HSA-422475	Axon guidance
R-HSA-9675108	Nervous system development

MSigDB gene sets: 359 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_SKELETAL_MUSCLE_ADAPTATION, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, REACTOME_NCAM_SIGNALING_FOR_NEURITE_OUT_GROWTH, CAGCTG_AP4_Q5, GOBP_MONOATOMIC_CATION_TRANSPORT, YOKOE_CANCER_TESTIS_ANTIGENS, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CONTRACTION, GOBP_RESPONSE_TO_ALKALOID, GOBP_CELL_JUNCTION_ORGANIZATION

GO Biological Process (21): skeletal system development (GO:0001501), extraocular skeletal muscle development (GO:0002074), calcium ion transport (GO:0006816), muscle contraction (GO:0006936), striated muscle contraction (GO:0006941), endoplasmic reticulum organization (GO:0007029), myoblast fusion (GO:0007520), neuromuscular junction development (GO:0007528), skeletal muscle adaptation (GO:0043501), positive regulation of muscle contraction (GO:0045933), skeletal muscle fiber development (GO:0048741), release of sequestered calcium ion into cytosol (GO:0051209), calcium ion transmembrane transport (GO:0070588), cellular response to caffeine (GO:0071313), calcium ion import across plasma membrane (GO:0098703), system process (GO:0003008), monoatomic ion transport (GO:0006811), skeletal muscle tissue development (GO:0007519), monoatomic ion transmembrane transport (GO:0034220), muscle cell development (GO:0055001), transmembrane transport (GO:0055085)

GO Molecular Function (9): voltage-gated calcium channel activity (GO:0005245), calmodulin binding (GO:0005516), high voltage-gated calcium channel activity (GO:0008331), small molecule binding (GO:0036094), metal ion binding (GO:0046872), molecular function activator activity (GO:0140677), monoatomic ion channel activity (GO:0005216), calcium channel activity (GO:0005262), protein binding (GO:0005515)

GO Cellular Component (9): cytoplasm (GO:0005737), plasma membrane (GO:0005886), voltage-gated calcium channel complex (GO:0005891), sarcoplasmic reticulum (GO:0016529), T-tubule (GO:0030315), I band (GO:0031674), L-type voltage-gated calcium channel complex (GO:1990454), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
NCAM signaling for neurite out-growth	1
Axon guidance	1
Nervous system development	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
skeletal muscle tissue development	2
skeletal muscle organ development	2
muscle contraction	2
calcium ion transmembrane import into cytosol	2
binding	2
system development	1
camera-type eye development	1
metal ion transport	1
muscle system process	1
organelle organization	1
endomembrane system organization	1
syncytium formation by cell-cell fusion	1
myotube differentiation	1
synapse organization	1
striated muscle adaptation	1
regulation of muscle contraction	1
positive regulation of multicellular organismal process	1
myotube cell development	1
intercellular transport	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
response to caffeine	1
cellular response to alkaloid	1
cellular response to purine-containing compound	1
calcium ion import	1
inorganic cation import across plasma membrane	1
calcium ion import into cytosol	1
multicellular organismal process	1
transport	1
striated muscle tissue development	1
monoatomic ion transport	1
transmembrane transport	1
muscle cell differentiation	1
cell development	1
calcium channel activity	1
voltage-gated monoatomic cation channel activity	1
protein binding	1
voltage-gated calcium channel activity	1
cation binding	1

Protein interactions and networks

STRING

1786 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CACNA1S	RYR1	P21817	986
CACNA1S	KCNJ18	B7U540	909
CACNA1S	CAV3	P56539	907
CACNA1S	STAC3	Q96MF2	898
CACNA1S	CACNA1F	O60840	883
CACNA1S	JSRP1	Q96MG2	881
CACNA1S	CACNB1	Q02641	858
CACNA1S	CACNA2D1	P54289	850
CACNA1S	CALM1	P02593	843
CACNA1S	CACNG1	Q06432	842
CACNA1S	CALML3	P27482	838
CACNA1S	CALML5	Q9NZT1	838
CACNA1S	CALML6	Q8TD86	832
CACNA1S	CALML4	Q96GE6	832
CACNA1S	CACNA1C	Q13936	825

IntAct

21 interactions, top by confidence:

A	B	Type	Score
TNKS2	CACNA1S	psi-mi:“MI:0915”(physical association)	0.590
CACNA1S	TNKS2	psi-mi:“MI:0407”(direct interaction)	0.590
CACNA1S	NHERF4	psi-mi:“MI:0915”(physical association)	0.560
NHERF4	CACNA1S	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	CACNA1S	psi-mi:“MI:0915”(physical association)	0.560
CACNA1S	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
CACNA1S	CCDC106	psi-mi:“MI:0915”(physical association)	0.560
REL	CACNA1S	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	LMNA	psi-mi:“MI:0914”(association)	0.560
TNKS	CACNA1S	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1S	PCNA	psi-mi:“MI:0915”(physical association)	0.370
CACNA1S	REL	psi-mi:“MI:0915”(physical association)	0.000
CACNA1S	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
CACNA1S	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
CACNA1S	CCDC106	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): PDZD3 (Two-hybrid), MEOX2 (Two-hybrid), REL (Two-hybrid), CCDC106 (Two-hybrid), CYSRT1 (Two-hybrid), SRI (Reconstituted Complex), CACNA1S (Affinity Capture-MS), CACNA1S (Protein-peptide), CACNA1S (Affinity Capture-MS), CACNA1S (Affinity Capture-MS), PPP2R2A (Co-fractionation)

ESM2 similar proteins: B1AWN6, C9D7C2, D0E0C2, O00555, O08562, O35505, O55017, O57483, O60840, O73700, O88420, O88457, P02719, P07293, P15381, P22002, P22316, P27732, P27884, P54282, P56698, P56699, P91645, P97445, Q00975, Q01668, Q01815, Q02294, Q02343, Q02485, Q02789, Q05152, Q07652, Q13698, Q13936, Q15858, Q15878, Q25452, Q28644, Q2XVR3

Diamond homologs: A2APX8, A2ASI5, B1AWN6, B1AYL1, D0E0C2, F1LQQ7, O08562, O42398, O46669, O73705, O73706, O73707, O88420, O88457, P02719, P04774, P04775, P07293, P08104, P0DMA5, P15389, P15390, P35498, P35499, P35500, P56699, Q01118, Q02485, Q02789, Q05973, Q07652, Q13698, Q14524, Q15858, Q20JQ7, Q28371, Q28644, Q2XVR3, Q2XVR4, Q2XVR5

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PRKACA	“up-regulates activity”	CACNA1S	phosphorylation
CAMK2A	“up-regulates activity”	CACNA1S	phosphorylation
CSNK2A1	“up-regulates activity”	CACNA1S	phosphorylation
CSNK2B	“up-regulates activity”	CACNA1S	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

3508 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	73
Likely pathogenic	48
Uncertain significance	1565
Likely benign	1211
Benign	129

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012548	NM_000069.3(CACNA1S):c.2691G>C (p.Arg897Ser)	Pathogenic
1069371	NM_000069.3(CACNA1S):c.436del (p.Gln146fs)	Pathogenic
1074196	NM_000069.3(CACNA1S):c.1274del (p.Cys425fs)	Pathogenic
1180741	NM_000069.3(CACNA1S):c.3724A>G (p.Arg1242Gly)	Pathogenic
1206372	NM_000069.3(CACNA1S):c.1246C>T (p.Gln416Ter)	Pathogenic
1356276	NM_000069.3(CACNA1S):c.78del (p.Arg26fs)	Pathogenic
1431806	NM_000069.3(CACNA1S):c.4173G>A (p.Trp1391Ter)	Pathogenic
1446481	NM_000069.3(CACNA1S):c.1087del (p.Leu363fs)	Pathogenic
1451963	NM_000069.3(CACNA1S):c.5229C>A (p.Cys1743Ter)	Pathogenic
1452817	NM_000069.3(CACNA1S):c.4834del (p.Leu1612fs)	Pathogenic
1453569	NM_000069.3(CACNA1S):c.2324_2330del (p.Glu775fs)	Pathogenic
1454476	NC_000001.10:g.(?201012389)(201013604_?)del	Pathogenic
1455433	NM_000069.3(CACNA1S):c.4210del (p.Ala1404fs)	Pathogenic
1459071	NM_000069.3(CACNA1S):c.85del (p.Arg29fs)	Pathogenic
1708506	NM_000069.3(CACNA1S):c.1252_1253del (p.Asn418fs)	Pathogenic
1723135	NM_000069.3(CACNA1S):c.2700G>C (p.Arg900Ser)	Pathogenic
17623	NM_000069.3(CACNA1S):c.3716G>A (p.Arg1239His)	Pathogenic
17624	NM_000069.3(CACNA1S):c.3715C>G (p.Arg1239Gly)	Pathogenic
1922123	NM_000069.3(CACNA1S):c.1366C>T (p.Gln456Ter)	Pathogenic
1990993	NM_000069.3(CACNA1S):c.4819C>T (p.Gln1607Ter)	Pathogenic
1993906	NM_000069.3(CACNA1S):c.794G>A (p.Trp265Ter)	Pathogenic
2008122	NC_000001.11:g.201044429_201044459del	Pathogenic
2012122	NM_000069.3(CACNA1S):c.3472_3473del (p.Thr1158fs)	Pathogenic
2038462	NM_000069.3(CACNA1S):c.3760C>T (p.Arg1254Ter)	Pathogenic
2061561	NM_000069.3(CACNA1S):c.4967del (p.Leu1656fs)	Pathogenic
21034	NM_000069.3(CACNA1S):c.1582C>G (p.Arg528Gly)	Pathogenic
2174972	NM_000069.3(CACNA1S):c.4172G>A (p.Trp1391Ter)	Pathogenic
2428663	NM_000069.3(CACNA1S):c.2224C>T (p.Pro742Ser)	Pathogenic
2443900	NM_000069.3(CACNA1S):c.1189_1190del (p.Ser397fs)	Pathogenic
2443901	NM_000069.3(CACNA1S):c.4453C>T (p.Gln1485Ter)	Pathogenic

SpliceAI

7196 predictions. Top by Δscore:

Variant	Effect	Δscore
1:201040079:GAGC:G	acceptor_gain	1.0000
1:201040081:GC:G	acceptor_gain	1.0000
1:201040082:CC:C	acceptor_gain	1.0000
1:201040083:C:CC	acceptor_gain	1.0000
1:201040084:T:A	acceptor_loss	1.0000
1:201041448:T:TA	donor_gain	1.0000
1:201041449:C:A	donor_gain	1.0000
1:201041506:AGGAC:A	donor_gain	1.0000
1:201043530:CT:C	acceptor_gain	1.0000
1:201044338:C:A	donor_gain	1.0000
1:201044341:T:TA	donor_gain	1.0000
1:201044453:CTGC:C	acceptor_gain	1.0000
1:201045313:CAGA:C	acceptor_gain	1.0000
1:201045316:A:AC	acceptor_gain	1.0000
1:201045316:A:C	acceptor_gain	1.0000
1:201045325:A:C	acceptor_gain	1.0000
1:201047110:CTTAC:C	donor_loss	1.0000
1:201047111:TTAC:T	donor_loss	1.0000
1:201047112:TACC:T	donor_loss	1.0000
1:201047235:ATCAT:A	acceptor_gain	1.0000
1:201047236:TCAT:T	acceptor_gain	1.0000
1:201047237:CAT:C	acceptor_gain	1.0000
1:201047237:CATC:C	acceptor_gain	1.0000
1:201047238:AT:A	acceptor_gain	1.0000
1:201047238:ATCT:A	acceptor_loss	1.0000
1:201047239:TCTG:T	acceptor_loss	1.0000
1:201047240:C:CC	acceptor_gain	1.0000
1:201047240:CT:C	acceptor_loss	1.0000
1:201047241:T:A	acceptor_loss	1.0000
1:201047521:CTACC:C	donor_loss	1.0000

AlphaMissense

12413 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:201050414:A:G	W1406R	1.000
1:201050414:A:T	W1406R	1.000
1:201058438:G:C	S1193R	1.000
1:201058438:G:T	S1193R	1.000
1:201058440:T:G	S1193R	1.000
1:201047576:A:G	W1498R	0.999
1:201047576:A:T	W1498R	0.999
1:201047599:A:G	L1490P	0.999
1:201048611:A:T	V1471D	0.999
1:201048614:A:G	L1470P	0.999
1:201049064:A:G	L1426P	0.999
1:201049067:A:G	L1425P	0.999
1:201050412:C:A	W1406C	0.999
1:201050412:C:G	W1406C	0.999
1:201050425:A:G	F1402S	0.999
1:201051008:G:C	S1363R	0.999
1:201051008:G:T	S1363R	0.999
1:201051010:T:G	S1363R	0.999
1:201053529:C:A	R1242M	0.999
1:201058442:C:T	G1192D	0.999
1:201058443:C:G	G1192R	0.999
1:201058460:T:A	D1186V	0.999
1:201059231:G:C	F1161L	0.999
1:201059231:G:T	F1161L	0.999
1:201059233:A:G	F1161L	0.999
1:201061951:A:G	W1016R	0.999
1:201061951:A:T	W1016R	0.999
1:201069523:G:C	S813R	0.999
1:201069523:G:T	S813R	0.999
1:201069525:T:G	S813R	0.999

dbSNP variants (sampled 300 via entrez): RS1000133942 (1:201098193 C>T), RS1000134288 (1:201082630 T>C), RS1000210854 (1:201084287 CA>C,CAA), RS1000259582 (1:201070803 C>T), RS1000259842 (1:201106641 T>C), RS1000271942 (1:201082345 G>A), RS1000285348 (1:201041157 G>A,C), RS1000327896 (1:201076650 A>G), RS1000345706 (1:201111600 C>G,T), RS1000441989 (1:201040786 G>A,C,T), RS1000470898 (1:201081467 C>T), RS1000497441 (1:201067104 C>T), RS1000578812 (1:201046531 G>C), RS1000581100 (1:201086705 C>T), RS1000614023 (1:201051346 G>T)

Disease associations

OMIM: gene MIM:114208 | disease phenotypes: MIM:188580, MIM:601887, MIM:170400, MIM:620246, MIM:145600, MIM:117000, MIM:160150, MIM:162500

GenCC curated gene-disease

Disease	Classification	Inheritance
hypokalemic periodic paralysis, type 1	Strong	Autosomal dominant
malignant hyperthermia, susceptibility to, 5	Strong	Autosomal dominant
congenital myopathy	Strong	Autosomal dominant
congenital myopathy 18	Strong	Autosomal dominant
hypokalemic periodic paralysis	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
malignant hyperthermia, susceptibility to, 5	Moderate	AD

Mondo (14): thyrotoxic periodic paralysis, susceptibility to, 1 (MONDO:0008570), malignant hyperthermia, susceptibility to, 5 (MONDO:0011163), hypokalemic periodic paralysis, type 1 (MONDO:0042979), congenital myopathy 18 (MONDO:0859514), long QT syndrome (MONDO:0002442), malignant hyperthermia, susceptibility to, 1 (MONDO:0007783), malignant hyperthermia of anesthesia (MONDO:0018493), hypokalemic periodic paralysis (MONDO:0008223), congenital myopathy (MONDO:0019952), centronuclear myopathy (MONDO:0018947), hereditary neuropathy with liability to pressure palsies (MONDO:0008087), malignant hyperthermia, susceptibility to (MONDO:0800188), intellectual disability (MONDO:0001071), muscular atrophy (MONDO:0004323)

Orphanet (7): Malignant hyperthermia of anesthesia (Orphanet:423), Hypokalemic periodic paralysis (Orphanet:681), Thyrotoxic periodic paralysis (Orphanet:79102), Congenital myopathy (Orphanet:97245), Centronuclear myopathy (Orphanet:595), Hereditary neuropathy with liability to pressure palsies (Orphanet:640), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

95 total (30 of 95 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000016	Urinary retention
HP:0000218	High palate
HP:0000597	Ophthalmoparesis
HP:0000602	Ophthalmoplegia
HP:0000836	Hyperthyroidism
HP:0000853	Goiter
HP:0000975	Hyperhidrosis
HP:0001252	Hypotonia
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001315	Reduced tendon reflexes
HP:0001324	Muscle weakness
HP:0001337	Tremor
HP:0001513	Obesity
HP:0001649	Tachycardia
HP:0001657	Prolonged QT interval
HP:0001663	Ventricular fibrillation
HP:0001722	High-output congestive heart failure
HP:0001824	Weight loss
HP:0001919	Acute kidney injury
HP:0001942	Metabolic acidosis
HP:0001945	Fever
HP:0001962	Palpitations
HP:0002019	Constipation
HP:0002047	Malignant hyperthermia
HP:0002153	Hyperkalemia
HP:0002203	Respiratory paralysis
HP:0002445	Tetraplegia

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST000624_9	Ulcerative colitis	2.000000e-07
GCST001221_4	Permanent tooth development	8.000000e-17
GCST003401_5	Glomerular filtration rate in non diabetics (creatinine)	7.000000e-11
GCST004131_38	Inflammatory bowel disease	1.000000e-21
GCST004132_68	Crohn’s disease	1.000000e-10
GCST004133_18	Ulcerative colitis	4.000000e-16
GCST004292_31	Glomerular filtration rate (creatinine)	2.000000e-08
GCST005389_1	Tooth agenesis	2.000000e-16
GCST007344_55	Estimated glomerular filtration rate	3.000000e-09
GCST007876_144	Estimated glomerular filtration rate	2.000000e-08
GCST008058_82	Estimated glomerular filtration rate	2.000000e-22
GCST008059_70	Estimated glomerular filtration rate	3.000000e-22
GCST008310_5	Cardiac Troponin-T levels	8.000000e-08
GCST008790_7	Urinary albumin-to-creatinine ratio	1.000000e-08
GCST008794_46	Urinary albumin-to-creatinine ratio	1.000000e-08
GCST010397_34	Gut microbiota (bacterial taxa, rank normal transformation method)	2.000000e-06
GCST010697_41	Cortical surface area (min-P)	2.000000e-21
GCST010698_48	Subcortical volume (min-P)	4.000000e-11
GCST010699_65	Brain morphology (min-P)	2.000000e-23
GCST010700_61	Cortical thickness (MOSTest)	2.000000e-09
GCST010701_90	Cortical surface area (MOSTest)	4.000000e-14
GCST010702_100	Subcortical volume (MOSTest)	2.000000e-08
GCST010703_156	Brain morphology (MOSTest)	3.000000e-09
GCST90000025_839	Appendicular lean mass	3.000000e-18
GCST90000026_29	Appendicular lean mass	9.000000e-06
GCST90000027_4	Appendicular lean mass	9.000000e-14
GCST90002388_639	Lymphocyte count	2.000000e-16
GCST90002389_94	Lymphocyte percentage of white cells	3.000000e-11
GCST90011899_9	Aspartate aminotransferase levels	1.000000e-10

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0005043	cardiac troponin T measurement
EFO:0007778	urinary albumin to creatinine ratio
EFO:0007874	gut microbiome measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0004980	appendicular lean mass
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D020514	Hypokalemic Periodic Paralysis	C05.651.701.450; C10.668.491.650.450; C16.320.565.618.711.550; C18.452.648.618.711.550
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D008305	Malignant Hyperthermia	C23.550.505.700; C23.550.767.600; C23.888.119.455.500
D009133	Muscular Atrophy	C10.597.613.612; C23.300.070.500; C23.888.592.608.612
C535694	Malignant hyperthermia susceptibility type 1 (supp.)
C535698	Malignant hyperthermia susceptibility type 5 (supp.)
C536965	Tomaculous neuropathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2095229 (PROTEIN FAMILY), CHEMBL2363032 (PROTEIN COMPLEX GROUP), CHEMBL3805 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

48 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 646,199 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1107	HALOFANTRINE	4	9,722
CHEMBL1108	DROPERIDOL	4	16,888
CHEMBL114	SAQUINAVIR	4	39,899
CHEMBL1175	DULOXETINE	4	28,527
CHEMBL12	DIAZEPAM	4	92,281
CHEMBL12713	SERTINDOLE	4	8,984
CHEMBL1294	QUINIDINE	4	71,943
CHEMBL141	LAMIVUDINE	4	12,250
CHEMBL1423	PIMOZIDE	4	17,310
CHEMBL16	PHENYTOIN	4	53,375
CHEMBL17157	TERFENADINE	4	25,393
CHEMBL1729	CISAPRIDE	4	14,365
CHEMBL1734	SOLIFENACIN	4	296
CHEMBL193	NIFEDIPINE	4	74,353
CHEMBL23	DILTIAZEM	4	54,676
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL296419	ASTEMIZOLE	4	21,577
CHEMBL363295	TERODILINE	4	5,064
CHEMBL42	CLOZAPINE	4
CHEMBL45816	MIBEFRADIL	4
CHEMBL473	DOFETILIDE	4
CHEMBL479	THIORIDAZINE	4
CHEMBL490	PAROXETINE	4
CHEMBL502	DONEPEZIL	4
CHEMBL533	IBUTILIDE	4
CHEMBL535	SUNITINIB	4
CHEMBL54	HALOPERIDOL	4
CHEMBL5416410	DASATINIB	4

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

PharmGKB clinical annotations

14 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1800559	Toxicity	1A	enflurane	Malignant Hyperthermia
rs1800559	Toxicity	1A	halothane	Malignant Hyperthermia
rs1800559	Toxicity	1A	sevoflurane	Malignant Hyperthermia
rs1800559	Toxicity	1A	isoflurane	Malignant Hyperthermia
rs1800559	Toxicity	1A	succinylcholine	Malignant Hyperthermia
rs1800559	Toxicity	1A	desflurane	Malignant Hyperthermia
rs1800559	Toxicity	1A	methoxyflurane
rs772226819	Toxicity	1A	succinylcholine	Malignant Hyperthermia
rs772226819	Toxicity	1A	halothane	Malignant Hyperthermia
rs772226819	Toxicity	1A	sevoflurane	Malignant Hyperthermia
rs772226819	Toxicity	1A	desflurane	Malignant Hyperthermia
rs772226819	Toxicity	1A	isoflurane	Malignant Hyperthermia
rs772226819	Toxicity	1A	methoxyflurane	Malignant Hyperthermia
rs772226819	Toxicity	1A	enflurane	Malignant Hyperthermia

PharmGKB variants

9 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1800559	CACNA1S	1A	100.50	7	desflurane;enflurane;methoxyflurane;sevoflurane;halothane;isoflurane;succinylcholine
rs772226819	CACNA1S	1A	100.25	7	desflurane;enflurane;halothane;isoflurane;methoxyflurane;succinylcholine;sevoflurane
rs1204964501	CACNA1S		0.00	0
rs768445692	CACNA1S		0.00	0
rs377474103	CACNA1S		0.00	0
rs1225367412	CACNA1S		0.00	0
rs529038948	CACNA1S		0.00	0
rs183195890	CACNA1S		0.00	0
rs80338782	CACNA1S		0.00	0

PharmGKB dosing guidelines

1 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
CPIC	desflurane;enflurane;halothane;isoflurane;methoxyflurane;sevoflurane;succinylcholine	Annotation of CPIC Guideline for desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane, succinylcholine and CACNA1S, RYR1		yes

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: vgic — Voltage-gated calcium channels (Ca_V)

Most potent curated ligand interactions (12 total), top 12:

Ligand	Action	Affinity	Parameter
3H-isradipine	Antagonist	9.7	pKd
3Hdevapamil	Antagonist	8.7	pKd
(+)-isradipine	Antagonist	8.2	pIC50
FPL64176	Activator	7.8	pEC50
(-)-(S)-BayK8644	Activator	7.76	pEC50
3H-cis-diltiazem	Antagonist	7.4	pKd
nifedipine	Antagonist	6.3	pIC50
nitrendipine	Antagonist	6.0	pIC50
nimodipine	Antagonist	6.0	pIC50
verapamil	Antagonist	5.0	pIC50
Cd2+	Antagonist	4.3	pIC50
diltiazem	Antagonist	4.2	pIC50

ChEMBL bioactivities

235 potent at pChembl≥5 of 286 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL286157
10.89	IC50	0.013	nM	CHEMBL317044
10.82	IC50	0.015	nM	CHEMBL441428
10.77	IC50	0.017	nM	CHEMBL286598
10.66	IC50	0.022	nM	CHEMBL37402
10.57	IC50	0.027	nM	CHEMBL103806
10.52	IC50	0.03	nM	CHEMBL37899
10.48	IC50	0.033	nM	CHEMBL204616
10.35	IC50	0.045	nM	CHEMBL35368
10.34	IC50	0.046	nM	CHEMBL1099207
10.30	IC50	0.05	nM	CHEMBL285868
9.85	IC50	0.14	nM	CHEMBL321999
9.82	IC50	0.15	nM	NITRENDIPINE
9.60	IC50	0.25	nM	CHEMBL105444
9.46	IC50	0.35	nM	NITRENDIPINE
9.41	IC50	0.39	nM	CHEMBL35123
9.00	IC50	1	nM	NITRENDIPINE
8.82	IC50	1.5	nM	CHEMBL329897
8.82	IC50	1.5	nM	CHEMBL3891844
8.82	IC50	1.5	nM	CHEMBL319033
8.77	IC50	1.7	nM	CHEMBL89260
8.72	IC50	1.9	nM	CHEMBL3890624
8.70	IC50	2	nM	CHEMBL2092901
8.64	IC50	2.3	nM	CHEMBL102498
8.62	IC50	2.4	nM	CHEMBL3973392
8.59	IC50	2.6	nM	CHEMBL89049
8.57	IC50	2.7	nM	CHEMBL84906
8.57	IC50	2.7	nM	CHEMBL3891844
8.55	IC50	2.8	nM	CHEMBL318521
8.52	IC50	3	nM	CHEMBL3919024
8.51	IC50	3.1	nM	CHEMBL86415
8.51	IC50	3.1	nM	CHEMBL3919898
8.44	IC50	3.6	nM	CHEMBL89904
8.40	IC50	4	nM	CHEMBL3392282
8.35	IC50	4.5	nM	CHEMBL3965812
8.28	IC50	5.2	nM	CHEMBL89175
8.27	Ki	5.4	nM	GALLOPAMIL
8.23	IC50	5.9	nM	CHEMBL3906126
8.22	IC50	6	nM	CHEMBL3890916
8.15	IC50	7	nM	CHEMBL3940577
8.14	IC50	7.2	nM	CHEMBL3969562
8.12	IC50	7.6	nM	CHEMBL3937280
8.12	IC50	7.6	nM	CHEMBL3965812
8.10	IC50	8	nM	CHEMBL3983323
8.05	IC50	9	nM	CHEMBL3942512
8.03	IC50	9.4	nM	CHEMBL3922498
8.01	IC50	9.7	nM	CHEMBL3897303
8.00	IC50	10	nM	NIFEDIPINE
7.96	IC50	11	nM	CHEMBL315125
7.96	IC50	11	nM	GALLOPAMIL

PubChem BioAssay actives

178 with measured affinity, of 839 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-O-methyl 5-O-(2-methylpropyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45613: Inhibition of [3H]nitrendipine binding to guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
5-O-[6-[5-ethoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carbonyl]oxyhexyl] 3-O-ethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
5-O-[10-[5-ethoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carbonyl]oxydecyl] 3-O-ethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
5-O-[8-[5-ethoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carbonyl]oxyoctyl] 3-O-ethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
3-O-ethyl 5-O-octyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
diethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
5-O-[2-[2,6-dimethyl-4-(3-nitrophenyl)-5-propan-2-yloxycarbonyl-1,4-dihydropyridine-3-carbonyl]oxyethyl] 3-O-ethyl 2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
5-O-[4-[5-ethoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carbonyl]oxybutyl] 3-O-ethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
3-O-methyl 5-O-(2-methylpropyl) 4-(3-cyanophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate	45613: Inhibition of [3H]nitrendipine binding to guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
3-O-methyl 5-O-(2-methylpropyl) 2,6-dimethyl-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3,5-dicarboxylate	45613: Inhibition of [3H]nitrendipine binding to guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
Nisoldipine	45613: Inhibition of [3H]nitrendipine binding to guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
5-O-[12-[5-ethoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carbonyl]oxydodecyl] 3-O-ethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	0.0001	uM
3-O-methyl 5-O-(2-methylpropyl) 2,6-dimethyl-4-[3-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3,5-dicarboxylate	45613: Inhibition of [3H]nitrendipine binding to guinea pig ileal longitudinal smooth muscle	ic50	0.0001	uM
5-O-ethyl 3-O-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	0.0001	uM
3-O-methyl 5-O-(2-methylpropyl) 2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate	45613: Inhibition of [3H]nitrendipine binding to guinea pig ileal longitudinal smooth muscle	ic50	0.0003	uM
5-O-[2-[5-ethoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carbonyl]oxyethyl] 3-O-ethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	0.0004	uM
diethyl 4-(2,3-dichlorophenyl)-6-methyl-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0015	uM
3-O-methyl 5-O-(2-methylpropyl) 4-(4-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate	45613: Inhibition of [3H]nitrendipine binding to guinea pig ileal longitudinal smooth muscle	ic50	0.0015	uM
3-O-ethyl 5-O-propan-2-yl 6-methyl-4-(3-nitrophenyl)-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0017	uM
3-O-ethyl 5-O-propan-2-yl (4R)-6-methyl-4-(3-nitrophenyl)-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	45769: In vitro vasorelaxant activity (calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0020	uM
3-O-methyl 5-O-(2-methylpropyl) 4-(3-methoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate	45613: Inhibition of [3H]nitrendipine binding to guinea pig ileal longitudinal smooth muscle	ic50	0.0023	uM
3-O-ethyl 5-O-propan-2-yl 6-methyl-4-(3-nitrophenyl)-2-oxo-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0026	uM
diethyl 4-(2-chloro-3-nitrophenyl)-6-methyl-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0027	uM
3-O-methyl 5-O-(2-methylpropyl) 4-(4-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate	45613: Inhibition of [3H]nitrendipine binding to guinea pig ileal longitudinal smooth muscle	ic50	0.0028	uM
diethyl 6-methyl-4-(2-nitrophenyl)-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0031	uM
5-O-ethyl 3-O-methyl 6-methyl-4-(3-nitrophenyl)-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0036	uM
diethyl 2-ethylsulfanyl-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45769: In vitro vasorelaxant activity (calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0040	uM
ethyl 3-(benzenesulfonyl)-6-methyl-4-(3-nitrophenyl)-2-sulfanylidene-1,4-dihydropyrimidine-5-carboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0052	uM
5-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]-2-propan-2-yl-2-(3,4,5-trimethoxyphenyl)pentanenitrile	751841: Binding affinity to L-Ca2+ channel verapamil site (unknown origin) by radioligand displacement assay	ki	0.0054	uM
Nifedipine	1207754: Inhibition of Cav1.2 current measured using QPatch automatic path clamp system in CHO cells expressing Cav1.2, beta-2 and alpha-2/delta-1 subunits	ic50	0.0100	uM
ethyl 3-(4-methoxybenzoyl)-6-methyl-4-(3-nitrophenyl)-2-sulfanylidene-1,4-dihydropyrimidine-5-carboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0110	uM
5-O-ethyl 3-O-propan-2-yl 6-methyl-4-(3-nitrophenyl)-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0140	uM
diethyl 6-methyl-4-(3-nitrophenyl)-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	45769: In vitro vasorelaxant activity (calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0170	uM
diethyl 4-(2-chlorophenyl)-6-methyl-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0170	uM
diethyl 2,6-dimethyl-4-(5-methyl-3-phenyl-1,2-oxazol-4-yl)-1,4-dihydropyridine-3,5-dicarboxylate	45622: Inhibition of [3H]PN-200110 binding to Calcium channel in guinea pig ileum membrane	ki	0.0217	uM
diethyl 6-methyl-2-sulfanylidene-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyrimidine-3,5-dicarboxylate	45769: In vitro vasorelaxant activity (calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0260	uM
diethyl 2-ethoxy-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45769: In vitro vasorelaxant activity (calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0260	uM
diethyl 4-deuterio-4-(3,5-dimethyl-1,2-oxazol-4-yl)-2,6-dimethyl-1H-pyridine-3,5-dicarboxylate	45623: Inhibition of [3H]PN-200110 binding to Calcium channel in guinea pig ileum membrane.	ki	0.0299	uM
diethyl 4-(3,5-dimethyl-1,2-oxazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate	45622: Inhibition of [3H]PN-200110 binding to Calcium channel in guinea pig ileum membrane	ki	0.0328	uM
diethyl 4-[3-(4-bromophenyl)-5-methyl-1,2-oxazol-4-yl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate	1466481: Displacement of [3H]PN-200110 from voltage-dependent L-type calcium channel (unknown origin) by scintillation counting method	ic50	0.0360	uM
ethyl 6-methyl-4-(3-nitrophenyl)-3-propyl-2-sulfanylidene-1,4-dihydropyrimidine-5-carboxylate	45769: In vitro vasorelaxant activity (calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0500	uM
(3R,4R)-1-[2-(dimethylamino)ethyl]-4-(4-methoxyphenyl)-3-prop-2-enyl-4,5-dihydro-3H-1-benzazepin-2-one	56045: In vitro ability to displace the specific binding of [3H]diltiazem to diltiazem receptor in guinea pig skeletal muscle.	kd	0.0520	uM
diethyl 4-(5-ethyl-3-methyl-1,2-oxazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate	45622: Inhibition of [3H]PN-200110 binding to Calcium channel in guinea pig ileum membrane	ki	0.0625	uM
(3R,4R)-1-[2-(dimethylamino)ethyl]-4-(4-methoxyphenyl)-3-methyl-6-(trifluoromethyl)-4,5-dihydro-3H-1-benzazepin-2-one	56045: In vitro ability to displace the specific binding of [3H]diltiazem to diltiazem receptor in guinea pig skeletal muscle.	kd	0.0750	uM
diethyl 2,6-dimethyl-4-(5-pentyl-3-phenyl-1,2-oxazol-4-yl)-1,4-dihydropyridine-3,5-dicarboxylate	45622: Inhibition of [3H]PN-200110 binding to Calcium channel in guinea pig ileum membrane	ki	0.0784	uM
diethyl 4-(3-chlorophenyl)-6-methyl-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0880	uM
3-O-ethyl 5-O-methyl 6-methyl-4-(3-nitrophenyl)-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.1000	uM
(3R,4R)-7-bromo-1-[2-(dimethylamino)ethyl]-6-methoxy-4-(4-methoxyphenyl)-3-methyl-4,5-dihydro-3H-1-benzazepin-2-one	56045: In vitro ability to displace the specific binding of [3H]diltiazem to diltiazem receptor in guinea pig skeletal muscle.	kd	0.1200	uM
[(3R,4S)-7-bromo-1-[2-(dimethylamino)ethyl]-6-methoxy-4-(4-methoxyphenyl)-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl] acetate	56045: In vitro ability to displace the specific binding of [3H]diltiazem to diltiazem receptor in guinea pig skeletal muscle.	kd	0.1200	uM
[(3R,4S)-1-(2-aminoethyl)-4-(4-methoxyphenyl)-2-oxo-6-(trifluoromethyl)-4,5-dihydro-3H-1-benzazepin-3-yl] acetate	56045: In vitro ability to displace the specific binding of [3H]diltiazem to diltiazem receptor in guinea pig skeletal muscle.	kd	0.1200	uM

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	2
Benzo(a)pyrene	decreases methylation, increases methylation, increases mutagenesis	2
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
incobotulinumtoxinA	decreases expression	1
Sunitinib	increases expression	1
Copper	affects cotreatment, decreases expression	1
Daunorubicin	affects response to substance	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	affects methylation, decreases methylation	1
Okadaic Acid	increases expression	1
Coal Ash	decreases expression	1

ChEMBL screening assays

228 unique, capped per target: 142 binding, 79 functional, 5 toxicity, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003715	Functional	Antagonist activity at voltage-dependent L-type calcium channel in human SH-SY5Y cells assessed as inhibition of KCl-induced increase in cytosolic calcium concentration at 0.3 uM pretreated for 10 mins before KCl challenge relative to contr	Tacripyrines, the first tacrine-dihydropyridine hybrids, as multitarget-directed ligands for the treatment of Alzheimer’s disease. — J Med Chem
CHEMBL1059038	Binding	Inhibition of human L-type calcium channel at 100 uM	Spirocyclic delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-3-hydroxy-4-(spiro[chromene-2,4’-piperidine]-4-yl) benzamide (ADL5747). — J Med Chem
CHEMBL4236597	ADMET	Inhibition of L-type calcium channel (unknown origin) by patch clamp assay	Discovery of TRPM8 Antagonist ( S)-6-(((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)nicotinic Acid (AMG 333), a Clinical Candidate for the Treatment of Migraine. — J Med Chem

Cellosaurus cell lines

11 cell lines: 5 induced pluripotent stem cell, 3 transformed cell line, 3 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_BX22	GM25330	Transformed cell line	Male
CVCL_BX23	GM25331	Transformed cell line	Female
CVCL_BX27	GM25343	Finite cell line	Female
CVCL_BX28	GM25344	Finite cell line	Male
CVCL_RT79	GM26593	Transformed cell line	Female
CVCL_RT80	GM26594	Finite cell line	Female
CVCL_UL08	TRNDi002-A	Induced pluripotent stem cell	Male
CVCL_UL09	TRNDi002-B	Induced pluripotent stem cell	Male
CVCL_UL10	TRNDi002-C	Induced pluripotent stem cell	Male
CVCL_UL11	TRNDi002-D	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00004802	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Dichlorphenamide for Periodic Paralyses and Associated Sodium Channel Disorders
NCT00494507	PHASE3	COMPLETED	Hyper- and Hypokalemic Periodic Paralysis Study
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02582476	PHASE2	TERMINATED	Bumetanide in Hypokalaemic Periodic Paralysis
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT01401257	PHASE2	COMPLETED	Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT02020187	Not specified	COMPLETED	Aerobic Training in Patients With Congenital Myopathies
NCT03018184	Not specified	COMPLETED	Contractile Cross Sectional Areas and Muscle Strength in Patients With Congenital Myopathies
NCT04733976	Not specified	COMPLETED	Bullying in Youth With Muscular Dystrophy and Congenital Myopathies
NCT05099107	Not specified	COMPLETED	Changes of Motor Function Tests in Congenital Myopathy Subjects Treated With Oral Salbutamol as Compared to no Treatment
NCT05199246	Not specified	COMPLETED	Assessment of Safety and Acute Effects of a Lower-limb Powered Dermoskeleton in Patients With Neuromuscular Disorders
NCT05200702	Not specified	COMPLETED	Assessment of Safety and Acute Effects of a Knee-hip Powered Soft Exoskeleton in Patients With Neuromuscular Disorders
NCT05692349	Not specified	UNKNOWN	Magnetic Resonance Imaging and Ultrasonography in Evaluation of Muscle Diseases
NCT06791369	Not specified	NOT_YET_RECRUITING	The Prevalence of RYR1-related Disease
NCT06833489	Not specified	RECRUITING	Transcriptomic Analysis to Put an End to Misdiagnosis in Patients With Rare Muscle Diseases