CACNA1C

Summary

CACNA1C (calcium voltage-gated channel subunit alpha1 C, HGNC:1390) is a protein-coding gene on chromosome 12p13.33, encoding Voltage-dependent L-type calcium channel subunit alpha-1C (Q13936). Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents.

This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. There are multiple isoforms of each of these proteins, either encoded by different genes or the result of alternative splicing of transcripts. The protein encoded by this gene binds to and is inhibited by dihydropyridine. Alternative splicing results in many transcript variants encoding different proteins. Some of the predicted proteins may not produce functional ion channel subunits.

Source: NCBI Gene 775 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Timothy syndrome (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 91
• Clinical variants (ClinVar): 3,697 total — 42 pathogenic, 52 likely-pathogenic
• Phenotypes (HPO): 101
• Druggable target: yes — 85 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000719

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1390
Approved symbol	CACNA1C
Name	calcium voltage-gated channel subunit alpha1 C
Location	12p13.33
Locus type	gene with protein product
Status	Approved
Aliases	Cav1.2, CACH2, CACN2, TS, LQT8
Ensembl gene	ENSG00000151067
Ensembl biotype	protein_coding
OMIM	114205
Entrez	775

Gene structure

Transcript identifiers

Ensembl transcripts: 51 — 35 protein_coding, 8 protein_coding_CDS_not_defined, 5 retained_intron, 3 nonsense_mediated_decay

ENST00000327702, ENST00000335762, ENST00000344100, ENST00000347598, ENST00000399591, ENST00000399595, ENST00000399597, ENST00000399601, ENST00000399603, ENST00000399606, ENST00000399617, ENST00000399621, ENST00000399629, ENST00000399634, ENST00000399637, ENST00000399638, ENST00000399641, ENST00000399644, ENST00000399649, ENST00000399655, ENST00000402845, ENST00000406454, ENST00000465278, ENST00000465934, ENST00000480911, ENST00000483136, ENST00000491104, ENST00000492150, ENST00000496818, ENST00000541871, ENST00000616390, ENST00000672806, ENST00000673589, ENST00000682152, ENST00000682320, ENST00000682336, ENST00000682343, ENST00000682462, ENST00000682544, ENST00000682686, ENST00000682835, ENST00000682867, ENST00000683482, ENST00000683781, ENST00000683824, ENST00000683840, ENST00000683956, ENST00000684233, ENST00000684317, ENST00000684467, ENST00000684752

RefSeq mRNA: 23 — MANE Select: NM_000719 NM_000719, NM_001129827, NM_001129829, NM_001129830, NM_001129831, NM_001129832, NM_001129833, NM_001129834, NM_001129835, NM_001129836, NM_001129837, NM_001129838, NM_001129839, NM_001129840, NM_001129841, NM_001129842, NM_001129843, NM_001129844, NM_001129846, NM_001167623, NM_001167624, NM_001167625, NM_199460

CCDS: CCDS44787, CCDS44788, CCDS44789, CCDS44790, CCDS44791, CCDS44792, CCDS44793, CCDS44794, CCDS44795, CCDS44796, CCDS44797, CCDS44798, CCDS44799, CCDS44800, CCDS44801, CCDS53733, CCDS53734, CCDS53735, CCDS53736, CCDS91634, CCDS91636, CCDS91637

Canonical transcript exons

ENST00000399655 — 47 exons

Exon	Start	End
ENSE00000936250	2115224	2115545
ENSE00000997448	2504842	2504945
ENSE00000997453	2448976	2449115
ENSE00001539473	2690900	2697950
ENSE00001600371	2634297	2634380
ENSE00001623462	2666686	2666782
ENSE00001624188	2655147	2655238
ENSE00001624503	2664825	2664990
ENSE00001627598	2677733	2677867
ENSE00001631163	2567569	2567794
ENSE00001633479	2120325	2120430
ENSE00001638034	2601854	2601960
ENSE00001647420	2611903	2612013
ENSE00001650793	2686166	2686269
ENSE00001660805	2665581	2665708
ENSE00001661355	2685736	2685842
ENSE00001661913	2605679	2605786
ENSE00001677895	2486104	2486262
ENSE00001692129	2595874	2596003
ENSE00001695663	2606984	2607130
ENSE00001723402	2606611	2606663
ENSE00001730572	2582822	2582942
ENSE00001768958	2605081	2605168
ENSE00001773383	2493190	2493386
ENSE00001781867	2682550	2682678
ENSE00001782094	2688447	2688779
ENSE00001785119	2597230	2597289
ENSE00001788509	2457567	2457706
ENSE00001796396	2581590	2581797
ENSE00001801749	2679444	2679796
ENSE00003340133	2651640	2651768
ENSE00003520036	2556951	2556977
ENSE00003538674	2674541	2674642
ENSE00003575728	2648475	2648507
ENSE00003576212	2677094	2677221
ENSE00003629104	2668933	2669035
ENSE00003641511	2549943	2550033
ENSE00003668328	2653835	2653900
ENSE00003671284	2566422	2566582
ENSE00003674611	2512812	2512984
ENSE00003711924	2585376	2585496
ENSE00003712132	2593213	2593345
ENSE00003733926	2608511	2608712
ENSE00003745309	2584503	2584617
ENSE00003749463	2585835	2585904
ENSE00003787168	2610541	2610699
ENSE00003891918	2052987	2053611

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 94.75.

FANTOM5 (CAGE): breadth broad, TPM avg 6.7000 / max 305.2676, expressed in 854 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123414	5.4193	829
123410	0.3103	40
123416	0.2388	118
123415	0.2207	113
123417	0.1892	87
123412	0.1102	23
123418	0.0979	42
123407	0.0502	20
123411	0.0207	10
123409	0.0155	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	94.75	gold quality
right coronary artery	UBERON:0001625	93.88	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.33	gold quality
heart left ventricle	UBERON:0002084	93.02	gold quality
body of uterus	UBERON:0009853	92.88	gold quality
heart	UBERON:0000948	92.65	gold quality
right atrium auricular region	UBERON:0006631	92.53	gold quality
myometrium	UBERON:0001296	91.85	gold quality
smooth muscle tissue	UBERON:0001135	90.99	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.97	gold quality
lower esophagus	UBERON:0013473	90.92	gold quality
popliteal artery	UBERON:0002250	90.27	gold quality
tibial artery	UBERON:0007610	90.24	gold quality
left coronary artery	UBERON:0001626	89.90	gold quality
ascending aorta	UBERON:0001496	89.33	gold quality
thoracic aorta	UBERON:0001515	89.31	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.56	gold quality
sural nerve	UBERON:0015488	88.37	gold quality
descending thoracic aorta	UBERON:0002345	88.35	gold quality
colonic epithelium	UBERON:0000397	87.75	gold quality
urinary bladder	UBERON:0001255	86.80	gold quality
colon	UBERON:0001155	84.62	gold quality
fundus of stomach	UBERON:0001160	84.11	gold quality
prostate gland	UBERON:0002367	83.50	gold quality
stromal cell of endometrium	CL:0002255	83.12	gold quality
mucosa of stomach	UBERON:0001199	82.97	gold quality
corpus callosum	UBERON:0002336	82.24	gold quality
calcaneal tendon	UBERON:0003701	82.24	gold quality
cortical plate	UBERON:0005343	81.92	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.68	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	5240.27
E-CURD-119	yes	3879.55
E-HCAD-35	yes	2566.68
E-HCAD-25	yes	75.65
E-MTAB-5061	yes	70.92
E-MTAB-11268	no	7222.69
E-GEOD-83139	no	2.80
E-ANND-3	no	1.85

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KCNIP3, NFE2L2, SPI1, YY1

miRNA regulators (miRDB)

326 targeting CACNA1C, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4510	100.00	66.60	2050

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• new promoter which exhibits 69% homology to its rat counterpart and displays functional promoter activity when transfected into heart cells in culture in luciferase-expressing constructs (PMID:12163037)
• determination of whether the expression of this channel is regulated by different promoters in smooth muscle cells and in heart (PMID:12593842)
• tissue-secific expression of two isoforms under the control of distinct 5’ flanking regulatory elements (PMID:12832067)
• there are multiple residues within the inhibitory domain that are crucial to the inhibitory process as well as to the enhancement of expressed current by intracellular application of proteases (PMID:12962146)
• the inhibitory modulation of cardiac Ca2+ channels, present in both alpha(1C) isoforms, is G(q)- and PLC-independent and Ca(2+)-dependent, but only basal levels of Ca(2+) are essential (PMID:14722109)
• functional but non-voltage-gated L-type Ca2+ channels are expressed at the plasma membrane in T cells and play a role in the antigen receptor-mediated Ca2+ flux in these cells (PMID:14981074)
• there are extensive splice variations in the human l-type voltage-gated calcium channel, Cav1.2 alpha1 subunit (PMID:15299022)
• short splice variants of the human cardiac Cavbeta2 subunit are involved in modulation of the Cav1.2 channel (PMID:15339916)
• Timothy syndrome results from a Ca(V)1.2 missense mutation. Ca(V)1.2 is expressed in all affected tissues. Functional expression reveals that G406R produces maintained inward Ca(2+) currents by causing loss of voltage-dependent channel inactivation. (PMID:15454078)
• Ca(2+)-calmodulin assumes a novel conformation when it is part of a complex with the C-terminal tail of the Ca(V)1.2 alpha(1) subunit (PMID:15583004)
• cross-talk between the alpha1C C and N termini, beta subunit, and the cytoplasmic pore region confers the multifactorial regulation of Ca(v)1.2 channels (PMID:15671035)
• Expression of undeleted L-type calcium channel mRNAs correlates with normal testes cadmium and increased sperm count after varicocelectomy (PMID:15749491)
• activation of Ca(2+) conductance and Ca(2+)-dependent inactivation depend on extracellular Ca(2+) and are linked to changes in selectivity (PMID:15845581)
• data indicate that gain-of-function mutations of CaV1.2 exons 8 and 8A cause distinct forms of Timothy syndrome (PMID:15863612)
• the physicochemical properties of the amino acid residues at positions 1144 and 1152 are crucial to the CaV1.2 pore’s ability to distinguish between multiple Ba(2+) ions and Ca(2+) ions (PMID:15980164)
• the NT and IQ-domains of alpha(1)1.2 mediate functionally distinct interactions with CaBP1 and CaM that promote conformational alterations that either stabilize or inhibit inactivation of Ca(v)1.2. (PMID:15980432)
• L-type Ca(2+) channels play a critical role in maintaining lower esophageal sphinctor tone. (PMID:16020652)
• analysis of conformation and binding of CaV1.2 (PMID:16157588)
• The activation of p50 and p65 by tumor necrosis factor alpha suppresses the expression of the alpha1C subunit of Cav1.2 channels in human colonic circular smooth muscle cells (PMID:16285952)
• The high-resolution structure of the Ca(2+)/CaM-Ca(V)1.2 IQ domain complex was reported. (PMID:16299511)
• Ahnak has a critical role in cardiac Ca(V)1.2 calcium channel function and its beta-adrenergic regulation (PMID:16319140)
• single nucleotide polymorphisms in CANCA1C had significant associations with antihypertensive outcome, combining to yield a positive treatment outcome of less than 15 to 80% (PMID:16610939)
• We conclude that Rem is capable of regulating L-type current, that release of Rem block is modulated by cellular kinase pathways, and that the Ca(V)1.2 COOH terminus contributes to Rem-dependent channel inhibition. (PMID:16648185)
• voltage-dependent facilitation of the Ca(v)1.2 channel depends on the phosphorylation of Ser1512/Ser1570 by calmodulin kinase II (PMID:16820363)
• localized changes in cytokine expression generated by inflammation in atherosclerosis affect alternative splicing of the Ca(v)1.2alpha1 gene (PMID:17071743)
• testosterone inhibits currents in a concentration-dependent manner over the physiological range of testosterone concentrations (IC50 34 nM), and is not mimicked by the metabolite 5alpha-androstan-17beta-ol-3-one (DHT), nor by progesterone or estradiol. (PMID:17173968)
• loss-of-function mutations in genes encoding the cardiac L-type calcium channel to be associated with a familial sudden cardiac death syndrome in which a Brugada syndrome phenotype is combined with shorter-than-normal QT intervals (PMID:17224476)
• Indirect evidence for an impaired src kinase regulation of I (Ca,L) together with an increased phosphatase activity suggests that a complex alteration in the kinase/phosphatase balance leads to I (Ca,L) dysregulation in chronic AF. (PMID:17593353)
• a smooth muscle Ca(v)1.2 splice variant has been identified functionally to possess biophysical property that can be linked to enhanced state-dependent block by DHP (PMID:17916557)
• The COOH terminus of hCa(v)1.2b contains sites for the SH2 and SH3 binding of Src kinase. (PMID:17942635)
• CS(L) modulates Ca2+-channel activity through interacting with the calmodulin-binding site on the C-terminal tail of the Cav1.2 channel. (PMID:17950697)
• Knckout mice mice exhibit significant impairments in spatial memory when examined 30 days after training. (PMID:18174367)
• study found that the Timothy syndrome mutation powerfully and selectively slows voltage-dependent inactivation while sparing or possibly speeding the kinetics of calcium-dependent inactivation (PMID:18250309)
• Suggest that the decreased BAY K 8644 effects on Cav1.2 channels in failing cardiac myoyctes is caused by increased basal channel activity. (PMID:18359894)
• Coexpression of exogenous CaM (CaM(ex)) with alpha(1C)/alpha(2)delta in COS1 cells in the absence of Ca(v)beta subunits stimulates the plasma membrane targeting of alpha(1C). (PMID:18535142)
• Introduction into Ca(v)2.1 of the homologous mutation of Ca(v)1.2 causing the Timothy syndrome questions the role of V421 in the phenotypic definition of P-type Ca(2+) channel. (PMID:18536931)
• CO, a product of heme catabolism by HO-1, directly inhibits alpha1C subunit of the cardiac L-type Ca2+ channel (PMID:18596041)
• Sorcin modulates cardiac L-type Ca2+ current by functional interaction with the alpha1C subunit in rabbits. (PMID:18603601)
• Cav1.2 is subject to “denitration”. (PMID:18675806)
• found further support for the previously reported CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel in bipolar disorder (PMID:18711365)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cacna1c	ENSDARG00000008398
mus_musculus	Cacna1c	ENSMUSG00000051331
rattus_norvegicus	Cacna1c	ENSRNOG00000007090

Paralogs (26): CACNA1G (ENSG00000006283), SCN4A (ENSG00000007314), CACNA1S (ENSG00000081248), CACNA1I (ENSG00000100346), CACNA1F (ENSG00000102001), NALCN (ENSG00000102452), SCN2A (ENSG00000136531), SCN7A (ENSG00000136546), CACNA1A (ENSG00000141837), SCN1A (ENSG00000144285), CACNA1B (ENSG00000148408), 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-1C — Q13936 (reviewed: Q13936)

Alternative names: Calcium channel, L type, alpha-1 polypeptide, isoform 1, cardiac muscle, Voltage-gated calcium channel subunit alpha Cav1.2

All UniProt accessions (20): Q13936, A0A087WUX4, A0A0A0MR67, A0A0A0MSA1, A0A5F9ZHD9, A0A804HHT8, A0A804HI37, A0A804HIJ8, A0A804HIR0, A0A804HIZ0, A0A804HJB6, A0A804HJR1, A0A804HKC4, A0A804HKE9, A0AA34QVT1, E9PDI6, F5GY28, F5H522, F5H638, Q5V9X8

UniProt curated annotations — full annotation on UniProt →

Function. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm. Plays an important role in excitation-contraction coupling in the heart. Required for normal heart development and normal regulation of heart rhythm. Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells. Long-lasting (L-type) calcium channels belong to the ‘high-voltage activated’ (HVA) group. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. (Microbial infection) Acts as a receptor for Influenzavirus. May play a critical role in allowing virus entry when sialylated and expressed on lung tissues.

Subunit / interactions. Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1C) and ancillary beta, gamma and delta subunits. The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains only one of each type of subunit. CACNA1C channel activity is modulated by ancillary subunits, such as CACNB1, CACNB2, CACNB3, CACNA2D1 and CACNA2D4. Interacts with the gamma subunits CACNG4, CACNG6, CACNG7 and CACNG8. Interacts with CACNB1. Interacts with CACNB2. Identified in a complex with CACNA2D4 and CACNB3. Interacts with CACNB3. Interacts with CACNA2D1. Interacts with CACNA2D4. Interacts with CALM1. Interacts (via the N-terminus and the C-terminal C and IQ motifs) with CABP1; this inhibits Ca(2+)-dependent channel inactivation. The binding via the C motif is calcium independent whereas the binding via IQ requires the presence of calcium and is mutually exclusive with calmodulin binding. The binding to the cytoplasmic N-terminal domain is calcium independent but is essential for the channel modulation. Interacts (via C-terminal CDB motif) with CABP5; in a calcium-dependent manner. Interacts with CIB1; the interaction increases upon cardiomyocytes hypertrophy. Interacts with STAC2 and STAC3; this inhibits channel inactivation. (Microbial infection) Interacts with influenzavirus H1 hemagglutinin.

Subcellular location. Cell membrane. Sarcolemma. Perikaryon. Postsynaptic density membrane. Cell projection. Dendrite. T-tubule.

Tissue specificity. Detected throughout the brain, including hippocampus, cerebellum and amygdala, throughout the heart and vascular system, including ductus arteriosus, in urinary bladder, and in retina and sclera in the eye. Expressed in brain, heart, jejunum, ovary, pancreatic beta-cells and vascular smooth muscle. Overall expression is reduced in atherosclerotic vascular smooth muscle.

Post-translational modifications. Phosphorylation by PKA at Ser-1981 activates the channel. Elevated levels of blood glucose lead to increased phosphorylation by PKA.

Disease relevance. Timothy syndrome (TS) [MIM:601005] Disorder characterized by multiorgan dysfunction including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities and autism. The disease is caused by variants affecting the gene represented in this entry. Brugada syndrome 3 (BRGDA3) [MIM:611875] A heart disease characterized by the association of Brugada syndrome with shortened QT intervals. Brugada syndrome is a tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. The gene represented in this entry may be involved in disease pathogenesis. Long QT syndrome 8 (LQT8) [MIM:618447] A form of long QT syndrome, a heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. LQT8 transmission pattern is consistent with autosomal dominant inheritance with incomplete penetrance. The disease is caused by variants affecting the gene represented in this entry. Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures (NEDHLSS) [MIM:620029] An autosomal dominant disorder characterized by global developmental delay apparent from infancy, intellectual disability, poor or absent speech, behavioral abnormalities, and hypotonia with delayed walking or inability to walk. Additional features include epilepsy, mild skeletal defects, and non-specific dysmorphic features. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by dihydropyridines (DHP), such as isradipine. Inhibited by nifedipine. Channel activity is regulated by Ca(2+) and calmodulin. Binding of STAC1, STAC2 or STAC3 to a region that overlaps with the calmodulin binding site inhibits channel inactivation by Ca(2+) and calmodulin. Binding of calmodulin or CABP1 at the same regulatory sites results in opposite effects on the channel function. Shear stress and pressure increases calcium channel activity.

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. Binding of intracellular calcium through the EF-hand motif inhibits the opening of the channel.

Miscellaneous. Contains exon 8a. Lacks exon 21. Lacks exon 22. Lacks exon 31. Lacks exon 32. Lacks exon 33. Contains exon 40B and 43A. Contains exon 41A. Lacks exon 45. Predominant isoform in atherosclerotic vascular smooth muscle cells. Not inhibited by calcium. Enhanced by PKC activator.

Similarity. Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1C subfamily.

Isoforms (37)

UniProt ID	Names	Canonical?
Q13936-1	1, HFCC, Fibroblast	yes
Q13936-2	2
Q13936-3	3
Q13936-4	4
Q13936-5	5
Q13936-6	6
Q13936-7	7
Q13936-8	8
Q13936-9	9
Q13936-10	10
Q13936-11	11, Alpha-1C.90
Q13936-12	12, Alpha-1C.70
Q13936-13	13, Alpha-1C.127
Q13936-14	14, Alpha-1C.126
Q13936-15	15, Alpha-1C.125
Q13936-16	16
Q13936-17	17
Q13936-18	18, HHT-1
Q13936-19	19, Alpha-1C.76
Q13936-20	20, Alpha-1C.77
Q13936-21	21, Alpha-1C.69
Q13936-22	22, Alpha-1C.78
Q13936-23	23, Alpha-1C.105
Q13936-24	24, Alpha-1C.71
Q13936-25	25, Alpha-1C.73
Q13936-26	26, Alpha-1C.86
Q13936-27	27, Alpha-1C.72
Q13936-28	28
Q13936-29	29, Alpha-1C.74
Q13936-30	30, Alpha-1C.87
Q13936-31	31, Alpha-1C.88
Q13936-32	32, Alpha-1C.89
Q13936-33	33, Alpha-1C.85
Q13936-34	34, Alpha-1C,long-NT
Q13936-35	35
Q13936-36	36
Q13936-37	37

RefSeq proteins (23): NP_000710, NP_001123299, NP_001123301, NP_001123302, NP_001123303, NP_001123304, NP_001123305, NP_001123306, NP_001123307, NP_001123308, NP_001123309, NP_001123310, NP_001123311, NP_001123312, NP_001123313, NP_001123314, NP_001123315, NP_001123316, NP_001123318, NP_001161095, NP_001161096, NP_001161097, NP_955630 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002077	VDCCAlpha1	Family
IPR005446	VDCC_L_a1su	Family
IPR005451	VDCC_L_a1csu	Family
IPR005821	Ion_trans_dom	Domain
IPR014873	VDCC_a1su_IQ	Domain
IPR027359	Volt_channel_dom_sf	Homologous_superfamily
IPR031649	GPHH_dom	Domain
IPR031688	CAC1F_C	Domain
IPR050599	VDCC_alpha-1_subunit	Family

Pfam: PF00520, PF08763, PF16885, PF16905

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (345 total): sequence variant 74, helix 74, strand 36, topological domain 29, transmembrane region 24, turn 20, region of interest 16, splice variant 15, sequence conflict 9, mutagenesis site 8, modified residue 7, compositionally biased region 6, glycosylation site 4, disulfide bond 4, intramembrane region 4, repeat 4, short sequence motif 4, binding site 3, site 3, chain 1

Structure

Experimental structures (PDB)

33 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2F3Y	X-RAY DIFFRACTION	1.45
2F3Z	X-RAY DIFFRACTION	1.6
6DAD	X-RAY DIFFRACTION	1.65
6U3A	X-RAY DIFFRACTION	1.65
5V2Q	X-RAY DIFFRACTION	1.7
6U3B	X-RAY DIFFRACTION	1.7
6U3D	X-RAY DIFFRACTION	1.75
1T0J	X-RAY DIFFRACTION	2
2BE6	X-RAY DIFFRACTION	2
5V2P	X-RAY DIFFRACTION	2
6DAE	X-RAY DIFFRACTION	2
3G43	X-RAY DIFFRACTION	2.1
6DAF	X-RAY DIFFRACTION	2.4
6U39	X-RAY DIFFRACTION	2.4
3OXQ	X-RAY DIFFRACTION	2.55
8UKP	X-RAY DIFFRACTION	2.85
8UKO	X-RAY DIFFRACTION	2.89
8WE6	ELECTRON MICROSCOPY	2.9
8WE8	ELECTRON MICROSCOPY	2.9
8WE9	ELECTRON MICROSCOPY	3
8FD7	ELECTRON MICROSCOPY	3.1
8WE7	ELECTRON MICROSCOPY	3.2
8WEA	ELECTRON MICROSCOPY	3.2
8EOG	ELECTRON MICROSCOPY	3.3
8FHS	ELECTRON MICROSCOPY	3.3
8HMB	ELECTRON MICROSCOPY	3.3
8EOI	ELECTRON MICROSCOPY	3.4
8HMA	ELECTRON MICROSCOPY	3.4
8HLP	ELECTRON MICROSCOPY	3.5
2LQC	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13936-F1	62.73	0.11

Functional residue map

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

Catalytic / active sites (3): 363 (calcium ion selectivity and permeability); 1135 (calcium ion selectivity and permeability); 1464 (calcium ion selectivity and permeability)

Ligand- & substrate-binding residues (3): 363; 706; 1135

Post-translational modifications (7): 1981, 469, 476, 808, 815, 1718, 1739

Disulfide bonds (4): 298–326, 316–332, 1078–1089, 1479–1495

Glycosylation sites (4): 153, 328, 1436, 1487

Mutagenesis-validated functional residues (8):

Position	Phenotype
363	loss of selectivity for divalent over monovalent cations.
954	affects voltage-dependent inhibition by dihydropyridines; when associated with i-958.
958	affects voltage-dependent inhibition by dihydropyridines; when associated with f-954.
1135	decreased selectivity for divalent over monovalent cations.
1464	decreased selectivity for divalent over monovalent cations.
1610	loss of a low-affinity interaction with calm1. no effect on channel inactivation by ca(2+) and calmodulin.
1666–1670	mildly decreased channel activity. no effect on channel inactivation. loss of channel inactivation by ca(2+) and calmodu
1672	loss of channel inactivation by ca(2+) and calmodulin; when associated with 1666-a–a-1670.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-400042	Adrenaline,noradrenaline inhibits insulin secretion
R-HSA-419037	NCAM1 interactions
R-HSA-422356	Regulation of insulin secretion
R-HSA-5576892	Phase 0 - rapid depolarisation
R-HSA-5576893	Phase 2 - plateau phase
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-163685	Integration of energy metabolism
R-HSA-375165	NCAM signaling for neurite out-growth
R-HSA-397014	Muscle contraction
R-HSA-422475	Axon guidance
R-HSA-5576891	Cardiac conduction
R-HSA-9675108	Nervous system development

MSigDB gene sets: 557 (showing top): GOBP_MEMBRANE_DEPOLARIZATION, YAATNRNNNYNATT_UNKNOWN, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_ADRENALINE_NORADRENALINE_INHIBITS_INSULIN_SECRETION, NKX25_02, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_MEMBRANE_DEPOLARIZATION_DURING_ACTION_POTENTIAL, REACTOME_NCAM_SIGNALING_FOR_NEURITE_OUT_GROWTH, GOBP_POSITIVE_REGULATION_OF_LYASE_ACTIVITY, GOBP_FORELIMB_MORPHOGENESIS, GOBP_REGULATION_OF_CARDIAC_MUSCLE_CONTRACTION_BY_REGULATION_OF_THE_RELEASE_OF_SEQUESTERED_CALCIUM_ION, FOXD3_01, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS

GO Biological Process (31): immune system development (GO:0002520), positive regulation of cytosolic calcium ion concentration (GO:0007204), heart development (GO:0007507), regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion (GO:0010881), embryonic forelimb morphogenesis (GO:0035115), camera-type eye development (GO:0043010), positive regulation of adenylate cyclase activity (GO:0045762), positive regulation of muscle contraction (GO:0045933), calcium ion transport into cytosol (GO:0060402), cardiac conduction (GO:0061337), calcium ion transmembrane transport via high voltage-gated calcium channel (GO:0061577), calcium ion transmembrane transport (GO:0070588), cardiac muscle cell action potential involved in contraction (GO:0086002), membrane depolarization during cardiac muscle cell action potential (GO:0086012), membrane depolarization during AV node cell action potential (GO:0086045), cell communication by electrical coupling involved in cardiac conduction (GO:0086064), regulation of heart rate by cardiac conduction (GO:0086091), calcium ion import across plasma membrane (GO:0098703), regulation of ventricular cardiac muscle cell action potential (GO:0098911), membrane depolarization during atrial cardiac muscle cell action potential (GO:0098912), system process (GO:0003008), monoatomic ion transport (GO:0006811), calcium ion transport (GO:0006816), muscle contraction (GO:0006936), cell communication (GO:0007154), regulation of heart contraction (GO:0008016), signaling (GO:0023052), monoatomic ion transmembrane transport (GO:0034220), regulation of membrane potential (GO:0042391), transmembrane transport (GO:0055085), calcium ion transmembrane import into cytosol (GO:0097553)

GO Molecular Function (10): voltage-gated calcium channel activity (GO:0005245), calmodulin binding (GO:0005516), high voltage-gated calcium channel activity (GO:0008331), metal ion binding (GO:0046872), alpha-actinin binding (GO:0051393), voltage-gated calcium channel activity involved in cardiac muscle cell action potential (GO:0086007), voltage-gated calcium channel activity involved in AV node cell action potential (GO:0086056), monoatomic ion channel activity (GO:0005216), calcium channel activity (GO:0005262), protein binding (GO:0005515)

GO Cellular Component (18): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), plasma membrane (GO:0005886), voltage-gated calcium channel complex (GO:0005891), cilium (GO:0005929), postsynaptic density (GO:0014069), membrane (GO:0016020), Z disc (GO:0030018), dendrite (GO:0030425), perikaryon (GO:0043204), postsynaptic density membrane (GO:0098839), L-type voltage-gated calcium channel complex (GO:1990454), T-tubule (GO:0030315), monoatomic ion channel complex (GO:0034702), sarcolemma (GO:0042383), cell projection (GO:0042995), synapse (GO:0045202), postsynaptic membrane (GO:0045211)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Cardiac conduction	2
Regulation of insulin secretion	1
NCAM signaling for neurite out-growth	1
Integration of energy metabolism	1
Metabolism	1
Axon guidance	1
Nervous system development	1
Muscle contraction	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
membrane depolarization during cardiac muscle cell action potential	3
calcium ion transmembrane import into cytosol	2
cardiac muscle cell action potential	2
AV node cell action potential	2
cardiac conduction	2
voltage-gated calcium channel activity	2
immune system process	1
system development	1
regulation of biological quality	1
animal organ development	1
circulatory system development	1
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of cardiac muscle contraction by calcium ion signaling	1
embryonic limb morphogenesis	1
forelimb morphogenesis	1
eye development	1
adenylate cyclase activity	1
positive regulation of cyclase activity	1
regulation of adenylate cyclase activity	1
positive regulation of lyase activity	1
muscle contraction	1
regulation of muscle contraction	1
positive regulation of multicellular organismal process	1
positive regulation of cytosolic calcium ion concentration	1
regulation of heart contraction	1
high voltage-gated calcium channel activity	1
calcium ion transmembrane transport	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
cardiac muscle cell contraction	1
membrane depolarization during action potential	1
cell communication by electrical coupling	1
cell communication involved in cardiac conduction	1
regulation of heart rate	1
calcium ion import	1
inorganic cation import across plasma membrane	1
calcium ion import into cytosol	1
regulation of cardiac muscle cell contraction	1
ventricular cardiac muscle cell action potential	1

Protein interactions and networks

STRING

3010 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CACNA1C	CALM1	P02593	994
CACNA1C	CALML3	P27482	991
CACNA1C	CALML5	Q9NZT1	991
CACNA1C	CALML6	Q8TD86	990
CACNA1C	CALML4	Q96GE6	990
CACNA1C	CACNB2	Q08289	987
CACNA1C	RYR2	Q92736	970
CACNA1C	CACNA2D1	P54289	967
CACNA1C	STIM1	Q13586	949
CACNA1C	ADRB2	P07550	934
CACNA1C	CAV3	P56539	921
CACNA1C	TRPC1	P48995	891
CACNA1C	KCNH2	Q12809	885
CACNA1C	AKAP7	O43687	875
CACNA1C	CACNB3	P54284	875

IntAct

80 interactions, top by confidence:

A	B	Type	Score
CACNA1C	CALM1	psi-mi:“MI:0915”(physical association)	0.920
CACNA1C	CALM1	psi-mi:“MI:0407”(direct interaction)	0.920
CALM1	CACNA1C	psi-mi:“MI:0407”(direct interaction)	0.920
CACNA1C	CACNB3	psi-mi:“MI:0915”(physical association)	0.640
PICK1	CACNA1C	psi-mi:“MI:0915”(physical association)	0.630
SRRT	CACNA1C	psi-mi:“MI:0915”(physical association)	0.550
CABP1	CACNA1C	psi-mi:“MI:0915”(physical association)	0.520
CACNA1C	CABP1	psi-mi:“MI:0915”(physical association)	0.520

BioGRID (55): KCNE2 (Affinity Capture-Western), KCNE2 (Reconstituted Complex), KCNE2 (FRET), CACNA1C (Affinity Capture-Western), CACNA1C (Affinity Capture-RNA), CACNA1C (Co-crystal Structure), CACNA1C (Reconstituted Complex), CABP1 (Reconstituted Complex), CABP1 (Affinity Capture-Western), CACNA1C (Affinity Capture-MS), CACNA1C (Affinity Capture-Western), MDM2 (Affinity Capture-Western), CACNA1C (Two-hybrid), CACNA1C (Affinity Capture-Western), RYR2 (Reconstituted Complex)

ESM2 similar proteins: A2APX8, A2ASI5, B1AWN6, C9D7C2, D0E0C2, O08562, O35505, O46669, O73700, O88420, O88457, P02719, P04774, P04775, P08104, P0DMA5, P15381, P15389, P15390, P22002, P27732, P35498, P35499, P35500, Q01815, Q07652, Q13936, Q14524, Q15858, Q20JQ7, Q28371, Q28644, Q2XVR3, Q2XVR4, Q2XVR5, Q2XVR6, Q2XVR7, Q62205, Q62968, Q6QIY3

Diamond homologs: C9D7C2, O00555, O35505, O42398, O46669, O55017, O57483, O60840, O73700, O73705, O73706, O73707, P07293, P15381, P22002, P22316, P27732, P27884, P35500, P54282, P56698, P56699, P91645, P97445, Q00975, Q01668, Q01815, Q02294, Q02343, Q02485, Q02789, Q05152, Q07652, Q13698, Q13936, Q15878, Q24270, Q25452, Q61290, Q99244

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
PRKD1	up-regulates	CACNA1C	phosphorylation
Isradipine	“down-regulates activity”	CACNA1C	“chemical inhibition”
CACNA1C	“up-regulates quantity”	calcium(2+)	relocalization
CACNA1C	up-regulates	Excitatory_synaptic_transmission
DCC	“up-regulates activity”	CACNA1C
SRC	“up-regulates activity”	CACNA1C	phosphorylation
PRKACA	“up-regulates activity”	CACNA1C	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transmission across Chemical Synapses	6	14.7×	5e-04
Neuronal System	6	8.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

3697 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	42
Likely pathogenic	52
Uncertain significance	1440
Likely benign	1512
Benign	227

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1164022	NM_000719.7(CACNA1C):c.4087G>T (p.Val1363Leu)	Pathogenic
1208559	NM_000719.7(CACNA1C):c.481C>T (p.Arg161Ter)	Pathogenic
1218634	NM_000719.7(CACNA1C):c.4527-2A>G	Pathogenic
1302480	NM_000719.7(CACNA1C):c.3001C>T (p.Arg1001Ter)	Pathogenic
1313855	NM_000719.7(CACNA1C):c.5091+1G>A	Pathogenic
155775	NM_001167623.2(CACNA1C):c.1204G>A (p.Gly402Ser)	Pathogenic
1685596	NM_000719.7(CACNA1C):c.595G>A (p.Asp199Asn)	Pathogenic
1685597	NM_000719.7(CACNA1C):c.1853T>G (p.Val618Gly)	Pathogenic
1695801	NM_000719.7(CACNA1C):c.3606C>G (p.Tyr1202Ter)	Pathogenic
1699036	NM_000719.7(CACNA1C):c.1159dup (p.Thr387fs)	Pathogenic
1705744	NM_000719.7(CACNA1C):c.1969C>T (p.Leu657Phe)	Pathogenic
1705745	NM_000719.7(CACNA1C):c.4222C>G (p.Leu1408Val)	Pathogenic
1712194	NM_000719.7(CACNA1C):c.5897dup (p.Gln1967fs)	Pathogenic
1744618	NM_000719.7(CACNA1C):c.4996C>T (p.Arg1666Ter)	Pathogenic
17632	NM_000719.7(CACNA1C):c.1216G>A (p.Gly406Arg)	Pathogenic
17633	NM_000719.7(CACNA1C):c.1204G>A (p.Gly402Ser)	Pathogenic
17635	NM_000719.7(CACNA1C):c.116C>T (p.Ala39Val)	Pathogenic
190634	NM_001167623.2(CACNA1C):c.1216G>C (p.Gly406Arg)	Pathogenic
190642	NM_000719.7(CACNA1C):c.1552C>T (p.Arg518Cys)	Pathogenic
208682	NM_000719.7(CACNA1C):c.3497T>C (p.Ile1166Thr)	Pathogenic
2251969	NM_000719.7(CACNA1C):c.5403del (p.Ile1802fs)	Pathogenic
2452672	NM_000719.7(CACNA1C):c.3524_3527del (p.Gln1175fs)	Pathogenic
2501348	NM_000719.7(CACNA1C):c.2114G>A (p.Gly705Glu)	Pathogenic
2506866	NM_000719.7(CACNA1C):c.400_401del (p.Ile134fs)	Pathogenic
2626971	NM_000719.7(CACNA1C):c.5884C>T (p.Arg1962Ter)	Pathogenic
2921274	NM_000719.7(CACNA1C):c.4873C>T (p.Gln1625Ter)	Pathogenic
3252305	NM_000719.7(CACNA1C):c.478-2A>G	Pathogenic
3375805	NM_000719.7(CACNA1C):c.5583C>A (p.Tyr1861Ter)	Pathogenic
3377227	NM_000719.7(CACNA1C):c.4097_4101del (p.Leu1366fs)	Pathogenic
3393691	NM_000719.7(CACNA1C):c.3612del (p.Lys1205fs)	Pathogenic

SpliceAI

5663 predictions. Top by Δscore:

Variant	Effect	Δscore
12:1993262:A:AC	donor_gain	1.0000
12:1993263:C:CC	donor_gain	1.0000
12:1993263:CAT:C	donor_gain	1.0000
12:2004281:CCCA:C	donor_gain	1.0000
12:2004284:A:AC	donor_gain	1.0000
12:2004285:C:CC	donor_gain	1.0000
12:2053609:AAGGT:A	donor_loss	1.0000
12:2053610:AGG:A	donor_loss	1.0000
12:2053611:GGT:G	donor_loss	1.0000
12:2053613:T:A	donor_loss	1.0000
12:2115216:T:A	acceptor_gain	1.0000
12:2115218:CCACA:C	acceptor_loss	1.0000
12:2115219:CACAG:C	acceptor_loss	1.0000
12:2115221:CA:C	acceptor_loss	1.0000
12:2115222:A:AC	acceptor_loss	1.0000
12:2115222:A:AG	acceptor_gain	1.0000
12:2115222:AG:A	acceptor_gain	1.0000
12:2115223:G:GT	acceptor_gain	1.0000
12:2115223:GG:G	acceptor_gain	1.0000
12:2448962:T:G	acceptor_gain	1.0000
12:2448966:T:A	acceptor_gain	1.0000
12:2448971:CCTA:C	acceptor_loss	1.0000
12:2448973:TAGG:T	acceptor_loss	1.0000
12:2448974:A:AG	acceptor_gain	1.0000
12:2448975:G:GG	acceptor_gain	1.0000
12:2448975:GGAAC:G	acceptor_gain	1.0000
12:2449111:GTGGG:G	donor_gain	1.0000
12:2449112:TGGG:T	donor_gain	1.0000
12:2449113:GGG:G	donor_gain	1.0000
12:2449113:GGGG:G	donor_gain	1.0000

AlphaMissense

14171 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000032 (12:2363888 A>G), RS1000006012 (12:2288740 G>A), RS1000007202 (12:2467604 G>A,C,T), RS1000010943 (12:2543598 T>C), RS1000012208 (12:2404194 G>A), RS1000038513 (12:2437428 C>G), RS1000042155 (12:2460086 T>C), RS1000048475 (12:2250876 C>T), RS1000057968 (12:2667074 C>T), RS1000064599 (12:1997433 T>G), RS1000070517 (12:2085419 G>A), RS1000070787 (12:2667372 G>T), RS1000073411 (12:2617234 C>G), RS1000080401 (12:2174059 T>C), RS1000080639 (12:2542972 A>C,G)

Disease associations

OMIM: gene MIM:114205 | disease phenotypes: MIM:601005, MIM:611875, MIM:618447, MIM:620029, MIM:601144, MIM:603829, MIM:189800, MIM:192500, MIM:194200, MIM:609620, MIM:604772, MIM:617755, MIM:192600, MIM:617106, MIM:181500, MIM:115080

GenCC curated gene-disease

Disease	Classification	Inheritance
Timothy syndrome	Definitive	Autosomal dominant
neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures	Strong	Autosomal dominant
long QT syndrome 8	Moderate	Autosomal dominant
Brugada syndrome	Supportive	Autosomal dominant
short QT syndrome	Limited	Autosomal dominant
intellectual disability	Limited	Autosomal dominant
Brugada syndrome 3	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (4)

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

Disease	Classification	Inheritance
Brugada syndrome	Disputed	AD
short QT syndrome	Disputed	AD
Timothy syndrome	Definitive	AD
long QT syndrome	Moderate	AD

Mondo (36): long QT syndrome (MONDO:0002442), Timothy syndrome (MONDO:0010979), Brugada syndrome 3 (MONDO:0012742), long QT syndrome 8 (MONDO:0032756), CACNA1C-related disorder (MONDO:0700321), neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures (MONDO:0859286), Brugada syndrome (MONDO:0015263), ventricular fibrillation, paroxysmal familial, type 1 (MONDO:0011376), preeclampsia (MONDO:0005081), congestive heart failure (MONDO:0005009), Timothy syndrome type 1 (MONDO:0035678), post-traumatic stress disorder (MONDO:0005146), familial long QT syndrome (MONDO:0019171), intellectual disability (MONDO:0001071), Wolff-Parkinson-White syndrome (MONDO:0008685)

Orphanet (21): Brugada syndrome (Orphanet:130), Timothy syndrome (Orphanet:65283), Idiopathic ventricular fibrillation (Orphanet:228140), Preeclampsia (Orphanet:275555), Timothy syndrome type 1 (Orphanet:595098), Romano-Ward syndrome (Orphanet:101016), Congenital long QT syndrome (Orphanet:768), Rare cardiomyopathy (Orphanet:167848), Rare hypertrophic cardiomyopathy (Orphanet:217569), Congenital short QT syndrome (Orphanet:51083), Catecholaminergic polymorphic ventricular tachycardia (Orphanet:3286), BPTF-related intellectual disability-facial dysmorphism-skeletal anomalies syndrome (Orphanet:686482), Dilated cardiomyopathy (Orphanet:217604), Amyloidosis (Orphanet:69), Restrictive cardiomyopathy (Orphanet:217632)

HPO phenotypes

101 total (30 of 101 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000160	Narrow mouth
HP:0000219	Thin upper lip vermilion
HP:0000233	Thin vermilion border
HP:0000311	Round face
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000520	Proptosis
HP:0000586	Shallow orbits
HP:0000609	Optic nerve hypoplasia
HP:0000691	Microdontia
HP:0000717	Autism
HP:0000750	Delayed speech and language development
HP:0000821	Hypothyroidism
HP:0001159	Syndactyly
HP:0001195	Single umbilical artery
HP:0001197	Abnormality of prenatal development or birth
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001279	Syncope
HP:0001371	Flexion contracture
HP:0001601	Laryngomalacia
HP:0001629	Ventricular septal defect
HP:0001636	Tetralogy of Fallot
HP:0001640	Cardiomegaly
HP:0001643	Patent ductus arteriosus

GWAS associations

91 associations (top):

Study	Trait	p-value
GCST000204_3	Warfarin maintenance dose	9.000000e-07
GCST000220_19	Bipolar disorder	7.000000e-08
GCST000641_4	Bipolar disorder or major depressive disorder	3.000000e-08
GCST001242_19	Schizophrenia	2.000000e-06
GCST001565_3	Schizophrenia	2.000000e-07
GCST001765_10	Red blood cell traits	3.000000e-09
GCST001877_67	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	5.000000e-09
GCST002049_4	Sleep quality	4.000000e-06
GCST002149_5	Schizophrenia	5.000000e-12
GCST002295_12	Schizophrenia or bipolar disorder	7.000000e-08
GCST002295_5	Schizophrenia or bipolar disorder	6.000000e-13
GCST002295_8	Schizophrenia or bipolar disorder	2.000000e-06
GCST002304_9	Fractional exhaled nitric oxide (childhood)	8.000000e-06
GCST002539_13	Schizophrenia	3.000000e-18
GCST002708_6	Acoustic startle blink response	8.000000e-06
GCST003064_14	Exploratory eye movement dysfunction in schizophrenia (cognitive search score)	6.000000e-06
GCST003264_943	Post bronchodilator FEV1/FVC ratio	5.000000e-06
GCST003818_42	Resting heart rate	7.000000e-20
GCST003962_7	Bipolar disorder	3.000000e-09
GCST004521_297	Autism spectrum disorder or schizophrenia	6.000000e-14
GCST004521_71	Autism spectrum disorder or schizophrenia	8.000000e-14
GCST004601_160	Red blood cell count	1.000000e-16
GCST004604_69	Hematocrit	4.000000e-16
GCST004615_74	Hemoglobin concentration	2.000000e-12
GCST004651_4	Aortic root size	4.000000e-09
GCST004678_4	Psychosis proneness (hypomanic personality scale)	1.000000e-06
GCST004681_6	Psychosis proneness (hypomanic personality scale and revised physical anhedonia scale)	2.000000e-06
GCST004946_108	Schizophrenia	2.000000e-08
GCST004946_71	Schizophrenia	3.000000e-19
GCST005789_18	Resting heart rate	2.000000e-16

EFO canonical traits (26, from GWAS)

EFO ID	Trait name
EFO:0004348	hematocrit
EFO:0005536	nitric oxide exhalation measurement
EFO:0006875	acoustic startle blink response measurement
EFO:0007700	exploratory eye movement measurement
EFO:0004713	FEV/FVC ratio
EFO:0004305	erythrocyte count
EFO:0004509	hemoglobin measurement
EFO:0008337	psychosis predisposition measurement
EFO:0009270	heel bone mineral density
EFO:0006336	diastolic blood pressure
EFO:0007620	volumetric bone mineral density
EFO:0008579	risk-taking behaviour
EFO:0004335	short-term memory
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0009958	response to bisphosphonate
EFO:0009960	atypical femoral fracture
EFO:0009963	bipolar I disorder
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0008354	cognitive function measurement
EFO:0004327	electrocardiography
EFO:0007634	major depressive episode
EFO:0004980	appendicular lean mass
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0004309	platelet count

MeSH disease descriptors (23)

Descriptor	Name	Tree numbers
D000686	Amyloidosis	C18.452.845.500
D019571	Arrhythmogenic Right Ventricular Dysplasia	C14.240.400.145; C14.280.238.028; C14.280.400.145; C16.131.240.400.145
D053840	Brugada Syndrome	C14.280.067.322; C14.280.123.250; C16.320.100
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D002313	Cardiomyopathy, Restrictive	C14.280.238.160
D002547	Cerebral Palsy	C10.228.140.140.254
D004827	Epilepsy	C10.228.140.490
D004933	Esophageal Atresia	C06.198.330; C06.405.117.260; C16.131.314.330
D017219	Gastric Outlet Obstruction	C06.405.748.340
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
D011225	Pre-Eclampsia	C12.050.703.395.249
D011707	Pyloric Stenosis	C06.405.748.340.690
D013313	Stress Disorders, Post-Traumatic	F03.950.750.500
D017180	Tachycardia, Ventricular	C14.280.067.845.940; C14.280.123.875.940; C23.550.073.845.940
D014927	Wolff-Parkinson-White Syndrome	C14.280.067.780.977; C14.280.123.750.977; C16.131.240.400.980
C567509	Brugada Syndrome 3 (supp.)
C580439	Short Qt Syndrome (supp.)
C536962	Timothy syndrome (supp.)
C567851	Ventricular Fibrillation, Paroxysmal Familial, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL1940 (SINGLE PROTEIN), CHEMBL2095229 (PROTEIN FAMILY), CHEMBL2363032 (PROTEIN COMPLEX GROUP), CHEMBL3988638 (PROTEIN COMPLEX), CHEMBL4106164 (PROTEIN COMPLEX), CHEMBL6066567 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

85 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 610,677 (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
CHEMBL1005	REMIFENTANIL	4	10,990
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1078261	PROPIVERINE	4	4,890
CHEMBL1086	DIBUCAINE	4	17,231
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1175	DULOXETINE	4	28,527
CHEMBL1294	QUINIDINE	4	71,943
CHEMBL135	ESTRADIOL	4	123,080
CHEMBL1382	TOLTERODINE	4	13,460
CHEMBL1423	PIMOZIDE	4	17,310
CHEMBL1428	NIMODIPINE	4	32,587
CHEMBL1484	NICARDIPINE	4	30,866
CHEMBL1491	AMLODIPINE	4	39,495
CHEMBL1520	VARDENAFIL	4	21,078
CHEMBL1626	CLEMASTINE	4	17,590
CHEMBL1648	ISRADIPINE	4	20,026
CHEMBL17157	TERFENADINE	4	25,393
CHEMBL1726	NISOLDIPINE	4	18,921
CHEMBL1734	SOLIFENACIN	4	296
CHEMBL1909324	PINAVERIUM	4
CHEMBL192	SILDENAFIL	4
CHEMBL193	NIFEDIPINE	4
CHEMBL21536	XANOMELINE	4
CHEMBL23	DILTIAZEM	4
CHEMBL24072	PRENYLAMINE	4
CHEMBL2443262	OLICERIDINE	4
CHEMBL27	PROPRANOLOL	4
CHEMBL270190	ALVIMOPAN	4
CHEMBL296419	ASTEMIZOLE	4

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

PharmGKB clinical annotations

10 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1006737	Toxicity	3	citalopram	Major Depressive Disorder
rs1034936	Toxicity	3	ethanol	Alcohol abuse;Bipolar Disorder
rs1051375	Efficacy	3	atenolol;verapamil	Coronary Artery Disease;Hypertension
rs10774053	Toxicity	3	ritodrine	adverse events;Premature Birth
rs10848635	Toxicity	3	citalopram	Major Depressive Disorder
rs2238032	Efficacy	3	Calcium channel blockers	Hypertension
rs2239050	Efficacy	3	nimodipine
rs2239050	Efficacy	3	Calcium channel blockers	Hypertension
rs2239128	Efficacy	3	nimodipine
rs2239128	Efficacy	3	Calcium channel blockers	Hypertension

PharmGKB variants

21 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs215976	CACNA1C		0.00	0
rs216008	CACNA1C		0.00	0
rs216013	CACNA1C		0.00	0
rs723672	CACNA1C		0.00	0
rs758723	CACNA1C		0.00	0
rs1006737	CACNA1C	3	0.00	1	citalopram
rs1051375	CACNA1C	3	2.50	1	atenolol;verapamil
rs2238032	CACNA1C	3	6.75	1	Calcium channel blockers
rs2239050	CACNA1C	3	6.75	2	nimodipine;Calcium channel blockers
rs2239128	CACNA1C	3	2.50	2	Calcium channel blockers;nimodipine
rs2283271	CACNA1C		0.00	0
rs7295250	CACNA1C		0.00	0
rs7316246	CACNA1C		0.00	0
rs10848635	CACNA1C	3	0.00	1	citalopram
rs11062040	CACNA1C, DCP1B		0.00	0
rs12813888	CACNA1C		0.00	0
rs10774053	CACNA1C	3	1.50	1	ritodrine
rs215994	CACNA1C		0.00	0
rs2041135	CACNA1C, DCP1B		0.00	0
rs2238087	CACNA1C		0.00	0
rs1034936	CACNA1C	3	2.50	1	ethanol

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 (19 total), top 19:

Ligand	Action	Affinity	Parameter
3H-isradipine	Antagonist	11.0	pKd
nitrendipine	Antagonist	9.4	pIC50
amlodipine	Gating inhibitor	9.3	pIC50
nifedipine	Antagonist	8.7	pIC50
isradipine	Antagonist	8.5	pIC50
3Hdevapamil	Antagonist	8.4	pKd
calciseptine	Antagonist	7.8	pIC50
(-)-(S)-BayK8644	Activator	7.76	pEC50
(-)-devapamil	Antagonist	7.3	pIC50
3H-cis-diltiazem	Antagonist	7.2	pKd
nisoldipine	Antagonist	7.1	pIC50
nimodipine	Antagonist	6.8	pIC50
verapamil	Antagonist	6.5	pIC50
Pb2+	Antagonist	6.4	pIC50
diltiazem	Antagonist	6.3	pIC50
Cd2+	Channel blocker	6.0	pIC50
benidipine	Antagonist	5.31	pIC50
mibefradil	Antagonist	4.9	pIC50
(-)-(R)-efonidipine	Antagonist	3.5	pIC50

Binding affinities (BindingDB)

28 measured of 117 human assays (117 total across all organisms); most potent 28 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[(6S)-3-ethyl-6-(2H-tetrazol-5-ylmethyl)-6-bicyclo[3.2.0]hept-3-enyl]methanamine	IC50	2.1 nM	US-9663479: γ-aminobutyric acid (GABA) analogues for the treatment of pain and other disorders
[(1R,5S,6S)-3-ethyl-6-(2H-tetrazol-5-ylmethyl)-6-bicyclo[3.2.0]hept-3-enyl]methanamine	IC50	4.2 nM	US-9663479: γ-aminobutyric acid (GABA) analogues for the treatment of pain and other disorders
3-[[(1R,5S,6S)-6-(aminomethyl)-3-ethyl-6-bicyclo[3.2.0]hept-3-enyl]methyl]-1,2,4-oxadiazolidin-5-one	IC50	19 nM	US-9663479: γ-aminobutyric acid (GABA) analogues for the treatment of pain and other disorders
3-(aminomethyl)-5-methylhexanoic acid	IC50	23 nM	US-9663479: γ-aminobutyric acid (GABA) analogues for the treatment of pain and other disorders
CHEMBL2110302	KI	30 nM
[(6R)-3-ethyl-6-(2H-tetrazol-5-ylmethyl)-6-bicyclo[3.2.0]hept-3-enyl]methanamine	IC50	165 nM	US-9663479: γ-aminobutyric acid (GABA) analogues for the treatment of pain and other disorders
CHEMBL2110168	KI	250 nM
CHEMBL3609818	IC50	455 nM
CHEMBL2110303	KI	500 nM
CHEMBL3608947	IC50	648 nM
CHEMBL2110169	KI	650 nM
SR 147778	KI	1000 nM
CHEMBL2110298	KI	3000 nM
2-[3-[[4,6-bis(trifluoromethyl)-1H-benzimidazol-2-yl]methyl]azetidin-1-yl]-N-tert-butylacetamide	IC50	3560 nM	US-9688615: Benzimidazole inhibitors of the sodium channel
1-[4,6-bis(trifluoromethyl)-1H-benzimidazol-2-yl]-2-methylpropan-2-amine	IC50	3600 nM	US-9688615: Benzimidazole inhibitors of the sodium channel
2-(azetidin-3-ylmethyl)-5,6-bis(trifluoromethyl)-1H-benzimidazole	IC50	4300 nM	US-9688615: Benzimidazole inhibitors of the sodium channel
1-[[4,6-bis(trifluoromethyl)-1H-benzimidazol-2-yl]methyl]cyclohexan-1-amine	IC50	4650 nM	US-9688615: Benzimidazole inhibitors of the sodium channel
CHEMBL2110170	KI	5000 nM
CHEMBL2110167	KI	5000 nM
2-(2,2,2-trifluoroethyl)-4,6-bis(trifluoromethyl)-1H-benzimidazole	IC50	5300 nM	US-9688615: Benzimidazole inhibitors of the sodium channel
N-[[4,6-bis(trifluoromethyl)-1H-benzimidazol-2-yl]methyl]-3,3-dimethylbutanamide	IC50	6000 nM	US-9688615: Benzimidazole inhibitors of the sodium channel
CHEMBL2110301	KI	6000 nM
3-[4,6-bis(trifluoromethyl)-1H-benzimidazol-2-yl]propan-1-amine	IC50	7500 nM	US-9688615: Benzimidazole inhibitors of the sodium channel
1-[[4,6-bis(trifluoromethyl)-1H-benzimidazol-2-yl]methyl]-3-tert-butylurea	IC50	8100 nM	US-9688615: Benzimidazole inhibitors of the sodium channel
tert-butyl N-[[4,6-bis(trifluoromethyl)-1H-benzimidazol-2-yl]methyl]carbamate	IC50	8120 nM	US-9688615: Benzimidazole inhibitors of the sodium channel
tert-butyl N-[[4,6-bis(trifluoromethyl)-1H-benzimidazol-2-yl]methyl]-N-methylcarbamate	IC50	8300 nM	US-9688615: Benzimidazole inhibitors of the sodium channel
(3S)-3-(aminomethyl)-N-[[4,6-bis(trifluoromethyl)-1H-benzimidazol-2-yl]methyl]-5-methylhexanamide	IC50	9000 nM	US-9688615: Benzimidazole inhibitors of the sodium channel
N-[[4,6-bis(trifluoromethyl)-1H-benzimidazol-2-yl]methyl]-2-(tert-butylamino)-N-methylacetamide	IC50	9900 nM	US-9688615: Benzimidazole inhibitors of the sodium channel

ChEMBL bioactivities

445 potent at pChembl≥5 of 590 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	Ki	0.25	nM	NITRENDIPINE
9.60	IC50	0.25	nM	CHEMBL105444
9.59	Kd	0.26	nM	NITRENDIPINE
9.46	IC50	0.35	nM	NITRENDIPINE
9.41	IC50	0.39	nM	CHEMBL35123
9.40	Kd	0.4	nM	NIFEDIPINE
9.00	IC50	1	nM	NITRENDIPINE
9.00	Ki	1	nM	NIFEDIPINE
9.00	Ki	1	nM	CHEMBL159854
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
8.68	IC50	2.1	nM	CHEMBL5998077
8.66	IC50	2.2	nM	ISRADIPINE
8.64	IC50	2.3	nM	CHEMBL102498
8.62	IC50	2.4	nM	CHEMBL3973392
8.59	IC50	2.6	nM	CHEMBL89049
8.59	Kd	2.6	nM	CHEMBL3392281
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	NISOLDIPINE
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
8.39	Ki	4.11	nM	CHEMBL104455
8.38	IC50	4.2	nM	CHEMBL5769314
8.35	IC50	4.5	nM	CHEMBL3965812
8.30	Kd	5	nM	CHEMBL23692
8.28	IC50	5.2	nM	CHEMBL89175
8.27	Ki	5.4	nM	GALLOPAMIL
8.23	IC50	5.9	nM	CHEMBL3906126

PubChem BioAssay actives

338 with measured affinity, of 1768 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
Nifedipine	56025: Displacement of [3H]nitrendipine from dihydropyridine receptor of guinea pig myocardial membranes	kd	0.0004	uM
diethyl 2,6-dimethyl-4-(2-methylsulfanyl-3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	56027: Inhibition of [3H]nitrendipine binding to L-type calcium channel dihydropyridine site of porcine cardiac sarcolemma membrane vesicles	ki	0.0010	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
Isradipine	1207661: Inhibition of L-type calcium channel measured using 2-electrode voltage-clamp in human embryonic kidney cells heterologically expressing alpha-1C subunit	ic50	0.0022	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
butan-2-yl 6-methyl-2-methylsulfanyl-4-(3-nitrophenyl)-1,4-dihydropyrimidine-5-carboxylate	45616: Inhibition of [3H]nitrendipine binding to L-type calcium channel in guinea pig ventricular myocardium membranes	kd	0.0026	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
diethyl 2,6-dimethyl-4-[3-methyl-5-(2-naphthalen-1-ylethyl)-1,2-oxazol-4-yl]-1,4-dihydropyridine-3,5-dicarboxylate	45620: Displacement of 3H-PN200-110 binding to calcium channels in guinea pig cardiac membranes.	ki	0.0041	uM
6-methyl-4-methylsulfanyl-17-nitro-9-oxa-15-thia-3,5-diazatricyclo[14.4.0.02,7]icosa-1(16),3,6,17,19-pentaen-8-one	56025: Displacement of [3H]nitrendipine from dihydropyridine receptor of guinea pig myocardial membranes	kd	0.0050	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
diethyl 4-[5-[2-(3-bromophenyl)ethyl]-3-phenyl-1,2-oxazol-4-yl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate	45620: Displacement of 3H-PN200-110 binding to calcium channels in guinea pig cardiac membranes.	ki	0.0069	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
propan-2-yl 6-methyl-2-methylsulfanyl-4-(3-nitrophenyl)-1,4-dihydropyrimidine-5-carboxylate	45616: Inhibition of [3H]nitrendipine binding to L-type calcium channel in guinea pig ventricular myocardium membranes	kd	0.0120	uM
diethyl 2,6-dimethyl-4-(5-methyl-3-phenyl-1,2-oxazol-4-yl)-1,4-dihydropyridine-3,5-dicarboxylate	45624: Inhibition of [3H]PN-200110 binding to Calcium channel in guinea pig heart membrane	ki	0.0139	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
6-methyl-4-methylsulfanyl-9-oxa-15-thia-3,5-diazatricyclo[14.4.0.02,7]icosa-1(20),3,6,16,18-pentaen-8-one	56025: Displacement of [3H]nitrendipine from dihydropyridine receptor of guinea pig myocardial membranes	kd	0.0180	uM
methyl (4S)-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate	56025: Displacement of [3H]nitrendipine from dihydropyridine receptor of guinea pig myocardial membranes	kd	0.0180	uM
diethyl 2,6-dimethyl-4-[3-methyl-5-[2-(4-phenylphenyl)ethyl]-1,2-oxazol-4-yl]-1,4-dihydropyridine-3,5-dicarboxylate	45620: Displacement of 3H-PN200-110 binding to calcium channels in guinea pig cardiac membranes.	ki	0.0182	uM
diethyl 2,6-dimethyl-4-[3-methyl-5-(2-naphthalen-2-ylethyl)-1,2-oxazol-4-yl]-1,4-dihydropyridine-3,5-dicarboxylate	45620: Displacement of 3H-PN200-110 binding to calcium channels in guinea pig cardiac membranes.	ki	0.0202	uM
diethyl 2,6-dimethyl-4-[3-methyl-5-(2-phenylethyl)-1,2-oxazol-4-yl]-1,4-dihydropyridine-3,5-dicarboxylate	45620: Displacement of 3H-PN200-110 binding to calcium channels in guinea pig cardiac membranes.	ki	0.0229	uM
ethyl 6-methyl-2-methylsulfanyl-4-(3-nitrophenyl)-1,4-dihydropyrimidine-5-carboxylate	45616: Inhibition of [3H]nitrendipine binding to L-type calcium channel in guinea pig ventricular myocardium membranes	kd	0.0230	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

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression, increases expression	3
sodium arsenite	affects methylation, decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Cadmium	affects expression, decreases expression, increases abundance, increases expression	3
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	3
Sunitinib	decreases activity, decreases expression	2
Calcium	affects cotreatment, increases transport, affects binding, increases reaction	2
Methotrexate	decreases expression, increases expression	2
Valproic Acid	increases methylation, decreases methylation	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Peroxynitrous Acid	affects cotreatment, increases nitrosation, decreases reaction, increases phosphorylation, increases metabolic processing (+1 more)	2
MYK-461	decreases reaction, decreases expression	1
linsidomine	affects cotreatment, increases nitrosation	1
triphenyl phosphate	affects expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	increases abundance, affects methylation	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	increases expression	1
benzo(e)pyrene	affects methylation, increases methylation	1
aflatoxin B2	increases methylation	1
nefazodone	affects activity	1
astragaloside A	decreases reaction, increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
ezogabine	affects activity	1
bardoxolone methyl	decreases activity	1
torcetrapib	increases expression	1
Dasatinib	increases expression	1
Fulvestrant	increases methylation, affects cotreatment, decreases methylation	1
Deferiprone	decreases reaction, increases abundance, increases expression	1
Crizotinib	decreases activity	1

ChEMBL screening assays

575 unique, capped per target: 319 binding, 211 functional, 26 toxicity, 19 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001517	Binding	Activity at Cav 1.2 channel	Discovery of spirocyclic secondary amine-derived tertiary ureas as highly potent, selective and bioavailable soluble epoxide hydrolase inhibitors. — Bioorg Med Chem Lett
CHEMBL3430354	Functional	Inhibition of long-lasting type calcium current (hICa) in Chinese Hamster Ovary (CHO) cells expressing hCav1.2 measured using IonWorks Quattro automated patch clamp platform	Prediction of Thorough QT study results using action potential simulations based on ion channel screens. — J Pharmacol Toxicol Methods
CHEMBL4270327	ADMET	Inhibition of Cav1.2 (unknown origin)	Optimization of Preclinical Metabolism for Somatostatin Receptor Subtype 5-Selective Antagonists. — ACS Med Chem Lett

Cellosaurus cell lines

17 cell lines: 11 induced pluripotent stem cell, 4 transformed cell line, 1 cancer cell line, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_2491	HH-8	Transformed cell line	Female
CVCL_D7L7	Ubigene A-549 CACNA1C KO	Cancer cell line	Male
CVCL_D9AH	Ubigene HEK293 CACNA1C KO	Transformed cell line	Female
CVCL_N700	HL-2	Transformed cell line	Female
CVCL_RM56	T7643-3	Induced pluripotent stem cell	Female
CVCL_RM57	T7643-32	Induced pluripotent stem cell	Female
CVCL_RM58	T7643-5	Induced pluripotent stem cell	Female
CVCL_RM59	T7643-7	Induced pluripotent stem cell	Female
CVCL_RM60	T9862-35	Induced pluripotent stem cell	Sex unspecified
CVCL_RM61	T9862-40	Induced pluripotent stem cell	Sex unspecified

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT00702117	PHASE4	COMPLETED	Ajmaline Utilization in the Diagnosis and Treatment of Cardiac Arrhythmias
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
NCT02201914	PHASE4	UNKNOWN	Clomiphene Citrate Plus Gonadotropins and GnRH Antagonist Versus Flexible GnRH Antagonist Protocol Versus Microdose GnRH Agonist Protocol in Poor Responders Undergoing IVF
NCT02651285	PHASE4	UNKNOWN	Use of G-CSF Supplemented IVF Medium in Patients Undergoing IVF
NCT04002635	PHASE4	WITHDRAWN	Letrozole for Frozen Embryo Transfer (FET) in Patients With Polycystic Ovary Syndrome (PCOS)
NCT04385342	PHASE4	UNKNOWN	FSH Followed by HMG vs FSH Plus HMG in IVF
NCT04487925	PHASE4	RECRUITING	Controlled Ovarian Stimulation Versus Modified Natural Cycles in Poor Responders
NCT04654741	PHASE4	UNKNOWN	The Rate of Embryo Euploidy in Progestin-primed Ovarian Stimulation Cycles
NCT04728659	PHASE4	UNKNOWN	Desogestrel Versus GnRH Antagonist in IVF/ICSI
NCT04993924	PHASE4	UNKNOWN	GnRH Antagonist Pre-treatment in the Early Follicular Phase for Resolution of a Baseline Functional Ovarian Cyst
NCT05071339	PHASE4	UNKNOWN	GnRH Antagonist Pre-treatment for the Prevention of Asynchronous Follicular Growth
NCT05321511	PHASE4	UNKNOWN	Comparison of Triggers in Double Ovarian Stimulation (DuoStim).
NCT05954962	PHASE4	COMPLETED	Efficacy of Micronized Natural Progesterone vs GnRH Antagonist in the Prevention of LH Peak During Ovarian Stimulation.
NCT06181305	PHASE4	UNKNOWN	Endometrial Preparation in Frozen Embryo Transfer Cycles
NCT06396390	PHASE4	NOT_YET_RECRUITING	Comparison of Progestin Primed Ovarian Stimulation (PPOS) vs.GnRH Antagonist Methods on IVF Outcomes
NCT07499804	PHASE4	RECRUITING	Effect of Tadalafil on Endometrial Thickness and Frozen Embryo Transfer Outcomes
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
NCT00701077	PHASE3	TERMINATED	DAPERB 3,4-DiAminoPyridine and Electrophysiological Response in Brugada Syndrome
NCT00927732	PHASE3	TERMINATED	Hydroquinidine Versus Placebo in Patients With Brugada Syndrome
NCT04414761	PHASE3	COMPLETED	Live Birth Rate Between PPOS and GnRH Antagonist Protocol in Patients With Anticipated High Ovarian Response
NCT04806919	PHASE3	COMPLETED	Luteal Support in Artificial Vitrified/Warmed Cycles With Low Progesterone
NCT05972902	PHASE3	UNKNOWN	Dydrogesterone, Cetrorelix Acetate and Triptorelin in Intra Cytoplasmic Sperm Injection Outcomes
NCT06048666	PHASE3	UNKNOWN	Platelet Rich Plasma on Ovarian Reserve Parameters and Intra Cytoplasmic Sperm Injection Outcomes in Patients With Diminished Ovarian Reserve
NCT06405204	PHASE3	NOT_YET_RECRUITING	of Myo-inositol, Melatonin and Co-enzyme q10 on Ovarian Reserve
NCT07499817	PHASE3	RECRUITING	Effect of Pentoxyfilline on Endometrial Thickness and Frozen Embryo Transfer Outcomes
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
NCT02933437	PHASE2	UNKNOWN	The Response To Ajmaline Provocation in Healthy Subjects
NCT07146880	PHASE2	NOT_YET_RECRUITING	Empagliflozin as a Potential Therapeutic Solution for Patients With Brugada Syndrome
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns