CACNA2D1

Summary

CACNA2D1 (calcium voltage-gated channel auxiliary subunit alpha2delta 1, HGNC:1399) is a protein-coding gene on chromosome 7q21.11, encoding Voltage-dependent calcium channel subunit alpha-2/delta-1 (P54289). The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel.

The preproprotein encoded by this gene is cleaved into multiple chains that comprise the alpha-2 and delta subunits of the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. Mutations in this gene can cause cardiac deficiencies, including Brugada syndrome and short QT syndrome. Alternate splicing results in multiple transcript variants, some of which may lack the delta subunit portion.

Source: NCBI Gene 781 — RefSeq curated summary.

At a glance

• Gene–disease (curated): short QT syndrome (Supportive, GenCC) — +4 more curated relationships
• GWAS associations: 18
• Clinical variants (ClinVar): 1,160 total — 3 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 90
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000722

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1399
Approved symbol	CACNA2D1
Name	calcium voltage-gated channel auxiliary subunit alpha2delta 1
Location	7q21.11
Locus type	gene with protein product
Status	Approved
Aliases	lncRNA-N3, alpha2delta-1
Ensembl gene	ENSG00000153956
Ensembl biotype	protein_coding
OMIM	114204
Entrez	781

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 10 protein_coding, 5 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000356860, ENST00000423588, ENST00000443883, ENST00000461275, ENST00000464354, ENST00000466806, ENST00000469297, ENST00000475237, ENST00000484706, ENST00000486539, ENST00000492734, ENST00000705961, ENST00000705962, ENST00000855771, ENST00000957014, ENST00000957015, ENST00000957016, ENST00000957017

RefSeq mRNA: 3 — MANE Select: NM_000722 NM_000722, NM_001302890, NM_001366867

CCDS: CCDS5598, CCDS78253, CCDS94135

Canonical transcript exons

ENST00000356860 — 39 exons

Exon	Start	End
ENSE00001013277	82005423	82005497
ENSE00001013282	81997179	81997250
ENSE00001013289	81984635	81984711
ENSE00001013292	81991185	81991246
ENSE00001013295	81994868	81994939
ENSE00001382257	81983314	81983334
ENSE00001591696	81968887	81968973
ENSE00001591708	81971777	81971864
ENSE00001599950	81965594	81965665
ENSE00001614813	81959275	81959357
ENSE00001615998	81974455	81974552
ENSE00001650093	82349568	82349649
ENSE00001667342	81970675	81970737
ENSE00001669611	81964207	81964359
ENSE00001766198	82084769	82084900
ENSE00001776796	81967169	81967207
ENSE00001781834	81964056	81964108
ENSE00001785040	81959720	81959829
ENSE00001829870	81946444	81950508
ENSE00001957353	82443365	82443777
ENSE00002152258	81982567	81982627
ENSE00003466357	82060428	82060527
ENSE00003472969	82136635	82136676
ENSE00003477809	82335135	82335251
ENSE00003484524	82170550	82170609
ENSE00003488692	82005765	82005839
ENSE00003489599	82064304	82064354
ENSE00003497123	82038077	82038235
ENSE00003498673	82032797	82032901
ENSE00003511576	81962440	81962495
ENSE00003513045	82117044	82117173
ENSE00003516100	82066455	82066524
ENSE00003536806	82012154	82012243
ENSE00003568220	81961894	81962023
ENSE00003591271	82007679	82007756
ENSE00003619130	81967596	81967663
ENSE00003651871	82014401	82014479
ENSE00003671423	82013461	82013510
ENSE00003790630	81969881	81969984

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 99.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.2504 / max 524.8450, expressed in 1237 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84598	6.5346	1123
84596	4.4013	930
84595	1.3542	629
84597	1.2695	767
84592	0.8238	434
84591	0.6525	287
84593	0.4256	245
84579	0.2977	27
84594	0.1468	50
84599	0.1305	49

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
biceps brachii	UBERON:0001507	99.23	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.12	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.04	gold quality
body of tongue	UBERON:0011876	97.43	gold quality
endothelial cell	CL:0000115	97.41	gold quality
postcentral gyrus	UBERON:0002581	96.42	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.40	gold quality
parietal lobe	UBERON:0001872	96.18	gold quality
entorhinal cortex	UBERON:0002728	95.92	gold quality
adrenal tissue	UBERON:0018303	95.77	gold quality
heart right ventricle	UBERON:0002080	95.39	gold quality
middle temporal gyrus	UBERON:0002771	94.58	gold quality
superior frontal gyrus	UBERON:0002661	94.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.23	gold quality
gastrocnemius	UBERON:0001388	93.98	gold quality
muscle of leg	UBERON:0001383	93.90	gold quality
cortical plate	UBERON:0005343	93.85	gold quality
superior vestibular nucleus	UBERON:0007227	93.43	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.20	gold quality
colonic epithelium	UBERON:0000397	92.88	gold quality
dorsal root ganglion	UBERON:0000044	92.81	gold quality
germinal epithelium of ovary	UBERON:0001304	92.69	gold quality
tongue	UBERON:0001723	91.29	gold quality
corpus callosum	UBERON:0002336	91.13	gold quality
muscle organ	UBERON:0001630	91.03	gold quality
buccal mucosa cell	CL:0002336	90.76	gold quality
parietal pleura	UBERON:0002400	89.96	gold quality
calcaneal tendon	UBERON:0003701	89.95	gold quality
vena cava	UBERON:0004087	89.88	gold quality
trigeminal ganglion	UBERON:0001675	89.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	14.62
E-GEOD-83139	yes	8.92
E-ANND-3	yes	7.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

277 targeting CACNA2D1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
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-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593

Literature-anchored findings (GeneRIF, showing 28)

• CACNA2D1 has structural domains which contribute to the regulation of N-type calcium channel inactivation (PMID:14602720)
• 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)
• Ion channel gating is regulated by calcium and calmodulin binding. (PMID:17438119)
• Timothy syndrome is a disease of excessive cellular Ca(2+) entry and life-threatening arrhythmias caused by a mutation in the primary cardiac L-type Ca(2+) channel (Ca(V)1.2). (PMID:19001023)
• (Review) In neurons, alpha2delta1 subunits are present mainly in presynaptic terminals; peripheral sensory nerve injury results in up-regulation of alpha2delta1 in dorsal root ganglion neurons, and there is consequent increase in trafficking of alpha2delta1 to their terminals. (PMID:20579869)
• CACNA2D1 is a novel Brugada Syndrome susceptibility gene. (PMID:20817017)
• Results show that mutation of CACNA2D1 gene causes a new varant of SCTS. (PMID:21383000)
• In neocortical slices from transgenic mice having a point mutation (i.e., R217A) of the alpha2delta-1 subunit of voltage-sensitive calcium channels, pregabalin does not affect potassium-evoked glutamate release, yet inhibits this release in wild-type mice. (PMID:21464332)
• this study reports the identification and characterization of the human alpha2delta-1 subunit gene promoter region and its regulation by specific transcription factor 1. (PMID:23242029)
• High prevalence of CACNA2D1, SCN5A, and CACNB2 genetic variants in the Danish population previously associated with Brugada syndrome has been found in new exome data. (PMID:23414114)
• Functional expression of CACNA2D1 is inhibited by prion protein expression with competition at glycosylphosphatidylinositol. (PMID:24329154)
• Compound mutation of CACNA2D1 and RANGRF genes were found. To the best of our knowledge, this is the first comprehensive description of the concurrence of these two mutations and histiocytoid cardiomyopathy. (PMID:24438356)
• All three patients present with epilepsy and intellectual disability pinpointing the CACNA2D1 gene as an interesting candidate gene for these clinical features. (PMID:25074461)
• detected a joint effect of SNP and G x E interaction in BMP2 and CACNA2D1 for depressive state. (PMID:26845276)
• we report an additional patient with the 7q21.11 deletion syndrome and provide evidence that haploinsufficiency for a single gene may not be the disease mechanism. In vitro studies of the interaction between PCLO and CACNA2D1 will be required to examine the hypothesis that combined haploinsufficiency for these two synaptic proteins results in neuronal dysfunction (PMID:28240412)
• REVIEW: recent findings related to maladaptive changes in the dysregulated VGCC alpha2 delta1 subunit (Cav alpha2 delta1 ) with a focus on exploring the mechanisms underlying the contribution of Cav alpha2 delta1 to pain signal transduction (PMID:28646556)
• Using human genome-wide association study (GWAS) data, evidence for association of a CACNA2D1 single-nucleotide polymorphism and primary open angle glaucoma is found. (PMID:29176626)
• SCLC cells expressing alpha2delta1 demonstrated CSC-like properties, and may contribute to chemoresistance. ERK may play a key role in alpha2delta1-mediated chemoresistance. (PMID:29437792)
• alpha2delta-1-NMDAR complexes in the hypothalamus serve as an important molecular substrate for the interaction between the sympathetic nervous system and the renin-angiotensin system (PMID:29921713)
• TROY may therefore be a new molecular marker to aid in identifying and selecting patients undergoing radical cystectomy who could potentially benefit from multimodal treatment. (PMID:30475757)
• MicroRNA-107 inhibits proliferation and invasion of laryngeal squamous cell carcinoma cells by targeting CACNA2D1 in vitro. (PMID:31725046)
• CaV alpha2delta Autoimmune Encephalitis: A Novel Antibody and its Characteristics. (PMID:33415786)
• Calcium channel alpha2delta1 subunit is a functional marker and therapeutic target for tumor-initiating cells in non-small cell lung cancer. (PMID:33707423)
• The alpha2delta1 subunit of the voltage-gated calcium channel acts as a potential candidate for breast cancer tumor initial cells biomarker. (PMID:33896833)
• Calcium Channel Subunit alpha2delta-1 as a Potential Biomarker Reflecting Illness Severity and Neuroinflammation in Patients with Acute Ischemic Stroke. (PMID:34049015)
• Biallelic CACNA2D1 loss-of-function variants cause early-onset developmental epileptic encephalopathy. (PMID:35293990)
• EMC chaperone-CaV structure reveals an ion channel assembly intermediate. (PMID:37196677)
• CACNA2D1 regulates the progression and influences the microenvironment of colon cancer. (PMID:38536483)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cacna2d1a	ENSDARG00000014804
danio_rerio	CACNA2D1	ENSDARG00000073752
mus_musculus	Cacna2d1	ENSMUSG00000040118
rattus_norvegicus	Cacna2d1	ENSRNOG00000033531
drosophila_melanogaster	stj	FBGN0261041
caenorhabditis_elegans		WBGENE00006772

Paralogs (4): CACNA2D2 (ENSG00000007402), CACNA2D4 (ENSG00000151062), CACNA2D3 (ENSG00000157445), CACHD1 (ENSG00000158966)

Protein

Protein identifiers

Voltage-dependent calcium channel subunit alpha-2/delta-1 — P54289 (reviewed: P54289)

Alternative names: Voltage-gated calcium channel subunit alpha-2/delta-1

All UniProt accessions (5): P54289, A0A994J595, A0A994J5M8, E7ERK3, H0Y715

UniProt curated annotations — full annotation on UniProt →

Function. The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-contraction coupling.

Subunit / interactions. Dimer formed of alpha-2-1 and delta-1 chains; disulfide-linked. Voltage-dependent calcium channels are multisubunit complexes, consisting of alpha-1 (CACNA1), alpha-2 (CACNA2D), beta (CACNB) and delta (CACNA2D) subunits in a 1:1:1:1 ratio.

Subcellular location. Membrane. Cell membrane.

Tissue specificity. Isoform 1 is expressed in skeletal muscle. Isoform 2 is expressed in the central nervous system. Isoform 2, isoform 4 and isoform 5 are expressed in neuroblastoma cells. Isoform 3, isoform 4 and isoform 5 are expressed in the aorta.

Post-translational modifications. Proteolytically processed into subunits alpha-2-1 and delta-1 that are disulfide-linked.

Disease relevance. Developmental and epileptic encephalopathy 110 (DEE110) [MIM:620149] A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE110 is an autosomal recessive form characterized by profound global developmental delay and hypotonia apparent in infancy followed by onset of seizures in the first months or years of life. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The MIDAS-like motif in the VWFA domain binds divalent metal cations and is required to promote trafficking of the alpha-1 (CACNA1) subunit to the plasma membrane by an integrin-like switch.

Miscellaneous. Binds gabapentin, an antiepileptic drug.

Similarity. Belongs to the calcium channel subunit alpha-2/delta family.

Isoforms (5)

UniProt ID	Names	Canonical?
P54289-1	1, Alpha-2a	yes
P54289-2	2, Alpha-2b
P54289-3	3, Alpha-2c
P54289-4	4, Alpha-2d
P54289-5	5, Alpha-2e

RefSeq proteins (3): NP_000713, NP_001289819, NP_001353796 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002035	VWF_A	Domain
IPR013608	VWA_N	Domain
IPR013680	VDCC_a2/dsu	Domain
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR051173	Ca_channel_alpha-2/delta	Family

Pfam: PF00092, PF08399, PF08473

UniProt features (148 total): strand 59, helix 37, glycosylation site 16, turn 11, sequence conflict 4, chain 3, binding site 3, splice variant 3, sequence variant 3, topological domain 2, domain 2, signal peptide 1, modified residue 1, disulfide bond 1, transmembrane region 1, short sequence motif 1

Structure

Experimental structures (PDB)

30 structures.

PDB	Method	Resolution (Å)
7VFS	ELECTRON MICROSCOPY	2.8
8WE6	ELECTRON MICROSCOPY	2.9
8WE8	ELECTRON MICROSCOPY	2.9
8X93	ELECTRON MICROSCOPY	2.92
8X90	ELECTRON MICROSCOPY	2.95
7MIX	ELECTRON MICROSCOPY	3
7UHG	ELECTRON MICROSCOPY	3
7VFU	ELECTRON MICROSCOPY	3
7VFV	ELECTRON MICROSCOPY	3
7YG5	ELECTRON MICROSCOPY	3
8WE9	ELECTRON MICROSCOPY	3
9VLG	ELECTRON MICROSCOPY	3.01
7MIY	ELECTRON MICROSCOPY	3.1
7UHF	ELECTRON MICROSCOPY	3.1
7XLQ	ELECTRON MICROSCOPY	3.1
8E59	ELECTRON MICROSCOPY	3.1
8EPL	ELECTRON MICROSCOPY	3.1
8EPM	ELECTRON MICROSCOPY	3.1
8X91	ELECTRON MICROSCOPY	3.11
8WE7	ELECTRON MICROSCOPY	3.2
8WEA	ELECTRON MICROSCOPY	3.2
8IF3	ELECTRON MICROSCOPY	3.23
8IF4	ELECTRON MICROSCOPY	3.23
7VFW	ELECTRON MICROSCOPY	3.3
8E5A	ELECTRON MICROSCOPY	3.3
8E5B	ELECTRON MICROSCOPY	3.3
8FHS	ELECTRON MICROSCOPY	3.3
8HMB	ELECTRON MICROSCOPY	3.3
8HMA	ELECTRON MICROSCOPY	3.4
8HLP	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54289-F1	86.97	0.62

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): 259; 261; 263

Post-translational modifications (1): 119

Disulfide bonds (1): 404–1059

Glycosylation sites (16): 92, 136, 184, 324, 348, 468, 475, 604, 613, 675, 781, 824, 888, 895, 985, 998

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9856532	Mechanical load activates signaling by PIEZO1 and integrins in osteocytes
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9855142	Cellular responses to mechanical stimuli

MSigDB gene sets: 486 (showing top): GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_BUNDLE_OF_HIS_CELL_TO_PURKINJE_MYOCYTE_COMMUNICATION, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOCC_SECRETORY_GRANULE, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_MEMBRANE_DEPOLARIZATION_DURING_ACTION_POTENTIAL, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, CHANDRAN_METASTASIS_DN, MORF_RAD51L3, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_CARDIAC_MUSCLE_CELL_MEMBRANE_REPOLARIZATION

GO Biological Process (15): calcium ion transport (GO:0006816), regulation of calcium ion transport (GO:0051924), regulation of ventricular cardiac muscle cell membrane repolarization (GO:0060307), calcium ion transport into cytosol (GO:0060402), calcium ion transmembrane transport via high voltage-gated calcium channel (GO:0061577), cardiac muscle cell action potential involved in contraction (GO:0086002), membrane depolarization during bundle of His cell action potential (GO:0086048), regulation of heart rate by cardiac conduction (GO:0086091), calcium ion import across plasma membrane (GO:0098703), regulation of membrane repolarization during action potential (GO:0098903), regulation of calcium ion transmembrane transport via high voltage-gated calcium channel (GO:1902514), cellular response to amyloid-beta (GO:1904646), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), calcium ion transmembrane transport (GO:0070588)

GO Molecular Function (5): voltage-gated calcium channel activity (GO:0005245), metal ion binding (GO:0046872), calcium channel activity (GO:0005262), voltage-gated calcium channel activity involved in cardiac muscle cell action potential (GO:0086007), voltage-gated calcium channel activity involved in bundle of His cell action potential (GO:0086057)

GO Cellular Component (11): plasma membrane (GO:0005886), voltage-gated calcium channel complex (GO:0005891), sarcoplasmic reticulum (GO:0016529), presynaptic active zone membrane (GO:0048787), extracellular exosome (GO:0070062), GABA-ergic synapse (GO:0098982), neuronal dense core vesicle (GO:0098992), L-type voltage-gated calcium channel complex (GO:1990454), membrane (GO:0016020), T-tubule (GO:0030315), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cellular responses to mechanical stimuli	1
Cellular responses to stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
calcium ion transport	2
calcium ion transmembrane import into cytosol	2
membrane depolarization during cardiac muscle cell action potential	2
bundle of His cell action potential	2
cellular anatomical structure	2
metal ion transport	1
regulation of metal ion transport	1
regulation of cardiac muscle cell membrane repolarization	1
ventricular cardiac muscle cell membrane repolarization	1
positive regulation of cytosolic calcium ion concentration	1
high voltage-gated calcium channel activity	1
calcium ion transmembrane transport	1
cardiac muscle cell action potential	1
cardiac muscle cell contraction	1
regulation of heart rate	1
cardiac conduction	1
calcium ion import	1
inorganic cation import across plasma membrane	1
calcium ion import into cytosol	1
regulation of membrane repolarization	1
membrane repolarization during action potential	1
regulation of action potential	1
calcium ion transmembrane transport via high voltage-gated calcium channel	1
regulation of calcium ion transmembrane transport	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
response to amyloid-beta	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
monoatomic cation transmembrane transport	1
calcium channel activity	1
voltage-gated monoatomic cation channel activity	1
cation binding	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
voltage-gated calcium channel activity	1
voltage-gated calcium channel activity involved in cardiac muscle cell action potential	1
membrane depolarization during bundle of His cell action potential	1
membrane	1

Protein interactions and networks

STRING

1774 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CACNA2D1	CACNB1	Q02641	978
CACNA2D1	CACNB2	Q08289	973
CACNA2D1	CACNA1C	Q13936	967
CACNA2D1	CACNA1D	Q01668	940
CACNA2D1	CACNG1	Q06432	939
CACNA2D1	CACNA1A	P78510	856
CACNA2D1	CACNA1S	Q13698	850
CACNA2D1	SCN5A	Q14524	795
CACNA2D1	CACNA1F	O60840	793
CACNA2D1	CACNG3	O60359	791
CACNA2D1	CACNA1B	Q00975	749
CACNA2D1	RYR1	P21817	746
CACNA2D1	CACNB4	O00305	736
CACNA2D1	CACNG4	Q9UBN1	727
CACNA2D1	CACNA1E	Q15878	726

IntAct

98 interactions, top by confidence:

A	B	Type	Score
CNOT2	CNOT1	psi-mi:“MI:0914”(association)	0.740
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
SCGB1D4	EGFR	psi-mi:“MI:0914”(association)	0.530
GPIHBP1	ADAM10	psi-mi:“MI:0914”(association)	0.530
H2BC9	CACNA2D1	psi-mi:“MI:0915”(physical association)	0.400
H3-3A	CACNA2D1	psi-mi:“MI:0915”(physical association)	0.400
Itgb1	SSR3	psi-mi:“MI:0914”(association)	0.350
Baz2b	CACNA2D1	psi-mi:“MI:0914”(association)	0.350
Calu	CACNA2D1	psi-mi:“MI:0914”(association)	0.350
Ccdc77	TBC1D31	psi-mi:“MI:0914”(association)	0.350
HNRNPU		psi-mi:“MI:0914”(association)	0.350
MYH7B	SRRM1	psi-mi:“MI:0914”(association)	0.350
Plk2	NES	psi-mi:“MI:0914”(association)	0.350
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
SCARB2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
VMP1	TPM3	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
HASPIN	MYO1C	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
ANK2	IGKV2-40	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SYT5	psi-mi:“MI:0914”(association)	0.350
RIMS1	KIF2A	psi-mi:“MI:0914”(association)	0.350
CACNA1C	IGLL5	psi-mi:“MI:0914”(association)	0.350
CACNA1C	CACNB4	psi-mi:“MI:0914”(association)	0.350

BioGRID (130): CACNA2D1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS)

ESM2 similar proteins: A1A4K5, A4IID1, A7XY94, O08532, O54890, O77836, P05106, P13806, P18614, P26009, P54289, P54290, Q00960, Q01097, Q13224, Q13822, Q3V3R4, Q4R854, Q5M854, Q5NVB3, Q5R1P3, Q5REP8, Q5VU97, Q64610, Q659X0, Q6BEA0, Q6EV76, Q6EV77, Q6GMK0, Q6GQI7, Q6GQK9, Q6IS24, Q6NYS8, Q6PDJ1, Q6PHS9, Q7TT15, Q80UG2, Q812G0, Q86X52, Q8BFR2

Diamond homologs: O08532, P13806, P54289, P54290, Q6PHS9, Q8CFG6, Q9NY47, Q88KP1, Q8CFG5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1160 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	5
Uncertain significance	422
Likely benign	529
Benign	119

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1802179	NM_000722.4(CACNA2D1):c.818_821dup (p.Ser275fs)	Pathogenic
1802180	NM_000722.4(CACNA2D1):c.13_23dup (p.Leu9fs)	Pathogenic
1802181	NM_000722.4(CACNA2D1):c.626G>A (p.Gly209Asp)	Pathogenic
254280	Single allele	Likely pathogenic
254281	Single allele	Likely pathogenic
254282	t(X;7)(p10;q21.11)	Likely pathogenic
4277370	NM_000722.4(CACNA2D1):c.295-2080_354+3407del	Likely pathogenic
443616	GRCh37/hg19 7q21.11(chr7:80348675-83666606)x1	Likely pathogenic

SpliceAI

8194 predictions. Top by Δscore:

Variant	Effect	Δscore
7:81959692:T:A	donor_gain	1.0000
7:81961890:TTAC:T	donor_loss	1.0000
7:81961891:TAC:T	donor_loss	1.0000
7:81961892:ACC:A	donor_loss	1.0000
7:81961893:CCTG:C	donor_loss	1.0000
7:81962029:G:C	acceptor_gain	1.0000
7:81962033:C:CT	acceptor_gain	1.0000
7:81962034:G:T	acceptor_gain	1.0000
7:81962040:C:CT	acceptor_gain	1.0000
7:81962041:G:T	acceptor_gain	1.0000
7:81962042:G:GC	acceptor_gain	1.0000
7:81962044:G:C	acceptor_gain	1.0000
7:81962044:G:GC	acceptor_gain	1.0000
7:81964106:TGG:T	acceptor_gain	1.0000
7:81964109:C:CC	acceptor_gain	1.0000
7:81964201:A:AC	donor_gain	1.0000
7:81964202:C:CC	donor_gain	1.0000
7:81965589:CATA:C	donor_loss	1.0000
7:81965590:ATACC:A	donor_loss	1.0000
7:81965591:TA:T	donor_loss	1.0000
7:81965592:A:C	donor_loss	1.0000
7:81965593:C:A	donor_loss	1.0000
7:81965661:ATTAC:A	acceptor_gain	1.0000
7:81965662:TTAC:T	acceptor_gain	1.0000
7:81965663:TAC:T	acceptor_gain	1.0000
7:81965664:ACCTA:A	acceptor_loss	1.0000
7:81965666:C:CC	acceptor_gain	1.0000
7:81965666:CTAT:C	acceptor_loss	1.0000
7:81965667:T:C	acceptor_loss	1.0000
7:81965670:CAAAA:C	acceptor_gain	1.0000

AlphaMissense

7230 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:81959293:G:C	C1059W	1.000
7:81959294:C:G	C1059S	1.000
7:81959294:C:T	C1059Y	1.000
7:81959295:A:G	C1059R	1.000
7:81959295:A:T	C1059S	1.000
7:81959312:C:G	R1053P	1.000
7:81959339:C:G	C1044S	1.000
7:81959340:A:T	C1044S	1.000
7:81961974:G:C	C974W	1.000
7:81961975:C:G	C974S	1.000
7:81961976:A:T	C974S	1.000
7:81965630:A:C	F858L	1.000
7:81965630:A:T	F858L	1.000
7:81965632:A:G	F858L	1.000
7:81965635:C:A	G857W	1.000
7:81965646:A:G	L853P	1.000
7:81965656:A:G	C850R	1.000
7:81969922:A:G	L768P	1.000
7:81969924:G:C	S767R	1.000
7:81969924:G:T	S767R	1.000
7:81969926:T:G	S767R	1.000
7:81994935:C:G	R575P	1.000
7:82005433:A:G	L527P	1.000
7:82005457:C:A	G519V	1.000
7:82005457:C:T	G519D	1.000
7:82005458:C:G	G519R	1.000
7:82005484:C:T	G510E	1.000
7:82005485:C:A	G510W	1.000
7:82005485:C:G	G510R	1.000
7:82005485:C:T	G510R	1.000

dbSNP variants (sampled 300 via entrez): RS1000008747 (7:82223949 C>T), RS1000021662 (7:81978509 C>T), RS1000022028 (7:82065806 A>T), RS1000026160 (7:82393777 T>C), RS1000032132 (7:82065491 C>A,G,T), RS1000035862 (7:81968548 GT>G), RS1000047579 (7:82354421 T>A,C), RS1000049712 (7:82186593 A>C,G), RS1000056361 (7:82393767 T>A), RS1000062456 (7:82348473 C>T), RS1000070646 (7:82182006 T>C), RS1000076540 (7:82059654 T>C), RS1000078751 (7:82435333 G>A), RS1000093805 (7:82143557 T>A,C), RS1000096453 (7:82394825 A>T)

Disease associations

OMIM: gene MIM:114204 | disease phenotypes: MIM:601144, MIM:620149, MIM:609620

GenCC curated gene-disease

Disease	Classification	Inheritance
short QT syndrome	Supportive	Autosomal dominant
Brugada syndrome	Limited	Unknown
genetic developmental and epileptic encephalopathy	Limited	Autosomal dominant
developmental and epileptic encephalopathy 110	Limited	Autosomal recessive
Brugada syndrome 1	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
short QT syndrome	Disputed	AD
Brugada syndrome 1	Disputed	AD

Mondo (12): Brugada syndrome (MONDO:0015263), developmental and epileptic encephalopathy 110 (MONDO:0859327), long QT syndrome (MONDO:0002442), cardiac arrest (MONDO:0000745), intellectual disability (MONDO:0001071), short QT syndrome (MONDO:0000453), ventricular fibrillation (MONDO:0000190), breast carcinoma (MONDO:0004989), Brugada syndrome 1 (MONDO:0011001), paroxysmal atrial fibrillation (MONDO:1030011), neurodevelopmental disorder (MONDO:0700092), genetic developmental and epileptic encephalopathy (MONDO:0100062)

Orphanet (3): Brugada syndrome (Orphanet:130), Congenital short QT syndrome (Orphanet:51083), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

90 total (30 of 90 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000341	Narrow forehead
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001268	Mental deterioration
HP:0001273	Abnormal corpus callosum morphology
HP:0001279	Syncope
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000766_5	Non-alcoholic fatty liver disease histology (lobular)	7.000000e-06
GCST000853_5	Ulcerative colitis	8.000000e-06
GCST001692_5	Response to taxane treatment (docetaxel)	1.000000e-06
GCST001762_169	Obesity-related traits	6.000000e-07
GCST002017_2	Crohn’s disease (need for surgery)	6.000000e-06
GCST002120_2	Metabolite levels (Dihydroxy docosatrienoic acid)	7.000000e-06
GCST003319_1	Major depressive disorder (stressful life events interaction)	2.000000e-07
GCST003541_1	Survival in head and neck cancer	8.000000e-06
GCST004524_5	Energy expenditure (24h)	6.000000e-06
GCST004844_1	Gestational age at birth (maternal effect)	1.000000e-07
GCST004845_1	Spontaneous preterm birth (maternal effect)	3.000000e-08
GCST005175_56	Coronary artery calcified atherosclerotic plaque (90 or 130 HU threshold) in type 2 diabetes	6.000000e-06
GCST005231_6	Major depressive disorder	8.000000e-07
GCST006065_8	Glaucoma (primary open-angle)	7.000000e-09
GCST006948_48	Feeling nervous	2.000000e-08
GCST007465_10	Phoneme awareness	4.000000e-06
GCST011743_58	HDL cholesterol levels in HIV infection	4.000000e-06
GCST012488_27	L1-L4 bone mineral density x serum urate levels interaction	4.000000e-06

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0005275	dihydroxy docosatrienoic acid measurement
EFO:0004778	self rated health
EFO:0007781	stressful life event measurement
EFO:0000714	survival time
EFO:0005112	gestational age
EFO:0005939	parental genotype effect measurement
EFO:0006917	spontaneous preterm birth
EFO:0004723	coronary artery calcification
EFO:0009597	feeling nervous measurement
EFO:0005301	reading and spelling ability
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004531	urate measurement
EFO:0007701	spine bone mineral density

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D053840	Brugada Syndrome	C14.280.067.322; C14.280.123.250; C16.320.100
D006323	Heart Arrest	C14.280.383
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
D065886	Neurodevelopmental Disorders	F03.625
D014693	Ventricular Fibrillation	C14.280.067.922; C23.550.073.922
C580439	Short Qt Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (8): CHEMBL1919 (SINGLE PROTEIN), CHEMBL2363032 (PROTEIN COMPLEX GROUP), CHEMBL3430901 (PROTEIN COMPLEX), CHEMBL3988638 (PROTEIN COMPLEX), CHEMBL3988640 (PROTEIN COMPLEX), CHEMBL4106160 (PROTEIN COMPLEX), CHEMBL4106164 (PROTEIN COMPLEX), CHEMBL6066567 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 140,614 (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
CHEMBL1059	PREGABALIN	4	26,074
CHEMBL940	GABAPENTIN	4	46,522
CHEMBL1428	NIMODIPINE	4	32,587
CHEMBL95	TACRINE	4	35,360
CHEMBL604710	Z160	2	71

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

Binding affinities (BindingDB)

50 measured of 51 human assays (51 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-2,2,6,6-tetramethylthiane 1-oxide	IC50	1.5 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-2,2,6,6-tetramethylthiane 1,1-dioxide	IC50	1.9 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
[(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
4-[1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethyl-1,1-dioxothian-4-yl)oxypyrazol-5-yl]benzonitrile	IC50	2.4 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-2,2,6,6-tetramethylthiane 1-oxide	IC50	2.7 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[1-(2-methoxyphenyl)-5-(4-methoxyphenyl)pyrazol-3-yl]oxy-2,2,6,6-tetramethylthiane 1,1-dioxide	IC50	3 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-[(2,2,4,4-tetramethyloxetan-3-yl)methoxy]pyrazole	IC50	3.1 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
[(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
4-[1-(2-methoxyphenyl)-5-(4-methoxyphenyl)pyrazol-3-yl]oxy-2,2,6,6-tetramethylthiane 1-oxide	IC50	4.5 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethylthian-4-yl)oxypyrazole	IC50	5.9 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
1-(2-methoxyphenyl)-5-(4-methoxyphenyl)-3-(2,2,6,6-tetramethylthian-4-yl)oxypyrazole	IC50	6 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-propan-2-yloxyphenyl)pyrazol-3-yl]oxy-1-propan-2-ylsulfonylpiperidine	IC50	7 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethyloxan-4-yl)oxypyrazol-5-yl]benzonitrile	IC50	7.2 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethyloxan-4-yl)oxypyrazole	IC50	7.6 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[1-(2-methoxyphenyl)-5-(4-methoxyphenyl)pyrazol-3-yl]oxy-2,2,6,6-tetramethylthiane 1-oxide	IC50	7.6 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[3-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxyazetidin-1-yl]sulfonyl-3,5-dimethyl-1,2-oxazole	IC50	8 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-1-cyclopropylsulfonylpiperidine	IC50	9 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
1-(2-methoxyphenyl)-5-(4-methoxyphenyl)-3-(2,2,6,6-tetramethyloxan-4-yl)oxypyrazole	IC50	9.4 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-2,2,6,6-tetramethylcyclohexan-1-one	IC50	9.7 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
N-[4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxycyclohexyl]-2,2,2-trifluoroacetamide	IC50	11 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethylthian-4-yl)oxypyrazol-5-yl]benzonitrile	IC50	12 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-N,N-dimethylpiperidine-1-carboxamide	IC50	14 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
3-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-N-methoxy-N-methylazetidine-1-carboxamide	IC50	14 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethyl-1-oxothian-4-yl)oxypyrazol-5-yl]benzonitrile	IC50	14 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-1-methylsulfonylpiperidine	IC50	15 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-(oxan-4-yloxy)pyrazole	IC50	15 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
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
4-[5-(4-chlorophenyl)-1-(2-propan-2-yloxyphenyl)pyrazol-3-yl]oxy-1-methylsulfonylpiperidine	IC50	21.5 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
3-(aminomethyl)-5-methylhexanoic acid	IC50	23 nM	US-9663479: γ-aminobutyric acid (GABA) analogues for the treatment of pain and other disorders
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-1-(trifluoromethylsulfonyl)piperidine	IC50	24 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
1-[4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxypiperidin-1-yl]ethanone	IC50	26 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxycyclohexan-1-one	IC50	28 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-(thian-4-yloxy)pyrazole	IC50	28 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
tert-butyl 4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxypiperidine-1-carboxylate	IC50	30 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxythiane 1,1-dioxide	IC50	30 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-1-(2,2,2-trifluoroethyl)piperidine	IC50	31 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-(1-methylsulfonylazetidin-3-yl)oxypyrazole	IC50	31 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
1-[4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxypiperidin-1-yl]-2,2,2-trifluoroethanone	IC50	31.4 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-1-propan-2-ylsulfonylpiperidine	IC50	36 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-(1-propan-2-ylsulfonylazetidin-3-yl)oxypyrazole	IC50	36 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-2,2,6,6-tetramethylcyclohexan-1-ol	IC50	39 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
5-(4-chlorophenyl)-3-(4,4-difluorocyclohexyl)oxy-1-(2-methoxyphenyl)pyrazole	IC50	41 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
tert-butyl 4-[5-(4-chlorophenyl)-1-(2-ethylphenyl)pyrazol-3-yl]oxypiperidine-1-carboxylate	IC50	50 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
tert-butyl N-[4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxycyclohexyl]carbamate	IC50	62 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
tert-butyl 3-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxyazetidine-1-carboxylate	IC50	67 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
5-(4-chlorophenyl)-3-(1,4-dioxaspiro[4.5]decan-8-yloxy)-1-(2-ethylphenyl)pyrazole	IC50	81 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
[3-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxyazetidin-1-yl]-phenylmethanone	IC50	85 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-ethylphenyl)pyrazol-3-yl]oxy-1-methylsulfonylpiperidine	IC50	98.5 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers
[(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
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxycyclohexan-1-amine	IC50	400 nM	US-9434693: Substituted pyrazoles as N-type calcium channel blockers

ChEMBL bioactivities

1018 potent at pChembl≥5 of 1047 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL1801207
8.82	IC50	1.5	nM	CHEMBL3891844
8.72	IC50	1.9	nM	CHEMBL3890624
8.70	IC50	2	nM	CHEMBL1801206
8.70	IC50	2	nM	CHEMBL1801177
8.68	IC50	2.1	nM	CHEMBL5998077
8.62	IC50	2.4	nM	CHEMBL3973392
8.57	IC50	2.7	nM	CHEMBL3891844
8.52	IC50	3	nM	CHEMBL3919024
8.52	IC50	3	nM	CHEMBL1801185
8.52	IC50	3	nM	CHEMBL1801186
8.51	IC50	3.1	nM	CHEMBL3919898
8.38	IC50	4.2	nM	CHEMBL5769314
8.35	IC50	4.5	nM	CHEMBL3965812
8.30	IC50	5	nM	CHEMBL1801178
8.30	IC50	5	nM	CHEMBL1801180
8.23	IC50	5.9	nM	CHEMBL3906126
8.22	IC50	6	nM	CHEMBL3890916
8.22	Ki	6	nM	CHEMBL4847725
8.22	IC50	6	nM	CHEMBL1801179
8.15	IC50	7	nM	CHEMBL3940577
8.15	IC50	7	nM	CHEMBL1801205
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
8.10	Ki	8	nM	CHEMBL4847873
8.10	IC50	8	nM	CHEMBL1801191
8.10	IC50	8	nM	CHEMBL1801192
8.05	IC50	9	nM	CHEMBL3942512
8.05	IC50	9	nM	CHEMBL418138
8.03	IC50	9.4	nM	CHEMBL3922498
8.01	IC50	9.7	nM	CHEMBL3897303
7.96	IC50	11	nM	CHEMBL3948329
7.96	Ki	11	nM	CHEMBL4744000
7.96	Ki	11	nM	CHEMBL5273513
7.92	IC50	12	nM	CHEMBL3898359
7.85	IC50	14	nM	CHEMBL3911369
7.85	IC50	14	nM	CHEMBL3913505
7.85	IC50	14	nM	CHEMBL3936725
7.82	IC50	15	nM	CHEMBL84228
7.82	IC50	15	nM	CHEMBL3984596
7.82	IC50	15	nM	CHEMBL3902376
7.82	Ki	15	nM	CHEMBL4851929
7.80	Ki	16	nM	CHEMBL4859215
7.80	Ki	16	nM	CHEMBL4847073
7.75	IC50	18	nM	CHEMBL202120
7.75	Ki	18	nM	CHEMBL4868703
7.75	IC50	18	nM	CHEMBL57657
7.72	Ki	19	nM	PREGABALIN

PubChem BioAssay actives

307 with measured affinity, of 508 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
7-(azetidin-1-yl)-2-(4-ethoxyphenyl)-3,4-dimethylpyrazolo[3,4-d]pyridazine	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0010	uM
2-(4-ethoxyphenyl)-3,4-dimethyl-7-pyrrolidin-1-ylpyrazolo[3,4-d]pyridazine	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0020	uM
(3S)-1-[2-(4-ethoxyphenyl)-3,4-dimethylpyrazolo[3,4-d]pyridazin-7-yl]pyrrolidin-3-amine	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0020	uM
2-(4-ethoxyphenyl)-7-[(3R)-3-fluoropyrrolidin-1-yl]-3,4-dimethylpyrazolo[3,4-d]pyridazine	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0030	uM
2-[4-chloro-2-(trifluoromethoxy)phenyl]-3,4-dimethyl-7-pyrrolidin-1-ylpyrazolo[3,4-d]pyridazine	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0030	uM
2-(4-ethoxyphenyl)-7-(3-methoxyazetidin-1-yl)-3,4-dimethylpyrazolo[3,4-d]pyridazine	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0050	uM
(3R)-1-[2-(4-ethoxyphenyl)-3,4-dimethylpyrazolo[3,4-d]pyridazin-7-yl]pyrrolidin-3-ol	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0050	uM
3-ethyl-2-[(1R)-1-[(3R)-3-methylpiperazin-1-yl]butyl]pyrido[4,3-d]pyrimidin-4-one	1766516: Displacement of [3H]-gabapentin from human Cav alpha2delta1 expressed in CHO-K1 cell membranes incubated for 60 mins by scintillation counting method	ki	0.0060	uM
2-(4-ethoxyphenyl)-7-[(3R)-3-methoxypyrrolidin-1-yl]-3,4-dimethylpyrazolo[3,4-d]pyridazine	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0060	uM
2-(4-ethoxyphenyl)-N,N,3,4-tetramethylpyrazolo[3,4-d]pyridazin-7-amine	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0070	uM
6-bromo-2-[(1R)-1-[(3S,5R)-3,5-dimethylpiperazin-1-yl]butyl]-3-ethylquinazolin-4-one	1766516: Displacement of [3H]-gabapentin from human Cav alpha2delta1 expressed in CHO-K1 cell membranes incubated for 60 mins by scintillation counting method	ki	0.0080	uM
2-[4-chloro-2-(trifluoromethoxy)phenyl]-7-(3-methoxyazetidin-1-yl)-3,4-dimethylpyrazolo[3,4-d]pyridazine	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0080	uM
2-(4-ethoxy-2-fluorophenyl)-7-(3-methoxyazetidin-1-yl)-3,4-dimethylpyrazolo[3,4-d]pyridazine	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0080	uM
(4S)-4-N-acridin-9-yl-1-N,1-N-diethylheptane-1,4-diamine	35397: Binding affinity towards alpha2-delta subunit of a voltage gated calcium channel using [3H]gabapentin in human brain membrane (A710 membrane)	ic50	0.0090	uM
(6S)-13-(ethylamino)-8-[3-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-2,8,12,14-tetrazatricyclo[8.4.0.02,6]tetradeca-1(14),10,12-trien-9-one	1709032: Displacement of [3H]-gabapentin from human Cav alpha2delta1 expressed in CHO-K1 cell membranes incubated for 60 mins by scintillation counting method	ki	0.0110	uM
13-(ethylamino)-8-[3-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-2,8,12,14-tetrazatricyclo[8.4.0.02,6]tetradeca-1(14),10,12-trien-9-one	1925335: Binding affinity to calcium channel alpha2delta1 (unknown origin)	ki	0.0110	uM
2-(3-methylphenyl)-N-[[6-[[3-(trifluoromethyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]oxymethyl]-2-pyridinyl]methyl]ethanamine	217467: Binding affinity against alpha2 delta-1 subunit of voltage-gated calcium channel in human.	ic50	0.0150	uM
7-bromo-2-[1-[(3S,5R)-3,5-dimethylpiperazin-1-yl]butyl]-3-ethylquinazolin-4-one	1766516: Displacement of [3H]-gabapentin from human Cav alpha2delta1 expressed in CHO-K1 cell membranes incubated for 60 mins by scintillation counting method	ki	0.0150	uM
6-bromo-3-ethyl-2-[(1R)-1-[(3R)-3-methylpiperazin-1-yl]butyl]quinazolin-4-one	1766516: Displacement of [3H]-gabapentin from human Cav alpha2delta1 expressed in CHO-K1 cell membranes incubated for 60 mins by scintillation counting method	ki	0.0160	uM
6-bromo-2-[1-[(3R,5S)-3,5-dimethylpiperazin-1-yl]butyl]-3-ethylquinazolin-4-one	1766516: Displacement of [3H]-gabapentin from human Cav alpha2delta1 expressed in CHO-K1 cell membranes incubated for 60 mins by scintillation counting method	ki	0.0160	uM
4-N-acridin-9-yl-1-N,1-N-diethylheptane-1,4-diamine	35397: Binding affinity towards alpha2-delta subunit of a voltage gated calcium channel using [3H]gabapentin in human brain membrane (A710 membrane)	ic50	0.0180	uM
2-[1-[(3R,5S)-3,5-dimethylpiperazin-1-yl]butyl]-3-ethyl-7-pyridin-4-ylquinazolin-4-one	1766516: Displacement of [3H]-gabapentin from human Cav alpha2delta1 expressed in CHO-K1 cell membranes incubated for 60 mins by scintillation counting method	ki	0.0180	uM
6-(4-ethoxyphenyl)-N-[(3-fluorophenyl)methyl]-1,5,7-trimethylpyrrolo[3,4-d]pyridazin-4-amine	260173: [3H]Gabapentin binding in human A710 membrane expressing alpha-2delta subunit of calcium channel	ic50	0.0180	uM
Pregabalin	1709032: Displacement of [3H]-gabapentin from human Cav alpha2delta1 expressed in CHO-K1 cell membranes incubated for 60 mins by scintillation counting method	ki	0.0190	uM
3,4-dimethyl-7-pyrrolidin-1-yl-2-[4-(2,2,2-trifluoroethoxy)phenyl]pyrazolo[3,4-d]pyridazine	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0200	uM
2-(4-ethoxyphenyl)-N,3,4-trimethylpyrazolo[3,4-d]pyridazin-7-amine	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0220	uM
7-(azepan-1-yl)-2-(4-ethoxyphenyl)-3,4-dimethylpyrazolo[3,4-d]pyridazine	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0220	uM
2-(2,4-dichlorophenyl)-3,4-dimethyl-7-pyrrolidin-1-ylpyrazolo[3,4-d]pyridazine	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0250	uM
7-(3,3-difluoropyrrolidin-1-yl)-2-(4-ethoxyphenyl)-3,4-dimethylpyrazolo[3,4-d]pyridazine	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0250	uM
3-ethyl-2-[(1R)-1-[(3S)-3-methylpiperazin-1-yl]butyl]pyrido[4,3-d]pyrimidin-4-one	1766516: Displacement of [3H]-gabapentin from human Cav alpha2delta1 expressed in CHO-K1 cell membranes incubated for 60 mins by scintillation counting method	ki	0.0270	uM
Gabapentin	35397: Binding affinity towards alpha2-delta subunit of a voltage gated calcium channel using [3H]gabapentin in human brain membrane (A710 membrane)	ic50	0.0270	uM
(1S)-N-[2-(3-bromophenyl)ethyl]-1-[6-[[3-(trifluoromethyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]oxymethyl]-2-pyridinyl]ethanamine	217467: Binding affinity against alpha2 delta-1 subunit of voltage-gated calcium channel in human.	ic50	0.0280	uM
N-[2-(3-methylphenyl)ethyl]-1-[6-[[3-(trifluoromethyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]oxymethyl]-2-pyridinyl]ethanamine	217467: Binding affinity against alpha2 delta-1 subunit of voltage-gated calcium channel in human.	ic50	0.0290	uM
Nimodipine	1912088: Inhibition of human alpha1c/beta2a/alpha2delta1 Cav1.2 expressed in HEK293 cells assessed as Ca2+ current at -80 mV holding potential by patch clamp technique	ic50	0.0298	uM
(1S)-N-(2-phenylethyl)-1-[6-[[3-(trifluoromethyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]oxymethyl]-2-pyridinyl]ethanamine	217467: Binding affinity against alpha2 delta-1 subunit of voltage-gated calcium channel in human.	ic50	0.0300	uM
6-(4-ethoxyphenyl)-N-(1H-indol-5-yl)-1,5,7-trimethylpyrrolo[3,4-d]pyridazin-4-amine	260173: [3H]Gabapentin binding in human A710 membrane expressing alpha-2delta subunit of calcium channel	ic50	0.0300	uM
(1S)-1-[6-[[3-(trifluoromethyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]oxymethyl]-2-pyridinyl]-N-[2-(3-tritiophenyl)ethyl]ethanamine	217467: Binding affinity against alpha2 delta-1 subunit of voltage-gated calcium channel in human.	ic50	0.0300	uM
6-(4-ethoxyphenyl)-1,5,7-trimethyl-N-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-ylmethyl)pyrrolo[3,4-d]pyridazin-4-amine	260173: [3H]Gabapentin binding in human A710 membrane expressing alpha-2delta subunit of calcium channel	ic50	0.0320	uM
7-[(3R)-3-fluoropyrrolidin-1-yl]-3,4-dimethyl-2-[4-(2,2,2-trifluoroethoxy)phenyl]pyrazolo[3,4-d]pyridazine	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0320	uM
1-[2-(4-ethoxyphenyl)-3,4-dimethylpyrazolo[3,4-d]pyridazin-7-yl]piperidin-4-ol	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0320	uM
3,4-dimethyl-2-(4-propan-2-yloxyphenyl)-7-pyrrolidin-1-ylpyrazolo[3,4-d]pyridazine	604883: Binding affinity at voltage-gated calcium channel subunit alpha2delta1	ic50	0.0320	uM
6-(4-ethoxyphenyl)-N-(1H-indazol-5-yl)-1,5,7-trimethylpyrrolo[3,4-d]pyridazin-4-amine	260173: [3H]Gabapentin binding in human A710 membrane expressing alpha-2delta subunit of calcium channel	ic50	0.0360	uM
2-[1-[(3S,5R)-3,5-dimethylpiperazin-1-yl]butyl]-3-ethylquinazolin-4-one	1766516: Displacement of [3H]-gabapentin from human Cav alpha2delta1 expressed in CHO-K1 cell membranes incubated for 60 mins by scintillation counting method	ki	0.0360	uM
N-(2-phenylethyl)-1-[6-[[3-(trifluoromethyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-yl]oxymethyl]-2-pyridinyl]ethanamine	217467: Binding affinity against alpha2 delta-1 subunit of voltage-gated calcium channel in human.	ic50	0.0360	uM
N-[(3-chlorophenyl)methyl]-6-(4-ethoxyphenyl)-1,5,7-trimethylpyrrolo[3,4-d]pyridazin-4-amine	260173: [3H]Gabapentin binding in human A710 membrane expressing alpha-2delta subunit of calcium channel	ic50	0.0370	uM
4-N-acridin-9-yl-1-N,1-N-diethylhexane-1,4-diamine	35397: Binding affinity towards alpha2-delta subunit of a voltage gated calcium channel using [3H]gabapentin in human brain membrane (A710 membrane)	ic50	0.0380	uM
2-[1-[(3R,5S)-3,5-dimethylpiperazin-1-yl]butyl]-3-ethyl-6-pyridin-4-ylquinazolin-4-one	1766516: Displacement of [3H]-gabapentin from human Cav alpha2delta1 expressed in CHO-K1 cell membranes incubated for 60 mins by scintillation counting method	ki	0.0380	uM
1-[4-[(3-chlorophenyl)-phenylmethyl]piperazin-1-yl]-3,3-diphenylpropan-1-one	459232: Inhibition of N type calcium channel alpha-1b/alpha-2-delta-1/beta-1b expressed in HEK293 cells at holding potential of -100 mV by whole-cell patch clamp method	ic50	0.0400	uM
6-(4-ethoxyphenyl)-N,1,5,7-tetramethylpyrrolo[3,4-d]pyridazin-4-amine	35404: Binding affinity for huamn alpha2-delta1 subunit of voltage gated calcium channel over-expressed in A710 cell membranes using [3H]-gabapentin	ic50	0.0400	uM
1-[4-[(4-chlorophenyl)-(1-methylpiperidin-4-yl)methyl]piperazin-1-yl]-3,3-diphenylpropan-1-one	459232: Inhibition of N type calcium channel alpha-1b/alpha-2-delta-1/beta-1b expressed in HEK293 cells at holding potential of -100 mV by whole-cell patch clamp method	ic50	0.0400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	5
trichostatin A	affects cotreatment, increases expression	2
sodium arsenite	affects expression, increases expression	2
entinostat	decreases expression, increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression, decreases expression	2
Panobinostat	increases expression, affects cotreatment	2
Air Pollutants	decreases expression, decreases methylation, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
methyleugenol	decreases expression	1
oxybenzone	increases expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, decreases expression	1
bisphenol A	increases methylation	1
sodium arsenate	decreases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	increases expression	1
nefazodone	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
quinocetone	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	affects cotreatment, decreases expression	1
Asbestos	decreases expression	1

ChEMBL screening assays

47 unique, capped per target: 45 binding, 1 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1805878	Binding	Binding affinity at voltage-gated calcium channel subunit alpha2delta1	Pyrazolopyridazine alpha-2-delta-1 ligands for the treatment of neuropathic pain. — Bioorg Med Chem Lett
CHEMBL4039312	ADMET	Inhibition of human Cav1.2/beta2/alpha2delta1 expressed in CHO cells by automated patch clamp assay	Discovery of N-(5-Fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (VU0424238): A Novel Negative Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 5 Selected for Clinical Evaluation. — J Med Chem
CHEMBL5154401	Toxicity	Inhibition of human alpha1c/beta2a/alpha2delta1 Cav1.2 expressed in HEK293 cells assessed as effect on calcium flux by FLIPR analysis	Optimization of Benzamide Derivatives as Potent and Orally Active Tubulin Inhibitors Targeting the Colchicine Binding Site. — J Med Chem

Cellosaurus cell lines

8 cell lines: 5 cancer cell line, 3 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1LX	Abcam HeLa CACNA2D1 KO	Cancer cell line	Female
CVCL_D1JJ	PrecisION hCav2.2 alpha1B/beta3/alpha2delta1-HEK	Transformed cell line	Female
CVCL_D1RT	Abcam U-87MG CACNA2D1 KO	Cancer cell line	Male
CVCL_D7LB	Ubigene A-549 CACNA2D1 KO	Cancer cell line	Male
CVCL_D9AJ	Ubigene HEK293 CACNA2D1 KO	Transformed cell line	Female
CVCL_D9Z0	Ubigene HeLa CACNA2D1 KO	Cancer cell line	Female
CVCL_RQ69	PrecisION hCav1.2 alpha1C/beta2a/alpha2delta1-HEK	Transformed cell line	Female
CVCL_SG46	HAP1 CACNA2D1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT00101881	PHASE4	COMPLETED	Transthoracic Incremental Monophasic Versus Biphasic by Emergency Responders (TIMBER)
NCT00127907	PHASE4	COMPLETED	Vasopressin and Epinephrine Versus Epinephrine Alone in Cardiac Arrest
NCT00180362	PHASE4	COMPLETED	Quick ICD Study: Is Extensive Electrophysiological Testing Before, During and After ICD-Implantation Still Necessary ?
NCT00392639	PHASE4	COMPLETED	Clinical and Economical Interest of Endovascular Cooling in the Management of Cardiac Arrest (ICEREA Study)
NCT00644722	PHASE4	COMPLETED	Out-of-Hospital Intubation With Metal Single Use Laryngoscope Blades
NCT00827957	PHASE4	COMPLETED	Comparing Therapeutic Hypothermia Using External and Internal Cooling for Post-Cardiac Arrest Patients
NCT00843297	PHASE4	COMPLETED	COOL-Trial: Outcome With Invasive and Non-invasive Cooling After Cardiac Arrest
NCT01009606	PHASE4	COMPLETED	Cardiopulmonary Resuscitation Witnessing by a Relative
NCT01083784	PHASE4	UNKNOWN	The Benefit of Prophylactic Anticonvulsant in Post Cardiac Arrest Syndrome With Induced Mild Hypothermia
NCT01155622	PHASE4	COMPLETED	Trial of Different Hypothermia Temperatures in Patients Recovered From Out-of-hospital Cardiac Arrest
NCT01374061	PHASE4	WITHDRAWN	Pre Hospital Evaluation of Video Laryngoscopy
NCT02088736	PHASE4	COMPLETED	Intraosseous vs Intravenous Access for Cardiac Arrest Treatment
NCT02224274	PHASE4	COMPLETED	Antiplatelet Therapy After Cardiac Arrest
NCT02367755	PHASE4	UNKNOWN	Therapeutic Hypothermia With Propofol in Survival and Neurological Prognoses After Cardiac Arrest
NCT03317197	PHASE4	UNKNOWN	Effect of Vasopressin, Steroid, and Epinephrine Treatment in Patients With Out-of-hospital Cardiac Arrest
NCT04287842	PHASE4	WITHDRAWN	Impact if Desflurane Preconditioning on the Content of the Phospho-GSK-3b in the Rat’s Neurons in the Model of I/R
NCT05173740	PHASE4	RECRUITING	Rehabilitation for Survivors of Out-of-hospital Cardiac Arrest
NCT05205031	PHASE4	ACTIVE_NOT_RECRUITING	Intravenous Vs. Intraosseous Vascular Access During Out-of-Hospital
NCT05564130	PHASE4	ACTIVE_NOT_RECRUITING	Bicarbonate for In-Hospital Cardiac Arrest
NCT05956431	PHASE4	UNKNOWN	RCT Study of Levosimendan Improving Prognosis of Cardiac Arrest
NCT06081283	PHASE4	TERMINATED	Antiseizure Medication in Seizure Networks at Early Acute Brain Injury
NCT06156059	PHASE4	UNKNOWN	Oral Bedtime Melatonin in Critically Ill Patients
NCT06353334	PHASE4	RECRUITING	Butylphthalide’s Safety and Efficacy for Improving Neurological Function Prognosis in Patients With Cardiac Arrest (BNCA Trial)
NCT06530641	PHASE4	RECRUITING	Evaluation of Clinical Impact of the Type of Cardioplegia Used in the Patient Undergoing Major Cardiac Surgery.
NCT06572085	PHASE4	RECRUITING	Neuroprotective Effect of Butylphthalide for Cardiac Arrest Patients
NCT00701077	PHASE3	TERMINATED	DAPERB 3,4-DiAminoPyridine and Electrophysiological Response in Brugada Syndrome
NCT00927732	PHASE3	TERMINATED	Hydroquinidine Versus Placebo in Patients With Brugada Syndrome
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT00000464	PHASE3	COMPLETED	Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE)
NCT00000502	PHASE3	COMPLETED	Evaluation of SC-V Versus Conventional CPR
NCT00000525	PHASE3	COMPLETED	Diuretics, Hypertension, and Arrhythmias Clinical Trial
NCT00000526	PHASE3	COMPLETED	Cardiac Arrhythmia Suppression Trial (CAST)
NCT00004560	PHASE3	COMPLETED	Public Access Defibrillation (PAD) Community Trial
NCT00120965	PHASE3	TERMINATED	AutoPulse Assisted Prehospital International Resuscitation Trial (ASPIRE)