CACNA1H

Summary

CACNA1H (calcium voltage-gated channel subunit alpha1 H, HGNC:1395) is a protein-coding gene on chromosome 16p13.3, encoding Voltage-dependent T-type calcium channel subunit alpha-1H (O95180). Voltage-sensitive calcium channel that gives rise to T-type calcium currents.

This gene encodes a T-type member of the alpha-1 subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. The alpha-1 subunit has 24 transmembrane segments and forms the pore through which ions pass into the cell. There are multiple isoforms of each of the proteins in the complex, either encoded by different genes or the result of alternative splicing of transcripts. Alternate transcriptional splice variants, encoding different isoforms, have been characterized for the gene described here. Studies suggest certain mutations in this gene lead to childhood absence epilepsy (CAE).

Source: NCBI Gene 8912 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hyperaldosteronism, familial, type IV (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 4,211 total — 3 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 28
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_021098

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1395
Approved symbol	CACNA1H
Name	calcium voltage-gated channel subunit alpha1 H
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	Cav3.2
Ensembl gene	ENSG00000196557
Ensembl biotype	protein_coding
OMIM	607904
Entrez	8912

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 15 protein_coding, 15 nonsense_mediated_decay, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000348261, ENST00000562079, ENST00000564231, ENST00000564954, ENST00000565831, ENST00000569107, ENST00000569953, ENST00000621827, ENST00000637236, ENST00000638323, ENST00000639478, ENST00000640028, ENST00000711438, ENST00000711442, ENST00000711443, ENST00000711447, ENST00000711448, ENST00000711449, ENST00000711450, ENST00000711451, ENST00000711452, ENST00000711453, ENST00000711455, ENST00000711456, ENST00000711481, ENST00000711482, ENST00000711483, ENST00000711484, ENST00000711485, ENST00000711486, ENST00000711487, ENST00000711488, ENST00000711489, ENST00000711490, ENST00000711493

RefSeq mRNA: 2 — MANE Select: NM_021098 NM_001005407, NM_021098

CCDS: CCDS45375, CCDS45376

Canonical transcript exons

ENST00000348261 — 35 exons

Exon	Start	End
ENSE00001212382	1218970	1219130
ENSE00001212389	1218210	1218651
ENSE00001212395	1217919	1218040
ENSE00001212424	1214972	1215081
ENSE00001212429	1213780	1213931
ENSE00001212444	1211481	1211606
ENSE00001608851	1215242	1215375
ENSE00001618938	1211716	1211805
ENSE00001633222	1211946	1212138
ENSE00001668762	1216932	1217010
ENSE00001709615	1215523	1215593
ENSE00001729646	1211168	1211294
ENSE00002603462	1210035	1210135
ENSE00003551765	1210370	1210493
ENSE00003599033	1210787	1210971
ENSE00003649618	1210583	1210651
ENSE00004015626	1206104	1206289
ENSE00004015627	1204010	1204458
ENSE00004015630	1200716	1200808
ENSE00004015631	1205114	1205265
ENSE00004015633	1195432	1195565
ENSE00004015634	1200256	1200571
ENSE00004015635	1209032	1209412
ENSE00004015637	1195926	1196023
ENSE00004015640	1194972	1195083
ENSE00004015641	1207770	1207860
ENSE00004015642	1207001	1207118
ENSE00004015644	1201663	1202452
ENSE00004015645	1208013	1208221
ENSE00004015708	1212511	1212528
ENSE00004015709	1207275	1207430
ENSE00004015711	1153106	1153470
ENSE00004015779	1198615	1198774
ENSE00004015783	1153720	1154036
ENSE00004015796	1219981	1221768

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 97.50.

FANTOM5 (CAGE): breadth broad, TPM avg 5.4614 / max 101.3144, expressed in 703 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152022	3.6519	656
152023	1.7820	549
152024	0.0275	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus muscularis layer	UBERON:0035833	97.50	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.47	gold quality
lower esophagus	UBERON:0013473	97.44	gold quality
left ovary	UBERON:0002119	96.97	gold quality
right ovary	UBERON:0002118	96.82	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.54	gold quality
mucosa of stomach	UBERON:0001199	96.12	gold quality
popliteal artery	UBERON:0002250	95.52	gold quality
tibial artery	UBERON:0007610	95.51	gold quality
body of uterus	UBERON:0009853	95.48	gold quality
left uterine tube	UBERON:0001303	95.34	gold quality
right coronary artery	UBERON:0001625	94.79	gold quality
adenohypophysis	UBERON:0002196	92.74	gold quality
pituitary gland	UBERON:0000007	92.12	gold quality
left coronary artery	UBERON:0001626	91.80	gold quality
transverse colon	UBERON:0001157	91.37	gold quality
right adrenal gland cortex	UBERON:0035827	90.70	gold quality
coronary artery	UBERON:0001621	90.37	gold quality
right adrenal gland	UBERON:0001233	90.31	gold quality
left adrenal gland cortex	UBERON:0035825	89.59	gold quality
cortical plate	UBERON:0005343	89.39	gold quality
left adrenal gland	UBERON:0001234	89.27	gold quality
endocervix	UBERON:0000458	88.69	gold quality
aorta	UBERON:0000947	88.28	gold quality
ovary	UBERON:0000992	87.93	gold quality
adrenal cortex	UBERON:0001235	87.88	gold quality
stromal cell of endometrium	CL:0002255	87.27	gold quality
sigmoid colon	UBERON:0001159	86.96	gold quality
endometrium epithelium	UBERON:0004811	86.90	silver quality
left testis	UBERON:0004533	86.71	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.82
E-GEOD-83139	yes	3.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, REST

miRNA regulators (miRDB)

23 targeting CACNA1H, 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-552-5P	99.93	68.56	1583
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-4711-5P	98.89	68.00	965
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-649	97.96	67.21	704
HSA-MIR-4494	97.86	64.93	850
HSA-MIR-490-3P	97.79	65.54	606
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-3918	96.13	64.65	1300
HSA-MIR-10392-3P	88.79	61.83	122
HSA-MIR-5587-3P	82.90	60.79	138

Literature-anchored findings (GeneRIF, showing 40)

• We conclude that low voltage activated voltage-operated Ca(2+) channels are expressed in cells of the human male germ line. (PMID:11751928)
• characterization in terms of activation and inactivation properties as well as cation permeability (PMID:14529577)
• Ca(v)3.2 has a role in calcium influx during physiological activation and mutations may be causative in the propensity for seizures in patients with childhood absence epilepsy (PMID:14729682)
• recombinant low voltage-activated T-type Ca channels exhibit a small, though clearly evident, window T-type Ca(2)(+) current which is also present in native channels from different neuronal types–REVIEW (PMID:15498803)
• T-type calcium channel gene-CACNA1H might be a susceptibility gene to childhood absence epilepsy. (PMID:15833171)
• CACNA1H is a susceptibility gene in complex idiopathic generalized epilepsy (PMID:15852375)
• Data indicate that Domain IV/S4 of Ca(v)3.2 is an activation domain and is not involved in inactivation from the open state. (PMID:16133267)
• Cloning and calcium channel characteristics of Cav3.2 isoforms. (PMID:16301824)
• His-191 in the S3-S4 loop is a critical residue conferring nickel block to Ca(v)3.2 (PMID:16377633)
• inhibitory effects of amiodarone on the modified T-type Cav3.2 Ca2+ channel created by long-term amiodarone treatment (PMID:16443692)
• The expression of CACNA1H in breast cancer has been confirmed by RT-PCR. (PMID:16475676)
• Linkage analysis of 44 pedigrees provided no evidence for a locus in the CACNA1H region; no Chinese variants were found in 220 unrelated patients. (PMID:16504478)
• CACNA1H RNA is alternatively spliced at 12-14 sites where it can destroy, create or change the regulatory specificity of predicted exonic splicing enhancer sequences that may control splicing regulation. (PMID:16565161)
• functional analysis shows that missense mutations significantly reduce Ca(V)3.2 channel activity and thus could affect neuronal function and potentially brain development and could contribute to the development of the ASD phenotype (PMID:16754686)
• In conclusion, these data further support the hypothesis that CACNA1H is an important susceptibility gene for CAE in the Chinese Han population. (PMID:16905256)
• Recombinant Gbetagamma subunits were used to establish that the Gbeta(2)gamma(2) dimer can selectively reconstitute the inhibition of alpha(1H) channels in isolated membrane patches. (PMID:16973746)
• Case-control comparisons and the transmission disequilibrium test (TDT) both supported a coding SNP (cSNP) rs9934839 (R603R) in exon 9 as being close related to childhood absence epilepsy. (PMID:17156077)
• Intracellular loop connecting repeats I and II (I-II loop) control the regulation of Cav3.2 channel function and expression. (PMID:17215393)
• Variants in CACNA1H that alter channel properties are present in patients with various generalized epilepsy syndromes. These variants contribute to an individual’s susceptibility to epilepsy but are not sufficient to cause epilepsy on their own. (PMID:17696120)
• any mutations in the brake, including C456S, disrupted the structural integrity of the brake and its function to maintain these low voltage-activated channels closed at resting membrane potentials (PMID:18218623)
• CaV3.2 T-type calcium channel up-regulation may account for the alteration of secretion during prostate cancer development and that these channels, by promoting the secretion of potential mitogenic factors (PMID:18230611)
• These results imply that Cav3.2 channel activity is capable of being increased by activation of tyrosine phosphatases, but is decreased by activation of tyrosine kinases. (PMID:18309285)
• The sodium channel toxins tetrodotoxin and saxitoxin interact with the alpha-subunit of T-type Ca 2+ channels. (PMID:18591418)
• Report ligand-based virtual screening to identify new Cav3.2 channel blockers. (PMID:18708747)
• Protein kinase A activity controls the regulation of T-type CaV3.2 channels by Gbetagamma dimers. (PMID:19131331)
• Cav3.2 T-type calcium channel point mutation has splice-variant-specific effects on function and segregates with seizure expression in a polygenic rat model of absence epilepsy. (PMID:19144837)
• This study provides the first mechanistic demonstration of a nociceptive ion channel (Ca(V)3.2) modulation that may contribute to the documented analgesic properties of lipoic acid in vivo. (PMID:19641113)
• Review discusses mutations of the Cav3.2 isoform (CACNA1H gene) that enhance channel activity and their association with idiopathic generalized epilepsies, whereas mutations that disrupt its activity are associated with autism spectrum disorders. (PMID:19903827)
• Ca(V)3.2 alternative splicing generates significant T-type Ca channel structural and functional diversity with potential implications relevant to cardiac developmental and pathophysiological states (PMID:20699644)
• Present evidence that N2O-based inhibition of Cav3.2 channels is mediated by free radical signalling and results in analgesia. (PMID:21059758)
• functional modulation of the Ca(v)3.2 channels by Cav-3 is important for understanding the compartmentalized regulation of Ca(2+) signaling during normal and pathological processes. (PMID:21084288)
• Review: I-II loops of T-channels play critical roles in the trafficking and gating of these channels. This loop contains an intracellular gating brake that is essential to their ability open after small depolarizations of the membrane. (PMID:21099341)
• The function of T-type Ca(2+) channels is important for the proliferation of human ovarian cancer cells. (PMID:21438841)
• Data showed expression of L-type (Ca(v) 1.2), P/Q-type (Ca(v) 2.1), and T-type subtype (Ca(v) 3.1 and Ca(v) 3.2) voltage-gated calcium channels (Ca(v)s) in renal artery and dissected intrarenal blood vessels from nephrectomies. (PMID:21788606)
• A Ca(v)3.2/syntaxin-1A signaling complex controls T-type channel activity and low-threshold exocytosis. (PMID:22130660)
• Cav3.2 channels were expressed at the membrane of large portions of cells, with no likely relation to Cav3.1 expression or apoptosis. (PMID:22469755)
• Cav3.2 is differently expressed in normal pleura and malignant pleural mesothelioma (PMID:22564432)
• ZnT-1 enhances the activity of CaV3.1 and CaV3.2 via activation of Ras-ERK signaling pathways in the plasma membrane. (PMID:22572848)
• The abnormal mRNA expressions of T-type channel alpha1H and alpha1G may be one of the causes of declined semen quality and infertility in varicocele patients. (PMID:22574369)
• Our results support the notion that ion channel autoimmunity might at least partially contribute to HaNDL pathogenesis and occurrence of neurological symptoms. (PMID:23111027)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cacna1hb	ENSDARG00000099708
mus_musculus	Cacna1h	ENSMUSG00000024112
rattus_norvegicus	Cacna1h	ENSRNOG00000033893

Paralogs (26): CACNA1G (ENSG00000006283), SCN4A (ENSG00000007314), CACNA1S (ENSG00000081248), CACNA1I (ENSG00000100346), CACNA1F (ENSG00000102001), NALCN (ENSG00000102452), SCN2A (ENSG00000136531), SCN7A (ENSG00000136546), CACNA1A (ENSG00000141837), SCN1A (ENSG00000144285), CACNA1B (ENSG00000148408), CACNA1C (ENSG00000151067), CATSPER3 (ENSG00000152705), SCN3A (ENSG00000153253), CACNA1D (ENSG00000157388), TPCN2 (ENSG00000162341), CATSPER2 (ENSG00000166762), SCN11A (ENSG00000168356), SCN9A (ENSG00000169432), CATSPER1 (ENSG00000175294), SCN5A (ENSG00000183873), SCN10A (ENSG00000185313), TPCN1 (ENSG00000186815), CATSPER4 (ENSG00000188782), SCN8A (ENSG00000196876), CACNA1E (ENSG00000198216)

Protein

Protein identifiers

Voltage-dependent T-type calcium channel subunit alpha-1H — O95180 (reviewed: O95180)

Alternative names: Low-voltage-activated calcium channel alpha1 3.2 subunit, Voltage-gated calcium channel subunit alpha Cav3.2

All UniProt accessions (26): O95180, A0A1W2PQ19, A0A1W2PQW2, A0A1W2PR14, A0A1W2PS38, A0AAA9YHG1, A0AAA9YHG4, A0AAA9YHG8, A0AAA9YHH3, A0AAA9YHH8, A0AAA9YHI3, A0AAA9YHI7, A0AAA9YHL9, A0AAA9YHM0, A0AAA9YHM5, A0AAA9YHS1, A0AAA9YHS5, A0AAA9YHS9, A0AAA9YHT2, A0AAA9YHX7, A0AAA9YHX9, A0AAA9YHY2, A0AAA9YHY5, H3BMW6, H3BNT0, H3BUA8

UniProt curated annotations — full annotation on UniProt →

Function. Voltage-sensitive calcium channel that gives rise to T-type calcium currents. T-type calcium channels belong to the ’low-voltage activated (LVA)’ group. A particularity of this type of channel is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons. In the adrenal zona glomerulosa, participates in the signaling pathway leading to aldosterone production in response to either AGT/angiotensin II, or hyperkalemia.

Subunit / interactions. Interacts (via N-terminal cytoplasmic domain) with STAC.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in the adrenal glomerulosa (at protein level). In nonneuronal tissues, the highest expression levels are found in the kidney, liver, and heart. In the brain, most abundant in the amygdala, caudate nucleus, and putamen. In the heart, expressed in blood vessels. Expressed in testis, primarily in the germ cells, but not in other portions of the reproductive tract, such as ductus deferens. Expressed in the brain. Expressed in testis, primarily in the germ cells, but not in other portions of the reproductive tract, such as ductus deferens. Not expressed in the brain.

Post-translational modifications. In response to raising of intracellular calcium, the T-type channels are activated by CaM-kinase II.

Disease relevance. Epilepsy, idiopathic generalized 6 (EIG6) [MIM:611942] A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Epilepsy, childhood absence 6 (ECA6) [MIM:611942] A subtype of idiopathic generalized epilepsy characterized by an onset at age 6-7 years, frequent absence seizures (several per day) and bilateral, synchronous, symmetric 3-Hz spike waves on EEG. Tonic-clonic seizures often develop in adolescence. Absence seizures may either remit or persist into adulthood. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Hyperaldosteronism, familial, 4 (HALD4) [MIM:617027] A form of familial hyperaldosteronism, a disorder characterized by hypertension, elevated aldosterone levels despite low plasma renin activity, and abnormal adrenal steroid production. There is significant phenotypic heterogeneity, and some individuals never develop hypertension. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Channel activity is strongly inhibited by mibefradil. Channel activity is strongly inhibited by Ni(2+) ions.

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.

Similarity. Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1H subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
O95180-1	1, A1H-a	yes
O95180-2	2, A1H-b

RefSeq proteins (2): NP_001005407, NP_066921* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005445	VDCC_T_a1	Family
IPR005821	Ion_trans_dom	Domain
IPR027359	Volt_channel_dom_sf	Homologous_superfamily
IPR050599	VDCC_alpha-1_subunit	Family

Pfam: PF00520

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (198 total): helix 60, sequence variant 33, topological domain 25, transmembrane region 24, compositionally biased region 14, region of interest 9, strand 8, sequence conflict 6, repeat 4, site 4, turn 3, binding site 3, glycosylation site 3, chain 1, splice variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9AYL	ELECTRON MICROSCOPY	2.8
9AYG	ELECTRON MICROSCOPY	3
9AYK	ELECTRON MICROSCOPY	3
9AYH	ELECTRON MICROSCOPY	3.1
9AYJ	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95180-F1	59.35	0.12

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 (4): 378 (calcium ion selectivity and permeability); 974 (calcium ion selectivity and permeability); 1504 (calcium ion selectivity and permeability); 1808 (calcium ion selectivity and permeability)

Ligand- & substrate-binding residues (3): 140; 189; 191

Glycosylation sites (3): 192, 271, 1466

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-419037	NCAM1 interactions
R-HSA-445355	Smooth Muscle Contraction
R-HSA-9856532	Mechanical load activates signaling by PIEZO1 and integrins in osteocytes
R-HSA-1266738	Developmental Biology
R-HSA-375165	NCAM signaling for neurite out-growth
R-HSA-397014	Muscle contraction
R-HSA-422475	Axon guidance
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9675108	Nervous system development
R-HSA-9855142	Cellular responses to mechanical stimuli

MSigDB gene sets: 270 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_GLUCOCORTICOID_METABOLIC_PROCESS, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_C21_STEROID_HORMONE_METABOLIC_PROCESS, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_REGULATION_OF_HORMONE_LEVELS, REACTOME_NCAM_SIGNALING_FOR_NEURITE_OUT_GROWTH, GOBP_RESPONSE_TO_POTASSIUM_ION, GOBP_KETONE_METABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_RESPONSE_TO_METAL_ION

GO Biological Process (18): muscle contraction (GO:0006936), muscle organ development (GO:0007517), myoblast fusion (GO:0007520), regulation of heart contraction (GO:0008016), aldosterone biosynthetic process (GO:0032342), cellular response to hormone stimulus (GO:0032870), cortisol biosynthetic process (GO:0034651), cellular response to potassium ion (GO:0035865), regulation of membrane potential (GO:0042391), calcium ion import (GO:0070509), obsolete inorganic cation transmembrane transport (GO:0098662), calcium ion import across plasma membrane (GO:0098703), positive regulation of acrosome reaction (GO:2000344), monoatomic ion transport (GO:0006811), calcium ion transport (GO:0006816), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085), calcium ion transmembrane transport (GO:0070588)

GO Molecular Function (9): voltage-gated monoatomic ion channel activity (GO:0005244), voltage-gated calcium channel activity (GO:0005245), high voltage-gated calcium channel activity (GO:0008331), low voltage-gated calcium channel activity (GO:0008332), metal ion binding (GO:0046872), scaffold protein binding (GO:0097110), monoatomic ion channel activity (GO:0005216), calcium channel activity (GO:0005262), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), voltage-gated calcium channel complex (GO:0005891), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
NCAM signaling for neurite out-growth	1
Muscle contraction	1
Cellular responses to mechanical stimuli	1
Axon guidance	1
Nervous system development	1
Developmental Biology	1
Cellular responses to stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary alcohol biosynthetic process	2
ketone biosynthetic process	2
olefinic compound biosynthetic process	2
calcium ion transport	2
transport	2
voltage-gated calcium channel activity	2
muscle system process	1
animal organ development	1
muscle structure development	1
syncytium formation by cell-cell fusion	1
myotube differentiation	1
heart contraction	1
regulation of blood circulation	1
C21-steroid hormone biosynthetic process	1
mineralocorticoid biosynthetic process	1
aldosterone metabolic process	1
aldehyde biosynthetic process	1
response to hormone	1
cellular response to chemical stimulus	1
cellular response to endogenous stimulus	1
glucocorticoid biosynthetic process	1
cortisol metabolic process	1
tertiary alcohol biosynthetic process	1
response to potassium ion	1
cellular response to metal ion	1
monoatomic ion transmembrane transport	1
regulation of biological quality	1
calcium ion import	1
calcium ion transmembrane import into cytosol	1
inorganic cation import across plasma membrane	1
calcium ion import into cytosol	1
acrosome reaction	1
regulation of acrosome reaction	1
positive regulation of reproductive process	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
monoatomic cation transmembrane transport	1
monoatomic ion channel activity	1

Protein interactions and networks

STRING

1536 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CACNA1H	CLCN2	P51788	895
CACNA1H	CAV3	P56539	876
CACNA1H	GNB2	P11016	829
CACNA1H	CACNA1I	Q9P0X4	782
CACNA1H	USP5	P45974	763
CACNA1H	GNG2	P59768	763
CACNA1H	GABRG2	P18507	736
CACNA1H	CACNA2D1	P54289	712
CACNA1H	ATP2B3	Q16720	708
CACNA1H	GABRA1	P14867	707
CACNA1H	KCNJ5	P48544	706
CACNA1H	GABRB3	P28472	671
CACNA1H	STAC	Q99469	641
CACNA1H	CACNA2D3	Q8IZS8	623
CACNA1H	CACNB3	P54284	622

IntAct

10 interactions, top by confidence:

A	B	Type	Score
SRC	CACNA1H	psi-mi:“MI:0407”(direct interaction)	0.440
PPP3CB	CACNA1H	psi-mi:“MI:0915”(physical association)	0.400
CACNA1H	CCR4	psi-mi:“MI:0915”(physical association)	0.370
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
PCDH10	TMEM223	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
MAPK15	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): CACNA1H (Affinity Capture-MS), USP5 (Reconstituted Complex), USP5 (Affinity Capture-Western), CACNA1H (Affinity Capture-RNA), CACNA1H (Protein-peptide), CACNA1H (Affinity Capture-RNA), CACNA1H (Affinity Capture-MS), USP5 (Affinity Capture-Western), CACNA1H (Affinity Capture-MS), CACNA1H (Two-hybrid), CACNA1H (Affinity Capture-MS), CACNA1H (Affinity Capture-MS), CACNA1H (Affinity Capture-RNA), CACNA1H (Proximity Label-MS), CACNA1H (Affinity Capture-MS)

ESM2 similar proteins: C9D7C2, O00555, O08562, O35505, O43497, O46669, O54898, O55017, O73700, O88427, O88457, O95180, P0DMA5, P15381, P22002, P22316, P27732, P27884, P54282, P56698, P56699, P84309, P97445, Q00975, Q01668, Q01815, Q02294, Q02343, Q05152, Q07652, Q13698, Q13936, Q15858, Q15878, Q28644, Q2XVR5, Q2XVR7, Q61290, Q62205, Q62968

Diamond homologs: A2APX8, A2ASI5, B1AWN6, B1AYL1, C9D7C2, D0E0C2, O00555, O08562, O35505, O42398, O43497, O46669, O55017, O57483, O60840, O73700, O73705, O73706, O73707, O88420, O88427, O88457, O95180, P02719, P04774, P04775, P07293, P08104, P0DMA5, P15381, P15389, P15390, P22002, P22316, P27732, P27884, P35498, P35499, P35500, P54282

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
PRKACA	“down-regulates activity”	CACNA1H	phosphorylation
SCNN1A	“up-regulates activity”	CACNA1H	binding
SCNN1B	“up-regulates activity”	CACNA1H	binding
SCNN1G	“up-regulates activity”	CACNA1H	binding
CACNA1H	“up-regulates quantity”	calcium(2+)	relocalization
CAMK2A	“down-regulates activity”	CACNA1H	phosphorylation
Calcineurin	“up-regulates activity”	CACNA1H	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

4211 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	6
Uncertain significance	1586
Likely benign	1514
Benign	410

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
189779	NM_021098.3(CACNA1H):c.4645A>G (p.Met1549Val)	Pathogenic
253622	GRCh37/hg19 16p13.3(chr16:72769-1511716)x1	Pathogenic
2953366	NM_021098.3(CACNA1H):c.4647G>T (p.Met1549Ile)	Pathogenic
1677987	NM_021098.3(CACNA1H):c.5288A>G (p.Tyr1763Cys)	Likely pathogenic
3393187	NM_021098.3(CACNA1H):c.3434G>A (p.Trp1145Ter)	Likely pathogenic
372862	NM_021098.3(CACNA1H):c.1793C>T (p.Ala598Val)	Likely pathogenic
402205	NM_021098.3(CACNA1H):c.6898A>G (p.Ile2300Val)	Likely pathogenic
4279088	NM_021098.3(CACNA1H):c.1838A>T (p.Tyr613Phe)	Likely pathogenic
453072	NM_021098.3(CACNA1H):c.697G>C (p.Val233Leu)	Likely pathogenic

SpliceAI

8877 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1195463:C:CA	acceptor_gain	1.0000
16:1195924:AGCAT:A	acceptor_gain	1.0000
16:1195925:GC:G	acceptor_gain	1.0000
16:1195925:GCATG:G	acceptor_gain	1.0000
16:1196019:GCCTA:G	donor_gain	1.0000
16:1196024:G:GG	donor_gain	1.0000
16:1200237:T:TA	acceptor_gain	1.0000
16:1200241:T:A	acceptor_gain	1.0000
16:1200570:AG:A	donor_loss	1.0000
16:1200571:GG:G	donor_loss	1.0000
16:1201657:TCACA:T	acceptor_loss	1.0000
16:1201658:CACAG:C	acceptor_loss	1.0000
16:1201659:A:AG	acceptor_gain	1.0000
16:1201660:CAGG:C	acceptor_loss	1.0000
16:1201661:A:G	acceptor_loss	1.0000
16:1201661:AGGT:A	acceptor_gain	1.0000
16:1201661:AGGTG:A	acceptor_gain	1.0000
16:1201662:G:GA	acceptor_loss	1.0000
16:1201662:GGT:G	acceptor_gain	1.0000
16:1201662:GGTG:G	acceptor_gain	1.0000
16:1201662:GGTGG:G	acceptor_gain	1.0000
16:1204429:C:G	donor_gain	1.0000
16:1204456:CAG:C	donor_loss	1.0000
16:1204457:AGGTG:A	donor_loss	1.0000
16:1204458:GG:G	donor_loss	1.0000
16:1204459:G:GA	donor_loss	1.0000
16:1205111:CAGC:C	acceptor_loss	1.0000
16:1205112:A:AC	acceptor_loss	1.0000
16:1205112:A:AG	acceptor_gain	1.0000
16:1205112:AGCCC:A	acceptor_gain	1.0000

AlphaMissense

15322 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1198749:T:A	C260S	1.000
16:1198749:T:C	C260R	1.000
16:1198750:G:C	C260S	1.000
16:1198751:C:G	C260W	1.000
16:1200554:T:A	W368R	1.000
16:1200554:T:C	W368R	1.000
16:1200734:T:A	W380R	1.000
16:1200734:T:C	W380R	1.000
16:1200736:G:C	W380C	1.000
16:1200736:G:T	W380C	1.000
16:1201666:G:C	G406R	1.000
16:1201688:T:C	L413P	1.000
16:1207293:T:A	W976R	1.000
16:1207293:T:C	W976R	1.000
16:1207295:G:C	W976C	1.000
16:1207295:G:T	W976C	1.000
16:1211755:T:A	W1506R	1.000
16:1211755:T:C	W1506R	1.000
16:1216978:C:A	A1764D	1.000
16:1217991:T:C	L1799P	1.000
16:1217997:T:C	L1801P	1.000
16:1218003:G:C	R1803P	1.000
16:1218023:T:A	W1810R	1.000
16:1218023:T:C	W1810R	1.000
16:1218025:G:C	W1810C	1.000
16:1218025:G:T	W1810C	1.000
16:1196000:T:A	L207H	0.999
16:1198662:G:A	G231R	0.999
16:1198662:G:C	G231R	0.999
16:1198662:G:T	G231W	0.999

dbSNP variants (sampled 300 via entrez): RS1000002590 (16:1205423 C>T), RS1000007855 (16:1183621 G>A), RS1000021032 (16:1156622 C>A,G,T), RS1000044605 (16:1164690 C>T), RS1000049292 (16:1197070 A>C), RS1000063833 (16:1185211 C>G), RS1000070992 (16:1188345 G>C), RS1000083303 (16:1151497 CCGATTCAG>C), RS1000109484 (16:1179629 A>G), RS1000114902 (16:1213830 A>C,G,T), RS1000117384 (16:1218796 G>A), RS1000243166 (16:1167746 C>T), RS1000250958 (16:1164519 G>A), RS1000269272 (16:1221814 C>G), RS1000286125 (16:1161732 C>T)

Disease associations

OMIM: gene MIM:607904 | disease phenotypes: MIM:600669, MIM:611942, MIM:617027, MIM:108010

GenCC curated gene-disease

Disease	Classification	Inheritance
hyperaldosteronism, familial, type IV	Strong	Autosomal dominant
childhood absence epilepsy	Supportive	Autosomal dominant
epilepsy, childhood absence, susceptibility to, 6	Limited	Autosomal dominant

Mondo (10): idiopathic generalized epilepsy (MONDO:0005579), epilepsy, childhood absence, susceptibility to, 6 (MONDO:0012763), hyperaldosteronism, familial, type IV (MONDO:0014875), primary aldosteronism (MONDO:0001422), breast ductal adenocarcinoma (MONDO:0005590), epilepsy, idiopathic generalized, susceptibility to, 6 (MONDO:0800279), hyperaldosteronism (MONDO:0003009), focal epilepsy (MONDO:0005384), arteriovenous malformations of the brain (MONDO:0007154), childhood absence epilepsy (MONDO:0010826)

Orphanet (3): Familial hyperaldosteronism type IV (Orphanet:642671), Childhood absence epilepsy (Orphanet:64280), Brain arteriovenous malformation (Orphanet:46724)

HPO phenotypes

28 total (28 of 28 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000020	Urinary incontinence
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000822	Hypertension
HP:0000859	Increased circulating aldosterone concentration
HP:0000980	Pallor
HP:0001249	Intellectual disability
HP:0001328	Specific learning disability
HP:0002069	Bilateral tonic-clonic seizure
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0002883	Hyperventilation
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0006961	Jerky head movements
HP:0007018	Attention deficit hyperactivity disorder
HP:0007738	Uncontrolled eye movements
HP:0010522	Dyslexia
HP:0010794	Impaired visuospatial constructive cognition
HP:0010848	EEG with spike-wave complexes (2.5-3.5 Hz)
HP:0011147	Typical absence seizure
HP:0011150	Myoclonic absence seizure
HP:0011463	Childhood onset
HP:0012433	Abnormal social behavior
HP:0030218	Punding
HP:0031469	Low self-esteem
HP:0045084	Limb myoclonus
HP:6000318	Elevated aldosterone:renin ratio

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST009856_33	Leukocyte telomere length	3.000000e-06
GCST012017_7	Mastocytosis (KIT D816V positive)	9.000000e-06
GCST90002381_634	Eosinophil count	5.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004842	eosinophil count

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
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
D004828	Epilepsies, Partial	C10.228.140.490.360
D006929	Hyperaldosteronism	C19.053.800.604
D002538	Intracranial Arteriovenous Malformations	C10.228.140.300.520; C10.500.190.500; C14.240.850.750.295; C14.240.850.875.500; C14.907.150.295; C14.907.253.560.400; C16.131.240.850.750.295; C16.131.240.850.875.500; C16.131.666.190.500
C562694	Epilepsy, Idiopathic Generalized (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1859 (SINGLE PROTEIN), CHEMBL2362995 (PROTEIN FAMILY), CHEMBL2363032 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 110,134 (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
CHEMBL1423	PIMOZIDE	4	17,310
CHEMBL45816	MIBEFRADIL	4	7,838
CHEMBL1428	NIMODIPINE	4	32,587
CHEMBL95	TACRINE	4	35,360
CHEMBL452076	CILNIDIPINE	3	5,373
CHEMBL1684950	SUVECALTAMIDE	2	70
CHEMBL30008	FLUNARIZINE	2	11,439
CHEMBL4217292	APINOCALTAMIDE	2	37
CHEMBL604710	Z160	2	71
CHEMBL3934636	ULIXACALTAMIDE	1	49

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

PharmGKB variants

8 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1054645	CACNA1H		0.00	0
rs3751664	CACNA1H		0.00	0
rs3794619	CACNA1H		0.00	0
rs7191246	CACNA1H		0.00	0
rs11640796	CACNA1H		0.00	0
rs61734410	CACNA1H		0.00	0
rs2753326	CACNA1H		0.00	0
rs2753325	CACNA1H		0.00	0

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 (16 total), top 16:

Ligand	Action	Affinity	Parameter
suvecaltamide	Inhibition	8.09	pIC50
TTA-A2	Pore blocker	8.0	pIC50
ACT-709478	Inhibition	7.74	pIC50
kurtoxin	Antagonist	7.6	pIC50
mibefradil	Pore blocker	7.2	pIC50
TTA-P2	Pore blocker	7.0	pIC50
ulixacaltamide	Pore blocker	6.8	pIC50
pimozide	Pore blocker	6.8	pIC50
anandamide	Antagonist	6.5	pIC50
ML218	Pore blocker	6.5	pIC50
efonidipine	Pore blocker	6.4	pIC50
buxusemine L	Inhibition	6.29	pIC50
ABT-639	Pore blocker	5.7	pIC50
3β-OH	Pore blocker	5.52	pIC50
flunarizine	Antagonist	5.45	pIC50
Ni2+	Pore blocker	5.2	pIC50

Binding affinities (BindingDB)

1003 measured of 1121 human assays (1176 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-(1,3-benzodioxol-5-yl)-5-[(2-fluorobenzyl)thio]-1H-tetrazole	EC50	0.00446 nM
1-(3,4-dihydro-1H-isoquinolin-2-yl)-2-[[2-(2-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]methylsulfonyl]ethanone	EC50	0.0125 nM
N-[[(1S,5R)-8-[2-(tert-butylamino)-2-oxoethyl]-8-azabicyclo[3.2.1]octan-3-yl]methyl]-1-benzofuran-3-carboxamide	IC50	3 nM	US-9856250: Substituted tropane derivatives
N-[2-[(3,4-difluorophenyl)methyl]triazol-4-yl]-2-(1-methylindol-5-yl)acetamide	IC50	6.4 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(3,4-difluorophenyl)methyl]triazol-4-yl]-2-[6-(3,3-difluoropyrrolidin-1-yl)-3-pyridinyl]acetamide	IC50	7.3 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
2-(1-methylindol-5-yl)-N-[2-[[4-(trifluoromethoxy)phenyl]methyl]triazol-4-yl]acetamide	IC50	7.4 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-(3-Fluoro-4-trifluoromethoxy-benzyl)-2H-[1,2,3]triazol-4-yl]-2-(1-methyl-1H-indazol-5-yl)-acetamide	IC50	8.8 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(3,4-difluorophenyl)methyl]triazol-4-yl]-2-(1-methylindazol-5-yl)acetamide	IC50	9.5 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(3,4-difluorophenyl)methyl]triazol-4-yl]-2-(1,3,3-trimethyl-2-oxoindol-5-yl)acetamide	IC50	9.7 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(3,4-difluorophenyl)methyl]triazol-4-yl]-2-(1-ethylindazol-5-yl)acetamide	IC50	9.8 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
2-(1-methylindazol-5-yl)-N-[2-[[4-(trifluoromethoxy)phenyl]methyl]triazol-4-yl]acetamide	IC50	9.9 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[[(1S,5R)-8-[2-(tert-butylamino)-2-oxoethyl]-8-azabicyclo[3.2.1]octan-3-yl]methyl]-2-ethyl-3a,7a-dihydro-1-benzofuran-3-carboxamide	IC50	10 nM	US-9856250: Substituted tropane derivatives
2-[6-(3,3-difluoropyrrolidin-1-yl)-3-pyridinyl]-N-[2-[(4-fluorophenyl)methyl]triazol-4-yl]acetamide	IC50	10 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(3,4-difluorophenyl)methyl]triazol-4-yl]-2-(2-methyl-1H-indol-5-yl)acetamide	IC50	11 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
2-(1,3-Dimethyl-1H-indazol-5-yl)-N-[2-(3-fluoro-4-trifluoromethoxy-benzyl)-2H-[1,2,3]triazol-4-yl]-acetamide	IC50	11 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(4-fluorophenyl)methyl]triazol-4-yl]-2-(1-methylindol-5-yl)acetamide	IC50	12 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
3-chloro-5-fluoro-N-[[(1S,5R)-8-[2-[(1-methoxy-2-methylpropan-2-yl)amino]-2-oxoethyl]-8-azabicyclo[3.2.1]octan-3-yl]methyl]benzamide	IC50	13 nM	US-9856250: Substituted tropane derivatives
N-[2-[(3,5-difluoro-4-methoxyphenyl)methyl]triazol-4-yl]-2-(1-methylindol-5-yl)acetamide	IC50	13 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(3,5-difluoro-4-methoxyphenyl)methyl]triazol-4-yl]-2-[6-(3,3-difluoropyrrolidin-1-yl)-3-pyridinyl]acetamide	IC50	13 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-(4-Difluoromethoxy-3-fluoro-benzyl)-2H-[1,2,3]triazol-4-yl]-2-[6-(3,3-difluoro-pyrrolidin-1-yl)-pyridin-3-yl]-acetamide	IC50	13 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(4-cyano-3-fluorophenyl)methyl]triazol-4-yl]-2-(1,3-dimethylindol-5-yl)acetamide	IC50	14 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
2-(1-Ethyl-1H-indazol-5-yl)-N-[2-(3-fluoro-4-trifluoromethoxy-benzyl)-2H-[1,2,3]triazol-4-yl]-acetamide	IC50	14 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[[(1S,5R)-8-[2-(tert-butylamino)-2-oxoethyl]-8-azabicyclo[3.2.1]octan-3-yl]methyl]-2-methyl-3a,7a-dihydro-1-benzofuran-3-carboxamide	IC50	15 nM	US-9856250: Substituted tropane derivatives
2-[6-(diethylamino)-3-pyridinyl]-N-[2-[(3,4-difluorophenyl)methyl]triazol-4-yl]acetamide	IC50	15 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(3,4-difluorophenyl)methyl]triazol-4-yl]-2-(6-pyrrolidin-1-yl-3-pyridinyl)acetamide	IC50	15 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(3,4-difluorophenyl)methyl]triazol-4-yl]-2-[4-(3-methyloxetan-3-yl)phenyl]acetamide	IC50	15 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
2-[4-(3-methyloxetan-3-yl)phenyl]-N-[2-[[4-(trifluoromethoxy)phenyl]methyl]triazol-4-yl]acetamide	IC50	15 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(3,5-difluoro-4-methoxyphenyl)methyl]triazol-4-yl]-2-(1,3-dimethylindol-5-yl)acetamide	IC50	16 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
2-[4-(dimethylamino)phenyl]-N-[2-[(4-fluorophenyl)methyl]triazol-4-yl]acetamide	IC50	17 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(3,4-difluorophenyl)methyl]triazol-4-yl]-2-[4-(3-fluorooxetan-3-yl)phenyl]acetamide	IC50	17 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
2-(1-butylindazol-5-yl)-N-[2-[(3,4-difluorophenyl)methyl]triazol-4-yl]acetamide	IC50	17 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-(3-Fluoro-4-trifluoromethoxy-benzyl)-2H-[1,2,3]triazol-4-yl]-2-(1-methyl-1H-indazol-6-yl)-acetamide	IC50	17 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
2-[6-(3,3-Difluoro-pyrrolidin-1-yl)-pyridin-3-yl]-N-[2-(3-fluoro-4-trifluoromethoxy-benzyl)-2H-[1,2,3]triazol-4-yl]-acetamide	IC50	17 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-(4-Cyano-3-fluoro-benzyl)-2H-[1,2,3]triazol-4-yl]-2-[3-methyl-4-(2,2,2-trifluoro-ethoxy)-phenyl]-acetamide	IC50	17 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
MLS000570673	IC50	17.7 nM
N-[2-[(3,4-difluorophenyl)methyl]triazol-4-yl]-2-(1-propylindazol-5-yl)acetamide	IC50	18 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
2-[6-(3,3-difluoropyrrolidin-1-yl)-3-pyridinyl]-N-[2-[(4-ethoxyphenyl)methyl]triazol-4-yl]acetamide	IC50	18 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(4-cyano-3-fluorophenyl)methyl]triazol-4-yl]-2-(1-methylindol-5-yl)acetamide	IC50	18 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-(4-Cyano-3-methyl-benzyl)-2H-[1,2,3]triazol-4-yl]-2-(4-isopropyl-phenyl)-acetamide	IC50	18 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(4-cyanophenyl)methyl]triazol-4-yl]-2-(4-propan-2-ylphenyl)acetamide	IC50	19 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(4-cyanophenyl)methyl]triazol-4-yl]-2-(1-methylindol-5-yl)acetamide	IC50	19 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[[(1R,5S)-8-[2-(tert-butylamino)-2-oxoethyl]-8-azabicyclo[3.2.1]octan-3-yl]methyl]-3-chloro-5-hydroxybenzamide	IC50	20 nM	US-9856250: Substituted tropane derivatives
2-(1-methylindazol-5-yl)-N-[2-[(4-methylphenyl)methyl]triazol-4-yl]acetamide	IC50	20 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[[4-(difluoromethoxy)phenyl]methyl]triazol-4-yl]-2-(1-methylindol-5-yl)acetamide	IC50	20 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(4-cyano-3-fluorophenyl)methyl]triazol-4-yl]-2-(1,3-dimethylindol-6-yl)acetamide	IC50	20 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(4-fluorophenyl)methyl]triazol-4-yl]-2-(4-propan-2-ylphenyl)acetamide	IC50	21 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[[(1R,5S)-8-[2-(tert-butylamino)-2-oxoethyl]-8-azabicyclo[3.2.1]octan-3-yl]methyl]-4-methylbenzamide	IC50	22 nM	US-9856250: Substituted tropane derivatives
2-(4-cyclobutyloxyphenyl)-N-[2-[(3,4-difluorophenyl)methyl]triazol-4-yl]acetamide	IC50	22 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(3,4-difluorophenyl)methyl]triazol-4-yl]-2-(1,3-dimethylindazol-5-yl)acetamide	IC50	22 nM	US-10246426: Triazole compounds as T-type calcium channel blockers
N-[2-[(4-cyanophenyl)methyl]triazol-4-yl]-2-(1,3-dimethylindol-5-yl)acetamide	IC50	22 nM	US-10246426: Triazole compounds as T-type calcium channel blockers

ChEMBL bioactivities

868 potent at pChembl≥5 of 924 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.82	IC50	1.5	nM	CHEMBL3891844
8.72	IC50	1.9	nM	CHEMBL3890624
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	CHEMBL5987754
8.51	IC50	3.1	nM	CHEMBL3919898
8.47	IC50	3.4	nM	CHEMBL4205005
8.42	IC50	3.8	nM	CHEMBL4203101
8.40	IC50	4	nM	CHEMBL1210565
8.39	IC50	4.1	nM	CHEMBL4204077
8.37	IC50	4.3	nM	CHEMBL4215974
8.35	IC50	4.5	nM	CHEMBL3965812
8.29	IC50	5.1	nM	CHEMBL4204507
8.28	IC50	5.3	nM	CHEMBL4212039
8.26	IC50	5.5	nM	CHEMBL4205399
8.23	IC50	5.9	nM	CHEMBL3906126
8.22	IC50	6	nM	CHEMBL3906825
8.22	IC50	6	nM	CHEMBL3890916
8.22	IC50	6	nM	CHEMBL4207031
8.21	IC50	6.1	nM	CHEMBL4206509
8.19	IC50	6.4	nM	CHEMBL5837926
8.18	IC50	6.6	nM	CHEMBL4202587
8.17	IC50	6.7	nM	CHEMBL4214862
8.15	IC50	7	nM	CHEMBL3940577
8.15	IC50	7	nM	CHEMBL4208907
8.14	IC50	7.2	nM	CHEMBL3969562
8.14	IC50	7.3	nM	CHEMBL6028382
8.13	IC50	7.4	nM	CHEMBL5833167
8.12	IC50	7.6	nM	CHEMBL3937280
8.12	IC50	7.6	nM	CHEMBL3965812
8.12	IC50	7.5	nM	CHEMBL4218608
8.11	IC50	7.8	nM	CHEMBL4207291
8.11	IC50	7.8	nM	CHEMBL4216687
8.10	IC50	8	nM	CHEMBL3983323
8.09	IC50	8.2	nM	SUVECALTAMIDE
8.08	IC50	8.4	nM	CHEMBL4203847
8.07	IC50	8.6	nM	CHEMBL4209481
8.06	IC50	8.8	nM	CHEMBL5978528
8.05	IC50	9	nM	CHEMBL3906199
8.05	IC50	9	nM	CHEMBL3942512
8.03	IC50	9.4	nM	CHEMBL3922498
8.02	IC50	9.5	nM	CHEMBL4209481
8.01	IC50	9.7	nM	CHEMBL3897303
8.01	IC50	9.7	nM	CHEMBL5969453
8.01	IC50	9.8	nM	CHEMBL6001014
8.00	IC50	10	nM	CHEMBL4203748
8.00	IC50	10	nM	CHEMBL4209376
8.00	IC50	10	nM	CHEMBL4213335
8.00	IC50	10	nM	CHEMBL6015882

PubChem BioAssay actives

469 with measured affinity, of 1089 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
N-[1-[(3,4-difluorophenyl)methyl]pyrazol-3-yl]-2-[4-(dimethylamino)phenyl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0034	uM
N-[1-[(3,4-difluorophenyl)methyl]pyrazol-3-yl]-2-(1,3,3-trimethyl-2-oxoindol-5-yl)acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0038	uM
2-(3-chloro-4-fluorophenyl)-N-(3,5-difluorophenyl)-3-oxo-1-pyridin-2-yl-2,7-diazaspiro[3.5]nonane-7-carboxamide	493411: Inhibition of human CaV3.2 expressed in HEK293 cells at -100 mV membrane potential by Ionworks HT assay	ic50	0.0040	uM
N-[1-[(4-chlorophenyl)methyl]pyrazol-3-yl]-2-[4-(dimethylamino)phenyl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0041	uM
N-[1-[(3,4-difluorophenyl)methyl]pyrazol-3-yl]-2-[4-(3-methyloxetan-3-yl)phenyl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0043	uM
2-[4-(dimethylamino)phenyl]-N-[1-[[4-(trifluoromethoxy)phenyl]methyl]pyrazol-3-yl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0051	uM
N-[1-[(3,4-difluorophenyl)methyl]pyrazol-3-yl]-2-(1H-indol-6-yl)acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0053	uM
N-[1-[(5,5-difluorooxan-2-yl)methyl]pyrazol-3-yl]-2-(4-propan-2-ylphenyl)acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0055	uM
N-[1-[(3,4-difluorophenyl)methyl]pyrazol-3-yl]-2-(4-propan-2-ylphenyl)acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0060	uM
(3R,5S)-N,1-dibenzyl-8-fluoro-3,5-dimethyl-3,5-dihydro-2H-pyrido[2,3-e][1,4]diazepine-4-carboxamide	1325729: Channel blocking activity at recombinant human CaV 3.2 channel expressed in HEK293 cells assessed as inhibition of Ca2+ flux preincubated for 3 mins followed by CaCl2 addition by fluo-4 dye-based FLIPR assay	ic50	0.0060	uM
2-[4-(3,3-difluorocyclobutyl)phenyl]-N-[1-[(3,4-difluorophenyl)methyl]pyrazol-3-yl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0061	uM
3-chloro-2,5,5-trimethyl-N-[[2-(propan-2-yloxymethyl)phenyl]methyl]-6,7-dihydro-4H-isoindole-1-carboxamide	1366715: Inhibition of recombinant human Cav3.2 expressed in HEK293 cells assessed as reduction in CaCl2-induced intracellular calcium flux incubated for 20 mins measured at 10 secs interval for 2 to 6 mins by Fluo-4AM dye based FLIPR assay	ic50	0.0066	uM
N-[1-[(3,4-difluorophenyl)methyl]pyrazol-3-yl]-2-[6-(3,3-difluoropyrrolidin-1-yl)-3-pyridinyl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0067	uM
N-[1-[(5-cyano-2-pyridinyl)methyl]pyrazol-3-yl]-2-[3-methyl-4-(2,2,2-trifluoroethoxy)phenyl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0070	uM
2-(4-tert-butylphenyl)-N-[1-[(5-cyano-2-pyridinyl)methyl]pyrazol-3-yl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0075	uM
N-[1-[(3,5-difluoro-4-methoxyphenyl)methyl]pyrazol-3-yl]-2-[4-(dimethylamino)phenyl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0078	uM
N-[1-[(5-cyano-2-pyridinyl)methyl]pyrazol-3-yl]-2-[3-ethyl-4-(2,2,2-trifluoroethoxy)phenyl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0078	uM
2-(4-propan-2-ylphenyl)-N-[(1R)-1-[5-(2,2,2-trifluoroethoxy)-2-pyridinyl]ethyl]acetamide	1316439: Inhibition of recombinant T-type calcium channel Cav3.2 (unknown origin) expressed in HEK293 cells assessed as inhibition of CaCl2-induced calcium influx preincubated for 3 mins prior CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0082	uM
N-[1-[(3,4-difluorophenyl)methyl]pyrazol-3-yl]-2-(1-methylindazol-5-yl)acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0084	uM
N-[2-[(3,4-difluorophenyl)methyl]triazol-4-yl]-2-(1-methylindazol-5-yl)acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0086	uM
(3R,5S)-N-benzyl-1-[(2,3-difluorophenyl)methyl]-3,5-dimethyl-3,5-dihydro-2H-1,4-benzodiazepine-4-carboxamide	1325729: Channel blocking activity at recombinant human CaV 3.2 channel expressed in HEK293 cells assessed as inhibition of Ca2+ flux preincubated for 3 mins followed by CaCl2 addition by fluo-4 dye-based FLIPR assay	ic50	0.0090	uM
2-[4-(dimethylamino)phenyl]-N-[1-[(4-methylphenyl)methyl]pyrazol-3-yl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0100	uM
N-[1-[[4-(difluoromethoxy)phenyl]methyl]pyrazol-3-yl]-2-[4-(dimethylamino)phenyl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0100	uM
N-[1-[(3,4-difluorophenyl)methyl]pyrazol-3-yl]-2-[4-(2,2-dimethyl-1,3-dioxolan-4-yl)phenyl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0100	uM
2-[4-(3,3-difluorocyclobutyl)oxyphenyl]-N-[1-[(3,4-difluorophenyl)methyl]pyrazol-3-yl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0110	uM
(3R,5S)-1-[(2-fluorophenyl)methyl]-3,5-dimethyl-N-pyridin-3-yl-3,5-dihydro-2H-1,4-benzodiazepine-4-carboxamide	1325729: Channel blocking activity at recombinant human CaV 3.2 channel expressed in HEK293 cells assessed as inhibition of Ca2+ flux preincubated for 3 mins followed by CaCl2 addition by fluo-4 dye-based FLIPR assay	ic50	0.0110	uM
2-[4-(dimethylamino)phenyl]-N-[1-[(4-fluorophenyl)methyl]pyrazol-3-yl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0120	uM
(3R,5S)-1-benzyl-8-fluoro-3,5-dimethyl-N-pyridin-3-yl-3,5-dihydro-2H-1,4-benzodiazepine-4-carboxamide	1325729: Channel blocking activity at recombinant human CaV 3.2 channel expressed in HEK293 cells assessed as inhibition of Ca2+ flux preincubated for 3 mins followed by CaCl2 addition by fluo-4 dye-based FLIPR assay	ic50	0.0120	uM
3-chloro-2,5,5-trimethyl-N-[[2-(pyrazol-1-ylmethyl)phenyl]methyl]-6,7-dihydro-4H-isoindole-1-carboxamide	1366715: Inhibition of recombinant human Cav3.2 expressed in HEK293 cells assessed as reduction in CaCl2-induced intracellular calcium flux incubated for 20 mins measured at 10 secs interval for 2 to 6 mins by Fluo-4AM dye based FLIPR assay	ic50	0.0120	uM
N-[1-[(3,4-difluorophenyl)methyl]pyrazol-3-yl]-2-[4-(3-fluorooxetan-3-yl)phenyl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0130	uM
(3R,5S)-N-benzyl-3,5-dimethyl-1-[[5-(trifluoromethyl)furan-2-yl]methyl]-3,5-dihydro-2H-1,4-benzodiazepine-4-carboxamide	1325729: Channel blocking activity at recombinant human CaV 3.2 channel expressed in HEK293 cells assessed as inhibition of Ca2+ flux preincubated for 3 mins followed by CaCl2 addition by fluo-4 dye-based FLIPR assay	ic50	0.0130	uM
N-[1-[(4-cyano-3-fluorophenyl)methyl]pyrazol-3-yl]-2-[4-(dimethylamino)phenyl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0140	uM
N-[1-[(3,4-difluorophenyl)methyl]pyrazol-3-yl]-2-(1H-indol-5-yl)acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0140	uM
(3R,5S)-1-[(3-fluorophenyl)methyl]-3,5-dimethyl-N-pyridin-3-yl-3,5-dihydro-2H-1,4-benzodiazepine-4-carboxamide	1325729: Channel blocking activity at recombinant human CaV 3.2 channel expressed in HEK293 cells assessed as inhibition of Ca2+ flux preincubated for 3 mins followed by CaCl2 addition by fluo-4 dye-based FLIPR assay	ic50	0.0140	uM
(3R,5S)-3,5-dimethyl-N-pyridin-3-yl-1-[[5-(trifluoromethyl)furan-2-yl]methyl]-3,5-dihydro-2H-1,4-benzodiazepine-4-carboxamide	1325729: Channel blocking activity at recombinant human CaV 3.2 channel expressed in HEK293 cells assessed as inhibition of Ca2+ flux preincubated for 3 mins followed by CaCl2 addition by fluo-4 dye-based FLIPR assay	ic50	0.0140	uM
(3R,5S)-1-benzyl-N-[(4-methoxyphenyl)methyl]-3,5-dimethyl-3,5-dihydro-2H-1,4-benzodiazepine-4-carboxamide	1325729: Channel blocking activity at recombinant human CaV 3.2 channel expressed in HEK293 cells assessed as inhibition of Ca2+ flux preincubated for 3 mins followed by CaCl2 addition by fluo-4 dye-based FLIPR assay	ic50	0.0140	uM
N-[1-[(3,4-difluorophenyl)methyl]pyrazol-3-yl]-2-(3-methyl-2-oxo-1,3-benzoxazol-6-yl)acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0150	uM
(3R,5S)-N-benzyl-3,5-dimethyl-1-[[2-(trifluoromethyl)-1,3-thiazol-5-yl]methyl]-3,5-dihydro-2H-1,4-benzodiazepine-4-carboxamide	1325729: Channel blocking activity at recombinant human CaV 3.2 channel expressed in HEK293 cells assessed as inhibition of Ca2+ flux preincubated for 3 mins followed by CaCl2 addition by fluo-4 dye-based FLIPR assay	ic50	0.0150	uM
5-(4-bromophenyl)-N,3-bis(4-fluorophenyl)-3,4-dihydropyrazole-2-carboxamide	1316439: Inhibition of recombinant T-type calcium channel Cav3.2 (unknown origin) expressed in HEK293 cells assessed as inhibition of CaCl2-induced calcium influx preincubated for 3 mins prior CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0160	uM
(3R,5S)-N,1-dibenzyl-3,5-dimethyl-3,5-dihydro-2H-1,4-benzodiazepine-4-carboxamide	1325729: Channel blocking activity at recombinant human CaV 3.2 channel expressed in HEK293 cells assessed as inhibition of Ca2+ flux preincubated for 3 mins followed by CaCl2 addition by fluo-4 dye-based FLIPR assay	ic50	0.0170	uM
2-(3,4-difluorophenyl)-3-oxo-1-pyridin-2-yl-N-[3-(trifluoromethyl)phenyl]-2,7-diazaspiro[3.5]nonane-7-carboxamide	493411: Inhibition of human CaV3.2 expressed in HEK293 cells at -100 mV membrane potential by Ionworks HT assay	ic50	0.0170	uM
N-[1-[(5-cyano-2-pyridinyl)methyl]pyrazol-3-yl]-2-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0180	uM
N-[1-[(5-cyano-2-pyridinyl)methyl]pyrazol-3-yl]-2-[3-methyl-4-(3,3,3-trifluoropropoxy)phenyl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0180	uM
(3R,5S)-1-[(3,4-difluorophenyl)methyl]-3,5-dimethyl-N-pyridin-3-yl-3,5-dihydro-2H-1,4-benzodiazepine-4-carboxamide	1325729: Channel blocking activity at recombinant human CaV 3.2 channel expressed in HEK293 cells assessed as inhibition of Ca2+ flux preincubated for 3 mins followed by CaCl2 addition by fluo-4 dye-based FLIPR assay	ic50	0.0180	uM
2-(3-chlorophenyl)-N-(3,5-difluorophenyl)-3-oxo-1-pyridin-2-yl-2,7-diazaspiro[3.5]nonane-7-carboxamide	493411: Inhibition of human CaV3.2 expressed in HEK293 cells at -100 mV membrane potential by Ionworks HT assay	ic50	0.0180	uM
N-[1-[(4-cyanophenyl)methyl]pyrazol-3-yl]-2-[4-(dimethylamino)phenyl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0200	uM
(5S,6S)-3-chloro-2,5,6-trimethyl-N-[[2-(2-methylpropoxy)phenyl]methyl]-4,5,6,7-tetrahydroisoindole-1-carboxamide	1366715: Inhibition of recombinant human Cav3.2 expressed in HEK293 cells assessed as reduction in CaCl2-induced intracellular calcium flux incubated for 20 mins measured at 10 secs interval for 2 to 6 mins by Fluo-4AM dye based FLIPR assay	ic50	0.0200	uM
N-[1-[(3,4-difluorophenyl)methyl]pyrazol-3-yl]-2-[6-[(3S)-3-fluoropyrrolidin-1-yl]-3-pyridinyl]acetamide	1367822: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0210	uM
(3S)-N,3-bis(4-fluorophenyl)-5-pyridin-4-yl-3,4-dihydropyrazole-2-carboxamide	1316439: Inhibition of recombinant T-type calcium channel Cav3.2 (unknown origin) expressed in HEK293 cells assessed as inhibition of CaCl2-induced calcium influx preincubated for 3 mins prior CaCl2 addition by Fluo-4-AM dye-based FLIPR assay	ic50	0.0210	uM
3-chloro-N-[(2-ethoxyphenyl)methyl]-2,5,5-trimethyl-6,7-dihydro-4H-isoindole-1-carboxamide	1366715: Inhibition of recombinant human Cav3.2 expressed in HEK293 cells assessed as reduction in CaCl2-induced intracellular calcium flux incubated for 20 mins measured at 10 secs interval for 2 to 6 mins by Fluo-4AM dye based FLIPR assay	ic50	0.0210	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
dicrotophos	increases expression	1
bisphenol A	decreases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
1,6-hexamethylene diisocyanate	increases methylation	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	increases abundance, affects methylation	1
sodium arsenite	affects methylation	1
herbimycin	increases activity	1
benzo(e)pyrene	increases methylation	1
N-acetyl-4-benzoquinoneimine	affects response to substance	1
oxophenylarsine	decreases activity	1
tyrphostin 47	increases activity	1
ICG 001	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Air Pollutants, Occupational	affects expression	1
Amiloride	decreases reaction, increases transport	1
Arsenic	affects methylation	1
Barium	increases transport	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Calcium	decreases reaction, increases transport	1
Cannabinoids	affects methylation, increases abundance	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Menthol	decreases expression	1
Methapyrilene	increases methylation	1
Nickel	decreases reaction, increases transport	1
Niclosamide	increases expression	1

ChEMBL screening assays

124 unique, capped per target: 102 binding, 17 functional, 4 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1212315	Binding	Inhibition of human CaV3.2 expressed in HEK293 cells at -100 mV membrane potential by Ionworks HT assay	T-type calcium channel blockers: spiro-piperidine azetidines and azetidinones-optimization, design and synthesis. — Bioorg Med Chem Lett
CHEMBL1273187	Functional	Antagonist activity against T-type calcium channel subunit alpha-1H assessed as inactivation of channel current by cell based patch clamp assay	Design, syntheses, and SAR of 2,8-diazaspiro[4.5]decanones as T-type calcium channel antagonists. — Bioorg Med Chem Lett
CHEMBL4039284	ADMET	Inhibition of human Cav3.2 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

Cellosaurus cell lines

8 cell lines: 4 transformed cell line, 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0YH	B’SYS HEK 293 Cav3.2	Transformed cell line	Female
CVCL_D1JF	PrecisION hCav3.2-HEK	Transformed cell line	Female
CVCL_D7LA	Ubigene A-549 CACNA1H KO	Cancer cell line	Male
CVCL_D8I4	Ubigene HCT 116 CACNA1H KO	Cancer cell line	Male
CVCL_D9AI	Ubigene HEK293 CACNA1H KO	Transformed cell line	Female
CVCL_HC63	HEK293 Cav3.2	Transformed cell line	Female
CVCL_SG44	HAP1 CACNA1H (-) 1	Cancer cell line	Male
CVCL_SG45	HAP1 CACNA1H (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03590197	PHASE4	COMPLETED	Effect of Melatonin on Seizure Outcome, Neuronal Damage and Quality of Life in Patients With Generalized Epilepsy
NCT03940326	PHASE4	COMPLETED	Levetiracetam Versus Valproate in Idiopathic Generalized Tonic-clonic Seizures
NCT01959711	PHASE4	COMPLETED	Randomized Clinical Trial of Posterior Retroperitoneoscopic Adrenalectomy Versus Lateral Laparoscopic Adrenalectomy
NCT02127840	PHASE4	UNKNOWN	Influence of Synacthen Infusion on the Results of Adrenal Venous Sampling in Patient With Primary Aldosteronism
NCT05030545	PHASE4	RECRUITING	Cardiovascular Manifestations of MR Activation in Primary Aldosteronism: Pilot Clinical Study
NCT05814770	PHASE4	UNKNOWN	Comparing the Efficacy and Safety of Finerenone and Spironolactone in the Treatment of Primary Aldosteronism
NCT05924620	PHASE4	COMPLETED	Efficacy and Safety of Finerenone in Patients With Primary Aldosteronism
NCT06164379	PHASE4	UNKNOWN	Efficacy and Safety of Finerenone vs. Spironolactone in Patients With Primary Aldosteronism
NCT06381323	PHASE4	COMPLETED	The Clinical Efficacy and Safety of Finerenone in the Treatment of Primary Aldosteronism
NCT06457074	PHASE4	RECRUITING	Finerenone for Patients With Primary Aldosteronism (FAIRY)
NCT06523465	PHASE4	RECRUITING	Statin Combined with Amlodipine Treats Primary Aldosteronism
NCT00155064	PHASE4	COMPLETED	Kallikrein-kinin (KKS) and Renin-angiotensin-aldosterone System (RAAS) in Primary Aldosteronism
NCT00451672	PHASE4	UNKNOWN	The Therapeutic Effect of Bromocriptin in Patients With Primary Aldosteronism
NCT00553722	PHASE4	UNKNOWN	Does Aldosterone Cause Hypertension by a Non-Renal Mechanism?
NCT00438451	PHASE4	COMPLETED	Study on the Treatment of Elderly Patients With Older and Newer Antiepileptic Drugs
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00855738	PHASE4	COMPLETED	A Prospective, Observational Study On The Effectiveness Of New Antiepileptic Drugs As First Bitherapy In The Daily Clinical Practice
NCT00955357	PHASE4	COMPLETED	Trial to Assess Lacosamide as the First add-on Anti-epileptic Drug Treatment in Patients With Partial-onset Seizures
NCT01190098	PHASE4	COMPLETED	Randomized Controlled Trial to Assess Effects of Lacosamide on Sleep and Wake in Adults With Focal Epilepsy
NCT01235403	PHASE4	COMPLETED	Trial to Assess Optimized Dosage of Lacosamide as add-on Therapy in Patients With Partial Onset Seizure
NCT02208492	PHASE4	COMPLETED	The Effects on Cognitive Function of Levetiracetam (Keppra®) Compared to Carbamazepine (Tegretol®, Carmazepine®) as Monotherapy for Children With Partial Seizure; A Multicentric Randomized Controlled Study
NCT03607851	PHASE4	COMPLETED	Efficacy and Safety of Rapid Titration Protocols of Lacosamide
NCT05748236	PHASE4	UNKNOWN	The Efficacy and Safety of Lamotrigine Versus Carbamazepine in Focal Epilepsy
NCT07193277	PHASE4	RECRUITING	Butylphthalide for Cognitive Impairment in Elderly Patients With Focal Epilepsy
NCT00088452	PHASE3	COMPLETED	Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study
NCT04666610	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy, Safety, and Tolerability of Brivaracetam as Monotherapy in Patients 2 to 25 Years of Age With Childhood Absence Epilepsy or Juvenile Absence Epilepsy
NCT05109234	PHASE3	COMPLETED	A Study to Test the Long-term Safety, Tolerability and Efficacy of Brivaracetam in Study Participants 2 to 26 Years of Age With Childhood Absence Epilepsy or Juvenile Absence Epilepsy
NCT06315322	PHASE3	RECRUITING	A Study to Test the Long-term Safety and Tolerability of Brivaracetam in Study Participants With Childhood Absence Epilepsy or Juvenile Absence Epilepsy
NCT00150735	PHASE3	COMPLETED	Monotherapy With Levetiracetam in Newly Diagnosed Patients Suffering From Epilepsy
NCT00150748	PHASE3	COMPLETED	Long Term Follow up Treatment With Levetiracetam in Subjects of 4 Years and Older With Generalized Epilepsy
NCT03678753	PHASE3	COMPLETED	Randomized, Double-Blind Study to Evaluate Efficacy and Safety of Cenobamate Adjunctive Therapy in PGTC Seizures
NCT05147571	PHASE3	ACTIVE_NOT_RECRUITING	RNS System NAUTILUS Study
NCT03398785	PHASE3	COMPLETED	Adrenal Artery Ablation Treats Primary Aldosteronism
NCT03653845	PHASE3	UNKNOWN	Adrenal Artery Ablation for Primary Aldosteronism
NCT07007793	PHASE3	RECRUITING	A Study to Assess Efficacy and Safety of Baxdrostat in Participants With Primary Aldosteronism
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT01096654	PHASE3	COMPLETED	SPARTACUS: Subtyping Primary Aldosteronism: a Randomized Trial Comparing Adrenal Vein Sampling and Computed Tomography Scan.
NCT00391534	PHASE3	TERMINATED	EXTENT: EXtended Tolerability and Efficacy of a Novel Formulation of Oxcarbazepine in a Trial in Partial Epilepsy
NCT00522275	PHASE3	COMPLETED	Determine Safety and Efficacy of Long-term Oral Lacosamide in Patients With Partial Seizures
NCT00655486	PHASE3	COMPLETED	Study to Assess the Long-term Safety of Oral Lacosamide in Subjects With Partial-onset Seizures