CACNA1B

Summary

CACNA1B (calcium voltage-gated channel subunit alpha1 B, HGNC:1389) is a protein-coding gene on chromosome 9q34.3, encoding Voltage-dependent N-type calcium channel subunit alpha-1B (Q00975). Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division an….

The protein encoded by this gene is the pore-forming subunit of an N-type voltage-dependent calcium channel, which controls neurotransmitter release from neurons. The encoded protein forms a complex with alpha-2, beta, and delta subunits to form the high-voltage activated channel. This channel is sensitive to omega-conotoxin-GVIA and omega-agatoxin-IIIA but insensitive to dihydropyridines. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 774 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 1,979 total — 65 pathogenic, 20 likely-pathogenic
• Phenotypes (HPO): 71
• Druggable target: yes — 23 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000718

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1389
Approved symbol	CACNA1B
Name	calcium voltage-gated channel subunit alpha1 B
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	Cav2.2, CACNN
Ensembl gene	ENSG00000148408
Ensembl biotype	protein_coding
OMIM	601012
Entrez	774

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 3 nonsense_mediated_decay

ENST00000277551, ENST00000371357, ENST00000371363, ENST00000371372, ENST00000413253, ENST00000715544, ENST00000715545, ENST00000715546, ENST00000715547, ENST00000715548, ENST00000715549, ENST00000914235, ENST00000914236

RefSeq mRNA: 2 — MANE Select: NM_000718 NM_000718, NM_001243812

CCDS: CCDS59522, CCDS59523

Canonical transcript exons

ENST00000371372 — 47 exons

Exon	Start	End
ENSE00000985102	138049209	138049315
ENSE00000985104	138053846	138054006
ENSE00000985107	138058569	138058733
ENSE00000985108	138059079	138059189
ENSE00000985112	138075819	138075910
ENSE00000985119	138115552	138115679
ENSE00000985121	138118652	138118768
ENSE00000985122	138120165	138120372
ENSE00001097040	138059654	138059737
ENSE00001177441	138120631	138120881
ENSE00001177464	138117946	138118081
ENSE00001177477	138114378	138114490
ENSE00001177485	138112398	138112505
ENSE00001177501	138102711	138102807
ENSE00001177508	138078114	138078258
ENSE00001177538	138057732	138057869
ENSE00001177546	138052092	138052188
ENSE00001177568	138043774	138043900
ENSE00001177571	138024955	138025172
ENSE00001752036	138073488	138073604
ENSE00001774271	138058049	138058250
ENSE00002375973	138074001	138074066
ENSE00002382307	138069758	138069763
ENSE00002397867	138096484	138096611
ENSE00003542446	138047399	138047458
ENSE00003598743	138046904	138047033
ENSE00003668622	138105699	138105807
ENSE00003713307	137956771	137956827
ENSE00003715267	137975907	137976019
ENSE00003719647	137952274	137952377
ENSE00003720383	137957598	137957687
ENSE00003722372	137986782	137986854
ENSE00003725539	137986413	137986544
ENSE00003727731	137914654	137914806
ENSE00003736842	137882744	137882883
ENSE00003738108	138023011	138023811
ENSE00003739068	137879054	137879159
ENSE00003739094	138010010	138010077
ENSE00003740632	137955698	137955813
ENSE00003740907	137984138	137984250
ENSE00003742889	138013129	138013235
ENSE00003743465	137913180	137913271
ENSE00003745607	137917241	137917431
ENSE00003746441	138006767	138006884
ENSE00003751045	137971383	137971592
ENSE00003843749	137877782	137878217
ENSE00003845586	138121469	138124619

Expression profiles

Bgee: expression breadth ubiquitous, 146 present calls, max score 95.05.

FANTOM5 (CAGE): breadth broad, TPM avg 0.5379 / max 26.7140, expressed in 186 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99717	0.3967	156
205699	0.1413	73

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	95.05	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.64	gold quality
postcentral gyrus	UBERON:0002581	90.00	gold quality
endothelial cell	CL:0000115	89.86	gold quality
superior frontal gyrus	UBERON:0002661	89.66	gold quality
entorhinal cortex	UBERON:0002728	89.20	gold quality
parietal lobe	UBERON:0001872	88.72	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.72	gold quality
cortical plate	UBERON:0005343	88.14	gold quality
primary visual cortex	UBERON:0002436	88.10	gold quality
cerebellar hemisphere	UBERON:0002245	87.97	gold quality
cerebellar cortex	UBERON:0002129	87.90	gold quality
cerebellum	UBERON:0002037	87.75	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.40	gold quality
occipital lobe	UBERON:0002021	86.87	gold quality
frontal cortex	UBERON:0001870	84.85	gold quality
frontal lobe	UBERON:0016525	84.83	gold quality
cerebellar vermis	UBERON:0004720	84.82	gold quality
right frontal lobe	UBERON:0002810	83.89	gold quality
neocortex	UBERON:0001950	83.80	gold quality
prefrontal cortex	UBERON:0000451	83.69	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.26	gold quality
cerebral cortex	UBERON:0000956	83.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.51	gold quality
lateral nuclear group of thalamus	UBERON:0002736	81.96	gold quality
brain	UBERON:0000955	81.17	gold quality
substantia nigra pars compacta	UBERON:0001965	81.06	gold quality
central nervous system	UBERON:0001017	80.97	gold quality
nucleus accumbens	UBERON:0001882	80.92	gold quality
temporal lobe	UBERON:0001871	80.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	89.72
E-HCAD-25	yes	75.77
E-ANND-3	yes	4.72

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

106 targeting CACNA1B, 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-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394

Literature-anchored findings (GeneRIF, showing 30)

• Results suggest that a 39 bp DNA element in the N-type voltage-gated calcium channel alpha1B gene might act as repressor in non-neuronal cells through specific interactions with DNA. (PMID:12018859)
• molecular dissection of calcium current mechanosensitivity- electrophysiology of N-type calcium channels (PMID:12414690)
• the C-terminal region of Ca(v)2.2 does not have a critical role in regulation of the calcium channel (PMID:14602720)
• Cav2.2 alpha2delta auxiliary subunit binds to omega-conotoxins (PMID:15166237)
• Activation of PKC resulted in its recruitment to and phosphorylation of Ca(V)2.2 channels, but PKC phosphorylation did not dissociate Ca(V)2.2 channel/syntaxin 1A complexes. (PMID:15607937)
• The Y388S mutation had no effect on current density and cell surface expression of Ca(V)2.2/alpha2delta-2/beta1b channels expressed in human embryonic kidney tsA-201 cells, when equivalent proportions of cDNA were used. (PMID:16627564)
• Our studies of the e37a/e37b splice site reveal a multifunctional domain in the C-terminus of Ca(V)2.2 that regulates the overall activity of N-type calcium channels in nociceptors. (PMID:16857708)
• The orientation of the Ca(v)beta subunit relative to the alpha(1)2.2 subunit is critical, and suggests additional points of contact between these subunits are required for Ca(v)beta to regulate channel activity. (PMID:18958281)
• polymorphisms and haplotypes in the human CACNA1B gene show significant differences between cerebral infarction and control patients (PMID:21166801)
• Ca(2+) exits the channel through the Cav2.2. (PMID:22491326)
• new mechanistic perspectives, and reveal unexpected variations in determinants, underlying inhibition of Ca(V)1.2/Ca(V)2.2 channels by distinct RGK GTPases. (PMID:22590648)
• Results show that GABA(B) receptors R1 and R2 must be activated for the modulation of N-type (Ca(v)2.2) calcium channels by analgesic alpha-conotoxins Vc1.1 and RgIA. (PMID:22613715)
• The interaction between LC1 and the N-type channel (CaV2.2 channel) was demonstrated. (PMID:24566975)
• with membrane-localized CaV beta subunits, CaV2.2 channels are subject to Gbetagamma-mediated voltage-dependent inhibition, whereas cytosol-localized beta subunits confer more effective PIP2-mediated voltage-independent regulation (PMID:25225550)
• CACNA1B mutation is linked to unique myoclonus-dystonia syndrome. (PMID:25296916)
• These results do not support a causal association between the CACNA1B c.4166G>A; (p.R1389H) variant and M-D. (PMID:26157024)
• The first disease connection for Cav2.2 channels [review] (PMID:26218636)
• the consensus motifs of S-nitrosylation were much more abundant in Cav2.2 than in Cav1.2 and Cav2.1. (PMID:26507659)
• AP-1 binding motifs, present only in exon 37a, enhance intracellular trafficking of exon 37a-containing Ca(V)2.2 to the axons and plasma membrane of rat dorsal root ganglia neurons (PMID:26511252)
• CACNA1B protein expressions in tumorous tissues were correlated with NSCLC patients’ clinical characteristics and overall survival. CACNA1B mRNA and protein expression levels were higher in NSCLC tumorous tissues than in nontumorous tissues. (PMID:28127114)
• Cav2.2 alpha1 subunit alone could form a complex with the AMPAR in heterologous cells. The cell-surface AMPAR was increased by co-expression of Cav2.2 alpha1 subunit. (PMID:29448101)
• Bi-allelic Loss-of-Function CACNA1B Mutations are associated with Progressive Epilepsy-Dyskinesia. (PMID:30982612)
• CACNA1B gene variants in adult-onset isolated focal dystonia. (PMID:33051750)
• CACNA1B facilitates breast cancer cell growth and migration by regulating cyclin D1 and EMT: the implication of CACNA1B in breast cancer. (PMID:33100116)
• CaV2.2 (N-type) voltage-gated calcium channels are activated by SUMOylation pathways. (PMID:33360835)
• Structure of human Cav2.2 channel blocked by the painkiller ziconotide. (PMID:34234349)
• Closed-state inactivation and pore-blocker modulation mechanisms of human CaV2.2. (PMID:34731621)
• High expression of N-type calcium channel indicates a favorable prognosis in gliomas. (PMID:35777045)
• Cav2.2-NFAT2-USP43 axis promotes invadopodia formation and breast cancer metastasis through cortactin stabilization. (PMID:36137995)
• An orally available Cav2.2 calcium channel inhibitor for the treatment of neuropathic pain. (PMID:38157867)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cacna1ba	ENSDARG00000021735
danio_rerio	cacna1bb	ENSDARG00000079295
mus_musculus	Cacna1b	ENSMUSG00000004113
rattus_norvegicus	Cacna1b	ENSRNOG00000004560

Paralogs (26): CACNA1G (ENSG00000006283), SCN4A (ENSG00000007314), CACNA1S (ENSG00000081248), CACNA1I (ENSG00000100346), CACNA1F (ENSG00000102001), NALCN (ENSG00000102452), SCN2A (ENSG00000136531), SCN7A (ENSG00000136546), CACNA1A (ENSG00000141837), SCN1A (ENSG00000144285), CACNA1C (ENSG00000151067), CATSPER3 (ENSG00000152705), SCN3A (ENSG00000153253), CACNA1D (ENSG00000157388), TPCN2 (ENSG00000162341), CATSPER2 (ENSG00000166762), SCN11A (ENSG00000168356), SCN9A (ENSG00000169432), CATSPER1 (ENSG00000175294), SCN5A (ENSG00000183873), SCN10A (ENSG00000185313), TPCN1 (ENSG00000186815), CATSPER4 (ENSG00000188782), CACNA1H (ENSG00000196557), SCN8A (ENSG00000196876), CACNA1E (ENSG00000198216)

Protein

Protein identifiers

Voltage-dependent N-type calcium channel subunit alpha-1B — Q00975 (reviewed: Q00975)

Alternative names: Brain calcium channel III, Calcium channel, L type, alpha-1 polypeptide isoform 5, Voltage-gated calcium channel subunit alpha Cav2.2

All UniProt accessions (10): Q00975, A0AAQ5BIF3, A0AAQ5BII4, A0AAQ5BII6, A0AAQ5BII8, A0AAQ5BIJ0, A0AAQ5BIJ3, B1AQK6, B1AQK7, H0Y7I8

UniProt curated annotations — full annotation on UniProt →

Function. Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This alpha-1B subunit gives rise to N-type calcium currents. N-type calcium channels belong to the ‘high-voltage activated’ (HVA) group. They are involved in pain signaling. Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons. Mediates Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals. Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This alpha-1B subunit gives rise to N-type calcium currents.

Subunit / interactions. Multisubunit complex consisting of alpha-1, alpha-2, beta and delta subunits in a 1:1:1:1 ratio. The channel activity is directed by the pore-forming and voltage-sensitive alpha-1 subunit. In many cases, this subunit is sufficient to generate voltage-sensitive calcium channel activity. The auxiliary subunits beta and alpha-2/delta linked by a disulfide bridge regulate the channel activity. Interacts with RIMS1. Interacts with FMR1 (via C-terminus); this interaction induces a decrease in the number of presynaptic functional CACNA1B channels at the cell surface.

Subcellular location. Membrane.

Tissue specificity. Isoform Alpha-1b-1 and isoform Alpha-1b-2 are expressed in the central nervous system, but not in skeletal muscle or aorta. Expressed in the cerebral white matter, cortex, hippocampus, basal ganglia, and cerebellum.

Post-translational modifications. Phosphorylated in vitro by CaM-kinase II, PKA, PKC and CGPK.

Disease relevance. Neurodevelopmental disorder with seizures and non-epileptic hyperkinetic movements (NEDNEH) [MIM:618497] An autosomal recessive, complex and progressive neurologic disorder characterized by severe neurodevelopmental delay and developmental regression, epileptic encephalopathy, postnatal microcephaly, hypotonia, and non-epileptic hyperkinetic movement disorder, including myoclonus dystonia, choreoathetosis, or generalized dyskinesia. Disease onset in infancy or first years of life. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. Is specifically blocked by omega-conotoxin GVIA. Is specifically blocked by omega-conotoxin MVIIA (ziconotide). Is insensitive to dihydropyridines (DHP). Is specifically blocked by omega-conotoxin MVIIA (ziconotide). Is insensitive to dihydropyridines (DHP).

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. CACNA1B subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q00975-1	Alpha-1B-1	yes
Q00975-2	Alpha-1B-2

RefSeq proteins (2): NP_000709, NP_001230741 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR002077	VDCCAlpha1	Family
IPR005447	VDCC_N_a1su	Family
IPR005821	Ion_trans_dom	Domain
IPR014873	VDCC_a1su_IQ	Domain
IPR027359	Volt_channel_dom_sf	Homologous_superfamily
IPR031649	GPHH_dom	Domain
IPR050599	VDCC_alpha-1_subunit	Family

Pfam: PF00520, PF08763, PF16905

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (221 total): helix 72, strand 30, topological domain 25, transmembrane region 24, compositionally biased region 13, turn 12, modified residue 10, sequence variant 7, binding site 7, region of interest 6, repeat 4, site 4, glycosylation site 3, chain 1, sequence conflict 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7VFS	ELECTRON MICROSCOPY	2.8
7MIX	ELECTRON MICROSCOPY	3
7VFU	ELECTRON MICROSCOPY	3
7VFV	ELECTRON MICROSCOPY	3
7MIY	ELECTRON MICROSCOPY	3.1
7VFW	ELECTRON MICROSCOPY	3.3
2LCM	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q00975-F1	60.66	0.08

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): 314 (calcium ion selectivity and permeability); 663 (calcium ion selectivity and permeability); 1365 (calcium ion selectivity and permeability); 1655 (calcium ion selectivity and permeability)

Ligand- & substrate-binding residues (7): 451–458; 544; 584; 587; 1737; 1743; 1748

Post-translational modifications (10): 22, 411, 745, 748, 783, 1069, 2066, 2224, 2233, 2256

Glycosylation sites (3): 256, 1563, 1675

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-112308	Presynaptic depolarization and calcium channel opening
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System

MSigDB gene sets: 310 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BENPORATH_ES_WITH_H3K27ME3, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_DEPENDENT_EXOCYTOSIS, KEGG_MAPK_SIGNALING_PATHWAY, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, SRF_Q5_01, GOBP_EXOCYTOSIS, SRF_C, GOBP_POSITIVE_REGULATION_OF_REGULATED_SECRETORY_PATHWAY

GO Biological Process (10): chemical synaptic transmission (GO:0007268), modulation of chemical synaptic transmission (GO:0050804), calcium ion import across plasma membrane (GO:0098703), positive regulation of calcium ion-dependent exocytosis of neurotransmitter (GO:1903235), response to amyloid-beta (GO:1904645), 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 (11): amyloid-beta binding (GO:0001540), voltage-gated calcium channel activity (GO:0005245), calcium ion binding (GO:0005509), ATP binding (GO:0005524), high voltage-gated calcium channel activity (GO:0008331), nucleotide binding (GO:0000166), monoatomic ion channel activity (GO:0005216), calcium channel activity (GO:0005262), protein binding (GO:0005515), voltage-gated monoatomic cation channel activity (GO:0022843), metal ion binding (GO:0046872)

GO Cellular Component (6): plasma membrane (GO:0005886), voltage-gated calcium channel complex (GO:0005891), neuronal cell body (GO:0043025), synapse (GO:0045202), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Transmission across Chemical Synapses	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
monoatomic cation channel activity	2
anterograde trans-synaptic signaling	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	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
positive regulation of calcium ion-dependent exocytosis	1
calcium ion-regulated exocytosis of neurotransmitter	1
regulation of calcium ion-dependent exocytosis of neurotransmitter	1
positive regulation of synaptic vesicle exocytosis	1
response to nitrogen compound	1
response to oxygen-containing compound	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
peptide binding	1
calcium channel activity	1
voltage-gated monoatomic cation channel activity	1
metal ion binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
voltage-gated calcium channel activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
calcium ion transmembrane transporter activity	1
binding	1
voltage-gated monoatomic ion channel activity	1
cation binding	1
membrane	1
cell periphery	1
calcium channel complex	1
plasma membrane protein complex	1

Protein interactions and networks

STRING

2404 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CACNA1B	DPYSL2	Q16555	921
CACNA1B	STX1A	Q16623	898
CACNA1B	CACNB3	P54284	875
CACNA1B	SNAP25	P13795	861
CACNA1B	CAV2	P51636	793
CACNA1B	CACNA2D2	Q9NY47	793
CACNA1B	HTT	P42858	788
CACNA1B	A0A0A0MSP3	A0A0A0MSP3	782
CACNA1B	OLFM1	Q99784	765
CACNA1B	CACNA2D1	P54289	749
CACNA1B	SYT1	P21579	740
CACNA1B	CALM1	P02593	718
CACNA1B	CALML3	P27482	702
CACNA1B	CALML5	Q9NZT1	702
CACNA1B	CAV3	P56539	697

IntAct

18 interactions, top by confidence:

A	B	Type	Score
Ppm1a	CACNA1B	psi-mi:“MI:0915”(physical association)	0.540
Ppm1a	CACNA1B	psi-mi:“MI:0203”(dephosphorylation reaction)	0.540
RXRB	CACNA1B	psi-mi:“MI:0915”(physical association)	0.520
CACNA1B	Apba1	psi-mi:“MI:0915”(physical association)	0.510
Apba1	CACNA1B	psi-mi:“MI:0915”(physical association)	0.510
APBA2	CACNA1B	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1B	APBA1	psi-mi:“MI:0407”(direct interaction)	0.440
MTNR1A	CACNA1B	psi-mi:“MI:0915”(physical association)	0.400
	CACNA1B	psi-mi:“MI:0915”(physical association)	0.400
Rimbp2	CACNA1B	psi-mi:“MI:0915”(physical association)	0.370
Rims1	CACNA1B	psi-mi:“MI:0915”(physical association)	0.370
MRFAP1	CACNA1B	psi-mi:“MI:0915”(physical association)	0.000
RXRB	CACNA1B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): UBE2L3 (Affinity Capture-Western), MAP1B (Affinity Capture-Western), CACNA1B (Affinity Capture-Western), CACNA1B (Affinity Capture-Western), CACNA1B (Affinity Capture-MS), CACNA1B (Reconstituted Complex), SIGMAR1 (FRET), SIGMAR1 (Affinity Capture-Western), CACNA1B (Affinity Capture-Western), CACNA1B (PCA), CACNA1B (Positive Genetic), CACNA1B (Cross-Linking-MS (XL-MS)), CAMK2A (Reconstituted Complex), CACNA1B (Affinity Capture-MS), GNB2 (Affinity Capture-Western)

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

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

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CAMK2A	down-regulates	CACNA1B	phosphorylation
GNB/GNG	“down-regulates activity”	CACNA1B	binding
CACNA1B	“up-regulates quantity”	calcium(2+)	relocalization
ANK2	“up-regulates quantity”	CACNA1B	binding
ERK1/2	“up-regulates activity”	CACNA1B	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

1979 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	65
Likely pathogenic	20
Uncertain significance	702
Likely benign	967
Benign	132

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1073969	NC_000009.11:g.(?140513481)(141016451_?)del	Pathogenic
1073970	NC_000009.11:g.(?140622791)(141016451_?)del	Pathogenic
1340359	GRCh37/hg19 9q34.3(chr9:140694542-140918479)x1	Pathogenic
1527572	GRCh37/hg19 9q34.3(chr9:140620020-140854178)	Pathogenic
1910522	NM_000718.4(CACNA1B):c.6304C>T (p.Arg2102Ter)	Pathogenic
2007892	NM_000718.4(CACNA1B):c.5716C>T (p.Arg1906Ter)	Pathogenic
2028733	NM_000718.4(CACNA1B):c.2479dup (p.Arg827fs)	Pathogenic
2030344	NM_000718.4(CACNA1B):c.3429C>A (p.Cys1143Ter)	Pathogenic
2055667	NM_000718.4(CACNA1B):c.565C>T (p.Arg189Ter)	Pathogenic
2072840	NM_000718.4(CACNA1B):c.3052del (p.Arg1018fs)	Pathogenic
2073990	NM_000718.4(CACNA1B):c.5305C>T (p.Arg1769Ter)	Pathogenic
2082495	NM_000718.4(CACNA1B):c.5992C>T (p.Arg1998Ter)	Pathogenic
2101980	NM_000718.4(CACNA1B):c.2365del (p.Ser789fs)	Pathogenic
2131750	NM_000718.4(CACNA1B):c.2851_2875del (p.Lys951fs)	Pathogenic
2423352	NC_000009.11:g.(?140919387)(140919644_?)del	Pathogenic
2423354	NC_000009.11:g.(?140646763)(140881326_?)del	Pathogenic
2423355	NC_000009.11:g.(?140807612)(140811903_?)del	Pathogenic
2423356	NC_000009.11:g.(?140846706)(140851299_?)del	Pathogenic
2756096	NM_000718.4(CACNA1B):c.4325del (p.Phe1442fs)	Pathogenic
2807901	NM_000718.4(CACNA1B):c.3321del (p.Lys1108fs)	Pathogenic
2810711	NM_000718.4(CACNA1B):c.999G>A (p.Trp333Ter)	Pathogenic
2811501	NM_000718.4(CACNA1B):c.947G>A (p.Trp316Ter)	Pathogenic
2847135	NM_000718.4(CACNA1B):c.5986C>T (p.Gln1996Ter)	Pathogenic
2858601	NM_000718.4(CACNA1B):c.5475_5476del (p.Ser1826fs)	Pathogenic
2992758	NM_000718.4(CACNA1B):c.1553_1554del (p.Glu518fs)	Pathogenic
3063093	GRCh37/hg19 9q34.3(chr9:140705084-141020389)x1	Pathogenic
3238662	GRCh38/hg38 9q34.3(chr9:137728349-138052188)	Pathogenic
3238670	GRCh38/hg38 9q34.3(chr9:137800900-138059181)	Pathogenic
3238696	GRCh38/hg38 9q34.3(chr9:137640986-138143864)	Pathogenic
3238705	GRCh38/hg38 9q34.3(chr9:137782789-138068654)	Pathogenic

SpliceAI

11479 predictions. Top by Δscore:

Variant	Effect	Δscore
9:137879156:GCTG:G	donor_gain	1.0000
9:137879160:G:GG	donor_gain	1.0000
9:137913272:G:GG	donor_gain	1.0000
9:137913305:G:GT	donor_gain	1.0000
9:137913308:G:GG	donor_gain	1.0000
9:137917236:TGCA:T	acceptor_loss	1.0000
9:137917238:CAGA:C	acceptor_loss	1.0000
9:137917239:A:AG	acceptor_gain	1.0000
9:137917239:AGAT:A	acceptor_gain	1.0000
9:137917240:G:GA	acceptor_gain	1.0000
9:137917240:GA:G	acceptor_gain	1.0000
9:137917240:GAT:G	acceptor_gain	1.0000
9:137917240:GATG:G	acceptor_gain	1.0000
9:137917240:GATGC:G	acceptor_gain	1.0000
9:137917386:GTTCC:G	donor_gain	1.0000
9:137917432:G:GG	donor_gain	1.0000
9:137954438:G:GT	donor_gain	1.0000
9:137954439:G:T	donor_gain	1.0000
9:137955334:G:T	donor_gain	1.0000
9:137955338:G:GT	donor_gain	1.0000
9:137955681:C:A	acceptor_gain	1.0000
9:137955688:T:TA	acceptor_gain	1.0000
9:137955691:A:AG	acceptor_gain	1.0000
9:137955691:AT:A	acceptor_gain	1.0000
9:137955691:ATG:A	acceptor_gain	1.0000
9:137955692:T:G	acceptor_gain	1.0000
9:137955692:T:TA	acceptor_gain	1.0000
9:137955696:AG:A	acceptor_gain	1.0000
9:137955696:AGG:A	acceptor_gain	1.0000
9:137955697:G:GT	acceptor_gain	1.0000

AlphaMissense

15351 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:137879093:C:A	N108K	1.000
9:137879093:C:G	N108K	1.000
9:137879094:T:C	C109R	1.000
9:137879096:C:G	C109W	1.000
9:137882849:T:A	W166R	1.000
9:137882849:T:C	W166R	1.000
9:137882861:G:C	D170H	1.000
9:137882862:A:T	D170V	1.000
9:137913242:G:C	R198T	1.000
9:137913242:G:T	R198M	1.000
9:137913245:C:A	P199H	1.000
9:137913245:C:G	P199R	1.000
9:137913254:T:C	L202P	1.000
9:137914669:T:A	L213H	1.000
9:137914669:T:C	L213P	1.000
9:137914699:T:A	L223H	1.000
9:137914699:T:C	L223P	1.000
9:137914702:T:C	L224P	1.000
9:137914710:G:A	G227R	1.000
9:137914710:G:C	G227R	1.000
9:137914711:G:A	G227E	1.000
9:137914720:T:A	L230H	1.000
9:137914720:T:C	L230P	1.000
9:137917411:T:A	W316R	1.000
9:137917411:T:C	W316R	1.000
9:137917413:G:C	W316C	1.000
9:137917413:G:T	W316C	1.000
9:137952356:T:C	L350P	1.000
9:137952371:T:A	L355H	1.000
9:137952371:T:C	L355P	1.000

dbSNP variants (sampled 300 via entrez): RS1000014003 (9:138073816 T>C), RS1000033378 (9:137907951 T>C), RS1000033631 (9:137955234 G>A), RS1000085680 (9:137955594 G>A), RS1000089479 (9:137949761 G>A,C), RS1000091705 (9:138106157 C>T), RS1000097300 (9:138096935 T>C), RS1000099073 (9:137997846 A>G,T), RS1000114074 (9:137928024 G>T), RS1000120880 (9:138010522 G>T), RS1000122521 (9:137915032 G>A,T), RS1000126629 (9:137990771 C>T), RS1000169880 (9:137999246 AT>A), RS1000170781 (9:137931405 G>T), RS1000173910 (9:138036264 C>G,T)

Disease associations

OMIM: gene MIM:601012 | disease phenotypes: MIM:614860, MIM:618497, MIM:610253

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements	Strong	Autosomal recessive
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
complex neurodevelopmental disorder with motor features	Moderate	AR

Mondo (5): dystonia 23 (MONDO:0013928), neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements (MONDO:0032784), Kleefstra syndrome 1 (MONDO:0027407), complex neurodevelopmental disorder with motor features (MONDO:0100516), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (2): Adult-onset cervical dystonia, DYT23 type (Orphanet:420492), Kleefstra syndrome (Orphanet:261494)

HPO phenotypes

71 total (30 of 71 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000348	High forehead
HP:0000405	Conductive hearing impairment
HP:0000463	Anteverted nares
HP:0000486	Strabismus
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:0001266	Choreoathetosis
HP:0001268	Mental deterioration
HP:0001273	Abnormal corpus callosum morphology
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001315	Reduced tendon reflexes

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002915_4	Asparaginase hypersensitivity in acute lymphoblastic leukemia	3.000000e-06
GCST008103_132	Bipolar disorder	2.000000e-06
GCST008152_146	Weight	6.000000e-06
GCST008158_81	Body mass index	1.000000e-06
GCST010396_206	Gut microbiota (bacterial taxa, hurdle binary method)	4.000000e-06
GCST010991_8	Parkinson’s disease	3.000000e-07

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004881	asparaginase hypersensitivity
EFO:0004338	body weight
EFO:0004340	body mass index
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563043	Kleefstra Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2097170 (PROTEIN-PROTEIN INTERACTION), CHEMBL2363032 (PROTEIN COMPLEX GROUP), CHEMBL3430901 (PROTEIN COMPLEX), CHEMBL4106160 (PROTEIN COMPLEX), CHEMBL4478 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

23 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 502,206 (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
CHEMBL193	NIFEDIPINE	4	74,353
CHEMBL1428	NIMODIPINE	4	32,587
CHEMBL95	TACRINE	4	35,360
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL21731	MAPROTILINE	4	19,686
CHEMBL415	CLOMIPRAMINE	4	27,385
CHEMBL445	NORTRIPTYLINE	4	31,234
CHEMBL45816	MIBEFRADIL	4	7,838
CHEMBL4594214	ZICONOTIDE	4	1,201
CHEMBL629	AMITRIPTYLINE	4	52,595
CHEMBL643	PROMETHAZINE	4	36,306
CHEMBL644	TRIMIPRAMINE	4	19,638
CHEMBL668	PROTRIPTYLINE	4	19,348
CHEMBL669	CYCLOBENZAPRINE	4	11,673
CHEMBL72	DESIPRAMINE	4	34,909
CHEMBL449317	HESPERIDIN	3	18,753
CHEMBL370753	OPIPRAMOL	3	4,875
CHEMBL452076	CILNIDIPINE	3	5,373
CHEMBL604710	Z160	2	71
CHEMBL14762	SELICICLIB	2
CHEMBL29188	LOMERIZINE	2
CHEMBL30008	FLUNARIZINE	2

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

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2229949	CACNA1B		0.00	0
rs2739258	CACNA1B		0.00	0
rs2739260	CACNA1B		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 (14 total), top 14:

Ligand	Action	Affinity	Parameter
ω-conotoxin GVIA	Antagonist	10.4	pIC50
ω-conotoxin CVID	Antagonist	10.2	pIC50
ω-conotoxin CVIA	Antagonist	9.3	pIC50
DW13.3	Antagonist	8.6	pIC50
ω-conotoxin MVIIC	Antagonist	8.5	pIC50
ω-conotoxin CVIB	Antagonist	8.1	pIC50
ω-conotoxin CVIC	Antagonist	8.1	pIC50
NP118809	Gating inhibitor	7.0	pIC50
cilnidipine	Pore blocker	6.7	pIC50
TROX-1	Gating inhibitor	6.4	pIC50
kurtoxin	Antagonist	6.3	pEC50
C2230	Gating inhibitor	6.0	pIC50
Pb2+	Antagonist	5.9	pIC50
ziconotide	Antagonist	1.0	pIC50

Binding affinities (BindingDB)

302 measured of 413 human assays (524 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
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
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
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
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
cid_694792	KI	60 nM
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
2-[[2,2-difluoro-2-[3-(4,4,4-trifluorobutoxy)phenyl]ethyl]amino]-N,N-dimethylacetamide	KI	100 nM	US-9447029: Fluorinated arylalkylaminocarboxamide derivatives
cid_11957231	IC50	212 nM
2,6,7-trihydroxy-9-(2,4,5-trimethoxyphenyl)-3-xanthenone	EC50	258 nM
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
4-[[2-bromanyl-4-[(E)-2-cyano-2-(3-fluorophenyl)ethenyl]phenoxy]methyl]benzoic acid	IC50	400 nM

ChEMBL bioactivities

847 potent at pChembl≥5 of 1271 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL4279774
9.00	IC50	1	nM	CHEMBL4292697
9.00	IC50	1	nM	CHEMBL4288564
8.82	IC50	1.5	nM	CHEMBL3891844
8.72	IC50	1.9	nM	CHEMBL3890624
8.70	IC50	2	nM	CHEMBL4290426
8.70	IC50	2	nM	CHEMBL4289288
8.70	IC50	2	nM	CHEMBL4282095
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	CHEMBL4278633
8.52	IC50	3	nM	CHEMBL4293756
8.52	IC50	3	nM	CHEMBL5571780
8.51	IC50	3.1	nM	CHEMBL3919898
8.35	IC50	4.5	nM	CHEMBL3965812
8.34	IC50	4.6	nM	CHEMBL5570016
8.30	IC50	5	nM	CHEMBL4283590
8.23	IC50	5.9	nM	CHEMBL3906126
8.22	IC50	6	nM	CHEMBL3890916
8.22	IC50	6	nM	CHEMBL4277584
8.22	IC50	6	nM	CHEMBL4294178
8.15	IC50	7	nM	CHEMBL3940577
8.15	IC50	7	nM	CHEMBL4285527
8.15	IC50	7	nM	CHEMBL4291986
8.14	IC50	7.2	nM	CHEMBL3969562
8.12	IC50	7.6	nM	CHEMBL3937280
8.12	IC50	7.6	nM	CHEMBL3965812
8.10	IC50	8	nM	CHEMBL3983323
8.05	IC50	9	nM	CHEMBL3942512
8.03	IC50	9.4	nM	CHEMBL3922498
8.01	IC50	9.7	nM	CHEMBL3897303
7.96	IC50	11	nM	CHEMBL3948329
7.96	IC50	11	nM	CHEMBL4280661
7.92	IC50	12	nM	CHEMBL3898359
7.92	IC50	12	nM	CHEMBL4284117
7.92	IC50	12	nM	CHEMBL4278633
7.85	IC50	14	nM	CHEMBL3911369
7.85	IC50	14	nM	CHEMBL3913505
7.85	IC50	14	nM	CHEMBL3936725
7.82	IC50	15	nM	CHEMBL3984596
7.82	IC50	15	nM	CHEMBL3902376
7.80	IC50	16	nM	CHEMBL4279774
7.70	IC50	20	nM	CHEMBL1651027
7.70	IC50	20	nM	CHEMBL4285877
7.68	IC50	21	nM	CHEMBL3092205
7.67	IC50	21.5	nM	CHEMBL3952905
7.66	IC50	22	nM	CHEMBL4292404
7.62	IC50	24	nM	CHEMBL3972896
7.62	IC50	24	nM	CHEMBL4279774

PubChem BioAssay actives

473 with measured affinity, of 981 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
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethyloxan-4-yl)pyrazole	1414278: Inhibition of Cav2.2 (unknown origin) expressed in HEK293 cells assessed as decrease in KCl depolarization-induced Ca2+ influx measured for 5 mins by fluorescence based FDSS assay	ic50	0.0010	uM
4-[1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethyloxan-4-yl)pyrazol-5-yl]benzonitrile	1414278: Inhibition of Cav2.2 (unknown origin) expressed in HEK293 cells assessed as decrease in KCl depolarization-induced Ca2+ influx measured for 5 mins by fluorescence based FDSS assay	ic50	0.0010	uM
2-[5-(4-chlorophenyl)-3-(2,2,6,6-tetramethyloxan-4-yl)pyrazol-1-yl]-N,N-diethylaniline	1414278: Inhibition of Cav2.2 (unknown origin) expressed in HEK293 cells assessed as decrease in KCl depolarization-induced Ca2+ influx measured for 5 mins by fluorescence based FDSS assay	ic50	0.0010	uM
5-(4-chlorophenyl)-3-(2,2-dimethyloxan-4-yl)-1-(2-methoxyphenyl)pyrazole	1414278: Inhibition of Cav2.2 (unknown origin) expressed in HEK293 cells assessed as decrease in KCl depolarization-induced Ca2+ influx measured for 5 mins by fluorescence based FDSS assay	ic50	0.0020	uM
5-(4-ethoxyphenyl)-1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethyloxan-4-yl)pyrazole	1414278: Inhibition of Cav2.2 (unknown origin) expressed in HEK293 cells assessed as decrease in KCl depolarization-induced Ca2+ influx measured for 5 mins by fluorescence based FDSS assay	ic50	0.0020	uM
5-(4-chlorophenyl)-3-[(2S,6S)-2,6-dimethyloxan-4-yl]-1-(2-methoxyphenyl)pyrazole	1414278: Inhibition of Cav2.2 (unknown origin) expressed in HEK293 cells assessed as decrease in KCl depolarization-induced Ca2+ influx measured for 5 mins by fluorescence based FDSS assay	ic50	0.0020	uM
2-[(1S,4S,7S,13S,16S,19S,22S,25S,28S,31S,34S,37R,42R,45S,48S,51S,57S,60S,67S,70S,73S,76S,79S,82S,85S)-42-[[(2R,3S)-2-amino-3-hydroxybutanoyl]amino]-67-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]carbamoyl]-79-[(2S)-butan-2-yl]-4,22,25,28,31,45,57,82,85-nonakis(3-carbamimidamidopropyl)-73-(carboxymethyl)-76-[(1R)-1-hydroxyethyl]-7,48,51-tris(hydroxymethyl)-16,34,60-tris[(4-hydroxyphenyl)methyl]-70-methyl-2,5,8,14,17,20,23,26,29,32,35,43,46,49,52,55,58,61,69,72,75,78,81,84,87-pentacosaoxo-39,40,64,65-tetrathia-3,6,9,15,18,21,24,27,30,33,36,44,47,50,53,56,59,62,68,71,74,77,80,83,86-pentacosazatricyclo[35.25.25.09,13]heptaoctacontan-19-yl]acetic acid	2098878: Inhibition of human Cav2.2 channel transfected in HEK293T cells co-expressed with human GABAB receptor assessed as inhibition of Cav2.2-mediated Ba2+ current measured for 3 to 5 days by whole-cell patch clamp assay	ic50	0.0030	uM
5-(4-chlorophenyl)-3-[(2R,6S)-2,6-dimethyloxan-4-yl]-1-(2-methoxyphenyl)pyrazole	1414278: Inhibition of Cav2.2 (unknown origin) expressed in HEK293 cells assessed as decrease in KCl depolarization-induced Ca2+ influx measured for 5 mins by fluorescence based FDSS assay	ic50	0.0030	uM
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethyl-3H-pyran-4-yl)pyrazole	1414278: Inhibition of Cav2.2 (unknown origin) expressed in HEK293 cells assessed as decrease in KCl depolarization-induced Ca2+ influx measured for 5 mins by fluorescence based FDSS assay	ic50	0.0030	uM
(3S)-4-amino-3-[[(2S,3R)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-aminoacetyl)amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-carboxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-4-oxobutanoic acid	2098858: Inhibition of human Cav2.2 channel transfected in HEK293T cells assessed as inhibition of Cav2.2-mediated Ba2+ current measured for 3 to 5 days by whole-cell patch clamp assay	ic50	0.0046	uM
2-ethoxy-5-[1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethyloxan-4-yl)pyrazol-5-yl]pyridine	1414278: Inhibition of Cav2.2 (unknown origin) expressed in HEK293 cells assessed as decrease in KCl depolarization-induced Ca2+ influx measured for 5 mins by fluorescence based FDSS assay	ic50	0.0050	uM
5-(5-chlorothiophen-3-yl)-1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethyloxan-4-yl)pyrazole	1414278: Inhibition of Cav2.2 (unknown origin) expressed in HEK293 cells assessed as decrease in KCl depolarization-induced Ca2+ influx measured for 5 mins by fluorescence based FDSS assay	ic50	0.0060	uM
5-[1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethyloxan-4-yl)pyrazol-5-yl]-2-methylpyridine	1414278: Inhibition of Cav2.2 (unknown origin) expressed in HEK293 cells assessed as decrease in KCl depolarization-induced Ca2+ influx measured for 5 mins by fluorescence based FDSS assay	ic50	0.0060	uM
4-[5-(4-chlorophenyl)-3-(2,2,6,6-tetramethyloxan-4-yl)pyrazol-1-yl]pyridine	1414278: Inhibition of Cav2.2 (unknown origin) expressed in HEK293 cells assessed as decrease in KCl depolarization-induced Ca2+ influx measured for 5 mins by fluorescence based FDSS assay	ic50	0.0070	uM
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-[(2S,4R)-2-propan-2-yloxan-4-yl]pyrazole	1414278: Inhibition of Cav2.2 (unknown origin) expressed in HEK293 cells assessed as decrease in KCl depolarization-induced Ca2+ influx measured for 5 mins by fluorescence based FDSS assay	ic50	0.0070	uM
2-chloro-4-[1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethyloxan-4-yl)pyrazol-5-yl]pyridine	1414278: Inhibition of Cav2.2 (unknown origin) expressed in HEK293 cells assessed as decrease in KCl depolarization-induced Ca2+ influx measured for 5 mins by fluorescence based FDSS assay	ic50	0.0110	uM
2-[5-(4-chlorophenyl)-3-(2,2,6,6-tetramethyloxan-4-yl)pyrazol-1-yl]pyridine	1414278: Inhibition of Cav2.2 (unknown origin) expressed in HEK293 cells assessed as decrease in KCl depolarization-induced Ca2+ influx measured for 5 mins by fluorescence based FDSS assay	ic50	0.0120	uM
(1R,4S,8R,10S,13S,16S,19S,22S,25R,30R,33S,36S,39S,42S,45S,47R,51S,54R,57S,60S,63R,68R,71S,74S,78R,80S,86S,89S)-68-amino-36,71-bis(4-aminobutyl)-N-[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]-22,51-bis(2-amino-2-oxoethyl)-33,60-bis(3-carbamimidamidopropyl)-8,47,78-trihydroxy-13,39-bis[(1R)-1-hydroxyethyl]-4,16,57,74,86,89-hexakis(hydroxymethyl)-19,42-bis[(4-hydroxyphenyl)methyl]-2,5,11,14,17,20,23,32,35,38,41,44,50,53,56,59,62,69,72,75,81,84,87,90,97-pentacosaoxo-27,28,65,66,93,94-hexathia-3,6,12,15,18,21,24,31,34,37,40,43,49,52,55,58,61,70,73,76,82,85,88,91,96-pentacosazahexacyclo[52.37.4.225,63.06,10.045,49.076,80]heptanonacontane-30-carboxamide	710760: Inhibition of Cav2.2 expressed HEK293 cells assessed as inhibition of calcium flux by FLIPR assay in presence of 4 mM of potassium	ic50	0.0200	uM
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-[(2R,4R)-2-propan-2-yloxan-4-yl]pyrazole	1414278: Inhibition of Cav2.2 (unknown origin) expressed in HEK293 cells assessed as decrease in KCl depolarization-induced Ca2+ influx measured for 5 mins by fluorescence based FDSS assay	ic50	0.0200	uM
N-cyclopropyl-N-[1-[4-methylsulfonyl-2-(trifluoromethyl)benzoyl]piperidin-4-yl]-3-(trifluoromethyl)benzenesulfonamide	1056311: Inhibition of Cav2.2-mediated calcium influx in HEK cells by FLIPR assay	ic50	0.0210	uM
2-[(1R,4S,7S,13S,19S,22R,27R,30S,33S,36S,39S,42S,45S,52R)-22-amino-4,13,19-tris(4-aminobutyl)-52-[[(2S,3R)-1-[[2-[[(2S)-1-[[(4R,7S,13S,16S,19R)-7-(4-aminobutyl)-16-(3-carbamimidamidopropyl)-4-carbamoyl-13-(hydroxymethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicos-19-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxobutan-2-yl]carbamoyl]-42-(3-carbamimidamidopropyl)-45-(hydroxymethyl)-33-[(4-hydroxyphenyl)methyl]-7-methyl-39-(2-methylpropyl)-36-(2-methylsulfanylethyl)-3,6,9,12,15,18,21,29,32,35,38,41,44,47,54-pentadecaoxo-24,25,49,50-tetrathia-2,5,8,11,14,17,20,28,31,34,37,40,43,46,53-pentadecazabicyclo[25.20.7]tetrapentacontan-30-yl]acetic acid	1414278: Inhibition of Cav2.2 (unknown origin) expressed in HEK293 cells assessed as decrease in KCl depolarization-induced Ca2+ influx measured for 5 mins by fluorescence based FDSS assay	ic50	0.0220	uM
N-cyclopropyl-N-[1-[2-methylsulfonyl-4-(trifluoromethyl)benzoyl]piperidin-4-yl]-3-(trifluoromethyl)benzenesulfonamide	1056311: Inhibition of Cav2.2-mediated calcium influx in HEK cells by FLIPR assay	ic50	0.0270	uM
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-(oxan-4-yl)pyrazole	1414278: Inhibition of Cav2.2 (unknown origin) expressed in HEK293 cells assessed as decrease in KCl depolarization-induced Ca2+ influx measured for 5 mins by fluorescence based FDSS assay	ic50	0.0300	uM
[4-[(2S)-3-(tert-butylamino)-2-[[(2S)-2-[(4-tert-butylphenyl)methyl-methylamino]-4-methylpentanoyl]amino]-3-oxopropyl]phenyl] benzoate	144198: Inhibition of N-type calcium channels in IMR-32 human neuroblastoma cells	ic50	0.0360	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
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
(2S)-N-[(2S)-1-(tert-butylamino)-1-oxo-3-(4-phenylmethoxyphenyl)propan-2-yl]-2-[(4-tert-butylphenyl)methyl-methylamino]-4-methylpentanamide	144203: In vitro antagonism of N-type voltage sensitive calcium channel in IMR-32 assay using fluorescent [Ca2+] indicator Indo-11 in the presence of 5 uM nitrendipine	ic50	0.0400	uM
N-[(2S,3R)-1-(2-chloro-4-methylsulfonylbenzoyl)-2-methylazetidin-3-yl]-N-cyclopropyl-3-(trifluoromethyl)benzenesulfonamide	1056311: Inhibition of Cav2.2-mediated calcium influx in HEK cells by FLIPR assay	ic50	0.0480	uM
N-cyclopropyl-N-[1-[4-methylsulfonyl-2-(trifluoromethoxy)benzoyl]piperidin-4-yl]-3-(trifluoromethyl)benzenesulfonamide	1056311: Inhibition of Cav2.2-mediated calcium influx in HEK cells by FLIPR assay	ic50	0.0480	uM
2-[4-[(2-chlorophenyl)-phenylmethyl]piperazin-1-yl]-N,N-diphenylacetamide	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	0.0500	uM
1-[4-[(R)-(4-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	0.0500	uM
3,3-diphenyl-1-[4-[phenyl(piperidin-4-yl)methyl]piperazin-1-yl]propan-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	0.0600	uM
N-cyclopropyl-N-[1-[(2,6-dimethoxyphenyl)methyl]piperidin-4-yl]-3-(trifluoromethyl)benzenesulfonamide	710765: Inhibition of Cav2.2 expressed HEK293 cells assessed as inhibition of calcium flux by FLIPR assay in presence of 30 mM of potassium	ic50	0.0600	uM
3,3-diphenyl-1-[4-[phenyl-[4-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]propan-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	0.0700	uM
[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-[8-[3-(trifluoromethyl)phenyl]sulfonyl-2,8-diazaspiro[4.5]decan-2-yl]methanone	1056311: Inhibition of Cav2.2-mediated calcium influx in HEK cells by FLIPR assay	ic50	0.0720	uM
[4-methylsulfonyl-2-(trifluoromethoxy)phenyl]-[4-[1-[3-(trifluoromethyl)phenyl]sulfonylethyl]piperidin-1-yl]methanone	1056311: Inhibition of Cav2.2-mediated calcium influx in HEK cells by FLIPR assay	ic50	0.0880	uM
1-[4-[(2-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	0.0900	uM
(2S)-2-[(4-tert-butylphenyl)methyl-methylamino]-4-methyl-N-[(2S)-1-oxo-3-(4-phenylmethoxyphenyl)-1-piperidin-1-ylpropan-2-yl]pentanamide	144203: In vitro antagonism of N-type voltage sensitive calcium channel in IMR-32 assay using fluorescent [Ca2+] indicator Indo-11 in the presence of 5 uM nitrendipine	ic50	0.0900	uM
[4-methylsulfonyl-2-(trifluoromethoxy)phenyl]-[4-[2-[3-(trifluoromethyl)phenyl]sulfonylpropan-2-yl]piperidin-1-yl]methanone	1056311: Inhibition of Cav2.2-mediated calcium influx in HEK cells by FLIPR assay	ic50	0.0920	uM
1-[4-[(4-fluorophenyl)-(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	0.1000	uM
1-[4-[(4-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	0.1100	uM
2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]-N,N-diphenylacetamide	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	0.1100	uM
1-(4-benzhydrylpiperazin-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	0.1100	uM
3,3-diphenyl-1-[4-[phenyl-[3-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]propan-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	0.1100	uM
N-[1-[(2,6-dimethoxyphenyl)methyl]piperidin-4-yl]-N-propyl-3-(trifluoromethyl)benzenesulfonamide	710765: Inhibition of Cav2.2 expressed HEK293 cells assessed as inhibition of calcium flux by FLIPR assay in presence of 30 mM of potassium	ic50	0.1200	uM
(4R)-N-[(2R)-3-(cyclohexylmethylsulfanyl)-1-oxo-1-[(4-phenoxyphenyl)methylamino]propan-2-yl]-3-(2-methoxyacetyl)-1,3-thiazolidine-4-carboxamide	144199: In vitro inhibition of N-type calcium channels in IMR-32 cells.	ic50	0.1200	uM
methyl (4R)-4-[[(2R)-3-(cyclohexylmethylsulfanyl)-1-oxo-1-[(4-phenoxyphenyl)methylamino]propan-2-yl]carbamoyl]-1,3-thiazolidine-3-carboxylate	144199: In vitro inhibition of N-type calcium channels in IMR-32 cells.	ic50	0.1200	uM
N-cyclopropyl-N-[1-[2-(trifluoromethoxy)benzoyl]piperidin-4-yl]-3-(trifluoromethyl)benzenesulfonamide	710765: Inhibition of Cav2.2 expressed HEK293 cells assessed as inhibition of calcium flux by FLIPR assay in presence of 30 mM of potassium	ic50	0.1200	uM
[4-[(2S)-2-[[(2S)-2-[(4-bromophenyl)methyl-methylamino]-4-methylpentanoyl]amino]-3-(tert-butylamino)-3-oxopropyl]phenyl] benzoate	144198: Inhibition of N-type calcium channels in IMR-32 human neuroblastoma cells	ic50	0.1300	uM
1-[4-[(2,3-dichlorophenyl)-phenylmethyl]piperazin-1-yl]-2-(N-phenylanilino)ethanone	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	0.1400	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
Barium	affects binding, affects transport, increases transport, decreases reaction	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
propionaldehyde	decreases expression	1
bisphenol A	decreases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	increases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	increases abundance, affects methylation	1
sodium arsenite	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cannabinoids	affects methylation, increases abundance	1
Copper	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	increases expression	1
Menthol	decreases expression	1
Methylcholanthrene	affects binding, increases reaction	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Cyclosporine	decreases methylation	1
Cadmium Chloride	decreases reaction, increases transport	1

ChEMBL screening assays

135 unique, capped per target: 110 binding, 25 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1614128	Binding	PUBCHEM_BIOASSAY: Homogeneous Time-Resolved Fluorescence Resonance Energy Transfer (HTRF) Assay. Confirmatory Screen for inhibitors of association between Mint1-PDZ domains and N-type Ca2+ channel carboxyl-terminal peptide (NC peptide). (Cl	PubChem BioAssay data set
CHEMBL1738583	Functional	PUBCHEM_BIOASSAY: SAR analysis of small molecule inhibitors of Mint-PDZ and N-type Ca2+ channel carboxyl-terminal peptide association using HTRF - Set 2. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID2073, AI	PubChem BioAssay data set

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1JJ	PrecisION hCav2.2 alpha1B/beta3/alpha2delta1-HEK	Transformed cell line	Female
CVCL_D8I2	Ubigene HCT 116 CACNA1B KO	Cancer cell line	Male

Clinical trials (associated diseases)

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