CACNB2

Summary

CACNB2 (calcium voltage-gated channel auxiliary subunit beta 2, HGNC:1402) is a protein-coding gene on chromosome 10p12, encoding Voltage-dependent L-type calcium channel subunit beta-2 (Q08289). Beta subunit of voltage-dependent calcium channels which contributes to the function of the calcium channel by increasing peak calcium current.

This gene encodes a subunit of a voltage-dependent calcium channel protein that is a member of the voltage-gated calcium channel superfamily. The gene product was originally identified as an antigen target in Lambert-Eaton myasthenic syndrome, an autoimmune disorder. Mutations in this gene are associated with Brugada syndrome. Alternatively spliced variants encoding different isoforms have been described.

Source: NCBI Gene 783 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Brugada syndrome 4 (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 71
• Clinical variants (ClinVar): 1,145 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 15
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_201596

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1402
Approved symbol	CACNB2
Name	calcium voltage-gated channel auxiliary subunit beta 2
Location	10p12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000165995
Ensembl biotype	protein_coding
OMIM	600003
Entrez	783

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 15 protein_coding, 6 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000282343, ENST00000324631, ENST00000352115, ENST00000377315, ENST00000377319, ENST00000377328, ENST00000377329, ENST00000377331, ENST00000396576, ENST00000467034, ENST00000468177, ENST00000498816, ENST00000615785, ENST00000617363, ENST00000643096, ENST00000643330, ENST00000644004, ENST00000645287, ENST00000647168, ENST00000650685, ENST00000651330, ENST00000651468, ENST00000651896, ENST00000651928, ENST00000652391, ENST00000652478

RefSeq mRNA: 11 — MANE Select: NM_201596 NM_000724, NM_001167945, NM_001330060, NM_001410882, NM_201570, NM_201571, NM_201572, NM_201590, NM_201593, NM_201596, NM_201597

CCDS: CCDS41493, CCDS41494, CCDS7125, CCDS7126, CCDS7127, CCDS7128, CCDS7129, CCDS81442, CCDS91220

Canonical transcript exons

ENST00000324631 — 14 exons

Exon	Start	End
ENSE00001005446	18498355	18498477
ENSE00001005448	18500812	18500948
ENSE00001005450	18514236	18514369
ENSE00001005464	18506471	18506547
ENSE00001098795	18527588	18527697
ENSE00001098797	18518910	18518968
ENSE00001098799	18538180	18538365
ENSE00001098801	18518336	18518416
ENSE00001098805	18534076	18534227
ENSE00001552836	18140424	18140856
ENSE00001737387	18536101	18536196
ENSE00003471380	18401924	18402043
ENSE00003566244	18150883	18150975
ENSE00003828139	18539230	18543557

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 95.09.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6069 / max 444.9620, expressed in 416 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
104112	0.6549	237
104132	0.6250	93
104113	0.4601	178
104115	0.3545	153
104131	0.3497	89
104116	0.2650	84
104126	0.2020	31
104127	0.1617	26
104134	0.0980	48
104110	0.0810	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	95.09	gold quality
mucosa of stomach	UBERON:0001199	93.54	gold quality
buccal mucosa cell	CL:0002336	92.88	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.45	gold quality
lower esophagus	UBERON:0013473	92.39	gold quality
frontal pole	UBERON:0002795	91.16	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.76	gold quality
left ventricle myocardium	UBERON:0006566	89.81	gold quality
middle temporal gyrus	UBERON:0002771	88.86	gold quality
Brodmann (1909) area 46	UBERON:0006483	88.84	gold quality
myocardium	UBERON:0002349	88.76	gold quality
Brodmann (1909) area 10	UBERON:0013541	88.66	gold quality
orbitofrontal cortex	UBERON:0004167	88.26	gold quality
prefrontal cortex	UBERON:0000451	87.87	gold quality
cardiac muscle of right atrium	UBERON:0003379	87.77	gold quality
heart right ventricle	UBERON:0002080	87.47	gold quality
cerebellar cortex	UBERON:0002129	87.45	gold quality
cerebellar hemisphere	UBERON:0002245	87.41	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.38	gold quality
cerebellum	UBERON:0002037	87.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.05	gold quality
pituitary gland	UBERON:0000007	86.93	gold quality
frontal cortex	UBERON:0001870	86.90	gold quality
heart left ventricle	UBERON:0002084	86.86	gold quality
cardiac ventricle	UBERON:0002082	86.78	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.75	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.61	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.61	gold quality
superior frontal gyrus	UBERON:0002661	86.25	gold quality
right atrium auricular region	UBERON:0006631	86.17	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	73.05
E-MTAB-7008	yes	50.76
E-CURD-119	yes	45.78
E-GEOD-81547	yes	21.77
E-ANND-3	yes	16.11
E-HCAD-25	no	1579.41

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CLOCK

miRNA regulators (miRDB)

178 targeting CACNB2, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-381-3P	99.93	71.87	2854

Literature-anchored findings (GeneRIF, showing 30)

• loss-of-function mutations in genes encoding the cardiac L-type calcium channel to be associated with a familial sudden cardiac death syndrome in which a Brugada syndrome phenotype is combined with shorter-than-normal QT intervals (PMID:17224476)
• Functional properties of the CaV1.2 calcium channel activated by calmodulin in the absence of alpha2delta subunits. (PMID:19106618)
• CACNB2 SNPs show genotypic association with Alzheimer disease. (PMID:19241460)
• The first Brugada syndrome mutation in CaCNB2b resulting in accelerated inactivation of L-type calcium channel current, is reported. (PMID:19358333)
• We also identified a novel polymorphism (D601E) in CACNB2b that slowed inactivation of L-type calcium current (I(Ca,L)), significantly increased total charge. Slowed conduction was present. (PMID:20025708)
• This study provided that cacnb2 are associated with Bipolar I in the Han Chinese population. (PMID:20386566)
• CACNB2 is a possible novel early repolarization syndrome susceptibility gene. (PMID:20817017)
• that genetic variation within CACNB2 may influence treatment-related outcomes in high-risk patients with hypertension. (PMID:21156931)
• Genetic variations in CYP17A1, CACNB2 and PLEKHA7 were related to blood pressure traits and/or hypertension in Chinese She population. (PMID:21963141)
• Genetic testing reveals disease-causing mutations in depolarizing sodium (SCN5A) or calcium (CaCNB2b) channels in 5 infants with rapid ventricular tachycardia, conduction abnormalities, and Brugada-like syndrome. (PMID:22090166)
• High prevalence of CACNA2D1, SCN5A, and CACNB2 genetic variants in the Danish population previously associated with Brugada syndrome has been found in new exome data. (PMID:23414114)
• Association of the SNP rs2932538 in MOV10 and SNP rs4373814 in CACNB2 with an increased risk of hypertension in a Chinese Han population. (PMID:24338417)
• Three rare missense mutations of CACNB2 (G167S, S197F, and F240L) found in Autism Spectrum Disorders (ASD)-affected families, are reported. (PMID:24752249)
• In the gene-based analysis, CACNB2 and CTCF showed the strongest evidence for association with schizophrenia in both the present samples and in those of the Psychiatric Genetics Consortium datasets. (PMID:24901509)
• Chronic atrial fibrillation increases miR-21 expression in human atrial myocytes and decreases I(Ca,L) density by downregulating CACNA1C/CACNB2 expression. (PMID:25107449)
• ADM genotype AA was associated with the highest values of systolic and diastolic blood pressure (BP), while CACNB2 genotype CC carriers had the highest values of diastolic BP in childhood. (PMID:25313554)
• Five serious mental disorders and three major cardiovascular diseases have recently been linked to the CACNB2 gene coding for the Cavbeta2 subunits (PMID:25966706)
• Study showed that CACNB2 is a possible candidate hypertrophy-modifying gene contributing to disease variability of MYBPC3-associated familial hypertrophic cardiomyopathy (PMID:28614222)
• Our study shows that palmitoylation of CaVbeta2a is necessary for CaValpha1 trafficking to the plasma membrane. However, excessive number of palmitoylated CaVbeta2a leads to Ca(2+) overload and beta cell death. (PMID:28739256)
• The results indicate that CACNB2 gene polymorphism was significantly associated with higher odds of high blood pressure in Lithuanian adolescents aged 12-15 years. (PMID:29982197)
• Data show that an indispensable beta-subunit of the voltage-gated Ca(2+) channel Cav1.2 interaction with H-Ras is independently of Ca(2+) flux, suggesting the regulatory role of beta2 in transcriptional activation via the ERK/CREB pathway. (PMID:30150369)
• This genotype/phenotype association study uncovered a variant in CACNB2 that may be associated with both KD susceptibility and bifid T waves, a novel signature of altered myocardial repolarization. (PMID:30395415)
• Our study demonstrates that bipolar disorder patients with the CACNB2 rs11013860 AA/CA genotype may exhibit altered hippocampal-cortical connectivity. (PMID:30744588)
• Our data show that L-type calcium channels regulate VEGF expression and secretion from retinal pigment epithelial cells (ARPE19) and support the role of CACNB2 via regulation of VEGF in the pathogenesis of proliferative diabetic retinopathy. (PMID:31439644)
• Autism-associated mutations in the CaVbeta2 calcium-channel subunit increase Ba(2+)-currents and lead to differential modulation by the RGK-protein Gem. (PMID:31887354)
• CACNB2 rs11013860 polymorphism correlates of prefrontal cortex thickness in bipolar patients with first-episode mania. (PMID:32158010)
• Association study of hypertension susceptibility genes ITGA9, MOV10, and CACNB2 with preeclampsia in Chinese Han population. (PMID:33491517)
• Epigenetic mechanism of L-type calcium channel beta-subunit downregulation in short QT human induced pluripotent stem cell-derived cardiomyocytes with CACNB2 mutation. (PMID:35894107)
• A Preclinical Study on Brugada Syndrome with a CACNB2 Variant Using Human Cardiomyocytes from Induced Pluripotent Stem Cells. (PMID:35955449)
• Bipolar-associated miR-499-5p controls neuroplasticity by downregulating the Cav1.2 subunit CACNB2. (PMID:35969184)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cacnb2a	ENSDARG00000099045
mus_musculus	Cacnb2	ENSMUSG00000057914
rattus_norvegicus	Cacnb2	ENSRNOG00000018378
drosophila_melanogaster	Ca-beta	FBGN0287724
caenorhabditis_elegans	ccb-1	WBGENE00000368
caenorhabditis_elegans	ccb-2	WBGENE00021125

Paralogs (3): CACNB1 (ENSG00000067191), CACNB3 (ENSG00000167535), CACNB4 (ENSG00000182389)

Protein

Protein identifiers

Voltage-dependent L-type calcium channel subunit beta-2 — Q08289 (reviewed: Q08289)

Alternative names: Calcium channel voltage-dependent subunit beta 2, Lambert-Eaton myasthenic syndrome antigen B

All UniProt accessions (15): A0A087WVX5, A0A087WWJ0, A0A2R8Y555, A0A2R8Y7A6, A0A2R8YFX9, A0A2U3TZM7, A0A494C044, A0A494C0B2, A0A494C0C3, A0A494C0Z9, A0A494C184, A0A494C1Q6, A6PVM6, Q08289, Q5VVH1

UniProt curated annotations — full annotation on UniProt →

Function. Beta subunit of voltage-dependent calcium channels which contributes to the function of the calcium channel by increasing peak calcium current. Plays a role in shifting voltage dependencies of activation and inactivation of the channel. May modulate G protein inhibition. May contribute to beta-adrenergic augmentation of Ca(2+) influx in cardiomyocytes, thereby regulating increases in heart rate and contractile force. Involved in membrane targeting of the alpha-1 subunit CACNA1C.

Subunit / interactions. Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or CACNB2, CACNG1 and CACNA2D1. The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains either CACNB1 or CACNB2. Interacts with CACNA1C. Interacts with RRAD; interaction may be involved in beta-adrenergic regulation of heart rate and contractile force. Interaction with RRAD regulates the trafficking of CACNA1C to the cell membrane. Interacts with TMIGD2. Interacts with CAMK2D. Interacts with CBARP. Interacts with CAMK2A.

Subcellular location. Cell membrane. Sarcolemma.

Tissue specificity. Expressed in all tissues.

Post-translational modifications. Regulated through phosphorylation at Thr-554 by CaMK2D.

Disease relevance. Brugada syndrome 4 (BRGDA4) [MIM:611876] A heart disease characterized by the association of Brugada syndrome with shortened QT intervals. Brugada syndrome is a tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. The gene represented in this entry may be involved in disease pathogenesis.

Similarity. Belongs to the calcium channel beta subunit family.

Isoforms (10)

UniProt ID	Names	Canonical?
Q08289-1	2d, CACNB2d	yes
Q08289-2	2a, CACNB2a
Q08289-3	2b, CACNB2b, 2aN4
Q08289-4	2c, CACNB2c, 2aN2
Q08289-5	2e, CACNB2e
Q08289-6	2f
Q08289-7	2g
Q08289-8	2h, 2cN1
Q08289-9	2cN2
Q08289-10	2cN4

RefSeq proteins (11): NP_000715, NP_001161417, NP_001316989, NP_001397811, NP_963864, NP_963865, NP_963866, NP_963884, NP_963887, NP_963890, NP_963891 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000584	VDCC_L_bsu	Family
IPR001452	SH3_domain	Domain
IPR005444	VDCC_L_b2su	Family
IPR008145	GK/Ca_channel_bsu	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR035605	CACNB2_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR046937	CAB1-4_N_A-dom	Domain

Pfam: PF00625, PF12052

UniProt features (52 total): sequence conflict 10, compositionally biased region 7, helix 7, splice variant 6, modified residue 5, region of interest 3, mutagenesis site 3, strand 3, turn 3, sequence variant 2, chain 1, domain 1, site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8HMB	ELECTRON MICROSCOPY	3.3
8HMA	ELECTRON MICROSCOPY	3.4
8HLP	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08289-F1	65.78	0.38

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 (1): 549 (required for camk2d-binding)

Post-translational modifications (5): 204, 207, 218, 550, 554

Mutagenesis-validated functional residues (3):

Position	Phenotype
298	reduces binding to rrad; when associated with a-374 and a-376.
374	reduces binding to rrad; when associated with a-298 and a-376.
376	reduces binding to rrad; when associated with a-298 and a-374.

Function

Pathways and Gene Ontology

Reactome pathways

22 pathways

ID	Pathway
R-HSA-112308	Presynaptic depolarization and calcium channel opening
R-HSA-400042	Adrenaline,noradrenaline inhibits insulin secretion
R-HSA-419037	NCAM1 interactions
R-HSA-422356	Regulation of insulin secretion
R-HSA-5576892	Phase 0 - rapid depolarisation
R-HSA-5576893	Phase 2 - plateau phase
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea
R-HSA-9856532	Mechanical load activates signaling by PIEZO1 and integrins in osteocytes
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-163685	Integration of energy metabolism
R-HSA-375165	NCAM signaling for neurite out-growth
R-HSA-397014	Muscle contraction
R-HSA-422475	Axon guidance
R-HSA-5576891	Cardiac conduction
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9659379	Sensory processing of sound
R-HSA-9675108	Nervous system development
R-HSA-9709957	Sensory Perception
R-HSA-9855142	Cellular responses to mechanical stimuli

MSigDB gene sets: 378 (showing top): GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, RORA1_01, REACTOME_ADRENALINE_NORADRENALINE_INHIBITS_INSULIN_SECRETION, KEGG_MAPK_SIGNALING_PATHWAY, GCANCTGNY_MYOD_Q6, GOBP_MEMBRANE_DEPOLARIZATION_DURING_ACTION_POTENTIAL, MORF_ATRX, REACTOME_NCAM_SIGNALING_FOR_NEURITE_OUT_GROWTH, AP4_Q6, TGACCTY_ERR1_Q2, AAAYRNCTG_UNKNOWN, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP

GO Biological Process (16): calcium ion transport (GO:0006816), chemical synaptic transmission (GO:0007268), neuromuscular junction development (GO:0007528), visual perception (GO:0007601), positive regulation of muscle contraction (GO:0045933), positive regulation of calcium ion transport (GO:0051928), calcium ion import (GO:0070509), calcium ion transmembrane transport (GO:0070588), protein localization to plasma membrane (GO:0072659), membrane depolarization during AV node cell action potential (GO:0086045), regulation of heart rate by cardiac conduction (GO:0086091), membrane depolarization during atrial cardiac muscle cell action potential (GO:0098912), positive regulation of calcium ion transmembrane transport via high voltage-gated calcium channel (GO:1904879), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), regulation of presynaptic cytosolic calcium ion concentration (GO:0099509)

GO Molecular Function (8): voltage-gated calcium channel activity (GO:0005245), calcium channel activity (GO:0005262), actin filament binding (GO:0051015), voltage-gated calcium channel activity involved in regulation of presynaptic cytosolic calcium levels (GO:0099626), protein binding (GO:0005515), high voltage-gated calcium channel activity (GO:0008331), voltage-gated calcium channel activity involved in cardiac muscle cell action potential (GO:0086007), voltage-gated calcium channel activity involved in AV node cell action potential (GO:0086056)

GO Cellular Component (8): plasma membrane (GO:0005886), voltage-gated calcium channel complex (GO:0005891), photoreceptor ribbon synapse (GO:0098684), presynapse (GO:0098793), L-type voltage-gated calcium channel complex (GO:1990454), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702), sarcolemma (GO:0042383)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Cardiac conduction	2
Transmission across Chemical Synapses	1
Regulation of insulin secretion	1
NCAM signaling for neurite out-growth	1
Integration of energy metabolism	1
Sensory processing of sound	1
Cellular responses to mechanical stimuli	1
Neuronal System	1
Metabolism	1
Axon guidance	1
Nervous system development	1
Muscle contraction	1
Sensory Perception	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
calcium ion transport	3
membrane depolarization during cardiac muscle cell action potential	3
AV node cell action potential	2
presynapse	2
voltage-gated calcium channel activity	2
cellular anatomical structure	2
metal ion transport	1
anterograde trans-synaptic signaling	1
synapse organization	1
sensory perception of light stimulus	1
muscle contraction	1
regulation of muscle contraction	1
positive regulation of multicellular organismal process	1
positive regulation of monoatomic ion transport	1
regulation of calcium ion transport	1
monoatomic cation transmembrane transport	1
protein localization to membrane	1
protein localization to cell periphery	1
regulation of heart rate	1
cardiac conduction	1
atrial cardiac muscle cell action potential	1
calcium ion transmembrane transport via high voltage-gated calcium channel	1
regulation of calcium ion transmembrane transport via high voltage-gated calcium channel	1
positive regulation of calcium ion transmembrane transport	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
regulation of cytosolic calcium ion concentration	1
neuron cellular homeostasis	1
calcium channel activity	1
voltage-gated monoatomic cation channel activity	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
actin binding	1
protein-containing complex binding	1
regulation of presynaptic cytosolic calcium ion concentration	1
voltage-gated calcium channel activity involved in regulation of cytosolic calcium levels	1
binding	1
voltage-gated calcium channel activity involved in cardiac muscle cell action potential	1
membrane depolarization during AV node cell action potential	1

Protein interactions and networks

STRING

1390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CACNB2	CACNA1C	Q13936	987
CACNB2	CACNA2D1	P54289	973
CACNB2	CACNA1D	Q01668	939
CACNB2	CACNA2D2	Q9NY47	927
CACNB2	SCN5A	Q14524	869
CACNB2	GPD1L	Q8N335	868
CACNB2	CACNA1F	O60840	848
CACNB2	KCNE3	Q9Y6H6	841
CACNB2	SCN3B	Q9NY72	840
CACNB2	SCN1B	Q07699	825
CACNB2	CACNA2D3	Q8IZS8	822
CACNB2	HCN4	Q9Y3Q4	803
CACNB2	CACNA1A	P78510	796
CACNB2	CACNA1S	Q13698	796
CACNB2	KCNH2	Q12809	771

IntAct

23 interactions, top by confidence:

A	B	Type	Score
CACNB1	CACNB3	psi-mi:“MI:0914”(association)	0.640
CACNB2	TMEM174	psi-mi:“MI:0915”(physical association)	0.560
PRMT5	CACNB2	psi-mi:“MI:0915”(physical association)	0.560
CACNB2	HEXIM2	psi-mi:“MI:0915”(physical association)	0.560
CTBP2	CACNB2	psi-mi:“MI:0915”(physical association)	0.560
CACNB3	CACNB4	psi-mi:“MI:0914”(association)	0.530
CACNB3	CACNB2	psi-mi:“MI:0914”(association)	0.530
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
CACNB3	PLCG1	psi-mi:“MI:0914”(association)	0.350
CACNB1	KIF2A	psi-mi:“MI:0914”(association)	0.350
CACNB2	CTBP2	psi-mi:“MI:0915”(physical association)	0.000
CACNB2	PRMT5	psi-mi:“MI:0915”(physical association)	0.000
CACNB2	HEXIM2	psi-mi:“MI:0915”(physical association)	0.000
	CACNB2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): CACNB2 (Affinity Capture-MS), CACNB2 (Affinity Capture-MS), CACNB2 (Affinity Capture-RNA), CACNB2 (Proximity Label-MS), CACNB2 (Two-hybrid), CACNB2 (Two-hybrid), HEXIM2 (Two-hybrid), CTBP2 (Two-hybrid), CACNB2 (Affinity Capture-MS), CACNB2 (Affinity Capture-MS), CACNB2 (Affinity Capture-MS), CACNB2 (Proximity Label-MS)

ESM2 similar proteins: A1YFY6, A2A7Q9, A2AFR3, A2T6X9, B2RUJ5, F1LXF1, O08838, O35274, O35430, O35431, O43312, O55047, O75446, P11274, P22681, P22682, P49418, P54288, P81133, P98084, Q02410, Q08289, Q14CM0, Q3UR85, Q4KUS2, Q56A18, Q5RD33, Q5REE1, Q5UAK0, Q61045, Q62768, Q6PAJ1, Q6R891, Q6ZMZ0, Q765P7, Q7TQF7, Q80YA9, Q86UE8, Q8BIE6, Q8C0V0

Diamond homologs: D4A055, O00305, P19517, P54283, P54284, P54285, P54286, P54287, P54288, Q02641, Q08289, Q8CC27, Q8R0S4, Q8R3Z5, Q8VGC3, Q9MZL3, Q9MZL5, Q9MZL7

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CAMK2D	up-regulates	CACNB2	phosphorylation
GEM	“down-regulates activity”	CACNB2	binding
PRKACA	“up-regulates activity”	CACNB2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

1145 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	549
Likely benign	399
Benign	98

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
156228	NM_201590.3(CACNB2):c.32C>T (p.Thr11Ile)	Pathogenic
3774534	NM_201596.3(CACNB2):c.804+162G>T	Likely pathogenic

SpliceAI

5552 predictions. Top by Δscore:

Variant	Effect	Δscore
10:18150881:A:AG	acceptor_gain	1.0000
10:18150881:A:T	acceptor_loss	1.0000
10:18150882:G:GC	acceptor_gain	1.0000
10:18150882:GT:G	acceptor_gain	1.0000
10:18150882:GTC:G	acceptor_gain	1.0000
10:18150882:GTCA:G	acceptor_gain	1.0000
10:18150882:GTCAT:G	acceptor_gain	1.0000
10:18150973:CAGGT:C	donor_loss	1.0000
10:18150974:AGGT:A	donor_loss	1.0000
10:18150975:GGT:G	donor_loss	1.0000
10:18150976:G:GA	donor_loss	1.0000
10:18150977:T:A	donor_loss	1.0000
10:18205859:G:GT	donor_gain	1.0000
10:18366890:T:TA	acceptor_gain	1.0000
10:18401922:AG:A	acceptor_gain	1.0000
10:18401923:GG:G	acceptor_gain	1.0000
10:18402039:CAAAG:C	donor_loss	1.0000
10:18402040:AAAGG:A	donor_loss	1.0000
10:18402044:GT:G	donor_loss	1.0000
10:18402045:T:A	donor_loss	1.0000
10:18498348:A:AG	acceptor_gain	1.0000
10:18498349:C:G	acceptor_gain	1.0000
10:18498350:TTTA:T	acceptor_loss	1.0000
10:18498352:TA:T	acceptor_loss	1.0000
10:18498353:A:AG	acceptor_gain	1.0000
10:18498353:A:T	acceptor_loss	1.0000
10:18498354:G:A	acceptor_loss	1.0000
10:18498354:G:GT	acceptor_gain	1.0000
10:18498354:GA:G	acceptor_gain	1.0000
10:18498354:GAC:G	acceptor_gain	1.0000

AlphaMissense

4344 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:18402038:G:C	A110P	1.000
10:18498365:T:A	V115D	1.000
10:18498370:T:A	F117I	1.000
10:18498370:T:C	F117L	1.000
10:18498371:T:C	F117S	1.000
10:18498371:T:G	F117C	1.000
10:18498372:T:A	F117L	1.000
10:18498372:T:G	F117L	1.000
10:18498373:G:C	A118P	1.000
10:18498374:C:A	A118E	1.000
10:18498377:T:A	V119D	1.000
10:18498380:G:C	R120P	1.000
10:18498464:T:A	L148Q	1.000
10:18498464:T:C	L148P	1.000
10:18498470:T:A	V150D	1.000
10:18500827:T:A	W158R	1.000
10:18500827:T:C	W158R	1.000
10:18500830:T:A	W159R	1.000
10:18500830:T:C	W159R	1.000
10:18500832:G:C	W159C	1.000
10:18500832:G:T	W159C	1.000
10:18500836:G:A	G161R	1.000
10:18500836:G:C	G161R	1.000
10:18500836:G:T	G161W	1.000
10:18500837:G:A	G161E	1.000
10:18500837:G:T	G161V	1.000
10:18500840:G:C	R162P	1.000
10:18500869:T:C	F172L	1.000
10:18500870:T:C	F172S	1.000
10:18500871:C:A	F172L	1.000

dbSNP variants (sampled 300 via entrez): RS1000001363 (10:18415914 G>A,C), RS1000002914 (10:18374427 A>G), RS1000003159 (10:18305546 C>T), RS1000005939 (10:18449543 C>A,T), RS1000012554 (10:18229878 C>G,T), RS1000015411 (10:18192548 T>G), RS1000016937 (10:18158813 G>C), RS1000017570 (10:18164472 GGTTAGT>G), RS1000018542 (10:18343269 C>G), RS1000037129 (10:18163580 A>G,T), RS1000044485 (10:18446167 T>C), RS1000045140 (10:18541891 A>G), RS1000054488 (10:18379335 C>G), RS1000067043 (10:18228787 T>A), RS1000070589 (10:18305826 G>A)

Disease associations

OMIM: gene MIM:600003 | disease phenotypes: MIM:611876, MIM:601144, MIM:613601

GenCC curated gene-disease

Disease	Classification	Inheritance
Brugada syndrome 4	Limited	Unknown

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
cardiogenetic disease	Disputed	AD

Mondo (15): Brugada syndrome 4 (MONDO:0012743), paroxysmal familial ventricular fibrillation (MONDO:0100234), cardiomyopathy (MONDO:0004994), Brugada syndrome (MONDO:0015263), long QT syndrome (MONDO:0002442), early repolarization associated with ventricular fibrillation (MONDO:0013318), ventricular tachycardia (MONDO:0005477), hypertrophic cardiomyopathy (MONDO:0005045), ventricular fibrillation (MONDO:0000190), cardiac arrest (MONDO:0000745), cardiac rhythm disease (MONDO:0007263), dilated cardiomyopathy (MONDO:0005021), conduction system disorder (MONDO:0005449), autism spectrum disorder (MONDO:0005258), arrhythmogenic right ventricular cardiomyopathy (MONDO:0016587)

Orphanet (7): Brugada syndrome (Orphanet:130), Idiopathic ventricular fibrillation (Orphanet:228140), Rare cardiomyopathy (Orphanet:167848), Rare hypertrophic cardiomyopathy (Orphanet:217569), Dilated cardiomyopathy (Orphanet:217604), Inherited arrhythmogenic cardiomyopathy (Orphanet:247), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

15 total (17 of 15 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001279	Syncope
HP:0001649	Tachycardia
HP:0001663	Ventricular fibrillation
HP:0001695	Cardiac arrest
HP:0004308	Ventricular arrhythmia
HP:0004751	Paroxysmal ventricular tachycardia
HP:0004755	Supraventricular tachycardia
HP:0005110	Atrial fibrillation
HP:0011704	Sick sinus syndrome
HP:0011705	First degree atrioventricular block
HP:0011712	Complete right bundle branch block
HP:0011715	Trifascicular block
HP:0012232	Shortened QT interval
HP:0012251	ST segment elevation
HP:0001639	Hypertrophic cardiomyopathy
HP:0001644	Dilated cardiomyopathy

GWAS associations

71 associations (top):

Study	Trait	p-value
GCST000189_14	Protein quantitative trait loci	6.000000e-06
GCST000337_12	Quantitative traits	1.000000e-06
GCST000393_6	Systolic blood pressure	7.000000e-07
GCST000396_1	Diastolic blood pressure	1.000000e-08
GCST000398_4	Hypertension	6.000000e-08
GCST001227_10	Systolic blood pressure	5.000000e-11
GCST001228_4	Diastolic blood pressure	4.000000e-10
GCST001236_2	Blood pressure	2.000000e-16
GCST001238_3	Hypertension	9.000000e-08
GCST001762_357	Obesity-related traits	1.000000e-06
GCST001823_17	Metabolite levels (HVA/MHPG ratio)	3.000000e-06
GCST001877_45	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	4.000000e-08
GCST002030_3	Primary tooth development (time to first tooth eruption)	2.000000e-07
GCST002031_3	Primary tooth development (number of teeth)	2.000000e-09
GCST002149_6	Schizophrenia	1.000000e-10
GCST002539_3	Schizophrenia	2.000000e-12
GCST002936_23	Cadmium levels	8.000000e-07
GCST003321_1	Small vessel stroke	2.000000e-08
GCST004279_21	Systolic blood pressure	3.000000e-07
GCST004521_192	Autism spectrum disorder or schizophrenia	3.000000e-10
GCST004776_52	Systolic blood pressure	7.000000e-09
GCST004777_18	Diastolic blood pressure	4.000000e-13
GCST004797_10	Brain volume in infants (grey matter)	9.000000e-07
GCST004904_159	Body mass index	4.000000e-10
GCST004904_50	Body mass index	2.000000e-09
GCST004946_72	Schizophrenia	3.000000e-13
GCST006166_112	Diastolic blood pressure x alcohol consumption interaction (2df test)	7.000000e-09
GCST006166_74	Diastolic blood pressure x alcohol consumption interaction (2df test)	1.000000e-24
GCST006167_83	Mean arterial pressure x alcohol consumption interaction (2df test)	9.000000e-14
GCST006168_55	Pulse pressure x alcohol consumption interaction (2df test)	2.000000e-25

EFO canonical traits (26, from GWAS)

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0005115	metabolic rate measurement
EFO:0005131	HVA measurement
EFO:0005133	MHPG measurement
EFO:1001504	small vessel stroke
EFO:0008368	infant grey matter volume measurement
EFO:0004340	body mass index
EFO:0004329	alcohol drinking
EFO:0005763	pulse pressure measurement
EFO:0006527	smoking status measurement
EFO:0009959	diverticular disease
EFO:0009929	Beta blocking agent use measurement
EFO:0009928	Diuretic use measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0007969	cognitive inhibition measurement
EFO:0009262	nicotine dependence symptom count
EFO:0004615	apolipoprotein B measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004327	electrocardiography
EFO:0005665	white matter hyperintensity measurement

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D019571	Arrhythmogenic Right Ventricular Dysplasia	C14.240.400.145; C14.280.238.028; C14.280.400.145; C16.131.240.400.145
D053840	Brugada Syndrome	C14.280.067.322; C14.280.123.250; C16.320.100
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D006323	Heart Arrest	C14.280.383
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D017180	Tachycardia, Ventricular	C14.280.067.845.940; C14.280.123.875.940; C23.550.073.845.940
D014693	Ventricular Fibrillation	C14.280.067.922; C23.550.073.922
C567508	Brugada Syndrome 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2363032 (PROTEIN COMPLEX GROUP), CHEMBL3317336 (SINGLE PROTEIN), CHEMBL4106164 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 67,947 (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
CHEMBL1428	NIMODIPINE	4	32,587
CHEMBL95	TACRINE	4	35,360

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

PharmGKB variants

9 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2357928	CACNB2		0.00	0
rs11014166	CACNB2		0.00	0
rs10741058	CACNB2		0.00	0
rs982003	CACNB2		0.00	0
rs12245847	CACNB2		0.00	0
rs1277733	CACNB2		0.00	0
rs4237348	CACNB2		0.00	0
rs560765906	CACNB2		0.00	0
rs10764319	CACNB2		0.00	0

ChEMBL bioactivities

59 potent at pChembl≥5 of 78 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
8.51	IC50	3.1	nM	CHEMBL3919898
8.35	IC50	4.5	nM	CHEMBL3965812
8.23	IC50	5.9	nM	CHEMBL3906126
8.22	IC50	6	nM	CHEMBL3890916
8.15	IC50	7	nM	CHEMBL3940577
8.14	IC50	7.2	nM	CHEMBL3969562
8.12	IC50	7.6	nM	CHEMBL3937280
8.12	IC50	7.6	nM	CHEMBL3965812
8.10	IC50	8	nM	CHEMBL3983323
8.05	IC50	9	nM	CHEMBL3942512
8.03	IC50	9.4	nM	CHEMBL3922498
8.01	IC50	9.7	nM	CHEMBL3897303
7.96	IC50	11	nM	CHEMBL3948329
7.92	IC50	12	nM	CHEMBL3898359
7.85	IC50	14	nM	CHEMBL3911369
7.85	IC50	14	nM	CHEMBL3913505
7.85	IC50	14	nM	CHEMBL3936725
7.82	IC50	15	nM	CHEMBL3984596
7.82	IC50	15	nM	CHEMBL3902376
7.67	IC50	21.5	nM	CHEMBL3952905
7.62	IC50	24	nM	CHEMBL3972896
7.58	IC50	26	nM	CHEMBL3889804
7.55	IC50	28	nM	CHEMBL3958844
7.55	IC50	28	nM	CHEMBL3973382
7.53	IC50	29.8	nM	NIMODIPINE
7.52	IC50	30	nM	CHEMBL3978200
7.52	IC50	30	nM	CHEMBL3985660
7.51	IC50	31	nM	CHEMBL3896861
7.51	IC50	31	nM	CHEMBL3951956
7.50	IC50	31.4	nM	CHEMBL3962403
7.44	IC50	36	nM	CHEMBL3953976
7.44	IC50	36	nM	CHEMBL3925140
7.41	IC50	39	nM	CHEMBL3900691
7.39	IC50	41	nM	CHEMBL3930781
7.30	IC50	50	nM	CHEMBL3921840
7.21	IC50	62	nM	CHEMBL3956991
7.17	IC50	67	nM	CHEMBL3965293
7.09	IC50	81	nM	CHEMBL3958264
7.07	IC50	85	nM	CHEMBL3964411
7.01	IC50	98.5	nM	CHEMBL3953031
6.40	IC50	400	nM	CHEMBL3974355
6.10	IC50	800	nM	CHEMBL3734797
5.75	IC50	1800	nM	CHEMBL4228929
5.66	IC50	2200	nM	CHEMBL4226021
5.52	IC50	3000	nM	CHEMBL4228209

PubChem BioAssay actives

14 with measured affinity, of 116 total; 14 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
Nimodipine	1912088: Inhibition of human alpha1c/beta2a/alpha2delta1 Cav1.2 expressed in HEK293 cells assessed as Ca2+ current at -80 mV holding potential by patch clamp technique	ic50	0.0298	uM
N-tert-butyl-8-[[[(1S,2S)-2-(3-methyl-1,2,4-oxadiazol-5-yl)cyclopropanecarbonyl]amino]methyl]-5-[3-(trifluoromethoxy)phenyl]-3,4-dihydro-1H-isoquinoline-2-carboxamide	1262825: Inhibition of voltage-gated calcium channel (unknown origin)	ic50	0.8000	uM
5-methyl-1-[(2-nitrophenyl)methyl]-3-(piperidin-1-ylmethyl)indole	1392176: Inhibition of KCl-induced cytosolic voltage gated calcium channel opening in human SH-SY5Y cells by Fluo-4 AM dye based fluorescence assay	ic50	1.8000	uM
1-[(3-chlorophenyl)methyl]-5-methyl-3-(piperidin-1-ylmethyl)indole	1392176: Inhibition of KCl-induced cytosolic voltage gated calcium channel opening in human SH-SY5Y cells by Fluo-4 AM dye based fluorescence assay	ic50	2.2000	uM
5-methyl-1-[(3-nitrophenyl)methyl]-3-(piperidin-1-ylmethyl)indole	1392176: Inhibition of KCl-induced cytosolic voltage gated calcium channel opening in human SH-SY5Y cells by Fluo-4 AM dye based fluorescence assay	ic50	3.0000	uM
1-[(4-chlorophenyl)methyl]-5-methyl-3-(piperidin-1-ylmethyl)indole	1392176: Inhibition of KCl-induced cytosolic voltage gated calcium channel opening in human SH-SY5Y cells by Fluo-4 AM dye based fluorescence assay	ic50	3.0000	uM
1-benzyl-5-methyl-3-(piperidin-1-ylmethyl)indole	1392176: Inhibition of KCl-induced cytosolic voltage gated calcium channel opening in human SH-SY5Y cells by Fluo-4 AM dye based fluorescence assay	ic50	3.4000	uM
5-methyl-1-[(4-methylphenyl)methyl]-3-(piperidin-1-ylmethyl)indole	1392176: Inhibition of KCl-induced cytosolic voltage gated calcium channel opening in human SH-SY5Y cells by Fluo-4 AM dye based fluorescence assay	ic50	3.6000	uM
1-[(4-fluorophenyl)methyl]-5-methyl-3-(piperidin-1-ylmethyl)indole	1392176: Inhibition of KCl-induced cytosolic voltage gated calcium channel opening in human SH-SY5Y cells by Fluo-4 AM dye based fluorescence assay	ic50	4.8000	uM
N-heptyl-16,18-dioxo-17-azapentacyclo[6.6.5.02,7.09,14.015,19]nonadeca-2,4,6,9,11,13-hexaene-1-carboxamide	1612587: Inhibition of K+-induced voltage gated calcium channel opening in human SH-SY5Y cells assessed as decrease in Ca2+ level after 10 mins by Fluo-4 dye-based fluorescence assay	ic50	9.0000	uM
ethyl 5-amino-4-(3-methoxyphenyl)-2-methyl-7,8,9,10-tetrahydro-6H-cyclohepta[b][1,8]naphthyridine-3-carboxylate	1653244: Inhibition of VGCC (unknown origin)	ic50	9.0000	uM
ethyl 5-amino-4-(3,4-dimethoxyphenyl)-2-methyl-7,8,9,10-tetrahydro-6H-cyclohepta[b][1,8]naphthyridine-3-carboxylate	1653244: Inhibition of VGCC (unknown origin)	ic50	9.0000	uM
propan-2-yl 5-amino-2-methyl-4-phenyl-6,7,8,9-tetrahydrobenzo[b][1,8]naphthyridine-3-carboxylate	1653244: Inhibition of VGCC (unknown origin)	ic50	10.0000	uM
ethyl 5-amino-2-methyl-4-phenyl-6,7,8,9,10,11-hexahydrocycloocta[b][1,8]naphthyridine-3-carboxylate	1653244: Inhibition of VGCC (unknown origin)	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Panobinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Estradiol	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression	1
hydroxyhydroquinone	decreases expression	1
arsenite	increases methylation	1
tri-o-cresyl phosphate	increases expression	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
mercuric bromide	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
clothianidin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol Z	increases expression	1
asparanin A	decreases expression	1
licochalcone B	decreases expression	1
bisphenol S	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Clorgyline	increases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Menthol	decreases expression	1

ChEMBL screening assays

22 unique, capped per target: 20 binding, 1 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3737861	Binding	Inhibition of voltage-gated calcium channel (unknown origin)	Discovery and Pharmacology of a Novel Class of Diacylglycerol Acyltransferase 2 Inhibitors. — J Med Chem
CHEMBL4039312	ADMET	Inhibition of human Cav1.2/beta2/alpha2delta1 expressed in CHO cells by automated patch clamp assay	Discovery of N-(5-Fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (VU0424238): A Novel Negative Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 5 Selected for Clinical Evaluation. — J Med Chem
CHEMBL5154401	Toxicity	Inhibition of human alpha1c/beta2a/alpha2delta1 Cav1.2 expressed in HEK293 cells assessed as effect on calcium flux by FLIPR analysis	Optimization of Benzamide Derivatives as Potent and Orally Active Tubulin Inhibitors Targeting the Colchicine Binding Site. — J Med Chem

Cellosaurus cell lines

10 cell lines: 5 transformed cell line, 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B0KY	34893 2L	Transformed cell line	Female
CVCL_B0KZ	192C	Transformed cell line	Female
CVCL_D7LD	Ubigene A-549 CACNB2 KO	Cancer cell line	Male
CVCL_D8I6	Ubigene HCT 116 CACNB2 KO	Cancer cell line	Male
CVCL_D9AN	Ubigene HEK293 CACNB2 KO	Transformed cell line	Female
CVCL_D9Z2	Ubigene HeLa CACNB2 KO	Cancer cell line	Female
CVCL_RQ69	PrecisION hCav1.2 alpha1C/beta2a/alpha2delta1-HEK	Transformed cell line	Female
CVCL_SG50	HAP1 CACNB2 (-) 1	Cancer cell line	Male
CVCL_SG51	HAP1 CACNB2 (-) 2	Cancer cell line	Male
CVCL_YA26	IDG-HEK293T-CACNB2-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02201914	PHASE4	UNKNOWN	Clomiphene Citrate Plus Gonadotropins and GnRH Antagonist Versus Flexible GnRH Antagonist Protocol Versus Microdose GnRH Agonist Protocol in Poor Responders Undergoing IVF
NCT02651285	PHASE4	UNKNOWN	Use of G-CSF Supplemented IVF Medium in Patients Undergoing IVF
NCT04002635	PHASE4	WITHDRAWN	Letrozole for Frozen Embryo Transfer (FET) in Patients With Polycystic Ovary Syndrome (PCOS)
NCT04385342	PHASE4	UNKNOWN	FSH Followed by HMG vs FSH Plus HMG in IVF
NCT04487925	PHASE4	RECRUITING	Controlled Ovarian Stimulation Versus Modified Natural Cycles in Poor Responders
NCT04654741	PHASE4	UNKNOWN	The Rate of Embryo Euploidy in Progestin-primed Ovarian Stimulation Cycles
NCT04728659	PHASE4	UNKNOWN	Desogestrel Versus GnRH Antagonist in IVF/ICSI
NCT04993924	PHASE4	UNKNOWN	GnRH Antagonist Pre-treatment in the Early Follicular Phase for Resolution of a Baseline Functional Ovarian Cyst
NCT05071339	PHASE4	UNKNOWN	GnRH Antagonist Pre-treatment for the Prevention of Asynchronous Follicular Growth
NCT05321511	PHASE4	UNKNOWN	Comparison of Triggers in Double Ovarian Stimulation (DuoStim).
NCT05954962	PHASE4	COMPLETED	Efficacy of Micronized Natural Progesterone vs GnRH Antagonist in the Prevention of LH Peak During Ovarian Stimulation.
NCT06181305	PHASE4	UNKNOWN	Endometrial Preparation in Frozen Embryo Transfer Cycles
NCT06396390	PHASE4	NOT_YET_RECRUITING	Comparison of Progestin Primed Ovarian Stimulation (PPOS) vs.GnRH Antagonist Methods on IVF Outcomes
NCT07405229	PHASE4	RECRUITING	MEdical Treatment in Idiopathic Ventricular Fibrillation Patients
NCT07499804	PHASE4	RECRUITING	Effect of Tadalafil on Endometrial Thickness and Frozen Embryo Transfer Outcomes
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT04414761	PHASE3	COMPLETED	Live Birth Rate Between PPOS and GnRH Antagonist Protocol in Patients With Anticipated High Ovarian Response
NCT04806919	PHASE3	COMPLETED	Luteal Support in Artificial Vitrified/Warmed Cycles With Low Progesterone
NCT05972902	PHASE3	UNKNOWN	Dydrogesterone, Cetrorelix Acetate and Triptorelin in Intra Cytoplasmic Sperm Injection Outcomes
NCT06048666	PHASE3	UNKNOWN	Platelet Rich Plasma on Ovarian Reserve Parameters and Intra Cytoplasmic Sperm Injection Outcomes in Patients With Diminished Ovarian Reserve
NCT06405204	PHASE3	NOT_YET_RECRUITING	of Myo-inositol, Melatonin and Co-enzyme q10 on Ovarian Reserve
NCT07499817	PHASE3	RECRUITING	Effect of Pentoxyfilline on Endometrial Thickness and Frozen Embryo Transfer Outcomes