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) — +4 more curated relationships
• GWAS associations: 71 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 1,190 total — 1 pathogenic (top 2% of genes corpus-wide)
• GTEx eGene: eQTL in 26 tissues, sQTL in 4 (q < 0.05)
• Phenotypes (HPO): 15
• ChEMBL bioactivity: 2 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.77 (unconstrained)
• MANE Select transcript: NM_201596
• Notable: 1,190 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 29 — 17 protein_coding, 7 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 2 retained_intron

MANE Select: ENST00000324631 · MANE Plus Clinical: ENST00000377329

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 10, TSL 3: 2, TSL 5: 2

ENST00000324631, ENST00000377329, ENST00000282343, ENST00000352115, ENST00000377315, ENST00000377319, ENST00000377328, ENST00000377331, ENST00000396576, ENST00000467034, ENST00000468177, ENST00000498816, ENST00000615785, ENST00000617363, ENST00000643096, ENST00000643330, ENST00000644004, ENST00000645287, ENST00000647168, ENST00000650685, ENST00000651330, ENST00000651468, ENST00000651896, ENST00000651928, ENST00000652391, ENST00000652478, ENST00001129187, ENST00001129188, ENST00001142370

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.

Highest expression (Bgee): adrenal tissue, mucosa of stomach, buccal mucosa cell, lower esophagus muscularis layer, lower esophagus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CACNB2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 26 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 30 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	1.1e-40	+0.85	10:18308669:G:A
Thyroid	eqtl	2.3e-16	+0.55	10:18308669:G:A
Spleen	eqtl	2.7e-10	+0.52	10:18534710:T:C
Esophagus Muscularis	eqtl	6.3e-10	+0.21	10:18539442:C:T
Skin Sun Exposed Lower leg	eqtl	1.3e-08	+0.68	10:18071128:G:C
Brain Nucleus accumbens basal ganglia	eqtl	2.6e-07	-0.22	10:18110734:G:C
Brain Caudate basal ganglia	eqtl	2.7e-07	+0.17	10:18120578:C:G
Cells Cultured fibroblasts	eqtl	8.0e-07	-0.17	10:18172997:T:C
Whole Blood	eqtl	1.3e-06	+0.24	10:18534710:T:C
Brain Cerebellum	eqtl	2.4e-06	+0.45	10:18419634:C:G
Esophagus Gastroesophageal Junction	eqtl	1.5e-05	+0.17	10:18587479:G:A
Skin Not Sun Exposed Suprapubic	eqtl	1.7e-05	+0.19	10:18652741:A:G
Brain Amygdala	eqtl	4.8e-05	+0.25	10:18129875:A:G
Brain Cerebellar Hemisphere	eqtl	1.1e-04	+0.35	10:18434938:A:C
Pituitary	eqtl	1.5e-04	+0.26	10:18512085:T:C
Brain Putamen basal ganglia	eqtl	2.4e-04	-0.19	10:18086611:G:C
Nerve Tibial	eqtl	4.3e-04	+0.27	10:18102633:C:A
Esophagus Mucosa	eqtl	7.7e-04	+0.11	10:18521745:G:A
Liver	eqtl	3.4e-03	+0.23	10:18573799:G:A
Artery Aorta	eqtl	5.5e-03	-0.24	10:18079175:C:T

FANTOM5 promoters

showing 10 of 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

showing 100 of 286 tissues 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
cardiac atrium	UBERON:0002081	86.16	gold quality
adenohypophysis	UBERON:0002196	86.09	gold quality
neocortex	UBERON:0001950	85.75	gold quality
heart	UBERON:0000948	85.71	gold quality
right frontal lobe	UBERON:0002810	85.68	gold quality
colonic epithelium	UBERON:0000397	85.30	gold quality
pigmented layer of retina	UBERON:0001782	85.01	gold quality
retina	UBERON:0000966	84.99	gold quality
sigmoid colon	UBERON:0001159	84.74	gold quality
paraflocculus	UBERON:0005351	84.57	gold quality
apex of heart	UBERON:0002098	84.54	gold quality
left ovary	UBERON:0002119	84.25	gold quality
cingulate cortex	UBERON:0003027	84.23	gold quality
cerebral cortex	UBERON:0000956	84.13	gold quality
anterior cingulate cortex	UBERON:0009835	84.11	gold quality
postcentral gyrus	UBERON:0002581	83.71	gold quality
right ovary	UBERON:0002118	83.67	gold quality
cauda epididymis	UBERON:0004360	83.29	gold quality
popliteal artery	UBERON:0002250	82.84	gold quality
tibial artery	UBERON:0007610	82.84	gold quality
forebrain	UBERON:0001890	82.74	gold quality
left uterine tube	UBERON:0001303	82.70	gold quality
telencephalon	UBERON:0001893	82.70	gold quality
small intestine Peyer’s patch	UBERON:0003454	82.70	gold quality
middle frontal gyrus	UBERON:0002702	82.59	gold quality
brain	UBERON:0000955	82.50	gold quality
cerebellar vermis	UBERON:0004720	82.43	gold quality
parietal lobe	UBERON:0001872	82.36	gold quality
nucleus accumbens	UBERON:0001882	82.34	gold quality
blood vessel layer	UBERON:0004797	82.09	gold quality
central nervous system	UBERON:0001017	82.07	gold quality
ovary	UBERON:0000992	82.05	gold quality
seminal vesicle	UBERON:0000998	82.05	gold quality
transverse colon	UBERON:0001157	81.95	gold quality
body of uterus	UBERON:0009853	81.79	gold quality
colon	UBERON:0001155	81.75	gold quality
large intestine	UBERON:0000059	81.53	gold quality
intestine	UBERON:0000160	81.37	gold quality
medial globus pallidus	UBERON:0002477	81.36	gold quality
primary visual cortex	UBERON:0002436	81.26	gold quality
right lobe of liver	UBERON:0001114	81.22	gold quality
esophagus	UBERON:0001043	81.11	gold quality
small intestine	UBERON:0002108	80.75	gold quality
myometrium	UBERON:0001296	80.63	gold quality
caudate nucleus	UBERON:0001873	80.62	gold quality
putamen	UBERON:0001874	80.56	gold quality
lateral nuclear group of thalamus	UBERON:0002736	80.16	gold quality
aorta	UBERON:0000947	80.11	gold quality
cortical plate	UBERON:0005343	80.08	gold quality
body of pancreas	UBERON:0001150	80.01	gold quality
hypothalamus	UBERON:0001898	80.00	gold quality
entorhinal cortex	UBERON:0002728	79.72	gold quality
occipital lobe	UBERON:0002021	79.58	gold quality
CA1 field of hippocampus	UBERON:0003881	79.42	gold quality
islet of Langerhans	UBERON:0000006	78.91	gold quality
pancreas	UBERON:0001264	78.63	gold quality
right adrenal gland cortex	UBERON:0035827	78.61	gold quality
rectum	UBERON:0001052	78.48	gold quality
adrenal gland	UBERON:0002369	78.35	gold quality
globus pallidus	UBERON:0001875	78.25	gold quality
prostate gland	UBERON:0002367	78.09	gold quality
temporal lobe	UBERON:0001871	78.00	gold quality
descending thoracic aorta	UBERON:0002345	77.99	gold quality
calcaneal tendon	UBERON:0003701	77.98	gold quality
urinary bladder	UBERON:0001255	77.75	gold quality
left coronary artery	UBERON:0001626	77.70	gold quality
left adrenal gland cortex	UBERON:0035825	77.46	gold quality
Ammon’s horn	UBERON:0001954	77.42	gold quality
right adrenal gland	UBERON:0001233	77.16	gold quality
adrenal cortex	UBERON:0001235	77.08	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Postcentral gyrus	tissue	56.4
Putamen	tissue	51.5
Cerebral cortex	tissue	47.8	medium
Somatosensory cortex	tissue	47.8
Basal ganglia	tissue	46.5	high
Occipital cortex	tissue	45.0
Motor cortex	tissue	41.3
Prefrontal cortex	tissue	40.7
Retrosplenial and cingulate cortex	tissue	40.0
Temporal cortex	tissue	39.8
Hippocampal formation	tissue	36.5
Entorhinal cortex	tissue	36.5
Nucleus accumbens	tissue	36.3
Insular cortex	tissue	36.1
Ventral forebrain	tissue	34.9
Retrosplenial cortex	tissue	34.7
Caudate putamen	tissue	31.5
Hippocampus	tissue	30.7	medium
Thalamus	tissue	29.3
Septum	tissue	29.2
Superior colliculi	tissue	28.6
Amygdala	tissue	27.8
Choroid plexus	tissue	27.7
Hypothalamus	tissue	26.3
Pons	tissue	25.5
Midbrain	tissue	23.2
Substantia nigra	tissue	20.6
Cerebellum	tissue	19.9	high
Retina	tissue	19.5
Locus coeruleus	tissue	17.8
Periaqueductal gray	tissue	17.5
Corpus callosum	tissue	14.3
Olfactory bulb	tissue	14.2
Medulla oblongata	tissue	14.0
Frontal cortex	tissue	12.0
Spinal cord	tissue	10.4
Heart muscle	tissue	8.7	low
Seminal vesicle	tissue	7.0	not detected
Ovary	tissue	5.0	low
Pituitary gland	tissue	4.8
Esophagus	tissue	4.5	not detected
Smooth muscle	tissue	4.4	medium
Adrenal gland	tissue	4.4	low
Endometrium 1	tissue	3.7	not detected
Prostate	tissue	3.7	not detected
Urinary bladder	tissue	3.5	not detected
Pancreas	tissue	3.5	medium
Salivary gland	tissue	3.3	low
Skin 1	tissue	2.5	medium
Rectum	tissue	2.5	low
Small intestine	tissue	2.4	not detected
Epididymis	tissue	2.0	not detected
Colon	tissue	1.9	medium
Cervix	tissue	1.8	not detected
Gallbladder	tissue	1.8	not detected
Appendix	tissue	1.7	high
Vagina	tissue	1.6	not detected
Fallopian tube	tissue	1.6	not detected
Kidney	tissue	1.3	medium
Thyroid gland	tissue	1.0	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Arcuate nucleus (46.7), Orbitofrontal gyrus, anterior (44.1), Posterior cingulate cortex (43.8), Paracentral lobule, anterior (42.9), Parietal operculum (41.4).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CLOCK

miRNA regulators (miRDB)

Targeting CACNB2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 178 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 9e-06, LOEUF 0.77, missense Z -0.713 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000324631 — one region, missense o/e 1.10.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:894644) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 9 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal urinary bladder morphology	1
abnormal cardiovascular system physiology	1
abnormal vitelline vascular remodeling	1
abnormal myocardial fiber physiology	1
impaired glucose tolerance	1
decreased heart rate	1
increased circulating glucose level	1
embryonic lethality, complete penetrance	1
embryonic lethality during organogenesis, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q9MZL3	99.0%	Diamond
Oryctolagus cuniculus	P54286	97.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CACNB2-AS2	ncRNA	107984213
CACNB2-AS1	ncRNA	124902386
SLC39A12	protein-coding	221074
MRC1	protein-coding	4360
MIR511	ncRNA	574445
SLC39A12-AS1	ncRNA	100129213
NSUN6	protein-coding	221078
ARL5B	protein-coding	221079
TMEM236	protein-coding	653567
STAM	protein-coding	8027

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. Interacts with ZNT1.

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

Structure

Experimental structures (PDB)

3 structures by resolution:

PDB	Title	Method	Resolution (Å)
8HMB	Cryo-EM structure of human high-voltage activated L-type calcium channel CaV1.2 in …	ELECTRON MICROSCOPY	3.3
8HMA	Cryo-EM structure of human high-voltage activated L-type calcium channel CaV1.2 in …	ELECTRON MICROSCOPY	3.4
8HLP	Cryo-EM structure of human high-voltage activated L-type calcium channel CaV1.2 (apo)	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Transporters, Accessory Factors Involved in Transport, Predicted intracellular proteins, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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)

Position	Role
549	required for camk2d-binding

Post-translational modifications (5)

Type	Positions
Phosphoserine	204, 207, 218, 550
Phosphothreonine	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

3 curated (TAS) of 22; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

22 pathways:

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

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 (15): calcium ion transport (GO:0006816), chemical synaptic transmission (GO:0007268), neuromuscular junction development (GO:0007528), 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), T-tubule (GO:0030315), photoreceptor ribbon synapse (GO:0098684), presynapse (GO:0098793), L-type voltage-gated calcium channel complex (GO:1990454), monoatomic ion channel complex (GO:0034702), sarcolemma (GO:0042383)

Reactome top-level categories

14 top-level categories:

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

50 GO namespaces:

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
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
membrane	1
cell periphery	1
calcium channel complex	1
plasma membrane protein complex	1
sarcolemma	1
ribbon synapse	1
synapse	1
voltage-gated calcium channel complex	1
T-tubule	1
transmembrane transporter complex	1
plasma membrane	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 31 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
calcium ion import	BP	direct assay
membrane depolarization during AV node cell action potential	BP	mutant phenotype
membrane depolarization during atrial cardiac muscle cell action potential	BP	mutant phenotype
positive regulation of calcium ion transport	BP	direct assay
regulation of heart rate by cardiac conduction	BP	mutant phenotype
L-type voltage-gated calcium channel complex	CC	direct assay
voltage-gated calcium channel complex	CC	direct assay
voltage-gated calcium channel activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,232 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CACNB2	CACNA2D1	P54289	916
CACNB2	CACNA1C	Q13936	915
CACNB2	CACNA1D	Q01668	878
CACNB2	GPD1L	Q8N335	867
CACNB2	KCNE3	Q9Y6H6	838
CACNB2	SCN3B	Q9NY72	830
CACNB2	SCN1B	Q07699	824
CACNB2	HCN4	Q9Y3Q4	793
CACNB2	SCN5A	Q14524	792
CACNB2	KCNH2	Q12809	757
CACNB2	KCNE2	Q9Y6J6	742
CACNB2	CACNA1F	O60840	730
CACNB2	CACNA2D4	Q7Z3S7	709
CACNB2	CACNA2D2	Q9NY47	706
CACNB2	KCNE4	Q8WWG9	703

IntAct

Human interaction partners of CACNB2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
CTBP2	physical association	0.560	5
HEXIM2	physical association	0.560	3
PRMT5	physical association	0.560	3
TMEM174	physical association	0.560	3
CACNB3	association	0.530	1

BioGRID (14 interactions; top human partners by supporting records): CACNB1 (Affinity Capture-MS; 2 records), CACNB3 (Affinity Capture-MS; 2 records), AGR2 (Proximity Label-MS), CTBP2 (Two-hybrid), EPHA2 (Proximity Label-MS), HEXIM2 (Two-hybrid), HNRNPL (Affinity Capture-RNA), NEK4 (Affinity Capture-MS), PARP9 (Proximity Label-MS), PRMT5 (Two-hybrid), TMEM174 (Two-hybrid), TNKS (Proximity Label-MS)

SIGNOR signaling

showing 3 of 6 signaling interactions:

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

Disease & clinical

Genetic variants

Variant evidence for CACNB2: 1,190 ClinVar records (1 pathogenic / likely pathogenic); 71 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,190 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	557
Likely benign	429
Benign	91

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
156228	NM_201590.3(CACNB2):c.32C>T (p.Thr11Ile)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CACNB2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 2,951):

Position(s)	Effect	Δscore	Sites
10:18150881–18150882	acceptor_loss	1.0000	6
10:18150976–18150977	donor_loss	1.0000	5
10:18402044–18402045	donor_loss	1.0000	5
10:18498349	acceptor_gain	1.0000
10:18498353–18498354	acceptor_loss	1.0000	6
10:18498470	donor_gain	1.0000
10:18498475–18498476	donor_gain	1.0000	2
10:18498478–18498479	donor_loss	1.0000	4
10:18519779	donor_gain	1.0000
10:18534073	acceptor_gain	1.0000

AlphaMissense

1,918 missense substitutions predicted likely pathogenic (of 4,344 scored), across 396 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M299	9	0.996	1.000
M300	9	0.961	0.999
F117	8	0.999	1.000
D298	8	0.999	1.000
D374	8	0.998	0.999
D324	8	0.995	0.999
F362	8	0.993	1.000
F142	8	0.992	0.999
F172	8	0.992	1.000
D306	8	0.992	0.998
D376	8	0.991	0.999
H149	8	0.990	0.999
F305	8	0.986	0.998
S175	8	0.984	1.000
F312	8	0.983	0.999
D85	8	0.982	0.997
D438	8	0.980	0.998
D83	8	0.979	0.996
H452	8	0.972	0.995
F266	8	0.970	0.994

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000728
Glioblastoma Multiforme (validation)	favorable	0.00097

Disease associations

OMIM: gene MIM:600003 | disease phenotypes: MIM:611876

GenCC curated gene-disease

4 curated gene-disease records:

Disease	Classification	Inheritance	Records
Brugada syndrome 4	Limited	Unknown	4
short QT syndrome	Disputed Evidence	Autosomal dominant
Brugada syndrome	Disputed Evidence	Autosomal dominant
familial hypertrophic cardiomyopathy	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
cardiogenetic disease	Disputed	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (4 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

4 panels:

Panel	Rating
Cardiac arrhythmias	amber
Short QT syndrome	amber
Sudden unexplained death or survivors of a cardiac event	amber
Unexplained death in infancy and sudden unexplained death in childhood	amber

Mondo (4): Brugada syndrome 4 (MONDO:0012743), short QT syndrome (MONDO:0000453), Brugada syndrome (MONDO:0015263), familial hypertrophic cardiomyopathy (MONDO:0024573)

Orphanet (1): Brugada syndrome (Orphanet:130)

HPO phenotypes

15 phenotypes (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

GWAS associations

showing 30 of 71 associations:

Study	Trait	p-value
GCST006434_3	Systolic blood pressure x alcohol consumption interaction (2df test)	2e-41
GCST007267_100	Systolic blood pressure	8e-34
GCST006434_105	Systolic blood pressure x alcohol consumption interaction (2df test)	3e-32
GCST006188_2	Systolic blood pressure (cigarette smoking interaction)	3e-30
GCST006168_56	Pulse pressure x alcohol consumption interaction (2df test)	2e-25
GCST006166_24	Diastolic blood pressure x alcohol consumption interaction (2df test)	1e-24
GCST007094_41	Diastolic blood pressure	1e-22
GCST009685_27	Hypertension	1e-21
GCST006187_23	Diastolic blood pressure (cigarette smoking interaction)	2e-21
GCST006258_10	Diastolic blood pressure	8e-19
GCST007099_118	Systolic blood pressure	2e-18
GCST001236_2	Blood pressure	2e-16
GCST007269_305	Pulse pressure	8e-16
GCST007930_135	Medication use (agents acting on the renin-angiotensin system)	5e-15
GCST006167_74	Mean arterial pressure x alcohol consumption interaction (2df test)	9e-14
GCST007201_201	Schizophrenia	9e-14
GCST004946_62	Schizophrenia	3e-13
GCST004777_66	Diastolic blood pressure	4e-13
GCST006803_38	Schizophrenia	5e-13
GCST002539_76	Schizophrenia	2e-12
GCST006231_54	Mean arterial pressure	2e-12
GCST007928_16	Medication use (diuretics)	5e-12
GCST006170_38	Systolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	7e-12
GCST007930_161	Medication use (agents acting on the renin-angiotensin system)	2e-11
GCST007928_89	Medication use (diuretics)	3e-11
GCST007929_49	Medication use (calcium channel blockers)	3e-11
GCST001227_9	Systolic blood pressure	5e-11
GCST007927_40	Medication use (beta blocking agents)	5e-11
GCST008595_149	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	5e-11
GCST006259_15	Systolic blood pressure	6e-11

EFO canonical traits (from GWAS)

26 canonical traits:

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

4 disease descriptors:

Descriptor	Name	Tree numbers
D053840	Brugada Syndrome	C14.280.067.322; C14.280.123.250; C16.320.100
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
C567508	Brugada Syndrome 4 *(supp.)*
C580439	Short Qt Syndrome *(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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 68,316 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

2 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1428	NIMODIPINE	4	32,766
CHEMBL95	TACRINE	4	35,550

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

8 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs10741058	antipsychotics	Efficacy	Genotype TT is associated with increased response to antipsychotics in people with Schizophrenia as compared to genotype CC.	PMID:30032160
rs982003	antipsychotics	Efficacy	Genotype CC is associated with increased response to antipsychotics in people with Schizophrenia as compared to genotype TT.	PMID:30032160
rs12245847	antipsychotics	Efficacy	Genotype TT is associated with increased response to antipsychotics in people with Schizophrenia as compared to genotype CT.	PMID:30032160
rs1277733	antipsychotics	Efficacy	Genotype TT is associated with increased response to antipsychotics in people with Schizophrenia as compared to genotype CC.	PMID:30032160
rs4237348	antipsychotics	Efficacy	Genotype CC is associated with increased response to antipsychotics in people with Schizophrenia as compared to genotype CT.	PMID:30032160
rs10764319	dexmedetomidine	Toxicity	Genotype CT is associated with decreased likelihood of Bradycardia or Hypotensive disorder when treated with dexmedetomidine in children with Surgical procedure as compared to genotypes CC + TT.	PMID:39840108
rs2357928	verapamil	Efficacy, Toxicity	Genotype GG is associated with increased risk of adverse outcome when treated with verapamil in people with Hypertension and Coronary Artery Disease.	PMID:21156931
rs11014166	verapamil	Efficacy, Toxicity	Genotypes AT + TT are associated with increased risk of adverse outcome when treated with verapamil in people with Hypertension and Coronary Artery Disease.	PMID:21156931

Binding affinities (BindingDB)

3 measured of 5 human assays (5 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL2386850	IC50	1000 nM
CHEBI:66722	IC50	41300 nM
CHEMBL4874732	IC50	67300 nM

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	increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	decreases expression, affects cotreatment	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	decreases expression, affects cotreatment	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 346 trials:

NCT	Phase	Status	Title
NCT00702117	Phase 4	COMPLETED	Ajmaline Utilization in the Diagnosis and Treatment of Cardiac Arrhythmias
NCT02201914	Phase 4	UNKNOWN	Clomiphene Citrate Plus Gonadotropins and GnRH Antagonist Versus Flexible GnRH Antagonist Protocol Versus Microdose GnRH Agonist Protocol in Poor Responders Undergoing IVF
NCT02651285	Phase 4	UNKNOWN	Use of G-CSF Supplemented IVF Medium in Patients Undergoing IVF
NCT04002635	Phase 4	WITHDRAWN	Letrozole for Frozen Embryo Transfer (FET) in Patients With Polycystic Ovary Syndrome (PCOS)
NCT04385342	Phase 4	UNKNOWN	FSH Followed by HMG vs FSH Plus HMG in IVF
NCT04487925	Phase 4	UNKNOWN	Controlled Ovarian Stimulation Versus Modified Natural Cycles in Poor Responders
NCT04654741	Phase 4	UNKNOWN	The Rate of Embryo Euploidy in Progestin-primed Ovarian Stimulation Cycles
NCT04728659	Phase 4	UNKNOWN	Desogestrel Versus GnRH Antagonist in IVF/ICSI
NCT04993924	Phase 4	UNKNOWN	GnRH Antagonist Pre-treatment in the Early Follicular Phase for Resolution of a Baseline Functional Ovarian Cyst
NCT05071339	Phase 4	UNKNOWN	GnRH Antagonist Pre-treatment for the Prevention of Asynchronous Follicular Growth
NCT05321511	Phase 4	UNKNOWN	Comparison of Triggers in Double Ovarian Stimulation (DuoStim).
NCT05954962	Phase 4	COMPLETED	Efficacy of Micronized Natural Progesterone vs GnRH Antagonist in the Prevention of LH Peak During Ovarian Stimulation.
NCT06181305	Phase 4	UNKNOWN	Endometrial Preparation in Frozen Embryo Transfer Cycles
NCT06396390	Phase 4	UNKNOWN	Comparison of Progestin Primed Ovarian Stimulation (PPOS) vs.GnRH Antagonist Methods on IVF Outcomes
NCT07405229	Phase 4	RECRUITING	MEdical Treatment in Idiopathic Ventricular Fibrillation Patients
NCT07499804	Phase 4	RECRUITING	Effect of Tadalafil on Endometrial Thickness and Frozen Embryo Transfer Outcomes
NCT00348530	Phase 4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	Phase 4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	Phase 4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	Phase 4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	Phase 4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	Phase 4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	Phase 4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	Phase 4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	Phase 4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	Phase 4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	Phase 4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	Phase 4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	Phase 4	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	Phase 4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	Phase 4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	Phase 4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	Phase 4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05371496	Phase 4	COMPLETED	Cardiac and Metabolic Effects of Semaglutide in Heart Failure With Preserved Ejection Fraction
NCT05718128	Phase 4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	Phase 4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00701077	Phase 3	TERMINATED	DAPERB 3,4-DiAminoPyridine and Electrophysiological Response in Brugada Syndrome
NCT00927732	Phase 3	TERMINATED	Hydroquinidine Versus Placebo in Patients With Brugada Syndrome
NCT04414761	Phase 3	COMPLETED	Live Birth Rate Between PPOS and GnRH Antagonist Protocol in Patients With Anticipated High Ovarian Response
NCT04806919	Phase 3	COMPLETED	Luteal Support in Artificial Vitrified/Warmed Cycles With Low Progesterone
NCT05972902	Phase 3	UNKNOWN	Dydrogesterone, Cetrorelix Acetate and Triptorelin in Intra Cytoplasmic Sperm Injection Outcomes
NCT06048666	Phase 3	UNKNOWN	Platelet Rich Plasma on Ovarian Reserve Parameters and Intra Cytoplasmic Sperm Injection Outcomes in Patients With Diminished Ovarian Reserve
NCT06405204	Phase 3	UNKNOWN	of Myo-inositol, Melatonin and Co-enzyme q10 on Ovarian Reserve
NCT07499817	Phase 3	RECRUITING	Effect of Pentoxyfilline on Endometrial Thickness and Frozen Embryo Transfer Outcomes
NCT00170183	Phase 3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
NCT00270387	Phase 3	COMPLETED	A Study of Short-Term Outcomes and Economic Impact For Patients With Worsening Congestive Heart Failure When Natrecor (Nesiritide) is Added to Standard-Care Therapy, Compared to Administration of Placebo With Standard-Care Therapy
NCT00321295	Phase 3	COMPLETED	Biventricular Pacing In Patients With Left Ventricular Dysfunction After Cardiovascular Surgery
NCT00483197	Phase 3	UNKNOWN	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Pivotal Trial
NCT00490321	Phase 3	UNKNOWN	VentrAssistTM LVAD for the Treatment of Advanced Heart Failure - Destination Therapy
NCT00626028	Phase 3	COMPLETED	Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing
NCT01013714	Phase 3	UNKNOWN	Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias
NCT01217827	Phase 3	COMPLETED	Implantable Cardioverter-Defibrillator Use in the VA System
NCT01648634	Phase 3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02924285	Phase 3	COMPLETED	Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease
NCT03860935	Phase 3	COMPLETED	Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy
NCT04166331	Phase 3	COMPLETED	Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion
NCT05175066	Phase 3	COMPLETED	Bisoprolol Administration to Prevent Anthracycline-induced Cardiotoxicity
NCT05237323	Phase 3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT06158698	Phase 3	RECRUITING	CMP-MYTHiC Trial and Registry - CardioMyoPathy With MYocarditis THerapy With Colchicine
NCT06563895	Phase 3	RECRUITING	Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CACNB2 across ~30M SureChEMBL compounds — explore on Sugi Predict.