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CACNB3

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Summary

CACNB3 (calcium voltage-gated channel auxiliary subunit beta 3, HGNC:1403) is a protein-coding gene on chromosome 12q13.12, encoding Voltage-dependent L-type calcium channel subunit beta-3 (P54284). Regulatory subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. It is a selective cancer dependency (DepMap: 46.9% of cell lines).

This gene encodes a regulatory beta subunit of the voltage-dependent calcium channel. Beta subunits are composed of five domains, which contribute to the regulation of surface expression and gating of calcium channels and may also play a role in the regulation of transcription factors and calcium transport.

Source: NCBI Gene 784 — RefSeq curated summary.

At a glance

  • Clinical variants (ClinVar): 79 total
  • Druggable target: yes — 2 molecules with ChEMBL bioactivity
  • Cancer dependency (DepMap): dependent in 46.9% of screened cell lines
  • MANE Select transcript: NM_000725

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:1403
Approved symbolCACNB3
Namecalcium voltage-gated channel auxiliary subunit beta 3
Location12q13.12
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000167535
Ensembl biotypeprotein_coding
OMIM601958
Entrez784

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 10 protein_coding, 8 retained_intron, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000301050, ENST00000536187, ENST00000540990, ENST00000547230, ENST00000547392, ENST00000547693, ENST00000547818, ENST00000548279, ENST00000548860, ENST00000548874, ENST00000549226, ENST00000549971, ENST00000550064, ENST00000550168, ENST00000550190, ENST00000550391, ENST00000550483, ENST00000550771, ENST00000551544, ENST00000551716, ENST00000552022, ENST00000552465, ENST00000552480, ENST00000552812, ENST00000861431

RefSeq mRNA: 4 — MANE Select: NM_000725 NM_000725, NM_001206915, NM_001206916, NM_001206917

CCDS: CCDS55821, CCDS55822, CCDS55823, CCDS8769

Canonical transcript exons

ENST00000301050 — 13 exons

ExonStartEnd
ENSE000013234654881849648818974
ENSE000034867414882675948826854
ENSE000034943964882697448827123
ENSE000035285774882543448825492
ENSE000035346944882758548828941
ENSE000035643294882516348825243
ENSE000035695864882566048825769
ENSE000036079204882334448823466
ENSE000036394674882425848824373
ENSE000036496944882494948824968
ENSE000036580534882368148823803
ENSE000036818594882466948824733
ENSE000037887084882636748826518

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 97.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.3027 / max 110.7078, expressed in 1555 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter IDTPM avgSamples expressed
1252744.88131372
1252731.99671090
1252751.6806597
1252720.7441390

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
cortical plateUBERON:000534397.74gold quality
ganglionic eminenceUBERON:000402396.88gold quality
frontal poleUBERON:000279596.47gold quality
right uterine tubeUBERON:000130296.28gold quality
right frontal lobeUBERON:000281096.17gold quality
right ovaryUBERON:000211896.00gold quality
left ovaryUBERON:000211995.90gold quality
right hemisphere of cerebellumUBERON:001489095.84gold quality
cerebellar cortexUBERON:000212995.73gold quality
cerebellar hemisphereUBERON:000224595.72gold quality
endothelial cellCL:000011595.62gold quality
prefrontal cortexUBERON:000045195.54gold quality
stromal cell of endometriumCL:000225595.05gold quality
cerebellumUBERON:000203794.60gold quality
amygdalaUBERON:000187694.47gold quality
body of uterusUBERON:000985394.42gold quality
cingulate cortexUBERON:000302794.40gold quality
anterior cingulate cortexUBERON:000983594.39gold quality
dorsolateral prefrontal cortexUBERON:000983494.34gold quality
frontal cortexUBERON:000187094.32gold quality
neocortexUBERON:000195094.32gold quality
primary visual cortexUBERON:000243694.03gold quality
lower esophagus mucosaUBERON:003583493.84gold quality
Brodmann (1909) area 9UBERON:001354093.78gold quality
endocervixUBERON:000045893.64gold quality
ovaryUBERON:000099293.29gold quality
paraflocculusUBERON:000535193.11gold quality
cerebral cortexUBERON:000095692.94gold quality
endometrium epitheliumUBERON:000481192.62gold quality
Brodmann (1909) area 10UBERON:001354192.52gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes3.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

81 targeting CACNB3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-34A-5P99.9971.211784
HSA-MIR-449A99.9971.051776
HSA-MIR-10401-5P99.9965.79948
HSA-MIR-150-5P99.9966.691976
HSA-MIR-186-5P99.9970.833707
HSA-MIR-34C-5P99.9770.451577
HSA-MIR-449B-5P99.9770.261580
HSA-MIR-185-3P99.9567.011743
HSA-MIR-515-5P99.9269.822343
HSA-MIR-519E-5P99.9269.622358
HSA-MIR-652-5P99.9167.49505
HSA-MIR-219A-5P99.9173.36735
HSA-MIR-345-3P99.8970.231421
HSA-MIR-124-3P99.8973.743043
HSA-MIR-506-3P99.8973.553057
HSA-MIR-4782-3P99.8873.31735
HSA-MIR-6766-3P99.8873.38732
HSA-MIR-6780A-5P99.8866.692776
HSA-MIR-576-5P99.8470.462582
HSA-MIR-370-5P99.7866.81706
HSA-MIR-4713-5P99.7867.801794
HSA-MIR-1273H-5P99.7766.322471
HSA-MIR-431999.7669.832586
HSA-MIR-30B-3P99.7065.762325
HSA-MIR-3689A-3P99.7065.732306
HSA-MIR-3689B-3P99.7065.712311
HSA-MIR-3689C99.7065.712311
HSA-MIR-6779-5P99.7065.762363
HSA-MIR-670-5P99.6769.941565
HSA-MIR-613499.6365.681537

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 46.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

  • in the presence of Pax6(S), beta(3) is translocated from the cytoplasm to the nucleus;full-length Ca(v)beta may act directly as a transcription regulator independent of its role in regulating Ca(2+) channel activity (PMID:19917615)
  • EMC chaperone-CaV structure reveals an ion channel assembly intermediate. (PMID:37196677)

Cross-species orthologs

7 orthologs

OrganismSymbolGene ID
danio_reriocacnb3aENSDARG00000001881
danio_reriocacnb3bENSDARG00000076030
mus_musculusCacnb3ENSMUSG00000003352
rattus_norvegicusCacnb3ENSRNOG00000054274
drosophila_melanogasterCa-betaFBGN0287724
caenorhabditis_elegansccb-1WBGENE00000368
caenorhabditis_elegansccb-2WBGENE00021125

Paralogs (3): CACNB1 (ENSG00000067191), CACNB2 (ENSG00000165995), CACNB4 (ENSG00000182389)

Protein

Protein identifiers

Voltage-dependent L-type calcium channel subunit beta-3 — P54284 (reviewed: P54284)

Alternative names: Calcium channel voltage-dependent subunit beta 3

All UniProt accessions (10): P54284, F8VNV8, F8VU10, F8VUW8, F8VV14, F8VWK1, F8W0F8, F8W1N3, H0YHK1, H0YHY2

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Increases CACNA1B peak calcium current and shifts the voltage dependencies of channel activation and inactivation. Increases CACNA1C peak calcium current and shifts the voltage dependencies of channel activation and inactivation.

Subunit / interactions. Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1C) and the ancillary subunits CACNB3 and CACNA2D1. The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio. Interacts with CACNA2D4. Interacts with FASLG. Interacts with CBARP; prevents the interaction of CACNB3 with the alpha subunit CACNA1C thereby negatively regulating the activity of the corresponding calcium channel.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed mostly in brain, colon and ovary.

Similarity. Belongs to the calcium channel beta subunit family.

Isoforms (5)

UniProt IDNamesCanonical?
P54284-11, 3Ayes
P54284-22, 3B
P54284-33
P54284-44
P54284-55

RefSeq proteins (4): NP_000716, NP_001193844, NP_001193845, NP_001193846 (=MANE)

Domains & families (InterPro)

IDNameType
IPR000584VDCC_L_bsuFamily
IPR001452SH3_domainDomain
IPR008079VDCC_L_b3suFamily
IPR008145GK/Ca_channel_bsuDomain
IPR027417P-loop_NTPaseHomologous_superfamily
IPR035760CACNB3_SH3Domain
IPR036028SH3-like_dom_sfHomologous_superfamily
IPR046937CAB1-4_N_A-domDomain

Pfam: PF00625, PF12052

UniProt features (70 total): strand 24, helix 14, sequence conflict 10, turn 6, splice variant 4, region of interest 4, compositionally biased region 3, modified residue 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

16 structures.

PDBMethodResolution (Å)
8WE6ELECTRON MICROSCOPY2.9
8WE8ELECTRON MICROSCOPY2.9
8X93ELECTRON MICROSCOPY2.92
8X90ELECTRON MICROSCOPY2.95
7MIXELECTRON MICROSCOPY3
7UHGELECTRON MICROSCOPY3
8WE9ELECTRON MICROSCOPY3
7MIYELECTRON MICROSCOPY3.1
7UHFELECTRON MICROSCOPY3.1
8E59ELECTRON MICROSCOPY3.1
8EPLELECTRON MICROSCOPY3.1
8X91ELECTRON MICROSCOPY3.11
8WE7ELECTRON MICROSCOPY3.2
8E5AELECTRON MICROSCOPY3.3
8E5BELECTRON MICROSCOPY3.3
8FHSELECTRON MICROSCOPY3.3

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P54284-F174.210.52

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 393, 152

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

IDPathway
R-HSA-112308Presynaptic depolarization and calcium channel opening
R-HSA-400042Adrenaline,noradrenaline inhibits insulin secretion
R-HSA-419037NCAM1 interactions
R-HSA-422356Regulation of insulin secretion
R-HSA-9856532Mechanical load activates signaling by PIEZO1 and integrins in osteocytes
R-HSA-112315Transmission across Chemical Synapses
R-HSA-112316Neuronal System
R-HSA-1266738Developmental Biology
R-HSA-1430728Metabolism
R-HSA-163685Integration of energy metabolism
R-HSA-375165NCAM signaling for neurite out-growth
R-HSA-422475Axon guidance
R-HSA-8953897Cellular responses to stimuli
R-HSA-9675108Nervous system development
R-HSA-9855142Cellular responses to mechanical stimuli

MSigDB gene sets: 332 (showing top): RNGTGGGC_UNKNOWN, BENPORATH_ES_WITH_H3K27ME3, GOBP_POSITIVE_REGULATION_OF_CATION_CHANNEL_ACTIVITY, REACTOME_ADRENALINE_NORADRENALINE_INHIBITS_INSULIN_SECRETION, KEGG_MAPK_SIGNALING_PATHWAY, GCANCTGNY_MYOD_Q6, BECKER_TAMOXIFEN_RESISTANCE_UP, AREB6_03, GOBP_POSITIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, REACTOME_NCAM_SIGNALING_FOR_NEURITE_OUT_GROWTH, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_DN, GOBP_REGULATION_OF_VOLTAGE_GATED_CALCIUM_CHANNEL_ACTIVITY, CHX10_01, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY

GO Biological Process (11): calcium ion transport (GO:0006816), chemical synaptic transmission (GO:0007268), T cell receptor signaling pathway (GO:0050852), calcium ion transport into cytosol (GO:0060402), calcium ion transmembrane transport via high voltage-gated calcium channel (GO:0061577), protein localization to plasma membrane (GO:0072659), regulation of membrane repolarization during action potential (GO:0098903), positive regulation of high voltage-gated calcium channel activity (GO:1901843), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), calcium ion transmembrane transport (GO:0070588)

GO Molecular Function (5): voltage-gated calcium channel activity (GO:0005245), calcium channel regulator activity (GO:0005246), high voltage-gated calcium channel activity (GO:0008331), calcium channel activity (GO:0005262), protein binding (GO:0005515)

GO Cellular Component (7): cytosol (GO:0005829), voltage-gated calcium channel complex (GO:0005891), membrane (GO:0016020), synapse (GO:0045202), L-type voltage-gated calcium channel complex (GO:1990454), cytoplasm (GO:0005737), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-11 pathways:

CategoryPathways
Transmission across Chemical Synapses1
Regulation of insulin secretion1
NCAM signaling for neurite out-growth1
Integration of energy metabolism1
Cellular responses to mechanical stimuli1
Neuronal System1
Metabolism1
Axon guidance1
Nervous system development1
Developmental Biology1
Cellular responses to stimuli1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure3
high voltage-gated calcium channel activity2
calcium channel activity2
metal ion transport1
anterograde trans-synaptic signaling1
antigen receptor-mediated signaling pathway1
positive regulation of cytosolic calcium ion concentration1
calcium ion transmembrane import into cytosol1
calcium ion transmembrane transport1
protein localization to membrane1
protein localization to cell periphery1
regulation of membrane repolarization1
membrane repolarization during action potential1
regulation of action potential1
positive regulation of voltage-gated calcium channel activity1
transport1
monoatomic ion transport1
transmembrane transport1
calcium ion transport1
monoatomic cation transmembrane transport1
voltage-gated monoatomic cation channel activity1
ion channel regulator activity1
voltage-gated calcium channel activity1
monoatomic cation channel activity1
calcium ion transmembrane transporter activity1
binding1
cytoplasm1
calcium channel complex1
plasma membrane protein complex1
cell junction1
voltage-gated calcium channel complex1
T-tubule1
intracellular anatomical structure1
transmembrane transporter complex1

Protein interactions and networks

STRING

902 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
CACNB3CACNA1CQ13936875
CACNB3CACNA1BQ00975875
CACNB3CACNA2D4Q7Z3S7866
CACNB3GUK1Q16774835
CACNB3CACNA2D1P54289687
CACNB3CACNA2D3Q8IZS8679
CACNB3CACNG4Q9UBN1638
CACNB3CACNA1GO43497629
CACNB3CACNA1HO95180622
CACNB3CACNA1AP78510576
CACNB3CACNA1FO60840568
CACNB3CACNA1DQ01668564
CACNB3CACNA2D2Q9NY47553
CACNB3CACNA1EQ15878509
CACNB3CACNB4O00305446
CACNB3JPH2Q9BR39446

IntAct

68 interactions, top by confidence:

ABTypeScore
CIAPIN1GLRX3psi-mi:“MI:0914”(association)0.960
CACNB3CIAPIN1psi-mi:“MI:0915”(physical association)0.740
CACNA1CCACNB3psi-mi:“MI:0915”(physical association)0.640
CACNB1CACNB3psi-mi:“MI:0914”(association)0.640
CACNB3GEMpsi-mi:“MI:0915”(physical association)0.600
GEMCACNB3psi-mi:“MI:0915”(physical association)0.600
CACNB3CEP76psi-mi:“MI:0915”(physical association)0.560
MEOX1CACNB3psi-mi:“MI:0915”(physical association)0.560
CACNB3SKIC2psi-mi:“MI:0915”(physical association)0.560
CACNB3MTUS2psi-mi:“MI:0915”(physical association)0.560
CACNB3CTBP2psi-mi:“MI:0915”(physical association)0.560
CACNB3CIMIP1psi-mi:“MI:0915”(physical association)0.560
CACNB4CACNB3psi-mi:“MI:0914”(association)0.530
EYA1PTPN9psi-mi:“MI:0914”(association)0.530
CACNB3CACNB4psi-mi:“MI:0914”(association)0.530
CACNB3CACNB2psi-mi:“MI:0914”(association)0.530
FASLGCACNB3psi-mi:“MI:0407”(direct interaction)0.440
SYT1CACNB3psi-mi:“MI:0915”(physical association)0.370
CIAPIN1GLRX3psi-mi:“MI:0914”(association)0.350
ZFYZFXpsi-mi:“MI:0914”(association)0.350
CACNB3PLCG1psi-mi:“MI:0914”(association)0.350
Mpsi-mi:“MI:0914”(association)0.350
CACNA1CSYT5psi-mi:“MI:0914”(association)0.350
CACNA1CIGLL5psi-mi:“MI:0914”(association)0.350
CACNA1CCACNB4psi-mi:“MI:0914”(association)0.350

BioGRID (38): CACNB3 (Affinity Capture-MS), CACNB2 (Affinity Capture-MS), CACNB3 (Affinity Capture-MS), CACNB3 (Affinity Capture-MS), C19orf26 (Affinity Capture-MS), CACNB3 (Affinity Capture-MS), CACNB3 (Affinity Capture-MS), PLCG1 (Affinity Capture-MS), WDR45B (Affinity Capture-MS), CACNB3 (Affinity Capture-RNA), CACNA1C (Co-crystal Structure), CACNB3 (Two-hybrid), CACNB3 (Two-hybrid), CACNB3 (Two-hybrid), CACNB3 (Two-hybrid)

ESM2 similar proteins: A5D7H2, A6QL72, D4A055, D4AB66, F1QH17, F1QWK4, O43237, O60447, O60941, O70585, O94776, P19517, P54283, P54284, P54285, P54286, P54287, P54288, P58405, P70175, P84060, Q02641, Q08289, Q13033, Q15700, Q28C55, Q4R5P6, Q5PYH7, Q5RE09, Q62936, Q63622, Q6PDL0, Q6R005, Q811S7, Q8CC27, Q8R0S4, Q8R3Z5, Q8VGC3, Q90ZY6, Q91XM9

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

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO termPartnersFoldFDR
chemical synaptic transmission513.3×2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance67
Likely benign0
Benign1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1940 predictions. Top by Δscore:

VariantEffectΔscore
12:48818971:GGCG:Gdonor_gain1.0000
12:48818972:GCG:Gdonor_gain1.0000
12:48818972:GCGG:Gdonor_gain1.0000
12:48818973:CGG:Cdonor_loss1.0000
12:48818975:G:GAdonor_loss1.0000
12:48818975:G:GGdonor_gain1.0000
12:48823340:CCA:Cacceptor_loss1.0000
12:48823341:CA:Cacceptor_loss1.0000
12:48823342:A:ACacceptor_loss1.0000
12:48823342:A:AGacceptor_gain1.0000
12:48823342:AG:Aacceptor_gain1.0000
12:48823343:G:GGacceptor_gain1.0000
12:48823343:GG:Gacceptor_gain1.0000
12:48823463:CAAGG:Cdonor_loss1.0000
12:48823464:AAGGT:Adonor_loss1.0000
12:48823465:AGGT:Adonor_loss1.0000
12:48823467:G:GAdonor_loss1.0000
12:48824249:T:TAacceptor_gain1.0000
12:48824256:A:AGacceptor_gain1.0000
12:48824257:G:GGacceptor_gain1.0000
12:48824257:GAA:Gacceptor_gain1.0000
12:48824371:CAGG:Cdonor_loss1.0000
12:48824374:G:Adonor_loss1.0000
12:48824375:T:Gdonor_loss1.0000
12:48824943:A:AGacceptor_gain1.0000
12:48825159:GCAG:Gacceptor_loss1.0000
12:48825160:CAGGC:Cacceptor_loss1.0000
12:48825161:A:Cacceptor_loss1.0000
12:48825430:CCAG:Cacceptor_loss1.0000
12:48825431:CAG:Cacceptor_loss1.0000

AlphaMissense

3163 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
12:48823696:T:CF62L1.000
12:48823697:T:CF62S1.000
12:48823697:T:GF62C1.000
12:48823698:T:AF62L1.000
12:48823698:T:GF62L1.000
12:48823699:G:CA63P1.000
12:48823790:T:AL93Q1.000
12:48823790:T:CL93P1.000
12:48823796:T:AI95N1.000
12:48824273:T:AW103R1.000
12:48824273:T:CW103R1.000
12:48824276:T:AW104R1.000
12:48824276:T:CW104R1.000
12:48824278:G:CW104C1.000
12:48824278:G:TW104C1.000
12:48824282:G:AG106R1.000
12:48824282:G:CG106R1.000
12:48824282:G:TG106W1.000
12:48824283:G:AG106E1.000
12:48824283:G:TG106V1.000
12:48824286:G:CR107P1.000
12:48824316:T:CF117S1.000
12:48824322:C:AP119H1.000
12:48824322:C:GP119R1.000
12:48825181:T:GY171D1.000
12:48825193:C:AP175T1.000
12:48825193:C:TP175S1.000
12:48825194:C:AP175H1.000
12:48825194:C:GP175R1.000
12:48825206:C:AP179H1.000

dbSNP variants (sampled 300 via entrez): RS1000017083 (12:48826157 T>C), RS1000292650 (12:48819675 T>C), RS1000605683 (12:48816459 G>A), RS1000732899 (12:48815160 G>A), RS1000796469 (12:48823206 G>A), RS1000815753 (12:48829083 C>T), RS1000946912 (12:48814465 C>T), RS1001128622 (12:48820910 G>A), RS1001773188 (12:48815793 G>C), RS1001794598 (12:48818372 T>C), RS1001911696 (12:48822781 G>A), RS1001959106 (12:48822682 G>A), RS1001979338 (12:48816206 G>A), RS1002059015 (12:48822016 T>G), RS1002328566 (12:48815673 C>T)

Disease associations

OMIM: gene MIM:601958 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2363032 (PROTEIN COMPLEX GROUP), CHEMBL3351206 (SINGLE PROTEIN), CHEMBL3430901 (PROTEIN COMPLEX), CHEMBL6066567 (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).

MoleculeNamePhasePatents
CHEMBL1428NIMODIPINE432,587
CHEMBL95TACRINE435,360

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

Binding affinities (BindingDB)

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

LigandMeasureValuePatent
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-2,2,6,6-tetramethylthiane 1-oxideIC501.5 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-2,2,6,6-tetramethylthiane 1,1-dioxideIC501.9 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
[(6S)-3-ethyl-6-(2H-tetrazol-5-ylmethyl)-6-bicyclo[3.2.0]hept-3-enyl]methanamineIC502.1 nMUS-9663479: γ-aminobutyric acid (GABA) analogues for the treatment of pain and other disorders
4-[1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethyl-1,1-dioxothian-4-yl)oxypyrazol-5-yl]benzonitrileIC502.4 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-2,2,6,6-tetramethylthiane 1-oxideIC502.7 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[1-(2-methoxyphenyl)-5-(4-methoxyphenyl)pyrazol-3-yl]oxy-2,2,6,6-tetramethylthiane 1,1-dioxideIC503 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-[(2,2,4,4-tetramethyloxetan-3-yl)methoxy]pyrazoleIC503.1 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
[(1R,5S,6S)-3-ethyl-6-(2H-tetrazol-5-ylmethyl)-6-bicyclo[3.2.0]hept-3-enyl]methanamineIC504.2 nMUS-9663479: γ-aminobutyric acid (GABA) analogues for the treatment of pain and other disorders
4-[1-(2-methoxyphenyl)-5-(4-methoxyphenyl)pyrazol-3-yl]oxy-2,2,6,6-tetramethylthiane 1-oxideIC504.5 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethylthian-4-yl)oxypyrazoleIC505.9 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
1-(2-methoxyphenyl)-5-(4-methoxyphenyl)-3-(2,2,6,6-tetramethylthian-4-yl)oxypyrazoleIC506 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-propan-2-yloxyphenyl)pyrazol-3-yl]oxy-1-propan-2-ylsulfonylpiperidineIC507 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethyloxan-4-yl)oxypyrazol-5-yl]benzonitrileIC507.2 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethyloxan-4-yl)oxypyrazoleIC507.6 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[1-(2-methoxyphenyl)-5-(4-methoxyphenyl)pyrazol-3-yl]oxy-2,2,6,6-tetramethylthiane 1-oxideIC507.6 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[3-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxyazetidin-1-yl]sulfonyl-3,5-dimethyl-1,2-oxazoleIC508 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-1-cyclopropylsulfonylpiperidineIC509 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
1-(2-methoxyphenyl)-5-(4-methoxyphenyl)-3-(2,2,6,6-tetramethyloxan-4-yl)oxypyrazoleIC509.4 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-2,2,6,6-tetramethylcyclohexan-1-oneIC509.7 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
N-[4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxycyclohexyl]-2,2,2-trifluoroacetamideIC5011 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethylthian-4-yl)oxypyrazol-5-yl]benzonitrileIC5012 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-N,N-dimethylpiperidine-1-carboxamideIC5014 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
3-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-N-methoxy-N-methylazetidine-1-carboxamideIC5014 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[1-(2-methoxyphenyl)-3-(2,2,6,6-tetramethyl-1-oxothian-4-yl)oxypyrazol-5-yl]benzonitrileIC5014 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-1-methylsulfonylpiperidineIC5015 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-(oxan-4-yloxy)pyrazoleIC5015 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
3-[[(1R,5S,6S)-6-(aminomethyl)-3-ethyl-6-bicyclo[3.2.0]hept-3-enyl]methyl]-1,2,4-oxadiazolidin-5-oneIC5019 nMUS-9663479: γ-aminobutyric acid (GABA) analogues for the treatment of pain and other disorders
4-[5-(4-chlorophenyl)-1-(2-propan-2-yloxyphenyl)pyrazol-3-yl]oxy-1-methylsulfonylpiperidineIC5021.5 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
3-(aminomethyl)-5-methylhexanoic acidIC5023 nMUS-9663479: γ-aminobutyric acid (GABA) analogues for the treatment of pain and other disorders
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-1-(trifluoromethylsulfonyl)piperidineIC5024 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
1-[4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxypiperidin-1-yl]ethanoneIC5026 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxycyclohexan-1-oneIC5028 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-(thian-4-yloxy)pyrazoleIC5028 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
tert-butyl 4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxypiperidine-1-carboxylateIC5030 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxythiane 1,1-dioxideIC5030 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-1-(2,2,2-trifluoroethyl)piperidineIC5031 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-(1-methylsulfonylazetidin-3-yl)oxypyrazoleIC5031 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
1-[4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxypiperidin-1-yl]-2,2,2-trifluoroethanoneIC5031.4 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-1-propan-2-ylsulfonylpiperidineIC5036 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
5-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-(1-propan-2-ylsulfonylazetidin-3-yl)oxypyrazoleIC5036 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxy-2,2,6,6-tetramethylcyclohexan-1-olIC5039 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
5-(4-chlorophenyl)-3-(4,4-difluorocyclohexyl)oxy-1-(2-methoxyphenyl)pyrazoleIC5041 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
tert-butyl 4-[5-(4-chlorophenyl)-1-(2-ethylphenyl)pyrazol-3-yl]oxypiperidine-1-carboxylateIC5050 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
tert-butyl N-[4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxycyclohexyl]carbamateIC5062 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
tert-butyl 3-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxyazetidine-1-carboxylateIC5067 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
5-(4-chlorophenyl)-3-(1,4-dioxaspiro[4.5]decan-8-yloxy)-1-(2-ethylphenyl)pyrazoleIC5081 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
[3-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxyazetidin-1-yl]-phenylmethanoneIC5085 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
4-[5-(4-chlorophenyl)-1-(2-ethylphenyl)pyrazol-3-yl]oxy-1-methylsulfonylpiperidineIC5098.5 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers
[(6R)-3-ethyl-6-(2H-tetrazol-5-ylmethyl)-6-bicyclo[3.2.0]hept-3-enyl]methanamineIC50165 nMUS-9663479: γ-aminobutyric acid (GABA) analogues for the treatment of pain and other disorders
4-[5-(4-chlorophenyl)-1-(2-methoxyphenyl)pyrazol-3-yl]oxycyclohexan-1-amineIC50400 nMUS-9434693: Substituted pyrazoles as N-type calcium channel blockers

ChEMBL bioactivities

63 potent at pChembl≥5 of 80 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
8.82IC501.5nMCHEMBL3891844
8.72IC501.9nMCHEMBL3890624
8.68IC502.1nMCHEMBL5998077
8.62IC502.4nMCHEMBL3973392
8.57IC502.7nMCHEMBL3891844
8.52IC503nMCHEMBL3919024
8.51IC503.1nMCHEMBL3919898
8.38IC504.2nMCHEMBL5769314
8.35IC504.5nMCHEMBL3965812
8.23IC505.9nMCHEMBL3906126
8.22IC506nMCHEMBL3890916
8.15IC507nMCHEMBL3940577
8.14IC507.2nMCHEMBL3969562
8.12IC507.6nMCHEMBL3937280
8.12IC507.6nMCHEMBL3965812
8.10IC508nMCHEMBL3983323
8.05IC509nMCHEMBL3942512
8.03IC509.4nMCHEMBL3922498
8.01IC509.7nMCHEMBL3897303
7.96IC5011nMCHEMBL3948329
7.92IC5012nMCHEMBL3898359
7.85IC5014nMCHEMBL3911369
7.85IC5014nMCHEMBL3913505
7.85IC5014nMCHEMBL3936725
7.82IC5015nMCHEMBL3984596
7.82IC5015nMCHEMBL3902376
7.72IC5019nMCHEMBL5872604
7.67IC5021.5nMCHEMBL3952905
7.64IC5023nMCHEMBL88034
7.62IC5024nMCHEMBL3972896
7.58IC5026nMCHEMBL3889804
7.55IC5028nMCHEMBL3958844
7.55IC5028nMCHEMBL3973382
7.52IC5030nMCHEMBL3978200
7.52IC5030nMCHEMBL3985660
7.51IC5031nMCHEMBL3896861
7.51IC5031nMCHEMBL3951956
7.50IC5031.4nMCHEMBL3962403
7.44IC5036nMCHEMBL3953976
7.44IC5036nMCHEMBL3925140
7.41IC5039nMCHEMBL3900691
7.39IC5041nMCHEMBL3930781
7.30IC5050nMCHEMBL3921840
7.21IC5062nMCHEMBL3956991
7.17IC5067nMCHEMBL3965293
7.09IC5081nMCHEMBL3958264
7.07IC5085nMCHEMBL3964411
7.01IC5098.5nMCHEMBL3953031
6.78IC50165nMCHEMBL5910936
6.40IC50400nMCHEMBL3974355

PubChem BioAssay actives

13 with measured affinity, of 119 total; 13 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
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-carboxamide1262825: Inhibition of voltage-gated calcium channel (unknown origin)ic500.8000uM
5-methyl-1-[(2-nitrophenyl)methyl]-3-(piperidin-1-ylmethyl)indole1392176: Inhibition of KCl-induced cytosolic voltage gated calcium channel opening in human SH-SY5Y cells by Fluo-4 AM dye based fluorescence assayic501.8000uM
1-[(3-chlorophenyl)methyl]-5-methyl-3-(piperidin-1-ylmethyl)indole1392176: Inhibition of KCl-induced cytosolic voltage gated calcium channel opening in human SH-SY5Y cells by Fluo-4 AM dye based fluorescence assayic502.2000uM
5-methyl-1-[(3-nitrophenyl)methyl]-3-(piperidin-1-ylmethyl)indole1392176: Inhibition of KCl-induced cytosolic voltage gated calcium channel opening in human SH-SY5Y cells by Fluo-4 AM dye based fluorescence assayic503.0000uM
1-[(4-chlorophenyl)methyl]-5-methyl-3-(piperidin-1-ylmethyl)indole1392176: Inhibition of KCl-induced cytosolic voltage gated calcium channel opening in human SH-SY5Y cells by Fluo-4 AM dye based fluorescence assayic503.0000uM
1-benzyl-5-methyl-3-(piperidin-1-ylmethyl)indole1392176: Inhibition of KCl-induced cytosolic voltage gated calcium channel opening in human SH-SY5Y cells by Fluo-4 AM dye based fluorescence assayic503.4000uM
5-methyl-1-[(4-methylphenyl)methyl]-3-(piperidin-1-ylmethyl)indole1392176: Inhibition of KCl-induced cytosolic voltage gated calcium channel opening in human SH-SY5Y cells by Fluo-4 AM dye based fluorescence assayic503.6000uM
1-[(4-fluorophenyl)methyl]-5-methyl-3-(piperidin-1-ylmethyl)indole1392176: Inhibition of KCl-induced cytosolic voltage gated calcium channel opening in human SH-SY5Y cells by Fluo-4 AM dye based fluorescence assayic504.8000uM
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-carboxamide1612587: 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 assayic509.0000uM
ethyl 5-amino-4-(3-methoxyphenyl)-2-methyl-7,8,9,10-tetrahydro-6H-cyclohepta[b][1,8]naphthyridine-3-carboxylate1653244: Inhibition of VGCC (unknown origin)ic509.0000uM
ethyl 5-amino-4-(3,4-dimethoxyphenyl)-2-methyl-7,8,9,10-tetrahydro-6H-cyclohepta[b][1,8]naphthyridine-3-carboxylate1653244: Inhibition of VGCC (unknown origin)ic509.0000uM
propan-2-yl 5-amino-2-methyl-4-phenyl-6,7,8,9-tetrahydrobenzo[b][1,8]naphthyridine-3-carboxylate1653244: Inhibition of VGCC (unknown origin)ic5010.0000uM
ethyl 5-amino-2-methyl-4-phenyl-6,7,8,9,10,11-hexahydrocycloocta[b][1,8]naphthyridine-3-carboxylate1653244: Inhibition of VGCC (unknown origin)ic5010.0000uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
bisphenol Aincreases reaction, increases expression, affects cotreatment, decreases methylation, affects binding (+1 more)3
Benzo(a)pyrenedecreases methylation, increases expression2
Valproic Acidaffects expression, increases expression2
1-Methyl-4-phenylpyridiniumaffects expression, affects reaction2
FR900359increases phosphorylation1
bisphenol Faffects cotreatment, decreases expression1
methyleugenolincreases expression1
trichostatin Aaffects expression1
sodium arseniteaffects methylation1
potassium chromate(VI)decreases expression1
U 0126affects reaction, affects expression1
ICG 001increases expression1
abrinedecreases expression1
jinfukangincreases expression1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acidincreases expression1
Decitabineaffects expression1
Fulvestrantaffects cotreatment, decreases methylation1
Air Pollutantsdecreases expression, increases abundance1
Bariumaffects transport1
Calciumincreases transport, affects binding, increases reaction, affects cotreatment1
Cisplatinaffects expression1
Dichlorodiphenyl Dichloroethylenedecreases expression1
Dexamethasoneaffects cotreatment, decreases expression1
Doxorubicindecreases expression1
Drugs, Chinese Herbaldecreases expression1
Estradiolaffects binding, decreases activity, increases reaction1
Indomethacinaffects cotreatment, decreases expression1
Smokedecreases expression1
Tobacco Smoke Pollutiondecreases expression1
1-Methyl-3-isobutylxanthineaffects cotreatment, decreases expression1

ChEMBL screening assays

17 unique, capped per target: 17 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL3737861BindingInhibition of voltage-gated calcium channel (unknown origin)Discovery and Pharmacology of a Novel Class of Diacylglycerol Acyltransferase 2 Inhibitors. — J Med Chem

Cellosaurus cell lines

7 cell lines: 5 cancer cell line, 2 transformed cell line

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

CellosaurusNameCategorySex
CVCL_B1LYAbcam HeLa CACNB3 KOCancer cell lineFemale
CVCL_D1JJPrecisION hCav2.2 alpha1B/beta3/alpha2delta1-HEKTransformed cell lineFemale
CVCL_D8I7Ubigene HCT 116 CACNB3 KOCancer cell lineMale
CVCL_D9APUbigene HEK293 CACNB3 KOTransformed cell lineFemale
CVCL_D9Z3Ubigene HeLa CACNB3 KOCancer cell lineFemale
CVCL_SG52HAP1 CACNB3 (-) 1Cancer cell lineMale
CVCL_SG53HAP1 CACNB3 (-) 2Cancer cell lineMale

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 80

This page pulls from 80 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot