CACNG3

Summary

CACNG3 (calcium voltage-gated channel auxiliary subunit gamma 3, HGNC:1407) is a protein-coding gene on chromosome 16p12.1, encoding Voltage-dependent calcium channel gamma-3 subunit (O60359). Regulates the trafficking to the somatodendritic compartment and gating properties of AMPA-selective glutamate receptors (AMPARs).

The protein encoded by this gene is a type I transmembrane AMPA receptor regulatory protein (TARP). TARPs regulate both trafficking and channel gating of the AMPA receptors. This gene is part of a functionally diverse eight-member protein subfamily of the PMP-22/EMP/MP20 family. This gene is a susceptibility locus for childhood absence epilepsy.

Source: NCBI Gene 10368 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 20 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006539

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1407
Approved symbol	CACNG3
Name	calcium voltage-gated channel auxiliary subunit gamma 3
Location	16p12.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000006116
Ensembl biotype	protein_coding
OMIM	606403
Entrez	10368

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000005284, ENST00000876789

RefSeq mRNA: 1 — MANE Select: NM_006539 NM_006539

CCDS: CCDS10620

Canonical transcript exons

ENST00000005284 — 4 exons

Exon	Start	End
ENSE00000357496	24346734	24346817
ENSE00000679381	24354833	24354973
ENSE00001175673	24361352	24362412
ENSE00001175679	24256335	24256965

Expression profiles

Bgee: expression breadth broad, 85 present calls, max score 96.26.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 4.4697 / max 342.0999, expressed in 105 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153221	2.2426	94
153220	1.5210	82
153217	0.3065	65
153216	0.2284	69
153219	0.0844	40
153214	0.0313	24
153218	0.0292	21
153215	0.0263	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 10	UBERON:0013541	96.26	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.00	gold quality
orbitofrontal cortex	UBERON:0004167	95.19	gold quality
CA1 field of hippocampus	UBERON:0003881	94.49	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.29	gold quality
superior frontal gyrus	UBERON:0002661	94.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.73	gold quality
right frontal lobe	UBERON:0002810	93.53	gold quality
postcentral gyrus	UBERON:0002581	93.42	gold quality
cingulate cortex	UBERON:0003027	93.26	gold quality
anterior cingulate cortex	UBERON:0009835	93.21	gold quality
frontal cortex	UBERON:0001870	93.19	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.18	gold quality
parietal lobe	UBERON:0001872	93.05	gold quality
entorhinal cortex	UBERON:0002728	92.81	gold quality
prefrontal cortex	UBERON:0000451	92.61	gold quality
neocortex	UBERON:0001950	92.25	gold quality
cerebral cortex	UBERON:0000956	92.06	gold quality
nucleus accumbens	UBERON:0001882	91.59	gold quality
temporal lobe	UBERON:0001871	91.46	gold quality
amygdala	UBERON:0001876	91.15	gold quality
telencephalon	UBERON:0001893	91.14	gold quality
caudate nucleus	UBERON:0001873	91.04	gold quality
frontal pole	UBERON:0002795	90.42	gold quality
Ammon’s horn	UBERON:0001954	90.13	gold quality
putamen	UBERON:0001874	89.89	gold quality
cortical plate	UBERON:0005343	87.73	gold quality
middle temporal gyrus	UBERON:0002771	84.97	gold quality
forebrain	UBERON:0001890	84.68	gold quality
occipital lobe	UBERON:0002021	84.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9154	yes	278.91
E-GEOD-137537	yes	4.96
E-ANND-3	yes	2.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting CACNG3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-3164	99.02	68.39	1071
HSA-MIR-6820-3P	99.02	68.50	1035
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-147A	98.33	66.40	795

Literature-anchored findings (GeneRIF, showing 4)

• examined distribution of the stargazin-like proteins gamma2, gamma3, and gamma4 in human CNS: gamma2 is expressed in cerebellum, cerebral cortex, hippocampus and thalamus, whereas gamma3 abounds in cerebral cortex & amygdala and gamma4 in basal ganglia (PMID:14505496)
• CACNG3 on chromosome 16p12-p13.1 may represent susceptibility loci for CAE. (PMID:17264864)
• These results suggest that CACNG3 is the best candidate for an age-related macular degeneration risk gene within the 16p12 linkage peak. (PMID:21169531)
• Integrated profiling identifies CACNG3 as a prognostic biomarker for patients with glioma. (PMID:37697240)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cacng3b	ENSDARG00000076401
mus_musculus	Cacng3	ENSMUSG00000066189
rattus_norvegicus	Cacng3	ENSRNOG00000012362
caenorhabditis_elegans		WBGENE00017400

Paralogs (5): CACNG5 (ENSG00000075429), CACNG4 (ENSG00000075461), CACNG7 (ENSG00000105605), CACNG8 (ENSG00000142408), CACNG2 (ENSG00000166862)

Protein

Protein identifiers

Voltage-dependent calcium channel gamma-3 subunit — O60359 (reviewed: O60359)

Alternative names: Neuronal voltage-gated calcium channel gamma-3 subunit, Transmembrane AMPAR regulatory protein gamma-3

All UniProt accessions (1): O60359

UniProt curated annotations — full annotation on UniProt →

Function. Regulates the trafficking to the somatodendritic compartment and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. Thought to stabilize the calcium channel in an inactivated (closed) state.

Subunit / interactions. The L-type calcium channel is composed of five subunits: alpha-1, alpha-2/delta, beta and gamma. Acts as an auxiliary subunit for AMPA-selective glutamate receptors (AMPARs). Found in a complex with GRIA1, GRIA2, GRIA3, GRIA4, CNIH2, CNIH3, CACNG2, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with AP4M1 and GRIA1; associates GRIA1 with the adaptor protein complex 4 (AP-4) to target GRIA1 to the somatodendritic compartment of neurons.

Subcellular location. Membrane.

Similarity. Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.

RefSeq proteins (1): NP_006530* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR008368	VDCC_gsu	Family
IPR051072	CACNG_subunit	Family

Pfam: PF00822

UniProt features (6 total): transmembrane region 4, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60359-F1	67.56	0.20

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 (1): 248

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-399719	Trafficking of AMPA receptors
R-HSA-5682910	LGI-ADAM interactions
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1266738	Developmental Biology
R-HSA-399721	Glutamate binding, activation of AMPA receptors and synaptic plasticity

MSigDB gene sets: 195 (showing top): CREL_01, GOBP_POSITIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, KEGG_MAPK_SIGNALING_PATHWAY, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_PROTEIN_TARGETING, MEF2_02, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, MODULE_66, TGCTGAY_UNKNOWN, MARZEC_IL2_SIGNALING_DN, ZIC1_01

GO Biological Process (11): protein targeting (GO:0006605), calcium ion transport (GO:0006816), intracellular protein localization (GO:0008104), transmission of nerve impulse (GO:0019226), positive regulation of synaptic transmission, glutamatergic (GO:0051968), postsynaptic neurotransmitter receptor diffusion trapping (GO:0098970), neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0099645), regulation of AMPA receptor activity (GO:2000311), 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), channel regulator activity (GO:0016247), PDZ domain binding (GO:0030165), ionotropic glutamate receptor binding (GO:0035255), calcium channel activity (GO:0005262)

GO Cellular Component (13): plasma membrane (GO:0005886), voltage-gated calcium channel complex (GO:0005891), dendrite (GO:0030425), endocytic vesicle membrane (GO:0030666), AMPA glutamate receptor complex (GO:0032281), somatodendritic compartment (GO:0036477), excitatory synapse (GO:0060076), Schaffer collateral - CA1 synapse (GO:0098685), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702), organelle (GO:0043226)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1
Developmental Biology	1
Transmission across Chemical Synapses	1
Neuronal System	1
Neurotransmitter receptors and postsynaptic signal transmission	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
synapse	3
postsynaptic membrane	2
receptor localization to synapse	2
regulation of postsynaptic membrane neurotransmitter receptor levels	2
postsynaptic specialization membrane	2
establishment of protein localization	1
metal ion transport	1
macromolecule localization	1
action potential	1
cell communication	1
chemical synaptic transmission	1
nervous system process	1
synaptic transmission, glutamatergic	1
positive regulation of synaptic transmission	1
regulation of synaptic transmission, glutamatergic	1
neurotransmitter receptor diffusion trapping	1
protein-containing complex localization	1
protein localization to postsynaptic specialization membrane	1
AMPA glutamate receptor activity	1
regulation of transmembrane transporter activity	1
regulation of neurotransmitter receptor activity	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
calcium channel activity	1
voltage-gated monoatomic cation channel activity	1
channel activity	1
transporter regulator activity	1
protein domain specific binding	1
glutamate receptor binding	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
membrane	1
cell periphery	1
calcium channel complex	1
plasma membrane protein complex	1
neuron projection	1

Protein interactions and networks

STRING

1464 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CACNG3	CACNG1	Q06432	914
CACNG3	CACNB1	Q02641	808
CACNG3	CACNA2D1	P54289	791
CACNG3	CACNA1D	Q01668	592
CACNG3	CACNB4	O00305	567
CACNG3	CACNA1A	P78510	542
CACNG3	DLG2	Q15700	495
CACNG3	GSG1L2	A8MUP6	481
CACNG3	GSG1L	Q6UXU4	447
CACNG3	CACNB3	P54284	398
CACNG3	CNIH1	O95406	381
CACNG3	CACNA1H	O95180	377
CACNG3	SHISA9	B4DS77	374
CACNG3	CNIH2	Q6PI25	367
CACNG3	SHISA6	Q6ZSJ9	343

IntAct

5 interactions, top by confidence:

A	B	Type	Score
CACNG3	POTEF	psi-mi:“MI:0914”(association)	0.530
TRPV2	CACNG3	psi-mi:“MI:0915”(physical association)	0.370
CACNG3	NOTCH2	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): POTEF (Affinity Capture-MS), PLK1 (Affinity Capture-MS), POTEF (Affinity Capture-MS), PLK1 (Affinity Capture-MS), POTEF (Affinity Capture-MS), PLK1 (Affinity Capture-MS), ACBD3 (Affinity Capture-MS), RGP1 (Affinity Capture-MS), NOTCH2 (Affinity Capture-MS), SEC63 (Affinity Capture-MS), CCDC51 (Affinity Capture-MS), MRS2 (Affinity Capture-MS), APP (Reconstituted Complex)

ESM2 similar proteins: A8MUP6, B2RVW2, O42281, O42282, O42581, O42582, O42583, O60359, P08033, P15499, P17438, P17810, P23942, P28230, P35906, P52204, Q0V9V9, Q0VD05, Q148L1, Q28EW0, Q32LT7, Q3KRC6, Q3KTM2, Q3TH73, Q4R589, Q5R5X2, Q5T197, Q640M6, Q66JT1, Q68F79, Q6AX57, Q6GM04, Q6GPA5, Q6ICI0, Q6NU09, Q6NUZ2, Q6P1U2, Q6P6V6, Q7ZWN9, Q8BXN9

Diamond homologs: O60359, O88602, Q0VD05, Q4R589, Q5R5X2, Q71RJ2, Q8VHW2, Q8VHW4, Q8VHW5, Q8VHW8, Q8VHW9, Q8VHX0, Q8WXS5, Q9JJV4, Q9JJV5, Q9UBN1, Q9UF02, Q9Y698, P62955, P62956, P62957

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1050 predictions. Top by Δscore:

Variant	Effect	Δscore
16:24346729:CACA:C	acceptor_loss	1.0000
16:24346732:A:AG	acceptor_gain	1.0000
16:24346732:AG:A	acceptor_gain	1.0000
16:24346732:AGG:A	acceptor_gain	1.0000
16:24346732:AGGG:A	acceptor_gain	1.0000
16:24346733:G:GG	acceptor_gain	1.0000
16:24346733:GG:G	acceptor_gain	1.0000
16:24346733:GGG:G	acceptor_gain	1.0000
16:24346733:GGGG:G	acceptor_gain	1.0000
16:24346813:CCTGC:C	donor_gain	1.0000
16:24346814:CTGC:C	donor_gain	1.0000
16:24346815:TGC:T	donor_gain	1.0000
16:24346816:GC:G	donor_gain	1.0000
16:24346816:GCG:G	donor_gain	1.0000
16:24346817:CG:C	donor_loss	1.0000
16:24346818:G:GG	donor_gain	1.0000
16:24346818:GTAA:G	donor_loss	1.0000
16:24346819:T:A	donor_loss	1.0000
16:24354974:GTG:G	donor_loss	1.0000
16:24354975:T:G	donor_loss	1.0000
16:24301542:A:T	donor_gain	0.9900
16:24322054:T:G	donor_gain	0.9900
16:24346730:ACAG:A	acceptor_gain	0.9900
16:24346730:ACAGG:A	acceptor_gain	0.9900
16:24346733:GGGGC:G	acceptor_gain	0.9900
16:24354832:GGA:G	acceptor_gain	0.9900
16:24354970:GCAG:G	donor_gain	0.9900
16:24355744:T:G	acceptor_gain	0.9900
16:24282657:AACT:A	donor_gain	0.9800
16:24346730:A:AG	acceptor_gain	0.9800

AlphaMissense

2070 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:24256939:G:A	G62E	1.000
16:24256946:G:C	W64C	1.000
16:24256946:G:T	W64C	1.000
16:24354868:A:C	S111R	1.000
16:24354870:T:A	S111R	1.000
16:24354870:T:G	S111R	1.000
16:24256818:A:C	S22R	0.999
16:24256820:T:A	S22R	0.999
16:24256820:T:G	S22R	0.999
16:24256834:C:A	A27E	0.999
16:24256846:A:T	D31V	0.999
16:24256851:T:A	W33R	0.999
16:24256851:T:C	W33R	0.999
16:24256853:G:C	W33C	0.999
16:24256853:G:T	W33C	0.999
16:24256935:T:C	S61P	0.999
16:24256938:G:A	G62R	0.999
16:24256938:G:C	G62R	0.999
16:24256938:G:T	G62W	0.999
16:24256939:G:T	G62V	0.999
16:24256944:T:A	W64R	0.999
16:24256944:T:C	W64R	0.999
16:24256953:T:A	C67S	0.999
16:24256954:G:C	C67S	0.999
16:24256955:C:G	C67W	0.999
16:24346751:T:A	C77S	0.999
16:24346751:T:C	C77R	0.999
16:24346752:G:A	C77Y	0.999
16:24346752:G:C	C77S	0.999
16:24354890:G:A	G118D	0.999

dbSNP variants (sampled 300 via entrez): RS1000003394 (16:24274193 A>C), RS1000054266 (16:24331967 T>C,G), RS1000057010 (16:24309588 G>A), RS1000087393 (16:24312676 G>C), RS1000089204 (16:24351976 C>A,G,T), RS1000103559 (16:24267893 A>T), RS1000112453 (16:24320039 G>A), RS1000166341 (16:24298320 C>T), RS1000183813 (16:24258225 T>A), RS1000192741 (16:24277267 G>A), RS1000206789 (16:24337383 A>G), RS1000217560 (16:24259749 C>G,T), RS1000225146 (16:24300305 G>C), RS1000241055 (16:24337811 C>T), RS1000310588 (16:24289755 G>A)

Disease associations

OMIM: gene MIM:606403 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST007576_217	Chronotype	5.000000e-10
GCST009391_1951	Metabolite levels	4.000000e-06
GCST009391_261	Metabolite levels	6.000000e-06
GCST009391_283	Metabolite levels	2.000000e-06
GCST009391_290	Metabolite levels	2.000000e-06
GCST009391_328	Metabolite levels	7.000000e-06
GCST009391_372	Metabolite levels	2.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0010423	triacylglycerol 54:5 measurement
EFO:0010426	triacylglycerol 54:8 measurement
EFO:0010424	triacylglycerol 54:6 measurement
EFO:0010425	triacylglycerol 54:7 measurement
EFO:0010432	triacylglycerol 56:5 measurement
EFO:0010436	triacylglycerol 56:9 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2363032 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 67,947 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1428	NIMODIPINE	4	32,587
CHEMBL95	TACRINE	4	35,360

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1859204	CACNG3		0.00	0

ChEMBL bioactivities

58 potent at pChembl≥5 of 75 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
7.52	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
5.52	IC50	3000	nM	CHEMBL4224773

PubChem BioAssay actives

13 with measured affinity, of 101 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.

Compound	Assay	Type	Value	Unit
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

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	increases abundance, affects methylation	1
sulindac sulfide	increases expression	1
CGP 52608	affects binding, increases reaction	1
Arsenic Trioxide	increases expression	1
Barium	affects transport	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cannabinoids	affects methylation, increases abundance	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

13 unique, capped per target: 13 binding

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

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_YA29	IDG-HEK293T-CACNG3-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

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