CACNG8

Summary

CACNG8 (calcium voltage-gated channel auxiliary subunit gamma 8, HGNC:13628) is a protein-coding gene on chromosome 19q13.42, encoding Voltage-dependent calcium channel gamma-8 subunit (Q8WXS5). Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit.

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 and is located in a cluster with two family members, a type II TARP and a calcium channel gamma subunit. The mRNA for this gene is believed to initiate translation from a non-AUG (CUG) start codon.

Source: NCBI Gene 59283 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 70 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_031895

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13628
Approved symbol	CACNG8
Name	calcium voltage-gated channel auxiliary subunit gamma 8
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000142408
Ensembl biotype	protein_coding
OMIM	606900
Entrez	59283

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000270458

RefSeq mRNA: 1 — MANE Select: NM_031895 NM_031895

CCDS: CCDS33104

Canonical transcript exons

ENST00000270458 — 4 exons

Exon	Start	End
ENSE00000953965	53978146	53978229
ENSE00000953966	53979867	53980007
ENSE00001245550	53982080	53990215
ENSE00001245555	53962937	53963425

Expression profiles

Bgee: expression breadth broad, 92 present calls, max score 91.37.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0539 / max 5.6556, expressed in 20 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177454	0.0539	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	91.37	gold quality
postcentral gyrus	UBERON:0002581	91.19	gold quality
parietal lobe	UBERON:0001872	91.18	gold quality
superior frontal gyrus	UBERON:0002661	90.59	gold quality
lateral globus pallidus	UBERON:0002476	90.18	gold quality
cardiac muscle of right atrium	UBERON:0003379	89.96	gold quality
Ammon’s horn	UBERON:0001954	89.18	gold quality
left ventricle myocardium	UBERON:0006566	89.08	gold quality
entorhinal cortex	UBERON:0002728	88.87	gold quality
occipital lobe	UBERON:0002021	88.10	gold quality
primary visual cortex	UBERON:0002436	87.93	gold quality
vena cava	UBERON:0004087	87.73	silver quality
epithelial cell of pancreas	CL:0000083	87.56	gold quality
cerebral cortex	UBERON:0000956	86.45	gold quality
cortical plate	UBERON:0005343	86.39	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.21	gold quality
frontal cortex	UBERON:0001870	86.18	gold quality
prefrontal cortex	UBERON:0000451	86.01	gold quality
temporal lobe	UBERON:0001871	85.93	gold quality
middle temporal gyrus	UBERON:0002771	85.87	gold quality
neocortex	UBERON:0001950	85.65	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.34	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.30	gold quality
anterior cingulate cortex	UBERON:0009835	85.10	gold quality
ventral tegmental area	UBERON:0002691	85.07	gold quality
right frontal lobe	UBERON:0002810	84.05	gold quality
amygdala	UBERON:0001876	83.96	gold quality
substantia nigra pars reticulata	UBERON:0001966	83.61	silver quality
substantia nigra pars compacta	UBERON:0001965	83.33	silver quality
superior vestibular nucleus	UBERON:0007227	83.17	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ENAD-27	yes	42.60
E-ANND-3	yes	4.55
E-GEOD-83139	no	17.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

185 targeting CACNG8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815

Literature-anchored findings (GeneRIF, showing 5)

• Patients with Dilated Cardiomyopathy and Sustained Monomorphic Ventricular Tachycardia Show Up-Regulation of KCNN3 and KCNJ2 Genes and CACNG8-Linked Left Ventricular Dysfunction (PMID:26710323)
• These results indicate that CACNG4, CACNG5, CACNG6 and CACNG8 may contribute to the risk of SCZ. The statistical epistasis identified between CACNG5 and CACNG6 suggests that there may be an underlying biological interaction between the two genes. (PMID:27102562)
• SNP rs10420324 in the AMPA receptor auxiliary subunit TARP gamma-8 regulates the susceptibility to antisocial personality disorder. (PMID:34099816)
• Deficiency of transmembrane AMPA receptor regulatory protein gamma-8 leads to attention-deficit hyperactivity disorder-like behavior in mice. (PMID:36031768)
• The impact of modifier genes on cone-rod dystrophy heterogeneity: An explorative familial pilot study and a hypothesis on neurotransmission impairment. (PMID:36490268)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cacng8a	ENSDARG00000020450
danio_rerio	cacng8b	ENSDARG00000070626
mus_musculus	Cacng8	ENSMUSG00000053395
rattus_norvegicus	Cacng8	ENSRNOG00000057848
caenorhabditis_elegans		WBGENE00017400

Paralogs (5): CACNG3 (ENSG00000006116), CACNG5 (ENSG00000075429), CACNG4 (ENSG00000075461), CACNG7 (ENSG00000105605), CACNG2 (ENSG00000166862)

Protein

Protein identifiers

Voltage-dependent calcium channel gamma-8 subunit — Q8WXS5 (reviewed: Q8WXS5)

Alternative names: Neuronal voltage-gated calcium channel gamma-8 subunit, Transmembrane AMPAR regulatory protein gamma-8

All UniProt accessions (2): Q8WXS5, A0A1X7SBR8

UniProt curated annotations — full annotation on UniProt →

Function. Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit. Regulates the trafficking 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 and by mediating their resensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits.

Subunit / interactions. Interacts with CACNA1C. Identified in a complex with the L-type calcium channel subunits CACNA1C, CACNA2D1 and either CACNB1 or CACNB2. Acts as an auxiliary subunit for AMPA-selective glutamate receptors (AMPARs). Found in a complex with GRIA1, GRIA2, GRIA3, GRIA4, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5 and CACNG7. Interacts with CNIH2. Found in a complex with GRIA1, GRIA2, GRIA3, GRIA4, DLG4 and CNIH2.

Subcellular location. Cell membrane. Postsynaptic density membrane.

Tissue specificity. Detected in heart left ventricle.

Post-translational modifications. Palmitoylated. Probably palmitoylated by ZDHHC3 and ZDHHC7.

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

RefSeq proteins (1): NP_114101* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR008368	VDCC_gsu	Family
IPR008372	VDCC_g8su	Family
IPR051072	CACNG_subunit	Family

Pfam: PF00822

UniProt features (20 total): transmembrane region 5, sequence conflict 5, compositionally biased region 4, region of interest 3, modified residue 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXS5-F1	60.04	0.13

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): 252, 255

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-399719	Trafficking of AMPA receptors
R-HSA-5576892	Phase 0 - rapid depolarisation
R-HSA-5576893	Phase 2 - plateau phase
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-397014	Muscle contraction
R-HSA-399721	Glutamate binding, activation of AMPA receptors and synaptic plasticity
R-HSA-5576891	Cardiac conduction

MSigDB gene sets: 162 (showing top): GOBP_POSITIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, BENPORATH_ES_WITH_H3K27ME3, CCAWYNNGAAR_UNKNOWN, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_SYNAPTIC_SIGNALING, GOCC_NEURON_PROJECTION, GOBP_POSITIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION, GOBP_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_REGULATION_OF_NEUROTRANSMITTER_RECEPTOR_ACTIVITY, REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES, GOMF_SIGNALING_RECEPTOR_BINDING, GOBP_LOCALIZATION_WITHIN_MEMBRANE

GO Biological Process (8): calcium ion transport (GO:0006816), transmission of nerve impulse (GO:0019226), positive regulation of synaptic transmission, glutamatergic (GO:0051968), postsynaptic neurotransmitter receptor diffusion trapping (GO:0098970), 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 (6): voltage-gated calcium channel activity (GO:0005245), calcium channel regulator activity (GO:0005246), channel regulator activity (GO:0016247), protein phosphatase 2B binding (GO:0030346), 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), postsynaptic density (GO:0014069), endocytic vesicle membrane (GO:0030666), AMPA glutamate receptor complex (GO:0032281), dendrite membrane (GO:0032590), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), L-type voltage-gated calcium channel complex (GO:1990454), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702), synapse (GO:0045202), postsynaptic membrane (GO:0045211)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Cardiac conduction	2
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
Muscle contraction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
postsynaptic membrane	2
postsynaptic specialization membrane	2
calcium channel activity	2
metal ion transport	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
receptor localization to synapse	1
regulation of postsynaptic membrane neurotransmitter receptor levels	1
neurotransmitter receptor diffusion trapping	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
voltage-gated monoatomic cation channel activity	1
ion channel regulator activity	1
channel activity	1
transporter regulator activity	1
protein phosphatase 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
asymmetric synapse	1
postsynaptic specialization	1
endocytic vesicle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
ionotropic glutamate receptor complex	1

Protein interactions and networks

STRING

1451 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CACNG8	CNIH4	Q9P003	908
CACNG8	CNIH2	Q6PI25	907
CACNG8	CACNG1	Q06432	891
CACNG8	GRIA1	P42261	882
CACNG8	GRIA2	P42262	853
CACNG8	SHISA9	B4DS77	812
CACNG8	CACNB1	Q02641	791
CACNG8	PRKCG	P05129	771
CACNG8	DLG4	P78352	765
CACNG8	CNIH1	O95406	752
CACNG8	GSG1L	Q6UXU4	670
CACNG8	CACNA1D	Q01668	669
CACNG8	CACNA2D1	P54289	667
CACNG8	FRRS1L	Q9P0K9	562
CACNG8	GRIA3	P42263	553
CACNG8	GRIA4	P48058	553

IntAct

112 interactions, top by confidence:

A	B	Type	Score
CACNG8	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG8	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG8	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG8	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG8	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
SNX27	CACNG8	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG8	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG8	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG8	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG8	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG8	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
MAGI1	CACNG8	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG8	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
DLG1	CACNG8	psi-mi:“MI:0407”(direct interaction)	0.440
TAMALIN	CACNG8	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG8	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
MAST1	CACNG8	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG8	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG8	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG8	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF12	CACNG8	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG8	TJP2	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG8	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG8	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG8	PDZRN3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (13): CACNG8 (Affinity Capture-RNA), MRS2 (Affinity Capture-MS), CLTCL1 (Affinity Capture-MS), BCCIP (Affinity Capture-MS), LRRC1 (Affinity Capture-MS), C17orf70 (Affinity Capture-MS), DIS3L2 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), IGSF21 (Affinity Capture-MS), VPS18 (Affinity Capture-MS), CACNG8 (Affinity Capture-Western), CACNG8 (Affinity Capture-MS), CACNG8 (Affinity Capture-MS)

ESM2 similar proteins: A5PJM7, A6QL63, A7YY62, A7Z026, B2RYF1, E9PV86, O35393, O54951, O70141, O75864, P42229, P42230, P42231, P51692, Q15768, Q29RM4, Q3SZB3, Q3U2I3, Q3UFK8, Q5R5M3, Q5R8V2, Q5U2R3, Q5ZJA4, Q5ZJB7, Q66H54, Q6DN14, Q6GQW0, Q6IA17, Q6ZN54, Q6ZUT9, Q7Z6G3, Q7Z6J6, Q86VR8, Q8BKR5, Q8N5X7, Q8N612, Q8NBT3, Q8TBP0, Q8TF64, Q8WXS5

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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	53.9×	1e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	51.3×	1e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	51.3×	1e-06
Assembly and cell surface presentation of NMDA receptors	10	47.9×	6e-13
Dopamine Neurotransmitter Release Cycle	5	46.8×	2e-06
Long-term potentiation	5	44.9×	2e-06
Neurexins and neuroligins	11	40.9×	3e-13
Protein-protein interactions at synapses	7	35.1×	6e-08

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	74.5×	2e-14
protein localization to synapse	6	58.9×	9e-08
receptor clustering	6	48.0×	3e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	7	44.5×	4e-08
protein-containing complex assembly	9	13.1×	2e-06
cell-cell adhesion	9	11.7×	5e-06
chemical synaptic transmission	7	6.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1083 predictions. Top by Δscore:

Variant	Effect	Δscore
19:53963422:GAAGG:G	donor_loss	1.0000
19:53963424:AGGTA:A	donor_loss	1.0000
19:53963426:G:GA	donor_loss	1.0000
19:53978216:G:GT	donor_gain	1.0000
19:53978230:G:GG	donor_gain	1.0000
19:53979862:CGCA:C	acceptor_loss	1.0000
19:53979863:GCA:G	acceptor_loss	1.0000
19:53979865:A:AG	acceptor_gain	1.0000
19:53979865:AG:A	acceptor_gain	1.0000
19:53979866:G:A	acceptor_loss	1.0000
19:53979866:G:GA	acceptor_gain	1.0000
19:53979866:GG:G	acceptor_gain	1.0000
19:53979866:GGA:G	acceptor_gain	1.0000
19:53979866:GGAGT:G	acceptor_gain	1.0000
19:53980004:GCAG:G	donor_gain	1.0000
19:53980006:AGGT:A	donor_loss	1.0000
19:53980008:G:GA	donor_loss	1.0000
19:53963422:G:GT	donor_gain	0.9900
19:53963423:A:T	donor_gain	0.9900
19:53977888:G:GG	donor_gain	0.9900
19:53978225:ACTCC:A	donor_gain	0.9900
19:53978226:CTCC:C	donor_gain	0.9900
19:53978227:TCC:T	donor_gain	0.9900
19:53978227:TCCGT:T	donor_loss	0.9900
19:53978228:CC:C	donor_gain	0.9900
19:53978228:CCGT:C	donor_loss	0.9900
19:53978231:T:TC	donor_loss	0.9900
19:53979864:CAGG:C	acceptor_gain	0.9900
19:53979865:AGGA:A	acceptor_gain	0.9900
19:53979866:GGAG:G	acceptor_gain	0.9900

AlphaMissense

2706 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:53963255:C:A	A38D	1.000
19:53963264:C:T	T41I	1.000
19:53963266:G:C	D42H	1.000
19:53963267:A:T	D42V	1.000
19:53963272:T:A	W44R	1.000
19:53963272:T:C	W44R	1.000
19:53963274:G:C	W44C	1.000
19:53963274:G:T	W44C	1.000
19:53963276:T:C	L45P	1.000
19:53963296:T:A	C52S	1.000
19:53963297:G:A	C52Y	1.000
19:53963297:G:C	C52S	1.000
19:53963398:G:C	G86R	1.000
19:53963398:G:T	G86C	1.000
19:53963399:G:A	G86D	1.000
19:53963399:G:T	G86V	1.000
19:53963402:T:A	L87H	1.000
19:53963404:T:A	W88R	1.000
19:53963404:T:C	W88R	1.000
19:53963406:G:C	W88C	1.000
19:53963406:G:T	W88C	1.000
19:53963413:T:A	C91S	1.000
19:53963413:T:C	C91R	1.000
19:53963414:G:A	C91Y	1.000
19:53963414:G:C	C91S	1.000
19:53963415:C:G	C91W	1.000
19:53963416:T:C	C92R	1.000
19:53978163:T:A	C101S	1.000
19:53978163:T:C	C101R	1.000
19:53978164:G:A	C101Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000088201 (19:53962738 G>T), RS1000234856 (19:53966359 A>G), RS1000239505 (19:53970103 T>C,G), RS1000289987 (19:53971660 C>T), RS1000475259 (19:53976814 A>G), RS1000562699 (19:53966690 G>A), RS1000627525 (19:53970439 A>C), RS1000658640 (19:53970231 G>A,T), RS1000781773 (19:53975786 A>G), RS1000835114 (19:53968791 A>G,T), RS1000974378 (19:53965323 C>G,T), RS1001115044 (19:53974395 GT>G), RS1001183935 (19:53988741 A>T), RS1001189280 (19:53961178 G>A), RS1001212732 (19:53981614 T>A)

Disease associations

OMIM: gene MIM:606900 | 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 (2): CHEMBL2363032 (PROTEIN COMPLEX GROUP), CHEMBL4296110 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

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

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

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

Binding affinities (BindingDB)

141 measured of 141 human assays (141 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
7-(7-chloro-1H-indazol-5-yl)-2-propan-2-yl-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine	IC50	0.01 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
5-[2,6-bis(trifluoromethyl)pyrazolo[1,5-a]pyridin-7-yl]-7-chloro-1,3-dihydroindol-2-one	IC50	0.013 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
7-chloro-5-[2-propan-2-yl-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-7-yl]-1,3-dihydroindol-2-one	IC50	0.013 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
7-(7-chloro-1H-indazol-5-yl)-2,6-bis(trifluoromethyl)pyrazolo[1,5-a]pyridine	IC50	0.016 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
7-(7-methyl-1H-indazol-5-yl)-2,6-bis(trifluoromethyl)pyrazolo[1,5-a]pyridine	IC50	0.016 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
5-[2,6-bis(trifluoromethyl)pyrazolo[1,5-a]pyridin-7-yl]-7-methyl-1,3-dihydroindol-2-one	IC50	0.016 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
7-methyl-5-[2-propan-2-yl-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-7-yl]-1,3-dihydroindol-2-one	IC50	0.016 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
7-(7-chloro-1H-indazol-5-yl)-6-(difluoromethyl)-2-(trifluoromethyl)pyrazolo[1,5-a]pyridine	IC50	0.016 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
7-chloro-5-[2-cyclopropyl-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-7-yl]-1,3-dihydroindol-2-one	IC50	0.02 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
6-(difluoromethyl)-7-(7-methyl-1H-indazol-5-yl)-2-(trifluoromethyl)pyrazolo[1,5-a]pyridine	IC50	0.025 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
3-(7-Chloro-1H-indazol-5-yl)-2-(3-fluorocyclobutyl)-5-	IC50	0.032 nM	US-11312712: Azabenzimidazoles and their use as AMPA receptor modulators
6-(4-fluorophenyl)-5-(7-methyl-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-5-yl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.04 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
5-(7-chloro-1H-indazol-5-yl)-6-(1,1-difluoroethyl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.05 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
5-[2-cyclopropyl-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-7-yl]-7-methyl-1,3-dihydroindol-2-one	IC50	0.05 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
2-cyclopropyl-7-(7-methyl-1H-indazol-5-yl)-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine	IC50	0.05 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
5-[6-(difluoromethyl)-2-(trifluoromethyl)pyrazolo[1,5-a]pyridin-7-yl]-7-methyl-1,3-dihydroindol-2-one	IC50	0.05 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
5-[6-(difluoromethyl)-4-methyl-2-(trifluoromethyl)pyrazolo[1,5-a]pyridin-7-yl]-7-methyl-1,3-dihydroindol-2-one	IC50	0.05 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
(*S)-2-(1-Fluoroethyl)-3-(7-methyl-1H-indazol-5-yl)-5-	IC50	0.05 nM	US-11312712: Azabenzimidazoles and their use as AMPA receptor modulators
5-(7-chloro-1H-indazol-5-yl)-2-(difluoromethyl)-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.063 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
5-[6-(4-fluorophenyl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl]-7-methyl-1,3-dihydroindol-2-one	IC50	0.063 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
7-(7-chloro-1H-indazol-5-yl)-2-cyclopropyl-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine	IC50	0.063 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
2-(3-Fluorocyclobutyl)-3-(7-methyl-1H-indazol-5-yl)-5-	IC50	0.063 nM	US-11312712: Azabenzimidazoles and their use as AMPA receptor modulators
2-[(2S)-butan-2-yl]-3-(7-chloro-1H-indazol-5-yl)-5-(trifluoromethyl)imidazo[4,5-b]pyridine	IC50	0.063 nM	US-11312712: Azabenzimidazoles and their use as AMPA receptor modulators
5-(7-chloro-1H-indazol-5-yl)-2,6-bis(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.079 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
5-(7-chloro-1H-indazol-5-yl)-2-propan-2-yl-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.079 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
7-(7-methyl-1H-indazol-5-yl)-2-propan-2-yl-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine	IC50	0.079 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
(*R)-2-(1-Fluoroethyl)-3-(7-methyl-1H-indazol-5-yl)-5-	IC50	0.079 nM	US-11312712: Azabenzimidazoles and their use as AMPA receptor modulators
3-(7-chloro-1H-indazol-5-yl)-2-[(1S)-1-fluoroethyl]-5-(trifluoromethyl)imidazo[4,5-b]pyridine	IC50	0.079 nM	US-11312712: Azabenzimidazoles and their use as AMPA receptor modulators
5-(7-chloro-1H-indazol-5-yl)-6-(difluoromethyl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.1 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
5-(7-chloro-1H-indazol-5-yl)-2-(1,1-difluoroethyl)-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.1 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
5-(7-chloro-1H-indazol-5-yl)-2-cyclopropyl-6-(difluoromethyl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.1 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
7-(7-chloro-1H-indazol-5-yl)-6-(difluoromethyl)-4-methyl-2-(trifluoromethyl)pyrazolo[1,5-a]pyridine	IC50	0.1 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
2-[(2R)-butan-2-yl]-3-(7-chloro-1H-indazol-5-yl)-5-(trifluoromethyl)imidazo[4,5-b]pyridine	IC50	0.1 nM	US-11312712: Azabenzimidazoles and their use as AMPA receptor modulators
2-[(2S)-butan-2-yl]-3-(7-methyl-1H-indazol-5-yl)-5-(trifluoromethyl)imidazo[4,5-b]pyridine	IC50	0.1 nM	US-11312712: Azabenzimidazoles and their use as AMPA receptor modulators
3-(7-chloro-1H-indazol-5-yl)-2-[(1R)-1-fluoroethyl]-5-(trifluoromethyl)imidazo[4,5-b]pyridine	IC50	0.1 nM	US-11312712: Azabenzimidazoles and their use as AMPA receptor modulators
5-(7-chloro-1H-indazol-5-yl)-2-cyclopropyl-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.126 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
2-cyclopropyl-6-(4-fluorophenyl)-5-(7-methyl-1H-indazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.126 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
7-chloro-5-[2-cyclopropyl-8-methyl-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl]-1,3-dihydroindol-2-one	IC50	0.126 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
5-(7-chloro-1H-indazol-5-yl)-2-(difluoromethyl)-8-methyl-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.126 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
6-(difluoromethyl)-4-methyl-7-(7-methyl-1H-indazol-5-yl)-2-(trifluoromethyl)pyrazolo[1,5-a]pyridine	IC50	0.126 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
2-(3-Fluorocyclobutyl)-3-(7-methyl-1H-indazol-5-yl)-5-	IC50	0.126 nM	US-11312712: Azabenzimidazoles and their use as AMPA receptor modulators
2-[(2R)-butan-2-yl]-3-(7-methyl-1H-indazol-5-yl)-5-(trifluoromethyl)imidazo[4,5-b]pyridine	IC50	0.126 nM	US-11312712: Azabenzimidazoles and their use as AMPA receptor modulators
2-(difluoromethyl)-6-(trifluoromethyl)-5-[7-(trifluoromethyl)-1H-indazol-5-yl]-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.158 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
6-(difluoromethyl)-5-(7-methyl-1H-indazol-5-yl)-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.158 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
2-cyclopropyl-8-methyl-5-(7-methyl-1H-indazol-5-yl)-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.158 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
5-(7-chloro-1H-indazol-5-yl)-2-cyclopropyl-8-ethyl-6-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.158 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
5-(7-chloro-1H-indazol-5-yl)-2-cyclopropyl-6-(difluoromethyl)-8-ethyl-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.158 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
7-chloro-5-[8-methyl-2,6-bis(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl]-1,3-dihydroindol-2-one	IC50	0.158 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
7-ethyl-5-[8-methyl-2,6-bis(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-5-yl]-1,3-dihydroindol-2-one	IC50	0.158 nM	US-10087185: Fused bicylic pyridine compounds and their use as AMPA receptor modulators
3-(7-Chloro-1H-indazol-5-yl)-2-(3-fluorocyclobutyl)-5-	IC50	0.158 nM	US-11312712: Azabenzimidazoles and their use as AMPA receptor modulators

ChEMBL bioactivities

79 potent at pChembl≥5 of 96 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	IC50	0.1995	nM	CHEMBL4211865
8.82	IC50	1.5	nM	CHEMBL3891844
8.72	IC50	1.9	nM	CHEMBL3890624
8.62	IC50	2.4	nM	CHEMBL3973392
8.60	IC50	2.512	nM	CHEMBL4212408
8.60	IC50	2.512	nM	CHEMBL4216837
8.60	IC50	2.512	nM	CHEMBL4203681
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
8.20	IC50	6.31	nM	CHEMBL4216045
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
8.10	IC50	7.943	nM	CHEMBL4215352
8.05	IC50	9	nM	CHEMBL3942512
8.03	IC50	9.4	nM	CHEMBL3922498
8.01	IC50	9.7	nM	CHEMBL3897303
8.00	IC50	10	nM	CHEMBL4214902
8.00	IC50	10	nM	CHEMBL4207238
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
7.80	IC50	15.85	nM	CHEMBL4207505
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
7.30	IC50	50.12	nM	CHEMBL4211080
7.30	IC50	50.12	nM	CHEMBL4214549

PubChem BioAssay actives

34 with measured affinity, of 122 total; 33 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[2-chloro-6-(trifluoromethoxy)phenyl]-7-methyl-1,3-dihydroindol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0002	uM
5-[3-chloro-5-(trifluoromethoxy)-4-pyridinyl]-7-methyl-1,3-dihydroindol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0025	uM
5-[2-chloro-6-(trifluoromethoxy)phenyl]-7-fluoro-1,3-dihydroindol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0025	uM
6-[2-chloro-6-(trifluoromethoxy)phenyl]-3H-1,3-benzothiazol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0025	uM
5-(2-chloro-6-cyclopropylphenyl)-1,3-dihydrobenzimidazol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0063	uM
5-[3-chloro-5-(difluoromethoxy)-4-pyridinyl]-7-methyl-1,3-dihydroindol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0079	uM
5-[2-chloro-6-(trifluoromethoxy)phenyl]-1,3-dihydrobenzimidazol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0100	uM
2-[3-chloro-2-(2-oxo-1,3-dihydrobenzimidazol-5-yl)phenyl]acetonitrile	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0100	uM
5-[2-chloro-6-(trifluoromethoxy)phenyl]-1,3-dihydroindol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0158	uM
5-(2-chloro-6-methylphenyl)-1,3-dihydrobenzimidazol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0501	uM
5-(2,6-dichlorophenyl)-1,3-dihydrobenzimidazol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0501	uM
5-(2-chloro-6-methoxyphenyl)-1,3-dihydrobenzimidazol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.1259	uM
4-[2-(4-chlorophenyl)-3-[1-(2-methoxyethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-yl]morpholine	1542528: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.1259	uM
5-(2,6-dimethylphenyl)-1,3-dihydrobenzimidazol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.1585	uM
4-[2-(4-fluorophenyl)benzimidazol-1-yl]phenol	1542528: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.1995	uM
5-(3,5-dichloro-4-pyridinyl)-1,3-dihydrobenzimidazol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.2512	uM
3-chloro-2-(2-oxo-1,3-dihydrobenzimidazol-5-yl)benzonitrile	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.2512	uM
5-(2,6-dimethylphenyl)-1,3-dihydroindol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.3981	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
6-[2-chloro-6-(trifluoromethoxy)phenyl]-3H-1,3-benzoxazol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	2.5119	uM
5-(2-methylphenyl)-1,3-dihydroindol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	2.5119	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

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	3
Benzo(a)pyrene	affects methylation, decreases methylation	2
ethylbenzene	affects cotreatment, decreases expression, increases methylation	1
arsenite	increases methylation	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
sodium arsenite	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
ferrous chloride	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
jinfukang	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Cannabinoids	affects methylation, increases abundance	1
Chelating Agents	affects binding, increases expression	1
Copper	affects binding, increases expression	1
Lead	affects expression	1
Methotrexate	increases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Toluene	affects cotreatment, decreases expression, increases methylation	1
Triclosan	increases expression	1
Xylenes	increases methylation, affects cotreatment, decreases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Asbestos, Serpentine	increases methylation	1

ChEMBL screening assays

16 unique, capped per target: 16 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

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

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

Cellosaurus	Name	Category	Sex
CVCL_D7LH	Ubigene A-549 CACNG8 KO	Cancer cell line	Male
CVCL_D9AR	Ubigene HEK293 CACNG8 KO	Transformed cell line	Female
CVCL_YA32	IDG-HEK293T-CACNG8-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

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