CACNG4

Summary

CACNG4 (calcium voltage-gated channel auxiliary subunit gamma 4, HGNC:1408) is a protein-coding gene on chromosome 17q24.2, encoding Voltage-dependent calcium channel gamma-4 subunit (Q9UBN1). 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.

Source: NCBI Gene 27092 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 46 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014405

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1408
Approved symbol	CACNG4
Name	calcium voltage-gated channel auxiliary subunit gamma 4
Location	17q24.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC11138, MGC24983
Ensembl gene	ENSG00000075461
Ensembl biotype	protein_coding
OMIM	606404
Entrez	27092

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000262138, ENST00000921465

RefSeq mRNA: 1 — MANE Select: NM_014405 NM_014405

CCDS: CCDS11667

Canonical transcript exons

ENST00000262138 — 4 exons

Exon	Start	End
ENSE00000547770	67018189	67018272
ENSE00000742723	67024860	67025000
ENSE00001149242	66964707	66965131
ENSE00001268756	67030466	67033398

Expression profiles

Bgee: expression breadth ubiquitous, 146 present calls, max score 96.90.

FANTOM5 (CAGE): breadth broad, TPM avg 19.9795 / max 407.8816, expressed in 627 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162320	12.5119	569
162319	3.9116	481
162321	3.3594	385
162322	0.1827	93
208354	0.0139	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.90	gold quality
ventricular zone	UBERON:0003053	95.42	gold quality
ganglionic eminence	UBERON:0004023	95.19	gold quality
type B pancreatic cell	CL:0000169	94.96	gold quality
nucleus accumbens	UBERON:0001882	93.75	gold quality
olfactory bulb	UBERON:0002264	93.21	gold quality
embryo	UBERON:0000922	93.04	gold quality
pancreatic ductal cell	CL:0002079	92.73	silver quality
putamen	UBERON:0001874	92.71	gold quality
caudate nucleus	UBERON:0001873	92.48	gold quality
amygdala	UBERON:0001876	90.63	gold quality
temporal lobe	UBERON:0001871	89.78	gold quality
vena cava	UBERON:0004087	89.72	gold quality
CA1 field of hippocampus	UBERON:0003881	89.65	gold quality
hypothalamus	UBERON:0001898	89.08	gold quality
entorhinal cortex	UBERON:0002728	88.98	silver quality
endothelial cell	CL:0000115	88.60	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	88.50	gold quality
body of tongue	UBERON:0011876	88.04	gold quality
inferior olivary complex	UBERON:0002127	88.01	silver quality
triceps brachii	UBERON:0001509	87.73	silver quality
Brodmann (1909) area 46	UBERON:0006483	87.57	silver quality
mammary duct	UBERON:0001765	87.51	gold quality
lateral nuclear group of thalamus	UBERON:0002736	87.44	silver quality
medulla oblongata	UBERON:0001896	87.43	silver quality
gluteal muscle	UBERON:0002000	87.26	silver quality
lateral globus pallidus	UBERON:0002476	87.22	silver quality
diaphragm	UBERON:0001103	87.19	gold quality
pons	UBERON:0000988	86.66	silver quality
superficial temporal artery	UBERON:0001614	86.53	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	22.24
E-ANND-3	no	1.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

81 targeting CACNG4, 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-6127	100.00	66.76	2188
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785

Literature-anchored findings (GeneRIF, showing 2)

• 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)
• 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)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cacng4b	ENSDARG00000074669
danio_rerio	cacng4a	ENSDARG00000115540
mus_musculus	Cacng4	ENSMUSG00000020723
rattus_norvegicus	Cacng4	ENSRNOG00000003262
caenorhabditis_elegans		WBGENE00017400

Paralogs (5): CACNG3 (ENSG00000006116), CACNG5 (ENSG00000075429), CACNG7 (ENSG00000105605), CACNG8 (ENSG00000142408), CACNG2 (ENSG00000166862)

Protein

Protein identifiers

Voltage-dependent calcium channel gamma-4 subunit — Q9UBN1 (reviewed: Q9UBN1)

Alternative names: Neuronal voltage-gated calcium channel gamma-4 subunit, Transmembrane AMPAR regulatory protein gamma-4

All UniProt accessions (1): Q9UBN1

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), including GRIA1 and GRIA4. 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.

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). Interacts with GRIA1.

Subcellular location. Cell membrane.

Tissue specificity. Detected in heart left ventricle.

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

RefSeq proteins (1): NP_055220* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR005423	VDCC_g4su	Family
IPR008368	VDCC_gsu	Family
IPR051072	CACNG_subunit	Family

Pfam: PF00822

UniProt features (15 total): topological domain 5, transmembrane region 4, glycosylation site 2, chain 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBN1-F1	65.80	0.17

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): 259

Glycosylation sites (2): 42, 45

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-112308	Presynaptic depolarization and calcium channel opening
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: 193 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_POSITIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_COCAINE, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, KEGG_MAPK_SIGNALING_PATHWAY, GOZGIT_ESR1_TARGETS_DN, GOCC_CELL_SURFACE, MODULE_313, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, GOBP_RESPONSE_TO_ALKALOID, MODULE_205, SMID_BREAST_CANCER_LUMINAL_B_UP

GO Biological Process (9): transmission of nerve impulse (GO:0019226), response to cocaine (GO:0042220), 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), calcium ion transport (GO:0006816), 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), channel regulator activity (GO:0016247), ionotropic glutamate receptor binding (GO:0035255), calcium channel activity (GO:0005262)

GO Cellular Component (12): plasma membrane (GO:0005886), cell surface (GO:0009986), endocytic vesicle membrane (GO:0030666), AMPA glutamate receptor complex (GO:0032281), somatodendritic compartment (GO:0036477), cell body (GO:0044297), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), L-type voltage-gated calcium channel complex (GO:1990454), voltage-gated calcium channel complex (GO:0005891), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Transmission across Chemical Synapses	2
Cardiac conduction	2
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1
Developmental Biology	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
cellular anatomical structure	4
postsynaptic membrane	2
postsynaptic specialization membrane	2
calcium channel activity	2
action potential	1
cell communication	1
chemical synaptic transmission	1
nervous system process	1
response to alkaloid	1
response to oxygen-containing compound	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
metal ion 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
glutamate receptor binding	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
membrane	1
cell periphery	1
endocytic vesicle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
ionotropic glutamate receptor complex	1
postsynaptic density	1
synapse	1

Protein interactions and networks

STRING

858 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CACNG4	CACNG1	Q06432	952
CACNG4	CACNA1D	Q01668	872
CACNG4	CACNB1	Q02641	851
CACNG4	CACNA2D1	P54289	727
CACNG4	CACNA1E	Q15878	676
CACNG4	CACNA2D2	Q9NY47	652
CACNG4	CACNB3	P54284	638
CACNG4	CACNA1G	O43497	617
CACNG4	CACNA1B	Q00975	610
CACNG4	CACNA1C	Q13936	556
CACNG4	CACNG7	P62955	475
CACNG4	TRPV2	Q9Y5S1	468
CACNG4	PRKCA	P17252	460
CACNG4	KCNB2	Q92953	456
CACNG4	SERTM1	A2A2V5	451

IntAct

126 interactions, top by confidence:

A	B	Type	Score
RFFL	TUSC2	psi-mi:“MI:0914”(association)	0.530
CACNG4	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG4	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
MAGI2	CACNG4	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG4	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG4	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG4	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG4	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
TAX1BP3	CACNG4	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG4	MAGI1	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG4	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG4	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG4	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
DLG1	CACNG4	psi-mi:“MI:0407”(direct interaction)	0.440
HTRA1	CACNG4	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG4	PDZRN3	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG4	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG4	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
MAST1	CACNG4	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG4	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG4	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG4	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG4	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG4	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
CACNG4	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (71): OCRL (Affinity Capture-MS), ALG5 (Affinity Capture-MS), COQ5 (Affinity Capture-MS), ANAPC7 (Affinity Capture-MS), RMND1 (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS), NCAPH2 (Affinity Capture-MS), CSNK1E (Affinity Capture-MS), CSNK1D (Affinity Capture-MS), TMEM126B (Affinity Capture-MS), YIF1A (Affinity Capture-MS), MRS2 (Affinity Capture-MS), ARL10 (Affinity Capture-MS), MTX1 (Affinity Capture-MS), DPY19L3 (Affinity Capture-MS)

ESM2 similar proteins: A2RRU4, A6QM06, B3SHH9, D3Z7H4, D3ZK93, D4A6L0, E1BBQ2, E9Q6C8, F6V1J6, O70578, P19518, P51810, P56726, P82352, P97260, P97698, P97707, Q08CE6, Q08DE1, Q0IIE5, Q12770, Q14714, Q17QQ5, Q2MJQ7, Q3ZCD2, Q4V922, Q5GH57, Q5GH73, Q5MNU5, Q5T848, Q5XGU1, Q62147, Q68FV0, Q6GQT6, Q6UXU4, Q8C419, Q8C4U2, Q8NBL3, Q8VHW3, Q8VHW7

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 86 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	51.9×	1e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	49.4×	1e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	49.4×	1e-06
Assembly and cell surface presentation of NMDA receptors	10	46.1×	8e-13
Dopamine Neurotransmitter Release Cycle	5	45.1×	2e-06
Long-term potentiation	5	43.3×	2e-06
Neurexins and neuroligins	11	39.4×	4e-13
Protein-protein interactions at synapses	7	33.8×	8e-08

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	69.2×	5e-14
protein localization to synapse	6	54.7×	2e-07
receptor clustering	7	52.0×	1e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	6	35.4×	1e-06
protein-containing complex assembly	9	12.2×	3e-06
cell-cell adhesion	10	12.1×	1e-06
chemical synaptic transmission	7	6.4×	3e-03
protein transport	9	4.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1188 predictions. Top by Δscore:

Variant	Effect	Δscore
17:67018177:C:CA	acceptor_gain	1.0000
17:67018185:CCAG:C	acceptor_loss	1.0000
17:67018186:CA:C	acceptor_loss	1.0000
17:67018187:A:AG	acceptor_gain	1.0000
17:67018187:AG:A	acceptor_gain	1.0000
17:67018187:AGG:A	acceptor_gain	1.0000
17:67018188:G:GG	acceptor_gain	1.0000
17:67018188:GG:G	acceptor_gain	1.0000
17:67018188:GGG:G	acceptor_gain	1.0000
17:67018188:GGGAT:G	acceptor_gain	1.0000
17:67018268:CCTCC:C	donor_gain	1.0000
17:67018270:TCC:T	donor_gain	1.0000
17:67018272:CGTG:C	donor_loss	1.0000
17:67018273:G:C	donor_loss	1.0000
17:67018273:G:GG	donor_gain	1.0000
17:67018277:GT:G	donor_gain	1.0000
17:67018284:G:GT	donor_gain	1.0000
17:67024846:A:AG	acceptor_gain	1.0000
17:67024847:C:G	acceptor_gain	1.0000
17:66965129:AAGGT:A	donor_loss	0.9900
17:66965130:AGGT:A	donor_loss	0.9900
17:66965131:GGT:G	donor_loss	0.9900
17:66965133:T:A	donor_loss	0.9900
17:67018188:GGGA:G	acceptor_gain	0.9900
17:67018259:G:GT	donor_gain	0.9900
17:67018269:CTCC:C	donor_gain	0.9900
17:67018271:CC:C	donor_gain	0.9900
17:67018275:GAGTG:G	donor_loss	0.9900
17:67018276:A:AT	donor_loss	0.9900
17:67024853:C:A	acceptor_gain	0.9900

AlphaMissense

2145 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:66965104:G:T	G65C	1.000
17:66965110:T:A	W67R	1.000
17:66965110:T:C	W67R	1.000
17:67024895:A:C	S114R	1.000
17:67024897:C:A	S114R	1.000
17:67024897:C:G	S114R	1.000
17:67030483:G:C	G155R	1.000
17:67030484:G:A	G155D	1.000
17:67030594:T:C	F192L	1.000
17:67030596:C:A	F192L	1.000
17:67030596:C:G	F192L	1.000
17:66964991:C:A	A27D	0.999
17:66965000:C:T	T30I	0.999
17:66965002:G:C	D31H	0.999
17:66965003:A:T	D31V	0.999
17:66965008:T:A	W33R	0.999
17:66965008:T:C	W33R	0.999
17:66965010:G:C	W33C	0.999
17:66965010:G:T	W33C	0.999
17:66965012:T:C	L34P	0.999
17:66965104:G:C	G65R	0.999
17:66965105:G:A	G65D	0.999
17:66965105:G:T	G65V	0.999
17:66965112:G:C	W67C	0.999
17:66965112:G:T	W67C	0.999
17:66965114:G:C	R68P	0.999
17:66965119:T:C	C70R	0.999
17:66965120:G:A	C70Y	0.999
17:66965121:C:G	C70W	0.999
17:66965131:G:A	G74R	0.999

dbSNP variants (sampled 300 via entrez): RS1000079560 (17:66996568 A>G), RS1000088783 (17:67033493 C>T), RS1000118250 (17:66986411 G>A,C,T), RS1000124109 (17:67013541 A>C,G), RS1000161237 (17:66991809 G>A), RS1000214069 (17:66970367 T>C), RS1000251897 (17:66992129 C>T), RS1000291240 (17:67028324 C>T), RS1000304320 (17:66991813 C>G,T), RS1000418213 (17:67032893 A>G), RS1000425473 (17:66997182 A>T), RS1000494839 (17:66986338 A>C,G), RS1000508796 (17:67023869 G>A), RS1000536133 (17:66996304 G>A), RS1000601621 (17:67033094 C>T)

Disease associations

OMIM: gene MIM:606404 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005024_88	Pursuit maintenance gain	2.000000e-06
GCST009723_92	Vertical cup-disc ratio (adjusted for vertical disc diameter)	1.000000e-07
GCST009724_72	Vertical cup-disc ratio (multi-trait analysis)	7.000000e-09
GCST011528_6	Response to antidepressants (symptom improvement)	4.000000e-06
GCST012256_10	SAPHO syndrome	7.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008433	pursuit maintenance gain measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0007006	depressive symptom 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)

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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Calcitriol	increases expression, affects cotreatment	2
Estradiol	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	2
propionaldehyde	decreases expression	1
bisphenol A	decreases methylation	1
ethyl-p-hydroxybenzoate	increases expression	1
beta-lapachone	decreases expression	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases mutagenesis	1
Diazinon	increases methylation	1
Diethylhexyl Phthalate	increases expression	1
Endosulfan	decreases expression	1
Formaldehyde	increases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Sarin	decreases expression, increases expression	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 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7LE	Ubigene A-549 CACNG4 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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