CACNA1D

Summary

CACNA1D (calcium voltage-gated channel subunit alpha1 D, HGNC:1391) is a protein-coding gene on chromosome 3p21.1, encoding Voltage-dependent L-type calcium channel subunit alpha-1D (Q01668). Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division an….

Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, namely alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1D subunit. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 776 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 45
• Clinical variants (ClinVar): 2,655 total — 7 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 47
• Druggable target: yes — 48 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 5 cancer types
• MANE Select transcript: NM_001128840

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1391
Approved symbol	CACNA1D
Name	calcium voltage-gated channel subunit alpha1 D
Location	3p21.1
Locus type	gene with protein product
Status	Approved
Aliases	Cav1.3, CACH3, CACN4
Ensembl gene	ENSG00000157388
Ensembl biotype	protein_coding
OMIM	114206
Entrez	776

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 17 protein_coding, 9 retained_intron, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000288139, ENST00000350061, ENST00000422281, ENST00000464429, ENST00000481085, ENST00000481478, ENST00000498251, ENST00000636138, ENST00000636448, ENST00000636480, ENST00000636570, ENST00000636581, ENST00000636595, ENST00000636627, ENST00000636629, ENST00000636633, ENST00000636723, ENST00000636938, ENST00000636999, ENST00000637078, ENST00000637081, ENST00000637301, ENST00000637424, ENST00000637589, ENST00000637714, ENST00000637844, ENST00000638120, ENST00000638129, ENST00000640483, ENST00000645528, ENST00000954170

RefSeq mRNA: 3 — MANE Select: NM_001128840 NM_000720, NM_001128839, NM_001128840

CCDS: CCDS2872, CCDS46848, CCDS46849

Canonical transcript exons

ENST00000350061 — 48 exons

Exon	Start	End
ENSE00001032209	53776860	53776956
ENSE00001032212	53751749	53751907
ENSE00001032221	53761998	53762081
ENSE00001032223	53804983	53805146
ENSE00001032233	53747302	53747448
ENSE00001032250	53802147	53802173
ENSE00001032258	53740280	53740339
ENSE00001032262	53801058	53801425
ENSE00001032272	53780026	53780128
ENSE00001032278	53803423	53803572
ENSE00001032282	53732815	53732962
ENSE00001032289	53808649	53808770
ENSE00001032293	53781566	53781667
ENSE00001032295	53800249	53800365
ENSE00001032308	53744740	53744827
ENSE00001032309	53774587	53774678
ENSE00001032316	53753572	53753682
ENSE00001032318	53809978	53810298
ENSE00001032330	53769973	53770017
ENSE00001032331	53770424	53770552
ENSE00001032337	53745823	53745875
ENSE00001134865	53735374	53735503
ENSE00001174440	53732016	53732082
ENSE00001174449	53731077	53731146
ENSE00001241625	53786822	53786952
ENSE00001241714	53730442	53730556
ENSE00001241729	53723792	53723999
ENSE00001241756	53719755	53719781
ENSE00001241802	53665660	53665812
ENSE00001241817	53650779	53650918
ENSE00001241884	53723434	53723659
ENSE00001241890	53722314	53722474
ENSE00001242272	53718301	53718388
ENSE00001242276	53702641	53702810
ENSE00001242286	53666339	53666535
ENSE00001242298	53660133	53660275
ENSE00001242316	53497152	53497461
ENSE00001365969	53811113	53813733
ENSE00001640159	53772833	53772898
ENSE00001673437	53673023	53673126
ENSE00001700327	53775886	53776045
ENSE00001799889	53776603	53776730
ENSE00002205122	53743011	53743117
ENSE00002208070	53501615	53501720
ENSE00002237924	53726879	53726999
ENSE00002357790	53745624	53745731
ENSE00002360758	53749268	53749469
ENSE00003980379	53494611	53495233

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 97.82.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5474 / max 54.7239, expressed in 394 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36928	1.0679	282
36927	0.3357	156
36926	0.1406	72
36932	0.0033	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.82	gold quality
adrenal tissue	UBERON:0018303	92.44	gold quality
right lung	UBERON:0002167	91.71	gold quality
sural nerve	UBERON:0015488	91.65	gold quality
right adrenal gland	UBERON:0001233	89.87	gold quality
islet of Langerhans	UBERON:0000006	89.24	gold quality
right adrenal gland cortex	UBERON:0035827	89.10	gold quality
left adrenal gland cortex	UBERON:0035825	89.04	gold quality
left adrenal gland	UBERON:0001234	89.02	gold quality
adrenal cortex	UBERON:0001235	87.92	gold quality
pituitary gland	UBERON:0000007	87.83	gold quality
adrenal gland	UBERON:0002369	87.83	gold quality
right uterine tube	UBERON:0001302	87.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.15	gold quality
adenohypophysis	UBERON:0002196	86.41	gold quality
upper lobe of left lung	UBERON:0008952	85.99	gold quality
metanephros cortex	UBERON:0010533	85.37	gold quality
upper lobe of lung	UBERON:0008948	85.24	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.12	gold quality
middle temporal gyrus	UBERON:0002771	84.86	gold quality
primary visual cortex	UBERON:0002436	84.75	gold quality
endothelial cell	CL:0000115	84.55	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.00	gold quality
Brodmann (1909) area 23	UBERON:0013554	83.63	gold quality
cerebellar hemisphere	UBERON:0002245	83.29	gold quality
cerebellar cortex	UBERON:0002129	83.16	gold quality
right frontal lobe	UBERON:0002810	81.49	gold quality
right lobe of thyroid gland	UBERON:0001119	81.42	gold quality
pancreas	UBERON:0001264	81.38	gold quality
cerebellum	UBERON:0002037	81.36	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	67.81
E-CURD-119	yes	48.94
E-HCAD-25	yes	36.47
E-MTAB-5061	yes	15.40
E-ANND-3	yes	8.02
E-GEOD-137537	yes	6.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

132 targeting CACNA1D, 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-656-3P	100.00	72.15	2788
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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371A-3P	99.99	66.77	91
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775

Literature-anchored findings (GeneRIF, showing 40)

• functional but non-voltage-gated L-type Ca2+ channels are expressed at the plasma membrane in T cells and play a role in the antigen receptor-mediated Ca2+ flux in these cells (PMID:14981074)
• demonstrate (1) expression of the alpha1D Ca channel in human fetal heart, (2) inhibition of alpha1D I(Ca-L) by positive IgG, and (3) direct cross-reactivity of positive IgG with the alpha1D Ca channel protein (PMID:15939813)
• The modulation of alpha(1D) Ca(2+) channel by PKC was prevented by dialyzing cells with a 35-amino acid peptide mimicking the alpha(1D) NH(2)-terminal region comprising S81. (PMID:16973824)
• analysis of Ca2+-dependent gating of CaV1.3 L-type calcium channels by alternative splicing of a C-terminal regulatory domain (PMID:18482979)
• Direct interaction of otoferlin with syntaxin 1A, SNAP-25, and the L-type voltage-gated calcium channel Cav1.3. (PMID:19004828)
• Three SNPs in CACNA1D or CACNA1C are genetic polymorphisms conferring sensitivity to the antihypertensive effects of L-type dCCBs in patients with hypertension. (PMID:19225208)
• Enhancement of calcium transport in Caco-2 monolayer through PKCzeta-dependent Cav1.3-mediated transcellular and rectifying paracellular pathways by prolactin. (PMID:19339512)
• Overexpression of the intracellular II-III loop domains of Cav1.2, and possibly Cav1.3, can dislodge the corresponding endogenous channels from the lipid raft regions of the membrane in rat insulinoma (INS-1) cells. (PMID:19351867)
• Ca(v)1.3 was the sole apical channel responsible for the PRL-stimulated transcellular calcium transport in intestine-like Caco-2 monolayer. (PMID:19885716)
• These data suggest that RIM2beta contributes to the stabilization of Ca(v)1.3 gating kinetics in immature cochlear inner hair cells. (PMID:20363327)
• We describe a human channelopathy (termed SANDD syndrome, sinoatrial node dysfunction and deafness) with a cardiac and auditory phenotype that closely resembles that of Cacna1d-/- mice. (PMID:21131953)
• Overexpression of Cav1.2 rescues electrocardiographic abnormalities, whereas deletion of Cav1.3 exacerbates the abnormalities in congenital heart block. (PMID:21352396)
• CaV1.3 channels and intracellular calcium mediate osmotic stress-induced N-terminal c-Jun kinase activation and disruption of tight junctions in Caco-2 CELL MONOLAYERS. (PMID:21737448)
• A novel pathway for ankyrin-B-dependent regulation of Cav1.3 channel membrane targeting and regulation is found in atrial myocytes. (PMID:21859974)
• analysis of functional characterization of alternative splicing in the C terminus of L-type CaV1.3 channels (PMID:21998309)
• Functional properties of a newly identified C-terminal splice variant of Cav1.3 L-type Ca2+ channels (PMID:21998310)
• conclude that the L-type calcium channel Cav1.3 is important in human glucose-induced insulin secretion, and common variants in CACNA1D might contribute to type 2 diabetes. (PMID:23229155)
• N-lobe of Ca(2+)-calmodulin binds an N-terminal spatial Ca(2+) transforming element module on the channel amino terminus, whereas the C-lobe binds an EF-hand region upstream of the IQ domain (PMID:23591884)
• modulation of Cav1.3 Ca channel by calreticulin may be involved in pathological settings such as autoimmune associated congenital heart block where Cav1.3 Ca channels are downregulated (PMID:23791743)
• These findings implicate gain-of-function CACNA1D Ca(2+) channel mutations in adrenal aldosterone-producing adenomas and primary aldosteronism. (PMID:23913001)
• Somatic mutations in either ATP1A1 and CACNA1D were found in a subset of adrenal aldosterone-producing adenomas with a zona glomerulosa-like phenotype. (PMID:23913004)
• A novel mechanism for modulation of the pharmacologic properties of the CaV1.3 channel is identified through posttranscriptional modification of the C terminus. (PMID:23924992)
• Mouse Rad Q65P (the murine equivalent of human Rad Q66P) inhibits L-type currents conducted by CaV1.2 or CaV1.3 channels as potently as wild-type Rad (>95% inhibition of both channels). (PMID:23973784)
• CACNA1D gene overexpression is associated with prostate cancer progression and might play an important role in Ca(2+) influx, AR activation, and cell growth in prostate cancer cells (PMID:24054868)
• RNA editing of CaV1.3 channels(CDI) acts to modulate CDI in ways that substantiate a recently emerging mechanism where apoCaM begins preassociated with the IQ domain and other channel elements. (PMID:24120865)
• Results illustrate that the voltage sensors of Cav1.3 channels respond more sensitively to depolarization than those of Cav1.2 or Cav3.1 (PMID:24703308)
• The calcium inflow through Cav1.2 and Cav1.3 channels in murine spiral ganglion neurons. (PMID:24849370)
• in patients with aldosterone-producing adenomas, CACNA1D mutations were associated with smaller adenomas. (PMID:24866132)
• Cp8 is a new of Cav1.2 and Cav1.3 channel activators. (PMID:24941892)
• Article summarises the latest findings and specify the roles of Cav1.2 and Cav1.3 in neurological and psychiatric diseases.Individually, CACNA1C polymorphisms and CACNA1D variants have been linked to a variety of psychiatric diseases and to congenital deafness, respectively. [Review] (PMID:24996399)
• A meta-analysis of genome-wide association studies of blood pressure and hypertension in Chinese identified three new loci (CACNA1D, CYP21A2, and MED13L) and a newly discovered variant near SLC4A7. (PMID:25249183)
• ablation of Cav1.3 results in a decrease in the protein expression of myosin light chain 2, which interacts and increases the membrane localization of SK2 channels. (PMID:25538241)
• Study found that two de novo CACNA1D missense mutations affect evolutionary highly conserved regions in the channel’s activation gate and disrupt normal channel activity by inducing a pronounced gain of channel function (PMID:25620733)
• Cav1.3 was overexpressed in atypical hyperplasia and endometrial carcinoma, and the estrogen-induced phosphorylation of downstream molecular ERK1/2 and CREB is the result of activation of the GPER pathway. (PMID:25805831)
• Studies indicate the function of L-type calcium channels Cav1.3 in chromaffin cells. (PMID:25966692)
• Studies indicate a role for L-type calcium channel Cav1.3 and Cav1.4 in cochlear inner hair cells (IHCs) and retinal photoreceptors (PRs). (PMID:25966695)
• In overall, we provide evidence that Cav1.2 and Cav1.3 isoforms are capable of potentially functioning as zinc permeation routes, through which zinc entry can be differentially augmented by mild acidifications. (PMID:26049024)
• CACNA1D might not be a risk gene for SCZ in Han Chinese population, which add to the current state of knowledge regarding the susceptibility of CACNA1D to schizophrenia. (PMID:26255836)
• Mutations in CACNA1D gene is associated with aldosterone-producing adenomas. (PMID:26285814)
• Different mutations (KCNJ5, ATP1A1, ATP2B3, and CACNA1D) are found in different aldosterone-producing nodules from the same adrenal, suggesting that somatic mutations are independent events triggered by mechanisms that remain to be identified. (PMID:26351028)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cacna1da	ENSDARG00000102773
danio_rerio		ENSDARG00000110642
danio_rerio		ENSDARG00000115603
mus_musculus	Cacna1d	ENSMUSG00000015968
rattus_norvegicus	Cacna1d	ENSRNOG00000013147

Paralogs (26): CACNA1G (ENSG00000006283), SCN4A (ENSG00000007314), CACNA1S (ENSG00000081248), CACNA1I (ENSG00000100346), CACNA1F (ENSG00000102001), NALCN (ENSG00000102452), SCN2A (ENSG00000136531), SCN7A (ENSG00000136546), CACNA1A (ENSG00000141837), SCN1A (ENSG00000144285), CACNA1B (ENSG00000148408), CACNA1C (ENSG00000151067), CATSPER3 (ENSG00000152705), SCN3A (ENSG00000153253), TPCN2 (ENSG00000162341), CATSPER2 (ENSG00000166762), SCN11A (ENSG00000168356), SCN9A (ENSG00000169432), CATSPER1 (ENSG00000175294), SCN5A (ENSG00000183873), SCN10A (ENSG00000185313), TPCN1 (ENSG00000186815), CATSPER4 (ENSG00000188782), CACNA1H (ENSG00000196557), SCN8A (ENSG00000196876), CACNA1E (ENSG00000198216)

Protein

Protein identifiers

Voltage-dependent L-type calcium channel subunit alpha-1D — Q01668 (reviewed: Q01668)

Alternative names: Calcium channel, L type, alpha-1 polypeptide, isoform 2, Voltage-gated calcium channel subunit alpha Cav1.3

All UniProt accessions (15): A0A1B0GTN0, A0A1B0GTP8, A0A1B0GU49, A0A1B0GUB6, Q01668, A0A1B0GUH2, A0A1B0GUN6, A0A1B0GVI2, A0A1B0GW98, A0A1B0GWE1, A0A1B0GWF7, A0A1W2PQ56, A0A5F9Z6M3, H0Y879, H7C4S8

UniProt curated annotations — full annotation on UniProt →

Function. Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the ‘high-voltage activated’ (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, and by benzothiazepines. Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents.

Subunit / interactions. Voltage-dependent calcium channels are multisubunit complexes, consisting of alpha-1, alpha-2, beta and delta subunits in a 1:1:1:1 ratio. The channel activity is directed by the pore-forming and voltage-sensitive alpha-1 subunit. In many cases, this subunit is sufficient to generate voltage-sensitive calcium channel activity. The auxiliary subunits beta and alpha-2/delta linked by a disulfide bridge regulate the channel activity. Channel activity is further modulated, depending on the presence of specific delta subunit isoforms. Interacts (via IQ domain) with CABP1 and CABP4 in a calcium independent manner. Interacts with RIMBP2.

Subcellular location. Membrane.

Tissue specificity. Expressed in pancreatic islets and in brain, where it has been seen in cerebral cortex, hippocampus, basal ganglia, habenula and thalamus. Expressed in the small cell lung carcinoma cell line SCC-9. No expression in skeletal muscle.

Disease relevance. Sinoatrial node dysfunction and deafness (SANDD) [MIM:614896] A disease characterized by congenital severe to profound deafness without vestibular dysfunction, associated with episodic syncope due to intermittent pronounced bradycardia. The disease is caused by variants affecting the gene represented in this entry. Primary aldosteronism, seizures, and neurologic abnormalities (PASNA) [MIM:615474] A disorder characterized by hypertension, hypokalemia, and high aldosterone levels with low plasma renin activity and an elevated aldosterone/renin ratio. Other features include generalized seizures, cerebral palsy, spasticity, intellectual disability, and developmental delay. The disease is caused by variants affecting the gene represented in this entry. Gain of function variations affecting the gene represented in this entry may be associated with susceptibility to autism spetrum disorders.

Domain organisation. Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position.

Polymorphism. A change from seven to eight ATG trinucleotide repeats, resulting in an additional N-terminal methionine, has been found in a patient with non-insulin-dependent diabetes mellitus (NIDDM).

Miscellaneous. Expressed at 5% to 15% of isoform Neuronal-type in brain tissues, increased current density.

Similarity. Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1D subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q01668-1	Neuronal-type	yes
Q01668-2	Beta-cell-type
Q01668-4	4, Ca(V)1.3(42A)
Q01668-3	3

RefSeq proteins (3): NP_000711, NP_001122311, NP_001122312* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002077	VDCCAlpha1	Family
IPR005446	VDCC_L_a1su	Family
IPR005452	LVDCC_a1dsu	Family
IPR005821	Ion_trans_dom	Domain
IPR014873	VDCC_a1su_IQ	Domain
IPR027359	Volt_channel_dom_sf	Homologous_superfamily
IPR031649	GPHH_dom	Domain
IPR031688	CAC1F_C	Domain
IPR050599	VDCC_alpha-1_subunit	Family

Pfam: PF00520, PF08763, PF16885, PF16905

Catalyzed reactions (Rhea), 1 shown:

• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)

UniProt features (211 total): helix 69, topological domain 25, transmembrane region 24, strand 22, turn 16, region of interest 13, compositionally biased region 9, sequence conflict 8, sequence variant 8, splice variant 6, repeat 4, binding site 3, glycosylation site 3, chain 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
3LV3	X-RAY DIFFRACTION	1.94
7UHG	ELECTRON MICROSCOPY	3
7UHF	ELECTRON MICROSCOPY	3.1
8E59	ELECTRON MICROSCOPY	3.1
8E5A	ELECTRON MICROSCOPY	3.3
8E5B	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01668-F1	64.60	0.12

Functional residue map

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

Ligand- & substrate-binding residues (3): 364; 705; 1101

Glycosylation sites (3): 155, 225, 329

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-400042	Adrenaline,noradrenaline inhibits insulin secretion
R-HSA-419037	NCAM1 interactions
R-HSA-422356	Regulation of insulin secretion
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-163685	Integration of energy metabolism
R-HSA-375165	NCAM signaling for neurite out-growth
R-HSA-422475	Axon guidance
R-HSA-9659379	Sensory processing of sound
R-HSA-9675108	Nervous system development
R-HSA-9709957	Sensory Perception

MSigDB gene sets: 400 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_MEMBRANE_DEPOLARIZATION, BENPORATH_ES_WITH_H3K27ME3, YAGI_AML_WITH_INV_16_TRANSLOCATION, PAX4_01, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_ADRENALINE_NORADRENALINE_INHIBITS_INSULIN_SECRETION, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_MEMBRANE_DEPOLARIZATION_DURING_ACTION_POTENTIAL, AAGCCAT_MIR135A_MIR135B, REACTOME_NCAM_SIGNALING_FOR_NEURITE_OUT_GROWTH, GOBP_POSITIVE_REGULATION_OF_LYASE_ACTIVITY, GGGTGGRR_PAX4_03

GO Biological Process (23): calcium ion transport (GO:0006816), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), sensory perception of sound (GO:0007605), positive regulation of adenylate cyclase activity (GO:0045762), positive regulation of calcium ion transport (GO:0051928), regulation of atrial cardiac muscle cell membrane repolarization (GO:0060372), calcium ion import (GO:0070509), calcium ion transmembrane transport (GO:0070588), cardiac muscle cell action potential involved in contraction (GO:0086002), membrane depolarization during cardiac muscle cell action potential (GO:0086012), membrane depolarization during SA node cell action potential (GO:0086046), regulation of heart rate by cardiac conduction (GO:0086091), calcium ion import across plasma membrane (GO:0098703), regulation of potassium ion transmembrane transport (GO:1901379), monoatomic ion transport (GO:0006811), muscle contraction (GO:0006936), cell communication (GO:0007154), regulation of metal ion transport (GO:0010959), signaling (GO:0023052), monoatomic ion transmembrane transport (GO:0034220), nervous system process (GO:0050877), positive regulation of transport (GO:0051050), transmembrane transport (GO:0055085)

GO Molecular Function (12): voltage-gated calcium channel activity (GO:0005245), calcium channel activity (GO:0005262), ankyrin binding (GO:0030506), metal ion binding (GO:0046872), alpha-actinin binding (GO:0051393), voltage-gated calcium channel activity involved in cardiac muscle cell action potential (GO:0086007), voltage-gated calcium channel activity involved SA node cell action potential (GO:0086059), monoatomic ion channel activity (GO:0005216), protein binding (GO:0005515), cytoskeletal protein binding (GO:0008092), high voltage-gated calcium channel activity (GO:0008331), voltage-gated monoatomic cation channel activity (GO:0022843)

GO Cellular Component (7): plasma membrane (GO:0005886), voltage-gated calcium channel complex (GO:0005891), Z disc (GO:0030018), L-type voltage-gated calcium channel complex (GO:1990454), membrane (GO:0016020), T-tubule (GO:0030315), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Regulation of insulin secretion	1
NCAM signaling for neurite out-growth	1
Integration of energy metabolism	1
Sensory processing of sound	1
Metabolism	1
Axon guidance	1
Nervous system development	1
Sensory Perception	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
calcium ion transport	3
cellular anatomical structure	3
metal ion transport	2
adenylate cyclase activity	2
cardiac muscle cell action potential	2
membrane depolarization during cardiac muscle cell action potential	2
SA node cell action potential	2
monoatomic cation channel activity	2
voltage-gated calcium channel activity	2
G protein-coupled receptor signaling pathway	1
sensory perception of mechanical stimulus	1
positive regulation of cyclase activity	1
regulation of adenylate cyclase activity	1
positive regulation of lyase activity	1
positive regulation of monoatomic ion transport	1
regulation of calcium ion transport	1
regulation of cardiac muscle cell membrane repolarization	1
atrial cardiac muscle cell membrane repolarization	1
monoatomic cation transmembrane transport	1
cardiac muscle cell contraction	1
membrane depolarization during action potential	1
regulation of heart rate	1
cardiac conduction	1
calcium ion import	1
calcium ion transmembrane import into cytosol	1
inorganic cation import across plasma membrane	1
calcium ion import into cytosol	1
regulation of potassium ion transport	1
potassium ion transmembrane transport	1
regulation of monoatomic cation transmembrane transport	1
transport	1
muscle system process	1
cellular process	1
regulation of monoatomic ion transport	1
regulation of biological process	1
monoatomic ion transport	1
transmembrane transport	1
calcium channel activity	1
voltage-gated monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1

Protein interactions and networks

STRING

2188 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CACNA1D	CACNA2D1	P54289	940
CACNA1D	CACNB2	Q08289	939
CACNA1D	CACNG1	Q06432	935
CACNA1D	CACNB1	Q02641	924
CACNA1D	RYR2	Q92736	911
CACNA1D	OTOF	Q9HC10	908
CACNA1D	CACNG4	Q9UBN1	872
CACNA1D	CALM1	P02593	852
CACNA1D	CALML3	P27482	852
CACNA1D	CALML5	Q9NZT1	852
CACNA1D	CALML6	Q8TD86	847
CACNA1D	CALML4	Q96GE6	847
CACNA1D	CAV1	Q03135	815
CACNA1D	CACNA1F	O60840	812
CACNA1D	ATP2B3	Q16720	807

IntAct

119 interactions, top by confidence:

A	B	Type	Score
CACNA1D	SHANK3	psi-mi:“MI:0407”(direct interaction)	0.560
SHANK1	CACNA1D	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	SHANK1	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
SCRIB	CACNA1D	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	GOPC	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	PARD3B	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	NHERF2	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
NHERF4	CACNA1D	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	LNX1	psi-mi:“MI:0407”(direct interaction)	0.440
SNTG2	CACNA1D	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (11): CACNA1D (Affinity Capture-RNA), CACNA1D (Reconstituted Complex), CACNA1D (Co-localization), CACNA1D (Co-localization), KCNN4 (FRET), CACNA1D (FRET), JPH3 (FRET), JPH4 (FRET), PARK2 (Affinity Capture-Western), CACNA1D (Cross-Linking-MS (XL-MS)), CACNA1D (Reconstituted Complex)

ESM2 similar proteins: B1AWN6, C9D7C2, D0E0C2, O00555, O08562, O35505, O55017, O57483, O60840, O73700, O88420, O88457, P02719, P07293, P15381, P22002, P22316, P27732, P27884, P54282, P56698, P56699, P91645, P97445, Q00975, Q01668, Q01815, Q02294, Q02343, Q02485, Q02789, Q05152, Q07652, Q13698, Q13936, Q15858, Q15878, Q25452, Q28644, Q2XVR3

Diamond homologs: C9D7C2, O00555, O35505, O42398, O46669, O55017, O57483, O60840, O73700, O73705, O73706, O73707, P07293, P15381, P22002, P22316, P27732, P27884, P35500, P54282, P56698, P56699, P91645, P97445, Q00975, Q01668, Q01815, Q02294, Q02343, Q02485, Q02789, Q05152, Q07652, Q13698, Q13936, Q15878, Q24270, Q25452, Q61290, Q99244

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
CACNA1D	“up-regulates quantity”	calcium(2+)	relocalization
CACNA1D	up-regulates	Excitatory_synaptic_transmission
RIMS2	“up-regulates activity”	CACNA1D	binding
RIMS3	“up-regulates activity”	CACNA1D	binding
RIMS1	“up-regulates activity”	CACNA1D	binding
DCC	“up-regulates activity”	CACNA1D
PRKACA	“up-regulates activity”	CACNA1D	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 78 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
Dopamine Neurotransmitter Release Cycle	5	49.6×	2e-06
Assembly and cell surface presentation of NMDA receptors	9	45.7×	2e-11
Neurexins and neuroligins	10	39.4×	9e-12
Protein-protein interactions at synapses	7	37.2×	4e-08
Activation of NMDA receptors and postsynaptic events	5	18.4×	1e-04
Neurotransmitter receptors and postsynaptic signal transmission	5	10.0×	1e-03
Transmission across Chemical Synapses	5	7.6×	4e-03
RHO GTPase cycle	6	7.2×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	8	61.2×	2e-10
protein localization to synapse	5	50.4×	5e-06
receptor clustering	5	41.1×	1e-05
regulation of postsynaptic membrane neurotransmitter receptor levels	5	32.6×	3e-05
protein-containing complex assembly	9	13.5×	3e-06
cell-cell adhesion	8	10.7×	5e-05
protein localization to plasma membrane	5	7.2×	7e-03
actin cytoskeleton organization	6	6.2×	5e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 5 cancer types — BRCA, CCRCC, HCC, SARCNOS, STAD.

Clinical variants and AI predictions

ClinVar

2655 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	12
Uncertain significance	1287
Likely benign	1103
Benign	127

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
1710231	NM_001128840.3(CACNA1D):c.2222-1G>A	Pathogenic
2250129	NM_001128840.3(CACNA1D):c.3964C>T (p.Arg1322Ter)	Pathogenic
2443440	NM_001128840.3(CACNA1D):c.1856G>C (p.Arg619Pro)	Pathogenic
2580195	NM_001128840.3(CACNA1D):c.776T>A (p.Val259Asp)	Pathogenic
2691773	NM_001128840.3(CACNA1D):c.2239T>C (p.Phe747Leu)	Pathogenic
39709	NM_000720.4(CACNA1D):c.1208_1209insGGG (p.Gly403dup)	Pathogenic
66072	NM_000720.4(CACNA1D):c.1208G>A (p.Gly403Asp)	Pathogenic
1188651	NM_001128840.3(CACNA1D):c.2969G>A (p.Arg990His)	Likely pathogenic
2446012	NM_001128840.3(CACNA1D):c.1201G>C (p.Val401Leu)	Likely pathogenic
3337877	NM_001128840.3(CACNA1D):c.2249T>G (p.Ile750Ser)	Likely pathogenic
3341037	NM_001128840.3(CACNA1D):c.1634A>G (p.Tyr545Cys)	Likely pathogenic
3376718	NM_001128840.3(CACNA1D):c.2907del (p.Phe970fs)	Likely pathogenic
421144	NM_001128840.3(CACNA1D):c.2245G>A (p.Ala749Thr)	Likely pathogenic
4686615	NM_001128840.3(CACNA1D):c.2241C>G (p.Phe747Leu)	Likely pathogenic
4795454	NM_001128840.3(CACNA1D):c.3323A>G (p.Tyr1108Cys)	Likely pathogenic
4796565	NM_001128840.3(CACNA1D):c.698G>A (p.Gly233Asp)	Likely pathogenic
521538	NM_001128840.3(CACNA1D):c.4362+1G>C	Likely pathogenic
801978	NM_001128840.3(CACNA1D):c.2248A>T (p.Ile750Phe)	Likely pathogenic
91930	NM_001128840.3(CACNA1D):c.1207G>C (p.Gly403Arg)	Likely pathogenic

SpliceAI

10975 predictions. Top by Δscore:

Variant	Effect	Δscore
3:53342135:TATAC:T	donor_loss	1.0000
3:53342136:ATAC:A	donor_loss	1.0000
3:53342137:TACTC:T	donor_loss	1.0000
3:53342138:ACTCA:A	donor_loss	1.0000
3:53342139:C:CA	donor_loss	1.0000
3:53342140:TCACA:T	donor_loss	1.0000
3:53342141:C:CT	donor_loss	1.0000
3:53342142:A:AC	donor_gain	1.0000
3:53342142:A:T	donor_loss	1.0000
3:53342142:ACAG:A	donor_gain	1.0000
3:53342143:C:CT	donor_gain	1.0000
3:53342143:CA:C	donor_gain	1.0000
3:53342143:CAG:C	donor_gain	1.0000
3:53342143:CAGC:C	donor_gain	1.0000
3:53342143:CAGCT:C	donor_gain	1.0000
3:53342271:CCT:C	acceptor_gain	1.0000
3:53342278:T:C	acceptor_gain	1.0000
3:53342278:T:TC	acceptor_gain	1.0000
3:53342279:T:C	acceptor_gain	1.0000
3:53342279:T:TC	acceptor_gain	1.0000
3:53342282:A:AC	acceptor_gain	1.0000
3:53342282:A:C	acceptor_gain	1.0000
3:53344896:ACTT:A	donor_loss	1.0000
3:53344898:TTA:T	donor_loss	1.0000
3:53344899:TA:T	donor_loss	1.0000
3:53344900:A:AC	donor_gain	1.0000
3:53344900:AC:A	donor_gain	1.0000
3:53344901:C:A	donor_loss	1.0000
3:53344901:C:CC	donor_gain	1.0000
3:53344901:CC:C	donor_gain	1.0000

AlphaMissense

14383 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:53497439:T:C	C119R	1.000
3:53501654:T:A	N139K	1.000
3:53501654:T:G	N139K	1.000
3:53501655:T:C	C140R	1.000
3:53501657:T:G	C140W	1.000
3:53650801:T:C	L169P	1.000
3:53650809:T:C	F172L	1.000
3:53650810:T:C	F172S	1.000
3:53650811:T:A	F172L	1.000
3:53650811:T:G	F172L	1.000
3:53650846:G:A	G184E	1.000
3:53650884:T:A	W197R	1.000
3:53650884:T:C	W197R	1.000
3:53650886:G:C	W197C	1.000
3:53650886:G:T	W197C	1.000
3:53650896:G:C	D201H	1.000
3:53650897:A:C	D201A	1.000
3:53650897:A:G	D201G	1.000
3:53650897:A:T	D201V	1.000
3:53650906:T:A	I204K	1.000
3:53650906:T:G	I204R	1.000
3:53650917:G:A	G208R	1.000
3:53650917:G:C	G208R	1.000
3:53650918:G:A	G208E	1.000
3:53660140:A:C	S211R	1.000
3:53660142:T:A	S211R	1.000
3:53660142:T:G	S211R	1.000
3:53660225:T:A	L239H	1.000
3:53660243:T:C	L245S	1.000
3:53660249:C:A	P247Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000005847 (3:53698004 G>A,T), RS1000006378 (3:53533391 T>A,G), RS1000011616 (3:53737027 G>A), RS1000034536 (3:53571484 A>G), RS1000034885 (3:53776118 C>A,T), RS1000044804 (3:53741530 C>A,T), RS1000051265 (3:53530180 C>T), RS1000074564 (3:53651937 G>T), RS1000084853 (3:53579612 A>C,G), RS1000099241 (3:53654439 T>A), RS1000109647 (3:53731057 C>T), RS1000120247 (3:53529347 G>A,T), RS1000124224 (3:53589608 C>T), RS1000124281 (3:53592225 G>T), RS1000129720 (3:53661681 C>T)

Disease associations

OMIM: gene MIM:114206 | disease phenotypes: MIM:615474, MIM:614896, MIM:619681, MIM:192350, MIM:156000, MIM:619714, MIM:192500, MIM:203780, MIM:610805

GenCC curated gene-disease

Disease	Classification	Inheritance
aldosterone-producing adenoma with seizures and neurological abnormalities	Definitive	Autosomal dominant
sinoatrial node dysfunction and deafness	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
sinoatrial node dysfunction and deafness	Moderate	AR
complex neurodevelopmental disorder	Definitive	AD

Mondo (15): aldosterone-producing adenoma with seizures and neurological abnormalities (MONDO:0014200), hearing loss disorder (MONDO:0005365), sinoatrial node dysfunction and deafness (MONDO:0013960), dystonia, early-onset, and/or spastic paraplegia (MONDO:0859215), long QT syndrome (MONDO:0002442), VACTERL/vater association (MONDO:0008642), prostate cancer (MONDO:0008315), Meniere disease (MONDO:0007972), autism spectrum disorder (MONDO:0005258), intellectual disability (MONDO:0001071), congenital disorder of glycosylation, type Iw, autosomal dominant (MONDO:0859223), skeletal dysplasia (MONDO:0018230), familial long QT syndrome (MONDO:0019171), autosomal recessive Alport syndrome (MONDO:0008762), congenital anomaly of kidney and urinary tract (MONDO:0019719)

Orphanet (13): Primary hyperaldosteronism-seizures-neurological abnormalities syndrome (Orphanet:369929), Sinoatrial node dysfunction and deafness (Orphanet:324321), VACTERL/VATER association (Orphanet:887), Familial prostate cancer (Orphanet:1331), Primary bone dysplasia (Orphanet:364526), Romano-Ward syndrome (Orphanet:101016), Congenital long QT syndrome (Orphanet:768), Alport syndrome (Orphanet:63), Autosomal recessive Alport syndrome (Orphanet:88919), Renal or urinary tract malformation (Orphanet:93545), NON RARE IN EUROPE: Menière disease (Orphanet:45360), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000360	Tinnitus
HP:0000365	Hearing impairment
HP:0000421	Epistaxis
HP:0000787	Nephrolithiasis
HP:0000822	Hypertension
HP:0000859	Increased circulating aldosterone concentration
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001258	Spastic paraplegia
HP:0001263	Global developmental delay
HP:0001279	Syncope
HP:0001629	Ventricular septal defect
HP:0001655	Patent foramen ovale
HP:0001662	Bradycardia
HP:0001712	Left ventricular hypertrophy
HP:0001714	Ventricular hypertrophy
HP:0001959	Polydipsia
HP:0002018	Nausea
HP:0002069	Bilateral tonic-clonic seizure
HP:0002092	Pulmonary arterial hypertension
HP:0002170	Intracranial hemorrhage
HP:0002305	Athetosis
HP:0002315	Headache
HP:0002384	Focal impaired awareness seizure
HP:0002510	Spastic tetraplegia
HP:0002900	Hypokalemia
HP:0003351	Decreased circulating renin concentration

GWAS associations

45 associations (top):

Study	Trait	p-value
GCST001208_13	Insulin resistance/response	3.000000e-06
GCST001208_4	Insulin resistance/response	5.000000e-06
GCST001858_9	Refractive error	2.000000e-08
GCST002115_6	Axial length	8.000000e-06
GCST002542_5	Electrocardiographic traits	4.000000e-07
GCST002627_1	Hypertension	4.000000e-06
GCST002630_1	Systolic blood pressure	5.000000e-08
GCST002631_5	Diastolic blood pressure	4.000000e-12
GCST002783_182	Body mass index	5.000000e-06
GCST002783_335	Body mass index	2.000000e-06
GCST003173_1	Visceral adipose tissue/subcutaneous adipose tissue ratio	6.000000e-07
GCST003818_44	Resting heart rate	4.000000e-09
GCST005024_23	Pursuit maintenance gain	8.000000e-06
GCST005566_5	Insomnia	5.000000e-07
GCST005978_8	Diastolic blood pressure	1.000000e-12
GCST005979_1	Systolic blood pressure	3.000000e-13
GCST006010_7	Mean arterial pressure	3.000000e-15
GCST006291_56	Spherical equivalent or myopia (age of diagnosis)	6.000000e-11
GCST007267_255	Systolic blood pressure	9.000000e-19
GCST007268_12	Diastolic blood pressure	1.000000e-13
GCST007325_225	General risk tolerance (MTAG)	4.000000e-09
GCST007335_8	Age at first sexual intercourse	9.000000e-09
GCST007703_124	Systolic blood pressure	2.000000e-14
GCST007703_45	Systolic blood pressure	2.000000e-14
GCST007703_76	Systolic blood pressure	1.000000e-07
GCST007704_101	Diastolic blood pressure	7.000000e-14
GCST007704_35	Diastolic blood pressure	5.000000e-08
GCST007704_56	Diastolic blood pressure	6.000000e-13
GCST007705_16	Pulse pressure	8.000000e-06
GCST007706_116	Mean arterial pressure	1.000000e-15

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0005318	axial length measurement
EFO:0004462	PR interval
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0004340	body mass index
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0008433	pursuit maintenance gain measurement
EFO:0006340	mean arterial pressure
EFO:0004847	age at onset
EFO:0008579	risk-taking behaviour
EFO:0009749	age at first sexual intercourse measurement
EFO:0005763	pulse pressure measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004980	appendicular lean mass

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D008575	Meniere Disease	C09.218.568.217.500
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C566906	Cakut (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2095229 (PROTEIN FAMILY), CHEMBL2363032 (PROTEIN COMPLEX GROUP), CHEMBL4138 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

48 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 646,199 (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
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1107	HALOFANTRINE	4	9,722
CHEMBL1108	DROPERIDOL	4	16,888
CHEMBL114	SAQUINAVIR	4	39,899
CHEMBL1175	DULOXETINE	4	28,527
CHEMBL12	DIAZEPAM	4	92,281
CHEMBL12713	SERTINDOLE	4	8,984
CHEMBL1294	QUINIDINE	4	71,943
CHEMBL141	LAMIVUDINE	4	12,250
CHEMBL1423	PIMOZIDE	4	17,310
CHEMBL16	PHENYTOIN	4	53,375
CHEMBL17157	TERFENADINE	4	25,393
CHEMBL1729	CISAPRIDE	4	14,365
CHEMBL1734	SOLIFENACIN	4	296
CHEMBL193	NIFEDIPINE	4	74,353
CHEMBL23	DILTIAZEM	4	54,676
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL296419	ASTEMIZOLE	4	21,577
CHEMBL363295	TERODILINE	4	5,064
CHEMBL42	CLOZAPINE	4
CHEMBL45816	MIBEFRADIL	4
CHEMBL473	DOFETILIDE	4
CHEMBL479	THIORIDAZINE	4
CHEMBL490	PAROXETINE	4
CHEMBL502	DONEPEZIL	4
CHEMBL533	IBUTILIDE	4
CHEMBL535	SUNITINIB	4
CHEMBL54	HALOPERIDOL	4
CHEMBL5416410	DASATINIB	4

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs312481	CACNA1D		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: vgic — Voltage-gated calcium channels (Ca_V)

Most potent curated ligand interactions (13 total), top 13:

Ligand	Action	Affinity	Parameter
3H-isradipine	Gating inhibitor	9.4	pKd
isradipine	Gating inhibitor	9.3	pIC50
azidopine	Inhibition	9.2	pIC50
nitrendipine	Inhibition	8.4	pIC50
FPL64176	Activator	7.8	pEC50
(-)-(S)-BayK8644	Activator	7.76	pEC50
nifedipine	Antagonist	7.7	pIC50
amlodipine	Inhibition	7.2	pIC50
nisoldipine	Gating inhibitor	7.0	pIC50
nimodipine	Antagonist	6.6	pIC50
cinnarizine	Pore blocker	5.82	pIC50
verapamil	Antagonist	3.7	pIC50
diltiazem	Channel blocker	3.5	pIC50

ChEMBL bioactivities

202 potent at pChembl≥5 of 271 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL286157
10.89	IC50	0.013	nM	CHEMBL317044
10.82	IC50	0.015	nM	CHEMBL441428
10.77	IC50	0.017	nM	CHEMBL286598
10.66	IC50	0.022	nM	CHEMBL37402
10.57	IC50	0.027	nM	CHEMBL103806
10.52	IC50	0.03	nM	CHEMBL37899
10.48	IC50	0.033	nM	CHEMBL204616
10.35	IC50	0.045	nM	CHEMBL35368
10.34	IC50	0.046	nM	CHEMBL1099207
10.30	IC50	0.05	nM	CHEMBL285868
9.85	IC50	0.14	nM	CHEMBL321999
9.82	IC50	0.15	nM	NITRENDIPINE
9.60	IC50	0.25	nM	CHEMBL105444
9.46	IC50	0.35	nM	NITRENDIPINE
9.41	IC50	0.39	nM	CHEMBL35123
9.00	IC50	1	nM	NITRENDIPINE
8.82	IC50	1.5	nM	CHEMBL329897
8.82	IC50	1.5	nM	CHEMBL3891844
8.82	IC50	1.5	nM	CHEMBL319033
8.77	IC50	1.7	nM	CHEMBL89260
8.72	IC50	1.9	nM	CHEMBL3890624
8.70	IC50	2	nM	CHEMBL2092901
8.64	IC50	2.3	nM	CHEMBL102498
8.62	IC50	2.4	nM	CHEMBL3973392
8.59	IC50	2.6	nM	CHEMBL89049
8.57	IC50	2.7	nM	CHEMBL84906
8.57	IC50	2.7	nM	CHEMBL3891844
8.55	IC50	2.8	nM	CHEMBL318521
8.52	IC50	3	nM	CHEMBL3919024
8.51	IC50	3.1	nM	CHEMBL86415
8.51	IC50	3.1	nM	CHEMBL3919898
8.44	IC50	3.6	nM	CHEMBL89904
8.40	IC50	4	nM	CHEMBL3392282
8.35	IC50	4.5	nM	CHEMBL3965812
8.28	IC50	5.2	nM	CHEMBL89175
8.27	Ki	5.4	nM	GALLOPAMIL
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
8.00	IC50	10	nM	NIFEDIPINE
7.96	IC50	11	nM	CHEMBL315125
7.96	IC50	11	nM	GALLOPAMIL

PubChem BioAssay actives

150 with measured affinity, of 847 total; 50 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
3-O-methyl 5-O-(2-methylpropyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45613: Inhibition of [3H]nitrendipine binding to guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
5-O-[6-[5-ethoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carbonyl]oxyhexyl] 3-O-ethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
5-O-[10-[5-ethoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carbonyl]oxydecyl] 3-O-ethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
5-O-[8-[5-ethoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carbonyl]oxyoctyl] 3-O-ethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
3-O-ethyl 5-O-octyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
diethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
5-O-[2-[2,6-dimethyl-4-(3-nitrophenyl)-5-propan-2-yloxycarbonyl-1,4-dihydropyridine-3-carbonyl]oxyethyl] 3-O-ethyl 2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
5-O-[4-[5-ethoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carbonyl]oxybutyl] 3-O-ethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
3-O-methyl 5-O-(2-methylpropyl) 4-(3-cyanophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate	45613: Inhibition of [3H]nitrendipine binding to guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
3-O-methyl 5-O-(2-methylpropyl) 2,6-dimethyl-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3,5-dicarboxylate	45613: Inhibition of [3H]nitrendipine binding to guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
Nisoldipine	45613: Inhibition of [3H]nitrendipine binding to guinea pig ileal longitudinal smooth muscle	ic50	<0.0001	uM
5-O-[12-[5-ethoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carbonyl]oxydodecyl] 3-O-ethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	0.0001	uM
3-O-methyl 5-O-(2-methylpropyl) 2,6-dimethyl-4-[3-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3,5-dicarboxylate	45613: Inhibition of [3H]nitrendipine binding to guinea pig ileal longitudinal smooth muscle	ic50	0.0001	uM
5-O-ethyl 3-O-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	0.0001	uM
3-O-methyl 5-O-(2-methylpropyl) 2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate	45613: Inhibition of [3H]nitrendipine binding to guinea pig ileal longitudinal smooth muscle	ic50	0.0003	uM
5-O-[2-[5-ethoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carbonyl]oxyethyl] 3-O-ethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45611: Inhibition of [3H]nitrendipine binding to L-type calcium channel of guinea pig ileal longitudinal smooth muscle	ic50	0.0004	uM
diethyl 4-(2,3-dichlorophenyl)-6-methyl-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0015	uM
3-O-methyl 5-O-(2-methylpropyl) 4-(4-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate	45613: Inhibition of [3H]nitrendipine binding to guinea pig ileal longitudinal smooth muscle	ic50	0.0015	uM
3-O-ethyl 5-O-propan-2-yl 6-methyl-4-(3-nitrophenyl)-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0017	uM
3-O-ethyl 5-O-propan-2-yl (4R)-6-methyl-4-(3-nitrophenyl)-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	45769: In vitro vasorelaxant activity (calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0020	uM
3-O-methyl 5-O-(2-methylpropyl) 4-(3-methoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate	45613: Inhibition of [3H]nitrendipine binding to guinea pig ileal longitudinal smooth muscle	ic50	0.0023	uM
3-O-ethyl 5-O-propan-2-yl 6-methyl-4-(3-nitrophenyl)-2-oxo-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0026	uM
diethyl 4-(2-chloro-3-nitrophenyl)-6-methyl-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0027	uM
3-O-methyl 5-O-(2-methylpropyl) 4-(4-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate	45613: Inhibition of [3H]nitrendipine binding to guinea pig ileal longitudinal smooth muscle	ic50	0.0028	uM
diethyl 6-methyl-4-(2-nitrophenyl)-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0031	uM
5-O-ethyl 3-O-methyl 6-methyl-4-(3-nitrophenyl)-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0036	uM
diethyl 2-ethylsulfanyl-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45769: In vitro vasorelaxant activity (calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0040	uM
ethyl 3-(benzenesulfonyl)-6-methyl-4-(3-nitrophenyl)-2-sulfanylidene-1,4-dihydropyrimidine-5-carboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0052	uM
5-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]-2-propan-2-yl-2-(3,4,5-trimethoxyphenyl)pentanenitrile	751841: Binding affinity to L-Ca2+ channel verapamil site (unknown origin) by radioligand displacement assay	ki	0.0054	uM
Nifedipine	1207754: Inhibition of Cav1.2 current measured using QPatch automatic path clamp system in CHO cells expressing Cav1.2, beta-2 and alpha-2/delta-1 subunits	ic50	0.0100	uM
ethyl 3-(4-methoxybenzoyl)-6-methyl-4-(3-nitrophenyl)-2-sulfanylidene-1,4-dihydropyrimidine-5-carboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0110	uM
5-O-ethyl 3-O-propan-2-yl 6-methyl-4-(3-nitrophenyl)-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0140	uM
diethyl 6-methyl-4-(3-nitrophenyl)-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	45769: In vitro vasorelaxant activity (calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0170	uM
diethyl 4-(2-chlorophenyl)-6-methyl-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0170	uM
diethyl 2,6-dimethyl-4-(5-methyl-3-phenyl-1,2-oxazol-4-yl)-1,4-dihydropyridine-3,5-dicarboxylate	45622: Inhibition of [3H]PN-200110 binding to Calcium channel in guinea pig ileum membrane	ki	0.0217	uM
diethyl 6-methyl-2-sulfanylidene-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyrimidine-3,5-dicarboxylate	45769: In vitro vasorelaxant activity (calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0260	uM
diethyl 2-ethoxy-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate	45769: In vitro vasorelaxant activity (calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0260	uM
diethyl 4-deuterio-4-(3,5-dimethyl-1,2-oxazol-4-yl)-2,6-dimethyl-1H-pyridine-3,5-dicarboxylate	45623: Inhibition of [3H]PN-200110 binding to Calcium channel in guinea pig ileum membrane.	ki	0.0299	uM
diethyl 4-(3,5-dimethyl-1,2-oxazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate	45622: Inhibition of [3H]PN-200110 binding to Calcium channel in guinea pig ileum membrane	ki	0.0328	uM
diethyl 4-[3-(4-bromophenyl)-5-methyl-1,2-oxazol-4-yl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate	1466481: Displacement of [3H]PN-200110 from voltage-dependent L-type calcium channel (unknown origin) by scintillation counting method	ic50	0.0360	uM
ethyl 6-methyl-4-(3-nitrophenyl)-3-propyl-2-sulfanylidene-1,4-dihydropyrimidine-5-carboxylate	45769: In vitro vasorelaxant activity (calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0500	uM
diethyl 4-(5-ethyl-3-methyl-1,2-oxazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate	45622: Inhibition of [3H]PN-200110 binding to Calcium channel in guinea pig ileum membrane	ki	0.0625	uM
diethyl 2,6-dimethyl-4-(5-pentyl-3-phenyl-1,2-oxazol-4-yl)-1,4-dihydropyridine-3,5-dicarboxylate	45622: Inhibition of [3H]PN-200110 binding to Calcium channel in guinea pig ileum membrane	ki	0.0784	uM
diethyl 4-(3-chlorophenyl)-6-methyl-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.0880	uM
3-O-ethyl 5-O-methyl 6-methyl-4-(3-nitrophenyl)-2-sulfanylidene-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.1000	uM
3-O-ethyl 5-O-[[1-(2-phenylethyl)triazol-4-yl]methyl] 4-[3-(4-bromophenyl)-5-methyl-1,2-oxazol-4-yl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate	1466481: Displacement of [3H]PN-200110 from voltage-dependent L-type calcium channel (unknown origin) by scintillation counting method	ic50	0.1270	uM
(3R)-1,1-dibutyl-3-(5-phenyl-1H-imidazol-2-yl)-2,3,4,9-tetrahydropyrido[3,4-b]indole	676783: Binding affinity to L-type calcium channel	ic50	0.1280	uM
ethyl 6-methyl-2-methylsulfanyl-4-(3-nitrophenyl)-1,4-dihydropyrimidine-5-carboxylate	45769: In vitro vasorelaxant activity (calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.1300	uM
diethyl 6-methyl-4-(3-nitrophenyl)-2-oxo-1,4-dihydropyrimidine-3,5-dicarboxylate	217468: In vitro vasorelaxant activity (voltage-gated calcium channel blocking activity) was determined with potassium-depolarized rabbit thoracic aorta	ic50	0.1400	uM
N-[4,6-dimethoxy-2-(3-morpholin-4-ylpropylamino)pyrimidin-5-yl]-5-[(3,3,6-trimethyl-1,2-dihydroinden-5-yl)oxy]furan-2-carboxamide	265813: Binding affinity to L type calcium channel	ki	0.1450	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	4
Valproic Acid	affects methylation, decreases expression, increases expression, increases methylation	3
sodium arsenite	affects expression, increases expression	2
Diethylhexyl Phthalate	decreases expression, increases abundance, increases methylation	2
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases methylation, decreases expression	2
sotorasib	affects cotreatment, increases expression	1
aminomethylphosphonic acid (AMPA)	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
deoxynivalenol	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	decreases methylation	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
tebuconazole	decreases expression	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Glyphosate	decreases expression	1
Air Pollutants	decreases expression	1
Cadmium	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Cocaine	affects response to substance	1

ChEMBL screening assays

233 unique, capped per target: 145 binding, 81 functional, 5 toxicity, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003715	Functional	Antagonist activity at voltage-dependent L-type calcium channel in human SH-SY5Y cells assessed as inhibition of KCl-induced increase in cytosolic calcium concentration at 0.3 uM pretreated for 10 mins before KCl challenge relative to contr	Tacripyrines, the first tacrine-dihydropyridine hybrids, as multitarget-directed ligands for the treatment of Alzheimer’s disease. — J Med Chem
CHEMBL1059038	Binding	Inhibition of human L-type calcium channel at 100 uM	Spirocyclic delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-3-hydroxy-4-(spiro[chromene-2,4’-piperidine]-4-yl) benzamide (ADL5747). — J Med Chem
CHEMBL4236597	ADMET	Inhibition of L-type calcium channel (unknown origin) by patch clamp assay	Discovery of TRPM8 Antagonist ( S)-6-(((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)nicotinic Acid (AMG 333), a Clinical Candidate for the Treatment of Migraine. — J Med Chem

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B8CB	Abcam HCT 116 CACNA1D KO	Cancer cell line	Male
CVCL_B9EH	Abcam A-549 CACNA1D KO	Cancer cell line	Male
CVCL_C0HB	IBKMOLi002-A	Induced pluripotent stem cell	Female
CVCL_D7L8	Ubigene A-549 CACNA1D KO	Cancer cell line	Male
CVCL_QX48	MCCI0001i-HCM	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
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NCT07304024	PHASE1/PHASE2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound
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