Timothy syndrome

Summary

Timothy syndrome (MONDO:0010979) is a disease caused by CACNA1C (GenCC Definitive), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CACNA1C (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 215
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		56	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Timothy syndrome
Mondo ID	MONDO:0010979
MeSH	C536962
OMIM	601005
Orphanet	65283
DOID	DOID:0060173
NCIT	C142894
UMLS	C1832916
MedGen	331395
GARD	0009294
NORD	1772
Is cancer (heuristic)	no

Also known as: long QT syndrome-syndactyly syndrome · LQT8 · TIMOTHY syndrome · Timothy syndrome · TS

Data availability: 215 ClinVar variants · 5 GenCC gene-disease records · 12 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › Timothy syndrome

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

Subtypes (2): Timothy syndrome, classic type, Timothy syndrome, atypical type

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

215 retrieved; paginated sample, class counts are floors:

76 conflicting classifications of pathogenicity, 66 uncertain significance, 29 benign, 11 benign/likely benign, 10 likely pathogenic, 9 likely benign, 9 pathogenic, 5 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1164022	NM_000719.7(CACNA1C):c.4087G>T (p.Val1363Leu)	CACNA1C	Pathogenic	no assertion criteria provided
1309258	NM_000719.7(CACNA1C):c.3500T>C (p.Val1167Ala)	CACNA1C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
155775	NM_001167623.2(CACNA1C):c.1204G>A (p.Gly402Ser)	CACNA1C	Pathogenic	criteria provided, multiple submitters, no conflicts
1685597	NM_000719.7(CACNA1C):c.1853T>G (p.Val618Gly)	CACNA1C	Pathogenic	criteria provided, single submitter
17632	NM_000719.7(CACNA1C):c.1216G>A (p.Gly406Arg)	CACNA1C	Pathogenic	criteria provided, multiple submitters, no conflicts
17633	NM_000719.7(CACNA1C):c.1204G>A (p.Gly402Ser)	CACNA1C	Pathogenic	criteria provided, multiple submitters, no conflicts
190633	NM_001167623.2(CACNA1C):c.1216G>A (p.Gly406Arg)	CACNA1C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
190634	NM_001167623.2(CACNA1C):c.1216G>C (p.Gly406Arg)	CACNA1C	Pathogenic	criteria provided, multiple submitters, no conflicts
190642	NM_000719.7(CACNA1C):c.1552C>T (p.Arg518Cys)	CACNA1C	Pathogenic	criteria provided, multiple submitters, no conflicts
208682	NM_000719.7(CACNA1C):c.3497T>C (p.Ile1166Thr)	CACNA1C	Pathogenic	criteria provided, multiple submitters, no conflicts
2626971	NM_000719.7(CACNA1C):c.5884C>T (p.Arg1962Ter)	CACNA1C	Pathogenic	criteria provided, single submitter
3382740	NM_000719.7(CACNA1C):c.1832T>C (p.Met611Thr)	CACNA1C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
372313	NM_000719.7(CACNA1C):c.1553G>A (p.Arg518His)	CACNA1C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
67554	NM_000719.7(CACNA1C):c.3343G>A (p.Glu1115Lys)	CACNA1C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1334090	NM_000719.7(CACNA1C):c.2451del (p.Ala818fs)	CACNA1C	Likely pathogenic	criteria provided, single submitter
1707563	NM_000719.7(CACNA1C):c.1928C>T (p.Ser643Phe)	CACNA1C	Likely pathogenic	criteria provided, single submitter
196966	NM_000719.7(CACNA1C):c.4418C>G (p.Ala1473Gly)	CACNA1C	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3066281	NM_000719.7(CACNA1C):c.788A>T (p.Lys263Met)	CACNA1C	Likely pathogenic	criteria provided, single submitter
3233417	NM_000719.7(CACNA1C):c.1552C>A (p.Arg518Ser)	CACNA1C	Likely pathogenic	no assertion criteria provided
3382973	NM_000719.7(CACNA1C):c.3487G>A (p.Gly1163Ser)	CACNA1C	Likely pathogenic	criteria provided, single submitter
3392514	NM_000719.7(CACNA1C):c.794T>A (p.Met265Lys)	CACNA1C	Likely pathogenic	criteria provided, single submitter
521136	NM_000719.7(CACNA1C):c.1609A>G (p.Asn537Asp)	CACNA1C	Likely pathogenic	criteria provided, multiple submitters, no conflicts
802809	NM_000719.7(CACNA1C):c.1113G>A (p.Trp371Ter)	CACNA1C	Likely pathogenic	criteria provided, single submitter
973262	NM_000719.7(CACNA1C):c.722T>C (p.Val241Ala)	CACNA1C	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1003227	NM_000719.7(CACNA1C):c.6091G>A (p.Gly2031Ser)	CACNA1C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1015055	NM_000719.7(CACNA1C):c.82G>A (p.Ala28Thr)	CACNA1C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029939	NM_000719.7(CACNA1C):c.1917C>T (p.Asn639=)	CACNA1C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1053141	NM_000719.7(CACNA1C):c.1026C>T (p.Gly342=)	CACNA1C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1197616	NM_000719.7(CACNA1C):c.3061T>C (p.Cys1021Arg)	CACNA1C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1342903	NM_000719.7(CACNA1C):c.583T>C (p.Trp195Arg)	CACNA1C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CACNA1C	Definitive	Autosomal dominant	Timothy syndrome	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CACNA1C	Orphanet:101016	Romano-Ward syndrome
CACNA1C	Orphanet:130	Brugada syndrome
CACNA1C	Orphanet:528084	Non-specific syndromic intellectual disability
CACNA1C	Orphanet:595098	Timothy syndrome type 1
CACNA1C	Orphanet:595105	Timothy syndrome type 2
CACNA1C	Orphanet:595109	Atypical Timothy syndrome

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CACNA1C	HGNC:1390	ENSG00000151067	Q13936	Voltage-dependent L-type calcium channel subunit alpha-1C	gencc,clinvar
ITFG2-AS1	HGNC:53128	ENSG00000258325		ITFG2 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CACNA1C	Voltage-dependent L-type calcium channel subunit alpha-1C	Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Ion channel	1	55.8×	0.036
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CACNA1C	Ion channel	yes		VDCCAlpha1, VDCC_L_a1su, VDCC_L_a1csu
ITFG2-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
muscle layer of sigmoid colon	1
right coronary artery	1
left testis	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CACNA1C	134	broad	marker	apex of heart, right coronary artery, muscle layer of sigmoid colon
ITFG2-AS1	131	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CACNA1C	3,145
ITFG2-AS1	0

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CACNA1C	Q13936	33

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Phase 2 - plateau phase	1	761.3×	0.010	CACNA1C
Adrenaline,noradrenaline inhibits insulin secretion	1	393.8×	0.010	CACNA1C
Phase 0 - rapid depolarisation	1	346.1×	0.010	CACNA1C
NCAM signaling for neurite out-growth	1	271.9×	0.010	CACNA1C
NCAM1 interactions	1	248.3×	0.010	CACNA1C
Regulation of insulin secretion	1	219.6×	0.010	CACNA1C
Integration of energy metabolism	1	175.7×	0.011	CACNA1C
Cardiac conduction	1	108.8×	0.015	CACNA1C
Muscle contraction	1	77.2×	0.019	CACNA1C
Axon guidance	1	45.1×	0.028	CACNA1C
Nervous system development	1	42.9×	0.028	CACNA1C
Developmental Biology	1	14.5×	0.075	CACNA1C
Metabolism	1	11.6×	0.086	CACNA1C

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
calcium ion transmembrane transport via high voltage-gated calcium channel	1	5617.3×	0.001	CACNA1C
membrane depolarization during atrial cardiac muscle cell action potential	1	5617.3×	0.001	CACNA1C
immune system development	1	4213.0×	0.001	CACNA1C
positive regulation of adenylate cyclase activity	1	3370.4×	0.001	CACNA1C
membrane depolarization during AV node cell action potential	1	3370.4×	0.001	CACNA1C
positive regulation of muscle contraction	1	2407.4×	0.001	CACNA1C
cardiac conduction	1	1685.2×	0.001	CACNA1C
membrane depolarization during cardiac muscle cell action potential	1	1404.3×	0.001	CACNA1C
cell communication by electrical coupling involved in cardiac conduction	1	1404.3×	0.001	CACNA1C
regulation of ventricular cardiac muscle cell action potential	1	1404.3×	0.001	CACNA1C
calcium ion transport into cytosol	1	1203.7×	0.002	CACNA1C
cardiac muscle cell action potential involved in contraction	1	702.2×	0.002	CACNA1C
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	1	674.1×	0.002	CACNA1C
calcium ion import across plasma membrane	1	543.6×	0.003	CACNA1C
embryonic forelimb morphogenesis	1	495.6×	0.003	CACNA1C
regulation of heart rate by cardiac conduction	1	374.5×	0.003	CACNA1C
camera-type eye development	1	358.6×	0.003	CACNA1C
calcium ion transmembrane transport	1	210.7×	0.005	CACNA1C
positive regulation of cytosolic calcium ion concentration	1	117.0×	0.009	CACNA1C
heart development	1	78.8×	0.013	CACNA1C

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CACNA1C	REMIFENTANIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CACNA1C	85	4
ITFG2-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
REMIFENTANIL	4	CACNA1C
BEPRIDIL	4	CACNA1C
CLOTRIMAZOLE	4	CACNA1C
PROPIVERINE	4	CACNA1C
DIBUCAINE	4	CACNA1C
IMIPRAMINE	4	CACNA1C
DULOXETINE	4	CACNA1C
QUINIDINE	4	CACNA1C
ESTRADIOL	4	CACNA1C
TOLTERODINE	4	CACNA1C
PIMOZIDE	4	CACNA1C
NIMODIPINE	4	CACNA1C
NICARDIPINE	4	CACNA1C
AMLODIPINE	4	CACNA1C
VARDENAFIL	4	CACNA1C
CLEMASTINE	4	CACNA1C
ISRADIPINE	4	CACNA1C
TERFENADINE	4	CACNA1C
NISOLDIPINE	4	CACNA1C
SOLIFENACIN	4	CACNA1C
PINAVERIUM	4	CACNA1C
SILDENAFIL	4	CACNA1C
NIFEDIPINE	4	CACNA1C
XANOMELINE	4	CACNA1C
DILTIAZEM	4	CACNA1C
PRENYLAMINE	4	CACNA1C
OLICERIDINE	4	CACNA1C
PROPRANOLOL	4	CACNA1C
ALVIMOPAN	4	CACNA1C
ASTEMIZOLE	4	CACNA1C

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CACNA1C	575	Binding:319, Functional:211, Toxicity:26, ADMET:19

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CACNA1C	575

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
REMIFENTANIL	4	CACNA1C
BEPRIDIL	4	CACNA1C
CLOTRIMAZOLE	4	CACNA1C
PROPIVERINE	4	CACNA1C
DIBUCAINE	4	CACNA1C
IMIPRAMINE	4	CACNA1C
DULOXETINE	4	CACNA1C
QUINIDINE	4	CACNA1C
ESTRADIOL	4	CACNA1C
TOLTERODINE	4	CACNA1C
PIMOZIDE	4	CACNA1C
NIMODIPINE	4	CACNA1C
NICARDIPINE	4	CACNA1C
AMLODIPINE	4	CACNA1C
VARDENAFIL	4	CACNA1C
CLEMASTINE	4	CACNA1C
ISRADIPINE	4	CACNA1C
TERFENADINE	4	CACNA1C
NISOLDIPINE	4	CACNA1C
SOLIFENACIN	4	CACNA1C
PINAVERIUM	4	CACNA1C
SILDENAFIL	4	CACNA1C
NIFEDIPINE	4	CACNA1C
XANOMELINE	4	CACNA1C
DILTIAZEM	4	CACNA1C
PRENYLAMINE	4	CACNA1C
OLICERIDINE	4	CACNA1C
PROPRANOLOL	4	CACNA1C
ALVIMOPAN	4	CACNA1C
ASTEMIZOLE	4	CACNA1C

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CACNA1C
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ITFG2-AS1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ITFG2-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening