hyperaldosteronism, familial, type IV
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Also known as familial hyperaldosteronism type IVHALD4hyperaldosteronism, familial, type IV
Summary
hyperaldosteronism, familial, type IV (MONDO:0014875) is a disease caused by CACNA1H (GenCC Strong), with 6 cohort genes.
At a glance
- Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
- Causal gene: CACNA1H (GenCC Strong)
- Cohort genes: 6
- ClinVar variants: 3,664
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Cases/families | 17 | Worldwide | Validated | |
| Point prevalence | <1 / 1 000 000 | Worldwide | Validated |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | hyperaldosteronism, familial, type IV |
| Mondo ID | MONDO:0014875 |
| OMIM | 617027 |
| Orphanet | 642671 |
| DOID | DOID:0061250 |
| UMLS | C4310756 |
| MedGen | 934723 |
| GARD | 0025028 |
| Is cancer (heuristic) | no |
Also known as: familial hyperaldosteronism type IV · HALD4 · hyperaldosteronism, familial, type IV · hyperaldosteronism, familial, type IV; HALD4
Data availability: 3,664 ClinVar variants · 1 GenCC gene-disease record.
Disease family
Classification path: disease › human disease › disease by body system or component › endocrine system disorder › adrenal gland disorder › adrenal cortex disorder › adrenal gland hyperfunction › hyperaldosteronism › primary aldosteronism › familial hyperaldosteronism › hyperaldosteronism, familial, type IV
Related subtypes (4): glucocorticoid-remediable aldosteronism, familial hyperaldosteronism type II, familial hyperaldosteronism type III, aldosterone-producing adenoma with seizures and neurological abnormalities
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
600 retrieved; paginated sample, class counts are floors:
237 likely benign, 210 uncertain significance, 106 conflicting classifications of pathogenicity, 33 benign, 14 benign/likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1000691 | NM_021098.3(CACNA1H):c.4814C>A (p.Pro1605His) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1001887 | NM_021098.3(CACNA1H):c.2231G>A (p.Arg744Gln) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1004965 | NM_021098.3(CACNA1H):c.3758G>A (p.Arg1253His) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1005249 | NM_021098.3(CACNA1H):c.1673C>T (p.Ser558Leu) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1008653 | NM_021098.3(CACNA1H):c.3884T>C (p.Met1295Thr) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1011552 | NM_021098.3(CACNA1H):c.391G>A (p.Glu131Lys) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1011782 | NM_021098.3(CACNA1H):c.4823G>A (p.Arg1608His) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1013845 | NM_021098.3(CACNA1H):c.560C>T (p.Ser187Leu) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1015188 | NM_021098.3(CACNA1H):c.3584G>A (p.Arg1195Gln) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1015270 | NM_021098.3(CACNA1H):c.6398G>T (p.Arg2133Leu) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1015641 | NM_021098.3(CACNA1H):c.1691G>A (p.Arg564His) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1016006 | NM_021098.3(CACNA1H):c.3347G>A (p.Gly1116Glu) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1020407 | NM_021098.3(CACNA1H):c.3143T>C (p.Leu1048Pro) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1021653 | NM_021098.3(CACNA1H):c.2995A>G (p.Met999Val) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1023131 | NM_021098.3(CACNA1H):c.3614G>C (p.Arg1205Pro) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1023368 | NM_021098.3(CACNA1H):c.6563G>A (p.Ser2188Asn) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1025264 | NM_021098.3(CACNA1H):c.3467G>A (p.Arg1156His) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1032113 | NM_021098.3(CACNA1H):c.2789+16C>T | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1032116 | NM_021098.3(CACNA1H):c.974C>T (p.Pro325Leu) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1038757 | NM_021098.3(CACNA1H):c.1046C>T (p.Ser349Leu) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1041003 | NM_021098.3(CACNA1H):c.6281C>T (p.Ser2094Leu) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1042192 | NM_021098.3(CACNA1H):c.2209G>A (p.Gly737Ser) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1044087 | NM_021098.3(CACNA1H):c.2545C>T (p.Pro849Ser) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1044825 | NM_021098.3(CACNA1H):c.1835A>C (p.Asn612Thr) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1046542 | NM_021098.3(CACNA1H):c.4741C>G (p.Leu1581Val) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1051387 | NM_021098.3(CACNA1H):c.1000C>T (p.Arg334Cys) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1051672 | NM_021098.3(CACNA1H):c.919G>A (p.Gly307Ser) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1052203 | NM_021098.3(CACNA1H):c.5957C>T (p.Ser1986Leu) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1054433 | NM_021098.3(CACNA1H):c.3359C>G (p.Pro1120Arg) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1057350 | NM_021098.3(CACNA1H):c.1765G>A (p.Ala589Thr) | CACNA1H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 4 · 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 |
|---|---|---|---|---|
| CACNA1H | Strong | Autosomal dominant | hyperaldosteronism, familial, type IV | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| CACNA1H | Orphanet:642671 | Familial hyperaldosteronism type IV |
| CACNA1H | Orphanet:64280 | Childhood absence epilepsy |
| ABCA3 | Orphanet:2032 | Idiopathic pulmonary fibrosis |
| ABCA3 | Orphanet:217563 | Neonatal acute respiratory distress syndrome |
| ABCA3 | Orphanet:440402 | Interstitial lung disease due to ABCA3 deficiency |
| ABCA3 | Orphanet:685082 | Pediatric acute respiratory distress syndrome |
Cohort genes → proteins
6 cohort genes, 6 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 6 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| CACNA1H | HGNC:1395 | ENSG00000196557 | O95180 | Voltage-dependent T-type calcium channel subunit alpha-1H | gencc,clinvar |
| ANTKMT | HGNC:14152 | ENSG00000103254 | Q9BQD7 | Adenine nucleotide translocase lysine N-methyltransferase | clinvar |
| RAB11FIP3 | HGNC:17224 | ENSG00000090565 | O75154 | Rab11 family-interacting protein 3 | clinvar |
| CHTF18 | HGNC:18435 | ENSG00000127586 | Q8WVB6 | Chromosome transmission fidelity protein 18 homolog | clinvar |
| C1QTNF8 | HGNC:31374 | ENSG00000184471 | P60827 | Complement C1q tumor necrosis factor-related protein 8 | clinvar |
| ABCA3 | HGNC:33 | ENSG00000167972 | Q99758 | Phospholipid-transporting ATPase ABCA3 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| CACNA1H | Voltage-dependent T-type calcium channel subunit alpha-1H | Voltage-sensitive calcium channel that gives rise to T-type calcium currents. |
| ANTKMT | Adenine nucleotide translocase lysine N-methyltransferase | Mitochondrial protein-lysine N-methyltransferase that trimethylates adenine nucleotide translocases ANT2/SLC25A5 and ANT3/SLC25A6, thereby regulating mitochondrial respiration. |
| RAB11FIP3 | Rab11 family-interacting protein 3 | Downstream effector molecule for Rab11 GTPase which is involved in endocytic trafficking, cytokinesis and intracellular ciliogenesis by participating in membrane delivery. |
| CHTF18 | Chromosome transmission fidelity protein 18 homolog | Chromosome cohesion factor involved in sister chromatid cohesion and fidelity of chromosome transmission. |
| C1QTNF8 | Complement C1q tumor necrosis factor-related protein 8 | May play a role as ligand of RXFP1. |
| ABCA3 | Phospholipid-transporting ATPase ABCA3 | Catalyzes the ATP-dependent transport of phospholipids such as phosphatidylcholine and phosphoglycerol from the cytoplasm into the lumen side of lamellar bodies, in turn participates in the lamellar bodies biogenesis and homeostasis of pul… |
Protein-family classification
Druggable: 2 · Difficult: 0 · Unknown: 4 · Druggable fraction: 0.33
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 | 18.6× | 0.112 |
| Transporter | 1 | 13.0× | 0.112 |
| Other/Unknown | 4 | 1.2× | 0.458 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| CACNA1H | Ion channel | yes | VDCC_T_a1, Ion_trans_dom, Volt_channel_dom_sf | |
| ANTKMT | Other/Unknown | no | FAM173A/B, SAM-dependent_MTases_sf | |
| RAB11FIP3 | Other/Unknown | no | EF_hand_dom, EF-hand-dom_pair, Rab-bd_FIP-RBD | |
| CHTF18 | Other/Unknown | no | AAA+_ATPase, ATPase_AAA_core, P-loop_NTPase | |
| C1QTNF8 | Other/Unknown | no | C1q_dom, Collagen, Tumour_necrosis_fac-like_dom | |
| ABCA3 | Transporter | yes | ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM |
Expression context
Cohort genes with no expression data: 0.
4 cohort genes 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) | 6 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| mucosa of transverse colon | 2 |
| lower esophagus | 1 |
| lower esophagus muscularis layer | 1 |
| muscle layer of sigmoid colon | 1 |
| anterior cingulate cortex | 1 |
| cingulate cortex | 1 |
| kidney epithelium | 1 |
| pancreatic ductal cell | 1 |
| right hemisphere of cerebellum | 1 |
| left testis | 1 |
| right testis | 1 |
| ascending aorta | 1 |
| right uterine tube | 1 |
| thoracic aorta | 1 |
| lower lobe of lung | 1 |
| upper lobe of left lung | 1 |
| upper lobe of lung | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| CACNA1H | 166 | broad | marker | lower esophagus muscularis layer, muscle layer of sigmoid colon, lower esophagus |
| ANTKMT | 243 | ubiquitous | marker | anterior cingulate cortex, cingulate cortex, mucosa of transverse colon |
| RAB11FIP3 | 246 | ubiquitous | marker | kidney epithelium, pancreatic ductal cell, right hemisphere of cerebellum |
| CHTF18 | 188 | ubiquitous | yes | right testis, left testis, mucosa of transverse colon |
| C1QTNF8 | 51 | yes | right uterine tube, ascending aorta, thoracic aorta | |
| ABCA3 | 222 | ubiquitous | marker | lower lobe of lung, upper lobe of lung, upper lobe of left lung |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| CHTF18 | 1,878 |
| CACNA1H | 1,564 |
| ABCA3 | 1,436 |
| ANTKMT | 1,032 |
| RAB11FIP3 | 863 |
| C1QTNF8 | 265 |
Structural data
PDB: 4 · AlphaFold-only: 2 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| CHTF18 | Q8WVB6 | 10 |
| CACNA1H | O95180 | 5 |
| RAB11FIP3 | O75154 | 5 |
| ABCA3 | Q99758 | 2 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| ANTKMT | Q9BQD7 | 82.01 |
| C1QTNF8 | P60827 | 78.89 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 24. Enrichment computed across 6 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Defective ABCA3 causes SMDP3 | 1 | 2855.0× | 0.004 | ABCA3 |
| Diseases associated with surfactant metabolism | 1 | 713.8× | 0.011 | ABCA3 |
| Mechanical load activates signaling by PIEZO1 and integrins in osteocytes | 1 | 167.9× | 0.028 | CACNA1H |
| ABC transporters in lipid homeostasis | 1 | 150.3× | 0.028 | ABCA3 |
| VxPx cargo-targeting to cilium | 1 | 129.8× | 0.028 | RAB11FIP3 |
| ABC transporter disorders | 1 | 109.8× | 0.028 | ABCA3 |
| Polymerase switching on the C-strand of the telomere | 1 | 105.7× | 0.028 | CHTF18 |
| Surfactant metabolism | 1 | 92.1× | 0.029 | ABCA3 |
| NCAM signaling for neurite out-growth | 1 | 68.0× | 0.030 | CACNA1H |
| Smooth Muscle Contraction | 1 | 66.4× | 0.030 | CACNA1H |
| Cellular responses to mechanical stimuli | 1 | 64.9× | 0.030 | CACNA1H |
| NCAM1 interactions | 1 | 62.1× | 0.030 | CACNA1H |
| Disorders of transmembrane transporters | 1 | 34.8× | 0.049 | ABCA3 |
| ABC-family protein mediated transport | 1 | 30.4× | 0.052 | ABCA3 |
| Diseases of metabolism | 1 | 20.1× | 0.072 | ABCA3 |
| Muscle contraction | 1 | 19.3× | 0.072 | CACNA1H |
| Axon guidance | 1 | 11.3× | 0.114 | CACNA1H |
| Nervous system development | 1 | 10.7× | 0.114 | CACNA1H |
| Cellular responses to stimuli | 1 | 7.9× | 0.145 | CACNA1H |
| Transport of small molecules | 1 | 6.3× | 0.171 | ABCA3 |
| Developmental Biology | 1 | 3.6× | 0.272 | CACNA1H |
| Disease | 1 | 3.3× | 0.284 | ABCA3 |
| Metabolism of proteins | 1 | 3.1× | 0.286 | ABCA3 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| positive regulation of protein homooligomerization | 1 | 2808.7× | 0.008 | ABCA3 |
| regulation of phosphatidylcholine metabolic process | 1 | 1404.3× | 0.008 | ABCA3 |
| protein localization to cleavage furrow | 1 | 1404.3× | 0.008 | RAB11FIP3 |
| xenobiotic export from cell | 1 | 936.2× | 0.008 | ABCA3 |
| obsolete regulation of early endosome to recycling endosome transport | 1 | 936.2× | 0.008 | RAB11FIP3 |
| regulation of protein localization to centrosome | 1 | 936.2× | 0.008 | RAB11FIP3 |
| regulation of mitochondrial ATP synthesis coupled proton transport | 1 | 936.2× | 0.008 | ANTKMT |
| negative regulation of adiponectin secretion | 1 | 702.2× | 0.008 | RAB11FIP3 |
| positive regulation of phospholipid efflux | 1 | 702.2× | 0.008 | ABCA3 |
| aldosterone biosynthetic process | 1 | 561.7× | 0.008 | CACNA1H |
| obsolete early endosome to recycling endosome transport | 1 | 561.7× | 0.008 | RAB11FIP3 |
| peptidyl-lysine trimethylation | 1 | 468.1× | 0.008 | ANTKMT |
| regulation of lipid biosynthetic process | 1 | 468.1× | 0.008 | ABCA3 |
| organelle assembly | 1 | 468.1× | 0.008 | ABCA3 |
| positive regulation of phospholipid transport | 1 | 401.2× | 0.008 | ABCA3 |
| cortisol biosynthetic process | 1 | 351.1× | 0.008 | CACNA1H |
| positive regulation of DNA-directed DNA polymerase activity | 1 | 351.1× | 0.008 | CHTF18 |
| positive regulation of mitotic cytokinetic process | 1 | 351.1× | 0.008 | RAB11FIP3 |
| regulation of endocytic recycling | 1 | 280.9× | 0.010 | RAB11FIP3 |
| positive regulation of acrosome reaction | 1 | 255.3× | 0.010 | CACNA1H |
| phosphatidylglycerol metabolic process | 1 | 234.1× | 0.011 | ABCA3 |
| regulation of vesicle-mediated transport | 1 | 187.2× | 0.013 | RAB11FIP3 |
| cellular response to potassium ion | 1 | 175.5× | 0.013 | CACNA1H |
| phospholipid homeostasis | 1 | 165.2× | 0.013 | ABCA3 |
| xenobiotic transmembrane transport | 1 | 156.0× | 0.013 | ABCA3 |
| obsolete inorganic cation transmembrane transport | 1 | 156.0× | 0.013 | CACNA1H |
| xenobiotic transport | 1 | 140.4× | 0.013 | ABCA3 |
| surfactant homeostasis | 1 | 133.8× | 0.013 | ABCA3 |
| phosphatidylcholine metabolic process | 1 | 133.8× | 0.013 | ABCA3 |
| calcium ion import | 1 | 133.8× | 0.013 | CACNA1H |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 5
Druggability breadth: 2 of 6 evidence-associated genes (33%) 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 |
|---|---|
| CACNA1H | PIMOZIDE |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| CACNA1H | 10 | 4 |
| ANTKMT | 0 | 0 |
| RAB11FIP3 | 0 | 0 |
| CHTF18 | 0 | 0 |
| C1QTNF8 | 0 | 0 |
| ABCA3 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| PIMOZIDE | 4 | CACNA1H |
| MIBEFRADIL | 4 | CACNA1H |
| NIMODIPINE | 4 | CACNA1H |
| TACRINE | 4 | CACNA1H |
| CILNIDIPINE | 3 | CACNA1H |
| SUVECALTAMIDE | 2 | CACNA1H |
| FLUNARIZINE | 2 | CACNA1H |
| APINOCALTAMIDE | 2 | CACNA1H |
| Z160 | 2 | CACNA1H |
| ULIXACALTAMIDE | 1 | CACNA1H |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| CACNA1H | 124 | Binding:102, Functional:17, ADMET:4, Toxicity:1 |
| CHTF18 | 1 | Binding:1 |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| CACNA1H | 124 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
10 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) |
|---|---|---|
| PIMOZIDE | 4 | CACNA1H |
| MIBEFRADIL | 4 | CACNA1H |
| NIMODIPINE | 4 | CACNA1H |
| TACRINE | 4 | CACNA1H |
| CILNIDIPINE | 3 | CACNA1H |
| SUVECALTAMIDE | 2 | CACNA1H |
| FLUNARIZINE | 2 | CACNA1H |
| APINOCALTAMIDE | 2 | CACNA1H |
| Z160 | 2 | CACNA1H |
| ULIXACALTAMIDE | 1 | CACNA1H |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | CACNA1H |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 1 | ABCA3 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 4 | ANTKMT, RAB11FIP3, CHTF18, C1QTNF8 |
Undrugged target profiles
5 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| ANTKMT | 0 | — |
| RAB11FIP3 | 0 | — |
| CHTF18 | 1 | — |
| C1QTNF8 | 0 | — |
| ABCA3 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.