CACNA1G

Voltage-dependent T-type calcium channel subunit alpha-1G

Score: 0.698 Price: $0.70 High Druggability Status: active Wiki: CACNA1G

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

DEBATES

3D Protein Structure

🧬 CACNA1G — PDB 6KZO Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

High

Score: 0.90

Clinical Stage

Approved

Target Class

Ion Channel

Safety

0.60

Druggability Analysis

Drug Development0.75

Structural Tractability0.70

Target Class0.85

Safety Profile0.60

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (2 compounds)

1 Approved

Therapeutic Areas:

Absence seizures Generalized epilepsy Neuropathic pain Essential tremor Neurodegeneration (Parkinson's disease) Ataxias Migraine prophylaxis

Druggability Rationale: CACNA1G exhibits high druggability (0.90 score) due to its well-defined ion channel architecture, availability of high-resolution structural data (3.1 Å cryo-EM), and validated clinical precedent with approved (ethosuximide) and withdrawn (mibefradil) drugs. The deep hydrophobic binding pocket characteristic of voltage-gated calcium channels provides an excellent substrate for small molecule inhibitors with favorable ligand binding kinetics.

Mechanism: Small molecule blocker of T-type calcium channel activity

Drug Pipeline (2 compounds)

1 Approved

Known Drugs:

Ethosuximide (approved) — Absence seizures

Mibefradil (withdrawn) — Hypertension

Structural Data:

PDB (2) ✓AlphaFold ✓Cryo-EM ✓

6KZO 6KZP

UniProt: A0A0B4J1X2

Binding Pocket Analysis:

The T-type calcium channel binding pocket is located within the transmembrane domain at the interface of the S5-S6 segments and the pore helix, forming a hydrophobic cavity accessible from the intracellular side. Available PDB structures (6KZO, 6KZP) reveal a fenestrated pore architecture with multiple binding sites for blockers, enabling structure-based drug design to optimize potency and selectivity.

🧬 3D Protein Structure

🧬 CACNA1G — PDB 6KZO Click to expand interactive 3D viewer

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

T-type calcium channel selectivity is challenging due to high sequence homology among CACNA1G (Cav3.1), CACNA1H (Cav3.2), and CACNA1I (Cav3.3) isoforms; achieving isoform-specific inhibition is critical to avoid off-target cardiovascular effects observed with mibefradil. Structural divergence in the selectivity filter and S5-S6 pore regions offers opportunities for isoform-selective ligand design.