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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
CACNA1H
calcium voltage-gated channel subunit alpha1 H
Chromosome 16 Β· 16p13.3
NCBI Gene: 8912Ensembl: ENSG00000196557.14HGNC: HGNC:1395UniProt: A0A1W2PQW2
129PubMed Papers
23Diseases
20Drugs
8Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneIon ChannelTransporter
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
plasma membranemembranecortisol biosynthetic processcellular response to potassium ionepilepsyneuropathic painfibromyalgiaSeizure
✦AI Summary

CACNA1H encodes CaV3.2, a T-type voltage-gated calcium channel that operates at low voltage thresholds and exhibits voltage-dependent inactivation 1. This channel serves critical pacemaking functions in neurons and cardiac cells, and plays essential roles in aldosterone biosynthesis in adrenal zona glomerulosa cells 1. In aldosterone regulation, CACNA1H mediates calcium oscillations that govern aldosterone production in response to angiotensin II and hyperkalemia 1. Beyond endocrine function, CACNA1H is required for smooth muscle cytoskeletal organization during tracheal development, where it maintains actin polymerization through RhoA activation 2. The channel also contributes to automaticity in immature cardiomyocytes 3. Disease-wise, CACNA1H mutations cause familial hyperaldosteronism type 4, leading to excessive aldosterone production and secondary hypertension 45. Somatic mutations in aldosterone-producing adenomas represent a rare cause of primary aldosteronism 1. Additionally, CACNA1H variants are associated with intellectual disability and developmental delay, with both gain- and loss-of-function mutations contributing to neurological phenotypes 6. Decreased CACNA1H expression is also linked to congenital tracheostenosis 2, highlighting its importance in respiratory tract development.

Sources cited
1
CACNA1H encodes CaV3.2 T-type calcium channel important for aldosterone regulation and electrical oscillations in zona glomerulosa
PMID: 37311830
2
CACNA1H is required for smooth muscle cytoskeletal organization and tracheal development through RhoA activation
PMID: 39360593
3
CACNA1H contributes to automaticity in immature cardiomyocytes
PMID: 37028405
4
Germline CACNA1H mutations cause familial hyperaldosteronism
PMID: 35139664
5
CACNA1H somatic mutations are found in aldosterone-producing adenomas
PMID: 35841527
6
CACNA1H variants are associated with intellectual disability and developmental delay
PMID: 33985586
Disease Associationsβ“˜23
epilepsyOpen Targets
0.61Moderate
neuropathic painOpen Targets
0.60Moderate
fibromyalgiaOpen Targets
0.60Moderate
SeizureOpen Targets
0.60Moderate
hyperaldosteronism, familial, type IVOpen Targets
0.59Moderate
restless legs syndromeOpen Targets
0.58Moderate
neuralgiaOpen Targets
0.58Moderate
anxiety disorderOpen Targets
0.57Moderate
postherpetic neuralgiaOpen Targets
0.57Moderate
spinal cord injuryOpen Targets
0.54Moderate
cardiovascular diseaseOpen Targets
0.50Moderate
Focal-onset seizureOpen Targets
0.48Moderate
childhood absence epilepsyOpen Targets
0.45Moderate
Urinary incontinenceOpen Targets
0.43Moderate
partial epilepsyOpen Targets
0.42Moderate
generalised epilepsyOpen Targets
0.42Moderate
PainOpen Targets
0.42Moderate
diabetic neuropathyOpen Targets
0.41Moderate
generalized anxiety disorderOpen Targets
0.40Weak
insomniaOpen Targets
0.40Weak
Epilepsy, childhood absence 6UniProt
Epilepsy, idiopathic generalized 6UniProt
Hyperaldosteronism, familial, 4UniProt
Pathogenic Variants8
NM_021098.3(CACNA1H):c.3434G>A (p.Trp1145Ter)Likely pathogenic
Epilepsy, childhood absence, susceptibility to, 6
β˜…β˜†β˜†β˜†2024β†’ Residue 1145
NM_021098.3(CACNA1H):c.4647G>T (p.Met1549Ile)Pathogenic
Idiopathic generalized epilepsy;Hyperaldosteronism, familial, type IV
β˜…β˜†β˜†β˜†2023β†’ Residue 1549
NM_021098.3(CACNA1H):c.4645A>G (p.Met1549Val)Pathogenic
Primary aldosteronism|Hyperaldosteronism, familial, type IV|not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 1549
NM_021098.3(CACNA1H):c.5288A>G (p.Tyr1763Cys)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 1763
NM_021098.3(CACNA1H):c.697G>C (p.Val233Leu)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2020β†’ Residue 233
NM_021098.3(CACNA1H):c.1793C>T (p.Ala598Val)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2016β†’ Residue 598
NM_021098.3(CACNA1H):c.6898A>G (p.Ile2300Val)Likely pathogenic
Abnormal brain morphology
β˜…β˜†β˜†β˜†β†’ Residue 2300
NM_021098.3(CACNA1H):c.1838A>T (p.Tyr613Phe)Likely pathogenic
Primary aldosteronism
β˜†β˜†β˜†β˜†2025β†’ Residue 613
View on ClinVar β†—
Drug Targets20
ABT-639Phase II
Voltage-gated T-type calcium channel alpha-1H subunit blocker
Pain
APINOCALTAMIDEPhase II
Voltage-gated T-type calcium channel blocker
photosensitive epilepsy
ATAGABALINPhase II
Voltage-gated calcium channel modulator
insomnia
BEPRIDILApproved
Voltage-gated calcium channel blocker
cardiovascular disease
ETHOSUXIMIDEApproved
Voltage-gated T-type calcium channel blocker
epilepsy
GABAPENTINApproved
Voltage-gated calcium channel modulator
epilepsy
GABAPENTIN ENACARBILApproved
Voltage-gated calcium channel modulator
restless legs syndrome
IMAGABALINPhase III
Voltage-gated calcium channel modulator
generalized anxiety disorder
METHSUXIMIDEApproved
Voltage-gated T-type calcium channel blocker
Seizure
MIBEFRADILApproved
Voltage-gated T-type calcium channel blocker
cardiovascular disease
MIBEFRADIL DIHYDROCHLORIDEUNKNOWN
Voltage-gated T-type calcium channel blocker
PARAMETHADIONEApproved
Voltage-gated T-type calcium channel blocker
fetal trimethadione syndrome
PHENSUXIMIDEApproved
Voltage-gated T-type calcium channel blocker
epilepsy
PHLOROGLUCINOLApproved
Voltage-gated calcium channel blocker
gastrointestinal disease
PREGABALINApproved
Voltage-gated calcium channel modulator
neuropathic pain
SULOCTIDILApproved
Voltage-gated calcium channel blocker
cardiovascular disease
SUVECALTAMIDEPhase II
Voltage-gated T-type calcium channel modulator
epilepsy
TERODILINEApproved
Muscarinic acetylcholine receptor antagonist
Urinary incontinence
TERODILINE HYDROCHLORIDEUNKNOWN
Muscarinic acetylcholine receptor antagonist
TRIMETHADIONEApproved
Voltage-gated T-type calcium channel blocker
epilepsy
Related Genes
CACNA2D2Protein interaction98%SCN8AProtein interaction96%CACNA2D3Protein interaction94%CACNG7Protein interaction94%TRPC1Protein interaction92%TRPC4Protein interaction92%
Tissue Expression6 tissues
Ovary
100%
Liver
14%
Lung
9%
Heart
5%
Brain
2%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
CACNA1HCACNA2D2SCN8ACACNA2D3CACNG7TRPC1TRPC4
PROTEIN STRUCTURE
Preparing viewer…
PDB9AYL Β· 2.80 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.06LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.92 [0.81–1.06]
RankingsWhere CACNA1H stands among ~20K protein-coding genes
  • #3,613of 20,598
    Most Researched129 Β· top quartile
  • #118of 1,025
    FDA-Approved Drug Targets13 Β· top quartile
  • #3,047of 5,498
    Most Pathogenic Variants8
  • #10,633of 17,882
    Most Constrained (LOEUF)1.06
Genes detectedCACNA1H
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Calcium channelopathies and intellectual disability: a systematic review.
PMID: 33985586
Orphanet J Rare Dis Β· 2021
1.00
2
Gene editing to prevent ventricular arrhythmias associated with cardiomyocyte cell therapy.
PMID: 37028405
Cell Stem Cell Β· 2023
0.90
3
The T-Type Calcium Channel CACNA1H is Required for Smooth Muscle Cytoskeletal Organization During Tracheal Tubulogenesis.
PMID: 39360593
Adv Sci (Weinh) Β· 2024
0.80
4
Ca
PMID: 37311830
Handb Exp Pharmacol Β· 2023
0.70
5
Genetics of Primary Aldosteronism.
PMID: 35139664
Hypertension Β· 2022
0.60