HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
CACNA1G
calcium voltage-gated channel subunit alpha1 G
Chromosome 17 · 17q21.33
NCBI Gene: 8913Ensembl: ENSG00000006283.18HGNC: HGNC:1394UniProt: O43497
79PubMed Papers
22Diseases
19Drugs
29Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytoplasmplasma membranelow voltage-gated calcium channel activityscaffold protein bindingSpinocerebellar ataxia type 42spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficitsepilepsyneuropathic pain
✦AI Summary

CACNA1G encodes the α1G subunit of T-type calcium channels, which mediate voltage-gated calcium ion entry into excitable cells and regulate calcium-dependent processes including muscle contraction, neurotransmitter release, and gene expression 1. The channel plays critical roles in thalamic and cardiac conduction, regulating thalamocortical pathway function, SA node automaticity, and AV node conduction 2. Pathogenic CACNA1G variants cause spinocerebellar ataxia 42 with neurodevelopmental deficits (SCA42ND), characterized by early-onset cerebellar atrophy and severe intellectual disability 3. Both gain- and loss-of-function variants are implicated in disease: gain-of-function mutations (particularly at the intracellular gate) cause increased calcium current and slower inactivation kinetics, while loss-of-function variants reduce channel activity 3. CACNA1G variants are also associated with absence seizures and schizophrenia risk, with the M1531V variant causing thalamic hyperactivity and abnormal thalamocortical connectivity 2. Loss-of-function variants increase schizophrenia susceptibility through aberrant axonal projections and spontaneous thalamic hyperactivity 2. CACNA1G variants represent a major cause of calcium channelopathy-related intellectual disability 1, with severe-to-profound phenotypes more common in gain-of-function cases. The gene also influences developmental and epileptic encephalopathies through compensatory mechanisms with other voltage-gated ion channels 4. Additionally, the CACNA1G-AS1 long non-coding RNA regulates cancer cell proliferation in diffuse large B cell lymphoma and keloid fibroblasts 56.

Sources cited
1
CACNA1G variants cause seizures, intellectual disability, and schizophrenia through altered T-type currents and abnormal thalamocortical connectivity
PMID: 39419023
2
CACNA1G variants are associated with intellectual disability/global developmental delay; gain-of-function variants cause more severe phenotypes
PMID: 33985586
3
CACNA1G missense variants affect Cav3.1 channel intracellular gate, cause slow inactivation/deactivation kinetics and increased window current (gain-of-function)
PMID: 39674904
4
CACNA1G-AS1 long non-coding RNA promotes diffuse large B cell lymphoma proliferation by regulating miR-3160-5p
PMID: 36160896
5
CACNA1G variants are causative for early-onset cerebellar atrophy with cerebellar hypoplasia
PMID: 38003592
6
CACNA1G expression increases intracellular calcium levels in various cancers, contributing to tumor development
PMID: 40849687
7
CACNA1G variants are implicated in developmental and epileptic encephalopathies with compensatory effects from other voltage-gated ion channels
PMID: 39513870
8
CACNA1G-AS1 promotes keloid fibroblast proliferation and invasion by regulating miR-205
PMID: 32495824
Disease Associationsⓘ22
Spinocerebellar ataxia type 42Open Targets
0.78Strong
spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficitsOpen Targets
0.75Strong
epilepsyOpen Targets
0.64Moderate
neuropathic painOpen Targets
0.60Moderate
fibromyalgiaOpen Targets
0.60Moderate
SeizureOpen Targets
0.60Moderate
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
Urinary incontinenceOpen Targets
0.43Moderate
PainOpen Targets
0.42Moderate
genetic disorderOpen Targets
0.42Moderate
diabetic neuropathyOpen Targets
0.41Moderate
generalized anxiety disorderOpen Targets
0.40Weak
insomniaOpen Targets
0.40Weak
partial epilepsyOpen Targets
0.39Weak
Spinocerebellar ataxia 42UniProt
Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficitsUniProt
Pathogenic Variants29
NM_018896.5(CACNA1G):c.2881G>A (p.Ala961Thr)Pathogenic
not provided|Inborn genetic diseases|Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits|Neurodevelopmental abnormality
★★☆☆2024→ Residue 961
NM_018896.5(CACNA1G):c.5144G>A (p.Arg1715His)Pathogenic
Spinocerebellar ataxia type 42|Spinocerebellar ataxia type 42;Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits|CACNA1G-related disorder|not provided
★★☆☆2022→ Residue 1715
NM_018896.5(CACNA1G):c.3787T>G (p.Ser1263Ala)Likely pathogenic
Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits
★☆☆☆2024→ Residue 1263
NM_018896.5(CACNA1G):c.5543C>G (p.Ala1848Gly)Likely pathogenic
Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits
★☆☆☆2024→ Residue 1848
NM_018896.5(CACNA1G):c.277C>T (p.Leu93Phe)Likely pathogenic
not provided
★☆☆☆2024→ Residue 93
NM_018896.5(CACNA1G):c.626C>T (p.Pro209Leu)Likely pathogenic
not provided
★☆☆☆2024→ Residue 209
NM_018896.5(CACNA1G):c.556C>T (p.Arg186Ter)Likely pathogenic
not provided
★☆☆☆2024→ Residue 186
NM_018896.5(CACNA1G):c.590T>G (p.Met197Arg)Likely pathogenic
not provided
★☆☆☆2022→ Residue 197
NM_018896.5(CACNA1G):c.337C>A (p.Arg113Ser)Likely pathogenic
not provided
★☆☆☆2022→ Residue 113
NM_018896.5(CACNA1G):c.2549C>T (p.Ala850Val)Likely pathogenic
Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits
★☆☆☆2022→ Residue 850
NM_018896.5(CACNA1G):c.5395T>A (p.Ser1799Thr)Likely pathogenic
Spastic ataxia
★☆☆☆2021→ Residue 1799
NM_018896.5(CACNA1G):c.3835G>A (p.Asp1279Asn)Likely pathogenic
Spinocerebellar ataxia type 42
★☆☆☆2021→ Residue 1279
NM_018896.5(CACNA1G):c.2740G>A (p.Val914Ile)Likely pathogenic
Spastic ataxia
★☆☆☆2021→ Residue 914
NM_018896.5(CACNA1G):c.4592T>C (p.Met1531Thr)Likely pathogenic
Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits
★☆☆☆2021→ Residue 1531
NM_018896.5(CACNA1G):c.4591A>G (p.Met1531Val)Pathogenic
Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits
★☆☆☆2020→ Residue 1531
NM_018896.5(CACNA1G):c.1103C>T (p.Ser368Phe)Likely pathogenic
not provided
★☆☆☆2019→ Residue 368
NM_018896.5(CACNA1G):c.4601G>A (p.Gly1534Asp)Likely pathogenic
not provided
★☆☆☆2019→ Residue 1534
NM_018896.5(CACNA1G):c.623T>C (p.Leu208Pro)Likely pathogenic
not provided
★☆☆☆2017→ Residue 208
NM_018896.5(CACNA1G):c.1890C>G (p.Ser630Arg)Likely pathogenic
not provided
★☆☆☆2016→ Residue 630
NM_018896.5(CACNA1G):c.2599A>C (p.Thr867Pro)Likely pathogenic
not provided
★☆☆☆2016→ Residue 867
View on ClinVar ↗
Drug Targets19
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
CACNG4Protein interaction99%CACNA2D2Protein interaction98%CACNG7Protein interaction98%CACNA2D4Protein interaction96%INSProtein interaction96%ESR2Protein interaction94%
Tissue Expression6 tissues
Ovary
100%
Brain
26%
Heart
5%
Lung
3%
Liver
1%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
CACNA1GCACNG4CACNA2D2CACNG7CACNA2D4INSESR2
PROTEIN STRUCTURE
Preparing viewer…
PDB6KZP · 3.10 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.41Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.33 [0.27–0.41]
RankingsWhere CACNA1G stands among ~20K protein-coding genes
  • #5,982of 20,598
    Most Researched79
  • #124of 1,025
    FDA-Approved Drug Targets13 · top quartile
  • #1,845of 5,498
    Most Pathogenic Variants29
  • #2,065of 17,882
    Most Constrained (LOEUF)0.41 · top quartile
Genes detectedCACNA1G
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Human assembloids reveal the consequences of CACNA1G gene variants in the thalamocortical pathway.
PMID: 39419023
Neuron · 2024
1.00
2
Calcium channelopathies and intellectual disability: a systematic review.
PMID: 33985586
Orphanet J Rare Dis · 2021
0.90
3
The characterization of new de novo CACNA1G variants affecting the intracellular gate of Cav3.1 channel broadens the spectrum of neurodevelopmental phenotypes in SCA42ND.
PMID: 39674904
Genet Med · 2025
0.80
4
Knockdown of the long non-coding RNA CACNA1G-AS1 enhances cytotoxicity and apoptosis of human diffuse large B cell lymphoma by regulating miR-3160-5p.
PMID: 36160896
Exp Ther Med · 2022
0.70
5
Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy.
PMID: 38003592
Int J Mol Sci · 2023
0.60