CACNA1G

calcium voltage-gated channel subunit alpha1 G, the group of Calcium voltage-gated channel alpha1 subunits

Basic information

Region (hg38): 17:50560714-50627474

Links

ENSG00000006283 ∙ NCBI:8913 ∙ OMIM:604065 ∙ HGNC:1394 ∙ Uniprot:O43497 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinocerebellar ataxia type 42 (Strong), mode of inheritance: AD
• spinocerebellar ataxia type 42 (Strong), mode of inheritance: AD
• spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits (Strong), mode of inheritance: AD
• spinocerebellar ataxia type 42 (Supportive), mode of inheritance: AD
• intellectual disability (Limited), mode of inheritance: AR
• spinocerebellar ataxia type 42 (Definitive), mode of inheritance: AD
• spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits (Definitive), mode of inheritance: AD
• spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits (Strong), mode of inheritance: AD
• spinocerebellar ataxia type 42 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia 42; Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	26456284; 26715324; 29878067

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CACNA1G gene.

• not provided (700 variants)
• Inborn genetic diseases (98 variants)
• Spinocerebellar ataxia type 42 (45 variants)
• Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits (36 variants)
• not specified (22 variants)
• CACNA1G-related condition (8 variants)
• Cerebellar ataxia (2 variants)
• Spinocerebellar ataxia type 42;Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits (2 variants)
• Spastic ataxia (2 variants)
• Intellectual disability (2 variants)
• Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits;Spinocerebellar ataxia type 42 (2 variants)
• Juvenile myoclonic epilepsy;Intellectual disability (2 variants)
• Hirsutism;Abnormality of the skeletal system;Abnormal facial shape;Intellectual disability, severe (1 variants)
• Intellectual disability;Seizure (1 variants)
• Neurodevelopmental abnormality (1 variants)
• Neonatal encephalopathy (1 variants)
• Developmental disorder (1 variants)
• Neurodevelopmental delay (1 variants)
• See cases (1 variants)
• CACNA1G-related disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CACNA1G gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	124	37	169
missense	2	18	354	64	18	456
nonsense			9			9
start loss						0
frameshift			12	1		13
inframe indel		1	5	1		7
splice donor/acceptor (+/-2bp)			5	1		6
splice region			13	13	2	28
non coding			3	58	59	120
Total	2	19	396	249	114

Highest pathogenic variant AF is 0.00000658

Variants in CACNA1G

This is a list of pathogenic ClinVar variants found in the CACNA1G region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-50560854-G-A			Benign (Mar 28, 2021)
17-50561465-CGAG-C			Uncertain significance (Jan 18, 2023)
17-50561472-G-C			Uncertain significance (Apr 26, 2023)
17-50561518-T-C			Uncertain significance (Apr 25, 2022)
17-50561527-A-C		Inborn genetic diseases	Uncertain significance (Aug 15, 2023)
17-50561529-G-A			Uncertain significance (Mar 31, 2022)
17-50561531-C-G			Likely benign (Aug 17, 2023)
17-50561532-C-T			Likely benign (Sep 13, 2023)
17-50561536-C-G			Uncertain significance (May 01, 2023)
17-50561537-G-A			Benign/Likely benign (Feb 01, 2024)
17-50561545-G-A		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
17-50561548-G-A			Uncertain significance (Nov 24, 2022)
17-50561562-G-A		CACNA1G-related disorder	Uncertain significance (Feb 27, 2024)
17-50561582-G-C			Likely benign (Sep 01, 2021)
17-50561582-G-T			Likely benign (Dec 07, 2023)
17-50561584-GC-G		Inborn genetic diseases	Uncertain significance (Apr 28, 2021)
17-50561605-A-T		CACNA1G-related disorder	Uncertain significance (Jun 06, 2023)
17-50561615-G-A			Likely benign (Nov 01, 2023)
17-50561623-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Feb 28, 2024)
17-50561624-G-A			Likely benign (Dec 11, 2023)
17-50561651-G-A			Likely benign (Sep 05, 2023)
17-50561674-G-A			Uncertain significance (Jul 27, 2022)
17-50561720-C-G			Uncertain significance (Jan 02, 2023)
17-50561720-C-T			Likely benign (Sep 18, 2022)
17-50561825-TG-T			Benign (Mar 28, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CACNA1G	protein_coding	protein_coding	ENST00000359106	38	66407

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.56e-7	124595	0	85	124680	0.000341

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.64	963	1.46e+3	0.659	0.0000932	15335
Missense in Polyphen		205	618.63	0.33138		6687
Synonymous	0.977	602	633	0.951	0.0000424	4868
Loss of Function	7.95	13	97.9	0.133	0.00000516	1067

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000486	0.000465
Ashkenazi Jewish	0.00137	0.00129
East Asian	0.000184	0.000167
Finnish	0.000105	0.0000928
European (Non-Finnish)	0.000417	0.000389
Middle Eastern	0.000184	0.000167
South Asian	0.000309	0.000294
Other	0.000545	0.000495

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by mibefradil. A particularity of this type of channel is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes. {ECO:0000269|PubMed:10648811, ECO:0000269|PubMed:10692398, ECO:0000269|PubMed:26456284, ECO:0000269|PubMed:26715324}.
• Disease: DISEASE: Spinocerebellar ataxia 42 (SCA42) [MIM:616795]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA42 is a slowly progressive, autosomal dominant form with variable severity. {ECO:0000269|PubMed:26456284, ECO:0000269|PubMed:26715324}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cortisol synthesis and secretion - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Type II diabetes mellitus - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Celecoxib Pathway, Pharmacodynamics;Nicotine Pathway (Chromaffin Cell), Pharmacodynamics;Antiarrhythmic Pathway, Pharmacodynamics;Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Muscle/Heart Contraction;Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Bupranolol Action Pathway;Nebivolol Action Pathway;Amlodipine Action Pathway;Verapamil Action Pathway;Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;Nicotine Activity on Chromaffin Cells;MAPK Signaling Pathway;Developmental Biology;NCAM signaling for neurite out-growth;NCAM1 interactions;Axon guidance;Regulation of nuclear beta catenin signaling and target gene transcription (Consensus)

Recessive Scores

• pRec: 0.174

Intolerance Scores

• loftool: 0.000620
• rvis_EVS: -2.37
• rvis_percentile_EVS: 1.11

Haploinsufficiency Scores

• pHI: 0.506
• hipred: Y
• hipred_score: 0.693
• ghis: 0.623

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.240

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cacna1g
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: chemical synaptic transmission;response to nickel cation;neuronal action potential;regulation of ion transmembrane transport;regulation of membrane potential;positive regulation of calcium ion-dependent exocytosis;regulation of atrial cardiac muscle cell membrane depolarization;calcium ion import;calcium ion transmembrane transport;cardiac muscle cell action potential involved in contraction;membrane depolarization during action potential;SA node cell action potential;AV node cell action potential;SA node cell to atrial cardiac muscle cell signaling;AV node cell to bundle of His cell signaling;membrane depolarization during AV node cell action potential;membrane depolarization during SA node cell action potential;regulation of heart rate by cardiac conduction
• Cellular component: cytoplasm;plasma membrane;voltage-gated calcium channel complex
• Molecular function: low voltage-gated calcium channel activity;voltage-gated calcium channel activity involved in AV node cell action potential;voltage-gated calcium channel activity involved SA node cell action potential;scaffold protein binding