CACNA1E

calcium voltage-gated channel subunit alpha1 E, the group of Calcium voltage-gated channel alpha1 subunits|EF-hand domain containing

Basic information

Region (hg38): 1:181317690-181813262

Previous symbols: [ "CACNL1A6" ]

Links

ENSG00000198216 ∙ NCBI:777 ∙ OMIM:601013 ∙ HGNC:1392 ∙ Uniprot:Q15878 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 69 (Strong), mode of inheritance: AD
• developmental and epileptic encephalopathy, 69 (Strong), mode of inheritance: AD
• developmental and epileptic encephalopathy, 69 (Strong), mode of inheritance: AD
• developmental and epileptic encephalopathy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 69	AD	Neurologic	The condition can result in severe seizures, and some individuals have been described as responding favorably to medical management with topiramate	Neurologic	30343943

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CACNA1E gene.

• Early infantile epileptic encephalopathy with suppression bursts (4 variants)
• not provided (4 variants)
• Developmental and epileptic encephalopathy, 69 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CACNA1E 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			6	450	28	484
missense	5	14	474	191	100	784
nonsense		1	18	1		20
start loss						0
frameshift			11			11
inframe indel			9	4		13
splice donor/acceptor (+/-2bp)			7			7
splice region			31	75	15	121
non coding			6	317	134	457
Total	5	15	531	963	262

Variants in CACNA1E

This is a list of pathogenic ClinVar variants found in the CACNA1E region.

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

Position	Type	Phenotype	Significance	ClinVar
1-181483210-G-C			Likely benign (Apr 08, 2021)
1-181483212-CTTTG-C			Benign (Mar 26, 2021)
1-181483467-C-T			Likely benign (Apr 12, 2021)
1-181483501-CT-C			Likely benign (May 04, 2021)
1-181483501-C-CT			Likely benign (Mar 23, 2021)
1-181483501-C-CTTT			Likely benign (Mar 28, 2021)
1-181483507-T-C			Likely benign (Mar 30, 2021)
1-181483507-T-TTC			Benign (Mar 28, 2021)
1-181483751-C-T			Uncertain significance (Jun 01, 2023)
1-181483756-C-G			Uncertain significance (Jan 17, 2022)
1-181483758-G-A			Uncertain significance (Feb 10, 2023)
1-181483772-G-T			Benign (Jan 03, 2024)
1-181483776-G-T		Developmental and epileptic encephalopathy, 69	Uncertain significance (May 21, 2020)
1-181483777-G-A			Likely benign (Sep 03, 2023)
1-181483780-A-G			Likely benign (Dec 14, 2023)
1-181483783-G-A			Likely benign (Mar 29, 2021)
1-181483787-G-A			Uncertain significance (Jan 22, 2021)
1-181483794-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 08, 2023)
1-181483797-A-G			Uncertain significance (Jul 28, 2023)
1-181483800-C-G			Uncertain significance (Mar 05, 2020)
1-181483800-C-T		Developmental and epileptic encephalopathy, 69 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 19, 2024)
1-181483801-G-A		Developmental and epileptic encephalopathy, 69	Benign/Likely benign (Jan 27, 2024)
1-181483804-C-A			Uncertain significance (Jul 13, 2023)
1-181483813-G-A			Likely benign (Nov 27, 2023)
1-181483819-G-T			Benign (Nov 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CACNA1E	protein_coding	protein_coding	ENST00000367573	48	394982

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.41e-13	124421	0	285	124706	0.00114

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.81	750	1.35e+3	0.555	0.0000825	15170
Missense in Polyphen		80	188.49	0.42443		1974
Synonymous	-0.213	527	521	1.01	0.0000314	4519
Loss of Function	9.29	8	116	0.0690	0.00000666	1288

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00455	0.00436
Ashkenazi Jewish	0.000200	0.000199
East Asian	0.000447	0.000445
Finnish	0.00146	0.00144
European (Non-Finnish)	0.00142	0.00140
Middle Eastern	0.000447	0.000445
South Asian	0.00	0.00
Other	0.00235	0.00231

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-1E gives rise to R-type calcium currents. R-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by nickel. They are however insensitive to dihydropyridines (DHP). Calcium channels containing alpha-1E subunit could be involved in the modulation of firing patterns of neurons which is important for information processing.
• Pathway: Type II diabetes mellitus - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Celecoxib Pathway, Pharmacodynamics;Sympathetic Nerve Pathway (Pre- and Post- Ganglionic Junction);MAPK Signaling Pathway;Calcium Regulation in the Cardiac Cell;Metabolism;Regulation of insulin secretion;Neuronal System;Presynaptic depolarization and calcium channel opening;Transmission across Chemical Synapses;Integration of energy metabolism (Consensus)

Recessive Scores

• pRec: 0.322

Intolerance Scores

• loftool: 0.00131
• rvis_EVS: -2.71
• rvis_percentile_EVS: 0.71

Haploinsufficiency Scores

• pHI: 0.533
• hipred: Y
• hipred_score: 0.774
• ghis: 0.640

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.796

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cacna1e
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal phenotype; 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)

Gene ontology

• Biological process: calcium ion transport;chemical synaptic transmission;regulation of ion transmembrane transport;regulation of insulin secretion;membrane depolarization;calcium ion import;calcium ion transmembrane transport
• Cellular component: plasma membrane;voltage-gated calcium channel complex
• Molecular function: voltage-gated calcium channel activity;calcium channel activity;calcium ion binding