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
genetic developmental and epileptic encephalopathy (Definitive), mode of inheritance: AD
developmental and epileptic encephalopathy, 69 (Strong), mode of inheritance: AD
neurodevelopmental disorder (Moderate), mode of inheritance: AD
developmental and epileptic encephalopathy, 69 (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.

not_provided (2112 variants)
Developmental_and_epileptic_encephalopathy,_69 (237 variants)
Inborn_genetic_diseases (232 variants)
CACNA1E-related_disorder (55 variants)
not_specified (21 variants)
Developmental_and_epileptic_encephalopathy (17 variants)
See_cases (3 variants)
Genetic_developmental_and_epileptic_encephalopathy (2 variants)
Wolff-Parkinson-White_pattern (1 variants)
Van_der_Woude_syndrome_1 (1 variants)
Developmental_and_epileptic_encephalopathy,_14 (1 variants)
Episodic_coma (1 variants)
Intellectual_disability (1 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. These statistics are base on transcript: NM_001205293.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			15 clinvar	525 clinvar	33 clinvar	573
missense	6 clinvar	25 clinvar	603 clinvar	314 clinvar	87 clinvar	1035
nonsense	2 clinvar	1 clinvar	26 clinvar	1 clinvar		30
start loss						0
frameshift		1 clinvar	23 clinvar			24
splice donor/acceptor (+/-2bp)			15 clinvar			15
Total	8	27	682	840	120

Highest pathogenic variant AF is 0.0000013684121

Loading clinvar variants...

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
essential_gene_gene_trap
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