CACNA1I

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

Basic information

Region (hg38): 22:39570753-39689735

Links

ENSG00000100346 ∙ NCBI:8911 ∙ OMIM:608230 ∙ HGNC:1396 ∙ Uniprot:Q9P0X4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Moderate), mode of inheritance: AD
• neurodevelopmental disorder with speech impairment and with or without seizures (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with speech impairment and with or without seizures	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	Musculoskeletal; Neurologic	33704440

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CACNA1I gene.

• not_specified (241 variants)
• not_provided (187 variants)
• CACNA1I-related_disorder (69 variants)
• Neurodevelopmental_disorder_with_speech_impairment_and_with_or_without_seizures (42 variants)
• EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
• Antenatal_intracerebral_hemorrhage (1 variants)
• Ventriculomegaly (1 variants)
• Global_developmental_delay (1 variants)
• Congenital_long_QT_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CACNA1I gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021096.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	41	14	56
missense	3	1	399	15	6	424
nonsense			4			4
start loss						0
frameshift			6			6
splice donor/acceptor (+/-2bp)	1		4			5
Total	4	1	414	56	20

Highest pathogenic variant AF is 0.0000897443

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CACNA1I	protein_coding	protein_coding	ENST00000402142	37	118985

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.35e-7	124684	0	14	124698	0.0000561

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.05	712	1.21e+3	0.591	0.0000759	14276
Missense in Polyphen		95	198.11	0.47953		2030
Synonymous	-1.48	577	533	1.08	0.0000365	4536
Loss of Function	7.47	10	83.8	0.119	0.00000425	938

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000872	0.0000872
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000608	0.0000556
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000628	0.0000531
Middle Eastern	0.0000608	0.0000556
South Asian	0.0000327	0.0000327
Other	0.00	0.00

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. This channel gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by nickel and mibefradil. A particularity of this type of channels 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. Gates in voltage ranges similar to, but higher than alpha 1G or alpha 1H (By similarity). {ECO:0000250}.
• Pathway: Cortisol synthesis and secretion - Homo sapiens (human);Aldosterone synthesis and secretion - 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;MAPK Signaling Pathway;Developmental Biology;NCAM signaling for neurite out-growth;NCAM1 interactions;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.124

Intolerance Scores

• loftool: 0.0132
• rvis_EVS: -0.83
• rvis_percentile_EVS: 11.55

Haploinsufficiency Scores

• pHI: 0.216
• hipred: Y
• hipred_score: 0.774
• ghis: 0.549

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.169

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Cacna1i
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland 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); hematopoietic system phenotype; immune system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: signal transduction;neuronal action potential;flagellated sperm motility;sleep;regulation of ion transmembrane transport;positive regulation of calcium ion-dependent exocytosis;calcium ion import;calcium ion transmembrane transport;membrane depolarization during action potential
• Cellular component: plasma membrane;voltage-gated calcium channel complex
• Molecular function: voltage-gated calcium channel activity;protein binding;low voltage-gated calcium channel activity