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

ENSG00000100346NCBI:8911OMIM:608230HGNC:1396Uniprot:Q9P0X4AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Neurodevelopmental disorder with speech impairment and with or without seizuresADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingMusculoskeletal; Neurologic33704440

ClinVar

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

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.

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
31
clinvar
15
clinvar
46
missense
166
clinvar
14
clinvar
6
clinvar
186
nonsense
2
clinvar
2
start loss
0
frameshift
2
clinvar
2
inframe indel
4
clinvar
4
splice donor/acceptor (+/-2bp)
1
clinvar
1
splice region
2
4
2
8
non coding
1
clinvar
1
Total 0 0 175 46 21

Variants in CACNA1I

This is a list of pathogenic ClinVar variants found in the CACNA1I region.

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

Position Type Phenotype Significance ClinVar
22-39570772-C-T CACNA1I-related disorder Benign (Jan 20, 2020)3055495
22-39570801-G-A not specified Uncertain significance (Jan 31, 2023)2480003
22-39570820-C-T not specified Uncertain significance (Jan 16, 2024)3136441
22-39570825-C-G not specified Uncertain significance (Feb 26, 2024)3136442
22-39570834-C-T CACNA1I-related disorder Uncertain significance (Jun 26, 2024)3344782
22-39570851-C-T CACNA1I-related disorder Benign (Oct 18, 2019)3060116
22-39570874-C-A not specified Uncertain significance (Apr 07, 2022)3136408
22-39570958-G-A not specified Uncertain significance (Jan 23, 2024)3136421
22-39598206-A-G Uncertain significance (Apr 01, 2024)3239324
22-39598223-C-G Uncertain significance (Feb 11, 2022)2082595
22-39598241-C-G Likely benign (Mar 01, 2024)3067364
22-39600512-C-T CACNA1I-related disorder Likely benign (Oct 28, 2019)3040784
22-39600560-T-G Uncertain significance (Apr 20, 2023)2662858
22-39600641-T-A Uncertain significance (Nov 16, 2019)1310307
22-39619316-C-T CACNA1I-related disorder Benign (Sep 29, 2017)716254
22-39619321-A-G Uncertain significance (Nov 09, 2023)3363982
22-39619356-A-G not specified Uncertain significance (Mar 30, 2024)3262793
22-39619404-C-T Uncertain significance (Dec 16, 2023)3365658
22-39619411-A-G Uncertain significance (Sep 03, 2021)1301215
22-39634648-A-T Uncertain significance (Dec 21, 2023)3365739
22-39634680-G-A CACNA1I-related disorder Likely benign (May 23, 2019)3039285
22-39634683-C-T CACNA1I-related disorder Likely benign (Mar 26, 2019)3047003
22-39634704-C-G Uncertain significance (Feb 01, 2022)1699635
22-39634705-C-A not specified Uncertain significance (Jul 09, 2021)2374676
22-39634709-A-C Ventriculomegaly;Antenatal intracerebral hemorrhage Uncertain significance (May 12, 2021)1077145

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
CACNA1Iprotein_codingprotein_codingENST00000402142 37118985
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.006.35e-71246840141246980.0000561
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense5.057121.21e+30.5910.000075914276
Missense in Polyphen95198.110.479532030
Synonymous-1.485775331.080.00003654536
Loss of Function7.471083.80.1190.00000425938

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00008720.0000872
Ashkenazi Jewish0.000.00
East Asian0.00006080.0000556
Finnish0.0001390.000139
European (Non-Finnish)0.00006280.0000531
Middle Eastern0.00006080.0000556
South Asian0.00003270.0000327
Other0.000.00

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

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

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