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.

  • 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
41
clinvar
14
clinvar
56
missense
3
clinvar
1
clinvar
399
clinvar
15
clinvar
6
clinvar
424
nonsense
4
clinvar
4
start loss
0
frameshift
6
clinvar
6
splice donor/acceptor (+/-2bp)
1
clinvar
4
clinvar
5
Total 4 1 414 56 20

Highest pathogenic variant AF is 0.0000897443

Loading clinvar variants...

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