CACNA1I
Basic information
Region (hg38): 22:39570753-39689735
Links
Phenotypes
GenCC
Source:
- 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:
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
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 | 15 | 46 | |||
missense | 166 | 14 | 186 | |||
nonsense | 2 | |||||
start loss | 0 | |||||
frameshift | 2 | |||||
inframe indel | 4 | |||||
splice donor/acceptor (+/-2bp) | 1 | |||||
splice region | 2 | 4 | 2 | 8 | ||
non coding | 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) | ||
22-39570801-G-A | not specified | Uncertain significance (Jan 31, 2023) | ||
22-39570820-C-T | not specified | Uncertain significance (Jan 16, 2024) | ||
22-39570825-C-G | not specified | Uncertain significance (Feb 26, 2024) | ||
22-39570834-C-T | CACNA1I-related disorder | Uncertain significance (Jun 26, 2024) | ||
22-39570851-C-T | CACNA1I-related disorder | Benign (Oct 18, 2019) | ||
22-39570874-C-A | not specified | Uncertain significance (Apr 07, 2022) | ||
22-39570958-G-A | not specified | Uncertain significance (Jan 23, 2024) | ||
22-39598206-A-G | Uncertain significance (Apr 01, 2024) | |||
22-39598223-C-G | Uncertain significance (Feb 11, 2022) | |||
22-39598241-C-G | Likely benign (Mar 01, 2024) | |||
22-39600512-C-T | CACNA1I-related disorder | Likely benign (Oct 28, 2019) | ||
22-39600560-T-G | Uncertain significance (Apr 20, 2023) | |||
22-39600641-T-A | Uncertain significance (Nov 16, 2019) | |||
22-39619316-C-T | CACNA1I-related disorder | Benign (Sep 29, 2017) | ||
22-39619321-A-G | Uncertain significance (Nov 09, 2023) | |||
22-39619356-A-G | not specified | Uncertain significance (Mar 30, 2024) | ||
22-39619404-C-T | Uncertain significance (Dec 16, 2023) | |||
22-39619411-A-G | Uncertain significance (Sep 03, 2021) | |||
22-39634648-A-T | Uncertain significance (Dec 21, 2023) | |||
22-39634680-G-A | CACNA1I-related disorder | Likely benign (May 23, 2019) | ||
22-39634683-C-T | CACNA1I-related disorder | Likely benign (Mar 26, 2019) | ||
22-39634704-C-G | Uncertain significance (Feb 01, 2022) | |||
22-39634705-C-A | not specified | Uncertain significance (Jul 09, 2021) | ||
22-39634709-A-C | Ventriculomegaly;Antenatal intracerebral hemorrhage | Uncertain significance (May 12, 2021) |
GnomAD
Source:
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:
- 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