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
- 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 41 | 14 | 56 | |||
missense | 399 | 15 | 424 | |||
nonsense | 4 | |||||
start loss | 0 | |||||
frameshift | 6 | |||||
splice donor/acceptor (+/-2bp) | 5 | |||||
Total | 4 | 1 | 414 | 56 | 20 |
Highest pathogenic variant AF is 0.0000897443
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