CACNA1H
calcium voltage-gated channel subunit alpha1 H, the group of Calcium voltage-gated channel alpha1 subunits
Basic information
Region (hg38): 16:1153103-1224169
Links
Phenotypes
GenCC
Source:
- childhood absence epilepsy (Supportive), mode of inheritance: AD
- epilepsy, childhood absence, susceptibility to, 6 (Limited), mode of inheritance: AD
- hyperaldosteronism, familial, type IV (Strong), mode of inheritance: AD
- epilepsy, childhood absence, susceptibility to, 6 (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Hyperaldosteronism, familial, type IV | AD | Endocrine | Individuals may have severe hypertension, and awareness may allow medical (and possibly surgical, with adrenalectomy) treatment | Endocrine; Neurologic | 12891677; 15048902; 17696120; 25907736 |
ClinVar
This is a list of variants' phenotypes submitted to
- Hyperaldosteronism,_familial,_type_IV (3414 variants)
- Idiopathic_generalized_epilepsy (3208 variants)
- Epilepsy,_childhood_absence,_susceptibility_to,_6 (1010 variants)
- not_provided (564 variants)
- Inborn_genetic_diseases (561 variants)
- CACNA1H-related_disorder (138 variants)
- not_specified (132 variants)
- See_cases (5 variants)
- Epilepsy,_idiopathic_generalized,_susceptibility_to,_6 (2 variants)
- Abnormal_brain_morphology (2 variants)
- Increased_circulating_aldosterone_concentration (2 variants)
- Hand_tremor (1 variants)
- Tremor (1 variants)
- Primary_aldosteronism (1 variants)
- Breast_ductal_adenocarcinoma (1 variants)
- Focal_epilepsy (1 variants)
- Arteriovenous_malformation (1 variants)
- Cerebral_arteriovenous_malformation (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CACNA1H gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021098.3. 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 | 23 | 939 | 118 | 1080 | ||
| missense | 1264 | 595 | 136 | 2003 | ||
| nonsense | 20 | 23 | ||||
| start loss | 0 | |||||
| frameshift | 38 | 38 | ||||
| splice donor/acceptor (+/-2bp) | 16 | 18 | ||||
| Total | 2 | 9 | 1361 | 1534 | 256 |
Highest pathogenic variant AF is 0.000021084068
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CACNA1H | protein_coding | protein_coding | ENST00000348261 | 34 | 68531 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 4.78e-10 | 1.00 | 124689 | 0 | 37 | 124726 | 0.000148 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -2.36 | 1717 | 1.46e+3 | 1.17 | 0.000105 | 14893 |
| Missense in Polyphen | 741 | 726.9 | 1.0194 | 7451 | ||
| Synonymous | -13.0 | 1076 | 653 | 1.65 | 0.0000524 | 4859 |
| Loss of Function | 5.35 | 32 | 85.3 | 0.375 | 0.00000430 | 944 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000243 | 0.000242 |
| Ashkenazi Jewish | 0.000101 | 0.0000994 |
| East Asian | 0.000168 | 0.000167 |
| Finnish | 0.0000508 | 0.0000464 |
| European (Non-Finnish) | 0.000205 | 0.000168 |
| Middle Eastern | 0.000168 | 0.000167 |
| South Asian | 0.0000987 | 0.0000980 |
| Other | 0.000686 | 0.000495 |
dbNSFP
Source:
- Function
- FUNCTION: Voltage-sensitive calcium channel that gives rise to T- type calcium currents. T-type calcium channels belong to the "low- voltage activated (LVA)" group. A particularity of this type of channel is an opening at quite negative potentials, and a voltage- dependent inactivation (PubMed:9670923, PubMed:9930755, PubMed:27149520). 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 (Probable). They may also be involved in the modulation of firing patterns of neurons (PubMed:15048902). In the adrenal zona glomerulosa, participates in the signaling pathway leading to aldosterone production in response to either AGT/angiotensin II, or hyperkalemia (PubMed:25907736, PubMed:27729216). {ECO:0000269|PubMed:25907736, ECO:0000269|PubMed:27149520, ECO:0000269|PubMed:27729216, ECO:0000269|PubMed:9670923, ECO:0000269|PubMed:9930755, ECO:0000305, ECO:0000305|PubMed:15048902}.;
- Disease
- DISEASE: Epilepsy, idiopathic generalized 6 (EIG6) [MIM:611942]: A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. {ECO:0000269|PubMed:15048902}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Epilepsy, childhood absence 6 (ECA6) [MIM:611942]: A subtype of idiopathic generalized epilepsy characterized by an onset at age 6-7 years, frequent absence seizures (several per day) and bilateral, synchronous, symmetric 3-Hz spike waves on EEG. Tonic-clonic seizures often develop in adolescence. Absence seizures may either remit or persist into adulthood. {ECO:0000269|PubMed:12891677}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Hyperaldosteronism, familial, 4 (HALD4) [MIM:617027]: A form of familial hyperaldosteronism, a disorder characterized by hypertension, elevated aldosterone levels despite low plasma renin activity, and abnormal adrenal steroid production. There is significant phenotypic heterogeneity, and some individuals never develop hypertension. {ECO:0000269|PubMed:25907736, ECO:0000269|PubMed:27729216}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- 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;Antiarrhythmic Pathway, Pharmacodynamics;Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Muscle/Heart Contraction;Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Bupranolol Action Pathway;Nebivolol Action Pathway;Amlodipine Action Pathway;Verapamil Action Pathway;Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;Corticotropin-releasing hormone signaling pathway;MAPK Signaling Pathway;Developmental Biology;NCAM signaling for neurite out-growth;NCAM1 interactions;Axon guidance
(Consensus)
Recessive Scores
- pRec
- 0.158
Intolerance Scores
- loftool
- 0.00510
- rvis_EVS
- -2.06
- rvis_percentile_EVS
- 1.63
Haploinsufficiency Scores
- pHI
- 0.121
- hipred
- Y
- hipred_score
- 0.649
- ghis
- 0.555
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.723
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cacna1h
- Phenotype
- nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); muscle phenotype; growth/size/body region phenotype;
Gene ontology
- Biological process
- muscle contraction;muscle organ development;myoblast fusion;regulation of heart contraction;neuronal action potential;aldosterone biosynthetic process;cellular response to hormone stimulus;cortisol biosynthetic process;regulation of ion transmembrane transport;cellular response to potassium ion;regulation of membrane potential;positive regulation of calcium ion-dependent exocytosis;calcium ion import;calcium ion transmembrane transport;membrane depolarization during action potential;inorganic cation transmembrane transport;positive regulation of acrosome reaction
- Cellular component
- plasma membrane;integral component of plasma membrane;voltage-gated calcium channel complex;integral component of membrane
- Molecular function
- voltage-gated ion channel activity;protein binding;low voltage-gated calcium channel activity;metal ion binding;scaffold protein binding