Gene: CACNA1C

Alternate names for this Gene: CACH2|CACN2|CACNL1A1|CCHL1A1|CaV1.2|LQT8|TS|TS. LQT8

Gene Summary: This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. There are multiple isoforms of each of these proteins, either encoded by different genes or the result of alternative splicing of transcripts. The protein encoded by this gene binds to and is inhibited by dihydropyridine. Alternative splicing results in many transcript variants encoding different proteins. Some of the predicted proteins may not produce functional ion channel subunits.

Gene is located in Chromosome: 12

Location in Chromosome : 12p13.33

Description of this Gene: calcium voltage-gated channel subunit alpha1 C

Type of Gene: protein-coding

rs11062098 in CACNA1C gene and Adolescent idiopathic scoliosis PMID 30019117 2018 The coexistence of copy number variations (CNVs) and single nucleotide polymorphisms (SNPs) at a locus can result in distorted calculations of the significance in associating SNPs to disease.

rs1006737 in CACNA1C gene and Attention deficit hyperactivity disorder PMID 23453885 2013 Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.

rs1006737 in CACNA1C gene and Bipolar Disorder PMID 23070075 2013 Replication of bipolar disorder susceptibility alleles and identification of two novel genome-wide significant associations in a new bipolar disorder case-control sample.

PMID 23453885 2013 Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.

PMID 18711365 2008 Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder.

PMID 20351715 2011 Meta-analysis of genome-wide association data of bipolar disorder and major depressive disorder.

PMID 24280982 2014 Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia.

PMID 23637625 2013 Improved detection of common variants associated with schizophrenia and bipolar disorder using pleiotropy-informed conditional false discovery rate.

PMID 21926972 2011 Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.

PMID 28072414 2017 Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder.

PMID 30626913 2019 Bivariate genome-wide association analyses of the broad depression phenotype combined with major depressive disorder, bipolar disorder or schizophrenia reveal eight novel genetic loci for depression.

rs2108635 in CACNA1C gene and Body mass index PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs121912775 in CACNA1C gene and Brugada Syndrome 3 PMID 17224476 2007 Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death.

rs1057517711 in CACNA1C gene and Cardiomyopathy, Familial Hypertrophic, 1 (disorder) PMID 26253506 2015 Identification and Functional Characterization of a Novel CACNA1C-Mediated Cardiac Disorder Characterized by Prolonged QT Intervals With Hypertrophic Cardiomyopathy, Congenital Heart Defects, and Sudden Cardiac Death.

rs1006737 in CACNA1C gene and Child Development Disorders, Pervasive PMID 23453885 2013 Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.

PMID 28540026 2017 Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

rs4765961 in CACNA1C gene and Common Variable Immunodeficiency PMID 21497890 2011 Genome-wide association identifies diverse causes of common variable immunodeficiency.

rs10491964 in CACNA1C gene and Corpuscular Hemoglobin Concentration Mean PMID 23222517 2012 Seventy-five genetic loci influencing the human red blood cell.

rs55935819 in CACNA1C gene and Diastolic blood pressure PMID 30224653 2018 Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.

rs7311607 in CACNA1C gene and Hematocrit procedure PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

PMID 23222517 2012 Seventy-five genetic loci influencing the human red blood cell.

rs2239051 in CACNA1C gene and High density lipoprotein measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs2007044 in CACNA1C gene and Intelligence PMID 31374203 2019 Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.

rs587782933 in CACNA1C gene and Long QT Syndrome PMID 26822303 2016 Arrhythmogenesis in Timothy Syndrome is associated with defects in Ca(2+)-dependent inactivation.

PMID 25691416 2015 Expanding the phenotype of Timothy syndrome type 2: an adolescent with ventricular fibrillation but normal development.

PMID 24773605 2014 Exome sequencing helped the fine diagnosis of two siblings afflicted with atypical Timothy syndrome (TS2).

PMID 23979604 2014 A rare mutation of CACNA1C in a patient with bipolar disorder, and decreased gene expression associated with a bipolar-associated common SNP of CACNA1C in brain.

PMID 21685391 2011 Timothy mutation disrupts the link between activation and inactivation in Ca(V)1.2 protein.

PMID 15863612 2005 Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations.

PMID 23677916 2013 This mutation, Pro857Arg-CACNA1C, cosegregated with the disease within the pedigree, was ranked by 3 disease-network algorithms as the most probable LQTS-susceptibility gene and involves a conserved residue localizing to the proline, gltamic acid, serine, and threonine (PEST) domain in the II-III linker.

PMID 26253506 2015 Through whole exome sequencing and expanded cohort screening, we identified a novel genetic substrate p.Arg518Cys/His-CACNA1C, in patients with a complex phenotype including LQTS, HCM, and congenital heart defects annotated as cardiac-only Timothy syndrome.

PMID 23578275 2014 Imaging diagnosis-ultrasonographic and CT findings in a gray seal (Halichoerus grypus) with hepatic cirrhosis, pyelonephritis, and nephrolithiasis.

PMID 23580742 2013 Timothy syndrome (TS) is a rare long-QT syndrome caused by CACNA1C mutations G406R in exon 8A (TS1) and G402S/G406R in exon 8 (TS2).

PMID 18250309 2008 The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels.

PMID 23690510 2013 Maternal mosaicism confounds the neonatal diagnosis of type 1 Timothy syndrome.

PMID 21910241 2011 Somatic mosaicism contributes to phenotypic variation in Timothy syndrome.

PMID 23631430 2013 Results of genetic testing in 855 consecutive unrelated patients referred for long QT syndrome in a clinical laboratory.

PMID 26227324 2015 Long QT syndrome with craniofacial, digital, and neurologic features: Is it useful to distinguish between Timothy syndrome types 1 and 2?

PMID 19074970 2009 The Timothy syndrome mutation of cardiac CaV1.2 (L-type) channels: multiple altered gating mechanisms and pharmacological restoration of inactivation.

PMID 15454078 2004 Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism.

rs1006737 in CACNA1C gene and Major Depressive Disorder PMID 23453885 2013 Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.

PMID 20351715 2011 Meta-analysis of genome-wide association data of bipolar disorder and major depressive disorder.

PMID 22472876 2013 A mega-analysis of genome-wide association studies for major depressive disorder.

PMID 30626913 2019 Bivariate genome-wide association analyses of the broad depression phenotype combined with major depressive disorder, bipolar disorder or schizophrenia reveal eight novel genetic loci for depression.

rs1006737 in CACNA1C gene and Mental disorders PMID 24280982 2014 Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia.

rs1006737 in CACNA1C gene and Psychotic Disorders PMID 24280982 2014 Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia.

rs2283274 in CACNA1C gene and RESTING HEART RATE PMID 29769521 2018 Thirty loci identified for heart rate response to exercise and recovery implicate autonomic nervous system.

PMID 27798624 2016 Identification of genomic loci associated with resting heart rate and shared genetic predictors with all-cause mortality.

rs16929368 in CACNA1C gene and Red Blood Cell Count measurement PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

PMID 29403010 2018 Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.

PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs11062098 in CACNA1C gene and SCOLIOSIS, ISOLATED, SUSCEPTIBILITY TO, 3 PMID 30019117 2018 The coexistence of copy number variations (CNVs) and single nucleotide polymorphisms (SNPs) at a locus can result in distorted calculations of the significance in associating SNPs to disease.

rs1006737 in CACNA1C gene and Schizophrenia PMID 24280982 2014 Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia.

PMID 23974872 2013 Genome-wide association analysis identifies 13 new risk loci for schizophrenia.

PMID 23453885 2013 Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.

PMID 28540026 2017 Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

PMID 30285260 2019 Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.

PMID 30626913 2019 Bivariate genome-wide association analyses of the broad depression phenotype combined with major depressive disorder, bipolar disorder or schizophrenia reveal eight novel genetic loci for depression.

PMID 26198764 2015 Genome-wide association study of schizophrenia in Ashkenazi Jews.

PMID 31268507 2019 Association of Schizophrenia Risk With Disordered Niacin Metabolism in an Indian Genome-wide Association Study.

PMID 31374203 2019 Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.

PMID 29483656 2018 Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection.

PMID 25056061 2014 Biological insights from 108 schizophrenia-associated genetic loci.

PMID 28991256 2017 Genome-wide association analysis identifies 30 new susceptibility loci for schizophrenia.

PMID 29503163 2018 Five novel loci associated with antipsychotic treatment response in patients with schizophrenia: a genome-wide association study.

PMID 22688191 2012 Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder.

PMID 23637625 2013 Improved detection of common variants associated with schizophrenia and bipolar disorder using pleiotropy-informed conditional false discovery rate.

PMID 21926974 2011 Genome-wide association study identifies five new schizophrenia loci.

rs2239051 in CACNA1C gene and Serum HDL cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs16929460 in CACNA1C gene and Serum total cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs786205745 in CACNA1C gene and Timothy syndrome PMID 15454078 2004 Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism.

rs12322010 in CACNA1C gene and Triglycerides measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs117888112 in CACNA1C gene and mathematical ability PMID 30038396 2018 Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.