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CACNA1D Gene

protein-coding   GIFtS: 64
GCID: GC03P053504

Calcium Channel, Voltage-Dependent, L Type, Alpha 1D Subunit


(Previous symbols: CCHL1A2, CACNL1A2)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Calcium Channel, Voltage-Dependent, L Type, Alpha 1D Subunit1 2     Calcium Channel, L Type, Alpha-1 Polypeptide2
CACNL1A21 2 3 5     Calcium Channel, Neuroendocrine/Brain-Type, Alpha 1 Subunit2
CCHL1A21 2 3 5     Voltage-Dependent L-Type Calcium Channel Subunit Alpha-1D2
CACH32 3     Voltage-Gated Calcium Channel Alpha 1 Subunit2
CACN42 3     Voltage-Gated Calcium Channel Alpha Subunit Cav1.32
PASNA2 5     Calcium Channel, L Type, Alpha-1 Polypeptide, Isoform 23
SANDD2 5     Voltage-Gated Calcium Channel Subunit Alpha Cav1.33
Cav1.32     

External Ids:    HGNC: 13911   Entrez Gene: 7762   Ensembl: ENSG000001573887   OMIM: 1142065   UniProtKB: Q016683   

Export aliases for CACNA1D gene to outside databases

Previous GC identifers: GC03P052645 GC03P052780 GC03P053383 GC03P053486


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for CACNA1D Gene:
Voltage-dependent calcium channels 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,
and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and
gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas the others act as
auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related
primarily to the expression of a variety of alpha-1 isoforms, namely alpha-1A, B, C, D, E, and S. This gene
encodes the alpha-1D subunit. Several transcript variants encoding different isoforms have been found for this
gene. (provided by RefSeq, Dec 2012)

GeneCards Summary for CACNA1D Gene:
CACNA1D (calcium channel, voltage-dependent, L type, alpha 1D subunit) is a protein-coding gene. Diseases associated with CACNA1D include sinoatrial node dysfunction and deafness, and primary aldosteronism, seizures, and neurologic abnormalities. GO annotations related to this gene include voltage-gated calcium channel activity and alpha-actinin binding. An important paralog of this gene is SCN5A.

UniProtKB/Swiss-Prot: CAC1D_HUMAN, Q01668
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. The isoform alpha-1D
gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage
activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by
omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and
omega-agatoxin-IVA (omega-Aga-IVA)

summary for CACNA1D Gene:
Voltage-gated calcium channels (CaV) are present in the membrane of most excitable cells and mediate calcium
influx in response to depolarisation. They regulate intracellular processes such as contraction, secretion,
neurotransmission and gene expression. Voltage-gated calcium channels are formed from four or five distinct
subunits; the alpha-subunit is the largest subunit and incorporates the voltage sensor, conduction pore and
gating apparatus. Using pharmacological and electrophysiological techniques, at least 6 types of
voltage-gated channels have been identified: L, N, P, Q, R and T, which are grouped into three families.
Cav1.x are high-voltage-activated dihydropyridine-sensitive (L-type), Cav2.x are high-voltage-activated
dihydropyridine-insensitive (N-, P- Q- and R-types) and Cav3.x are low-voltage-activated channels (T-type).

Gene Wiki entry for CACNA1D (Cav1.3) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000003.12  NT_022517.19  NC_018914.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the CACNA1D gene promoter:
         HOXA9   CREB   deltaCREB   Nkx2-5   Meis-1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidCACNA1D promoter sequence
   Search Chromatin IP Primers for CACNA1D

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat CACNA1D


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 3p14.3   Ensembl cytogenetic band:  3p21.1   HGNC cytogenetic band: 3p14.3

CACNA1D Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CACNA1D gene location

GeneLoc information about chromosome 3         GeneLoc Exon Structure

GeneLoc location for GC03P053504:  view genomic region     (about GC identifiers)

Start:
53,528,683 bp from pter      End:
53,847,760 bp from pter
Size:
319,078 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: CAC1D_HUMAN, Q01668 (See protein sequence)
Recommended Name: Voltage-dependent L-type calcium channel subunit alpha-1D  
Size: 2161 amino acids; 245141 Da
Subunit: Voltage-dependent calcium channels are multisubunit complexes, consisting of alpha-1, alpha-2, beta and
delta subunits in a 1:1:1:1 ratio. The channel activity is directed by the pore-forming and voltage-sensitive
alpha-1 subunit. In many cases, this subunit is sufficient to generate voltage-sensitive calcium channel
activity. The auxiliary subunits beta and alpha-2/delta linked by a disulfide bridge regulate the channel
activity. Channel activity is further modulated, depending on the presence of specific delta subunit isoforms.
Interacts (via IQ domain) with CABP1 and CABP4 in a calcium independent manner (By similarity). Interacts with
RIMBP2 (By similarity)
1 PDB 3D structure from and Proteopedia for CACNA1D:
3LV3 (3D)    
Secondary accessions: B0FYA3 Q13916 Q13931 Q71UT1 Q9UDC3
Alternative splicing: 4 isoforms:  Q01668-1   Q01668-2   Q01668-4   Q01668-3   (Expressed at 5% to 15% of isoform Neuronal-type in brain tissues, increased current density)

Explore the universe of human proteins at neXtProt for CACNA1D: NX_Q01668

Explore proteomics data for CACNA1D at MOPED

Post-translational modifications: 

  • Glycosylation2 at Asn155, Asn225, Asn329
  • Modification sites at PhosphoSitePlus

  • See CACNA1D Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (3 alternative transcripts): 
    NP_000711.1  NP_001122311.1  NP_001122312.1  

    ENSEMBL proteins: 
     ENSP00000288133   ENSP00000288139   ENSP00000409174   ENSP00000418045   ENSP00000418014  
     ENSP00000438229   ENSP00000440956  
    Reactome Protein details: Q01668

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    CACN: Calcium channel subunits
    CACN1: Voltage-gated ion channels / Calcium channels

    IUPHAR Guide to PHARMACOLOGY protein family classification: Cav1.3
    Voltage-gated calcium channels

    Selected InterPro protein domains (see all 6):
     IPR005446 VDCC_L_a1su
     IPR014873 VDCC_a1su_IQ
     IPR005821 Ion_trans_dom
     IPR027359 Channel_four-helix_dom
     IPR002077 VDCCAlpha1

    Graphical View of Domain Structure for InterPro Entry Q01668

    ProtoNet protein and cluster: Q01668

    3 Blocks protein domains:
    IPB002077 Calcium channel signature
    IPB005446 L-type voltage-dependent calcium channel alpha-1 subunit signature
    IPB005452 Voltage-dependent L-type calcium channel alpha-1D subunit signature


    UniProtKB/Swiss-Prot: CAC1D_HUMAN, Q01668
    Domain: Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6)
    and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are
    characterized by a series of positively charged amino acids at every third position
    Similarity: Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1D subfamily


    CACNA1D for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: CAC1D_HUMAN, Q01668
    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. The isoform alpha-1D
    gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage
    activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by
    omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and
    omega-agatoxin-IVA (omega-Aga-IVA)

         Genatlas biochemistry entry for CACNA1D:
    transverse tubule (TT) calcium voltage-gated channel (VDCC),L type,alpha 1D subunit,175kDa,dihydropyridine (DHP)
    sensitive,isoform 2,neuroendocrine/brain

         Gene Ontology (GO): Selected molecular function terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005216ion channel activity ----
    GO:0005245voltage-gated calcium channel activity IDA11160515
    GO:0005515protein binding ----
    GO:0008331contributes to high voltage-gated calcium channel activity IDA1309651
    GO:0030506ankyrin binding ISS--
         
    CACNA1D for ontologies           About GeneDecksing


    Phenotypes:
         9 MGI mutant phenotypes (inferred from 4 alleles(MGI details for Cacna1d):
     behavior/neurological  cardiovascular system  cellular  endocrine/exocrine gland  growth/size/body 
     hearing/vestibular/ear  homeostasis/metabolism  mortality/aging  nervous system 

    CACNA1D for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for CACNA1D: Cacna1dtm1Hssh Cacna1dtm1Jst

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for CACNA1D
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    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate CACNA1D (see all 48):
    hsa-miR-607 hsa-miR-3146 hsa-let-7d hsa-miR-938 hsa-let-7a-2* hsa-miR-30d hsa-let-7g hsa-miR-30a
    SwitchGear 3'UTR luciferase reporter plasmidCACNA1D 3' UTR sequence
    Inhib. RNA
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    CAC1D_HUMAN, Q01668: Membrane; Multi-pass membrane protein
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5
    cytosol1
    nucleus1

    Gene Ontology (GO): 4 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005886plasma membrane TAS--
    GO:0005891voltage-gated calcium channel complex IDA11160515
    GO:0016020membrane ----
    GO:0030018Z disc ISS--

    CACNA1D for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for CACNA1D About   (see all 46)  
    See pathways by source

    SuperPathContained pathways About
    1Hypertrophic cardiomyopathy (HCM)
    Hypertrophic cardiomyopathy (HCM)0.75
    Arrhythmogenic right ventricular cardiomyopathy (ARVC)0.54
    Dilated cardiomyopathy0.75
    Arrhythmogenic right ventricular cardiomyopathy0.54
    2ADP signalling through P2Y purinoceptor 12
    Inhibition of Insulin Secretion by Adrenaline/Noradrenaline0.64
    Beta-agonist/Beta-blocker Pathway, Pharmacodynamics0.34
    3Alzheimer's disease
    Alzheimers Disease0.44
    Alzheimer's disease0.44
    4Type II diabetes mellitus
    Type II diabetes mellitus0.38
    Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics0.38
    5Circadian entrainment
    GABAergic synapse0.53
    Dopaminergic synapse0.37
    Retrograde endocannabinoid signaling0.51
    Cholinergic synapse0.37
    Circadian entrainment0.40
    Serotonergic synapse0.33
    Glutamatergic synapse0.39

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for CACNA1D (see all 40)
        Caspase Cascade
    Fc-GammaR Pathway
    Intracellular Calcium Signaling
    PDGF Pathway
    BMP Pathway

    1 GeneGo (Thomson Reuters) Pathway for CACNA1D
        Transcription CREB pathway

    3 BioSystems Pathways for CACNA1D
        Calcium Regulation in the Cardiac Cell
    Arrhythmogenic right ventricular cardiomyopathy
    Alzheimers Disease

    3 Reactome Pathways for CACNA1D
        NCAM1 interactions
    Regulation of insulin secretion
    Adrenaline,noradrenaline inhibits insulin secretion

    Selected PharmGKB Pathways for CACNA1D (see all 7)
        Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics
    Antiarrhythmic Pathway, Pharmacodynamics
    Beta-agonist/Beta-blocker Pathway, Pharmacodynamics
    Celecoxib Pathway, Pharmacodynamics
    Sympathetic Nerve Pathway (Neuroeffector Junction)

    Selected Kegg Pathways  (Kegg details for CACNA1D) (see all 22):
        MAPK signaling pathway
    Calcium signaling pathway
    Cardiac muscle contraction
    Adrenergic signaling in cardiomyocytes
    Vascular smooth muscle contraction


    CACNA1D for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Array including CACNA1D: 
              Neuronal Ion Channels in human mouse rat

    Interactions:

        Search GeneGlobe Interaction Network for CACNA1D

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for CACNA1D (Q016683 ENSP000002881394) via UniProtKB, MINT, STRING, and/or I2D (see all 65)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CALB1P059373, ENSP000002654314I2D: score=1 STRING: ENSP00000265431
    STX1AQ166233, ENSP000002228124I2D: score=2 STRING: ENSP00000222812
    GABBR2O758993, ENSP000002594554I2D: score=1 STRING: ENSP00000259455
    CACNB4O003053I2D: score=1 
    CACNA1CENSP000002663764STRING: ENSP00000266376
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 19):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006112energy reserve metabolic process TAS--
    GO:0006811ion transport ----
    GO:0006816calcium ion transport IDA11160515
    GO:0007188adenylate cyclase-modulating G-protein coupled receptor signaling pathway ISS--
    GO:0007411axon guidance TAS--

    CACNA1D for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Compounds for CACNA1D available from Tocris Bioscience    About this table
    CompoundAction CAS #
    omega-Conotoxin GVIACa2+ channel blocker (N-type)[106375-28-4]
    (+-)-Bay K 8644Ca2+-channel activator (L-type)[71145-03-4]
    NNC 55-0396 dihydrochlorideHighly selective Ca2+ channel blocker (T-type)[357400-13-6]
    PregabalinAnticonvulsant. Selectively binds the alpha2delta subunit of voltage-sensitive calcium channels[148553-50-8]
    Mibefradil dihydrochlorideCa2+ channel blocker (T-type)[116644-53-2]

    2 HMDB Compounds for CACNA1D    About this table
    CompoundSynonyms CAS #PubMed Ids
    CalciumCa (see all 2)7440-70-2--
    VerapamilAkilen (see all 107)52-53-9--

    Selected DrugBank Compounds for CACNA1D (see all 14)    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    NimodipineNimodipino [INN-Spanish] (see all 2)66085-59-4targetinhibitor20335610 17705883 20334460 19844625 20661350 19029287
    Mibefradil-- 116644-53-2targetinhibitor10372226 10665814 16899990
    Cinnarizine-- 298-57-7targetinhibitor3530295 1281221
    Isradipine(+/-)-Isradipine (see all 5)75695-93-1targetinhibitor11285265 19029287
    Nifedipine-- 21829-25-4targetinhibitor11160515 19029287
    AmlodipineAmlodipine Benzenesulfonate (see all 6)88150-42-9targetinhibitor19029287
    Clevidipine-- 166432-28-6target--15492770
    FelodipineDl-Felodipine (see all 4)72509-76-3targetinhibitor19029287
    NicardipineNicardipine HCl (see all 3)55985-32-5targetinhibitor11160515
    Nilvadipine-- 75530-68-6targetinhibitor19029287

    5 IUPHAR Ligands for CACNA1D (Cav1.3)    About this table
    LigandTypeActionAffinityPubmed IDs
    [3H](+)-isradipine
    Gating inhibitorNone9.411285265
    (-)-(S)-BayK8644
    ActivatorNone9.4--
    isradipine
    Gating inhibitorNone9.411285265
    verapamil
    Channel blockerNone9.4--
    BAYK 8644
    ActivatorNone9.411285265 10929716

    2 Novoseek inferred chemical compound relationships for CACNA1D gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    calcium 54.1 24 1664412 (2), 7760845 (2), 8392192 (1), 1316766 (1) (see all 18)
    sodium 7.58 1 15072700 (1)



    CACNA1D for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for CACNA1D gene (3 alternative transcripts): 
    NM_000720.3  NM_001128839.2  NM_001128840.2  

    Unigene Cluster for CACNA1D:

    Calcium channel, voltage-dependent, L type, alpha 1D subunit
    Hs.476358  [show with all ESTs]
    Unigene Representative Sequence: NM_000720
    9 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000350061 ENST00000288139(uc003dgu.4 uc003dgv.4 uc003dgy.4 uc003dgw.4 uc011bes.2)
    ENST00000422281 ENST00000481085 ENST00000464429 ENST00000481478(uc003dgx.1)
    ENST00000498251 ENST00000540742 ENST00000544977
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    hsa-miR-607 hsa-miR-3146 hsa-let-7d hsa-miR-938 hsa-let-7a-2* hsa-miR-30d hsa-let-7g hsa-miR-30a
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    Additional mRNA sequence: 

    AB209171.1 AK294397.1 AK294585.1 EU363339.1 M76558.1 M83566.1 

    4 DOTS entries:

    DT.92419568  DT.112598  DT.40313005  DT.70100900 

    Selected AceView cDNA sequences (see all 125):

    AA885585 AA861160 NM_000720 AA701888 AI361691 BE672659 BQ016847 R46658 
    AI914244 CA389011 AA703120 BI758971 BE550599 M83566 C21063 BV197217 
    N85902 N46744 BU182632 AI248998 BQ549084 AA978315 AI051972 BQ549571 

    GeneLoc Exon Structure

    3 Alternative Splicing Database (ASD) splice patterns (SP) for CACNA1D    About this scheme

    ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^ 24 ^ 25 ^ 26 ^
    SP1:                                                                                                                                                            
    SP2:                                                                                                                                                            
    SP3:                                                                                                                                                            

    ExUns: 27 ^ 28 ^ 29 ^ 30 ^ 31 ^ 32 ^ 33 ^ 34 ^ 35 ^ 36 ^ 37 ^ 38 ^ 39 ^ 40a · 40b ^ 41 ^ 42 ^ 43 ^ 44a · 44b ^ 45 ^ 46 ^ 47
    SP1:                                                                                                                                          
    SP2:                                                                                                  -                                       
    SP3:                                                                                                                                          


    ECgene alternative splicing isoforms for CACNA1D

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    CACNA1D expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GGTCCTAATA
    CACNA1D Expression
    About this image


    CACNA1D expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 2) fully expand
     
     Dermis (Integumentary System)    fully expand to see all 2 entries
             Zigzag Dermal Papilla Cells Dermal Papilla
     
     Ovary (Reproductive System)
             Pre-Granulosa Cells Primordial Follicle
    CACNA1D Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    CACNA1D Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.476358

    UniProtKB/Swiss-Prot: CAC1D_HUMAN, Q01668
    Tissue specificity: Expressed in pancreatic islets and in brain, where it has been seen in cerebral cortex,
    hippocampus, basal ganglia, habenula and thalamus. Expressed in the small cell lung carcinoma cell line SCC-9. No
    expression in skeletal muscle

        Pathway & Disease-focused RT2 Profiler PCR Array including CACNA1D: 
              Neuronal Ion Channels in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

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    This gene was present in the common ancestor of animals.

    Orthologs for CACNA1D gene from Selected species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Cacna1d1 , 5 calcium channel, voltage-dependent, L type, alpha 1D more1, 5 91.07(n)1
    97.19(a)1
      14 (18.43 cM)5
    122891  NM_001083616.11  NP_001077085.11 
     300399495 
    chicken
    (Gallus gallus)
    Aves CACNA1D1 calcium channel, voltage-dependent, L type, alpha 1D more 80.48(n)
    88.22(a)
      395895  NM_205034.2  NP_990365.1 
    zebrafish
    (Danio rerio)
    Actinopterygii cacna1da1 calcium channel, voltage-dependent, L type, alpha 1D more 73(n)
    79.81(a)
      403310  NM_203484.1  NP_982351.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Ca-alpha1D1 , 3 epithelial fluid transport
    voltage-gated calcium more3
    Ca[2+]-channel protein alpha[[1]] subunit D1
    63(a)3
    62.11(n)1
    65.76(a)1
      349501  NM_001273555.11  NP_001260484.11 
    worm
    (Caenorhabditis elegans)
    Secernentea egl-191 , 3 Expression: neurons, preanal ganglion,
    ring neurons, more3
    egl-191
    66(a)
    (best of 3)3
    60.49(n)1
    64.33(a)1
      IV(7405770-7418097)3
    1775131  NM_001027908.31  NP_001023079.11 


    ENSEMBL Gene Tree for CACNA1D (if available)
    TreeFam Gene Tree for CACNA1D (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for CACNA1D gene
    SCN5A2  SCN9A2  SCN7A2  CACNA1I2  CACNA1F2  CACNA1G2  SCN8A2  SCN10A2  
    SCN3A2  SCN2A2  CACNA1S2  CACNA1C2  CACNA1H2  SCN11A2  SCN4A2  SCN1A2  
    11 SIMAP similar genes for CACNA1D using alignment to 5 protein entries:     CAC1D_HUMAN (see all proteins):
    CACNA1S    CACNA1H    CACNA1F    CACNA1C    CACNA1B    SCN1A
    SCN5A    CACNA1A    SCN3A    CACNA1E    SCN4A

    CACNA1D for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Polymorphic Variants from UniProtKB/Swiss-Prot
    CAC1D_HUMAN, Q01668: A change from seven to eight ATG trinucleotide repeats, resulting in an additional N-terminal
    methionine, has been found in a patient with non-insulin-dependent diabetes mellitus (NIDDM)


    Selected SNPs for CACNA1D (see all 6759)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 3 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0708684
    Primary aldosteronism, seizures, and neurologic abnormalities (PASNA)4--see VAR_0708682 G D mis40--------
    VAR_0708694
    Primary aldosteronism, seizures, and neurologic abnormalities (PASNA)4--see VAR_0708692 I M mis40--------
    rs1868498651,2
    --53459625(+) GGCTAA/GTTTCT 3 -- us2k10--------
    rs3124841,2
    C,F,A--53459747(-) GAGACT/CGGAGA 3 -- us2k110Minor allele frequency- C:0.31MN NA WA CSA EA 554
    rs37558151,2
    C,F--53459751(+) CAGTCT/GCCAAA 3 -- us2k15Minor allele frequency- G:0.31NA EA 246
    rs1447958651,2
    --53459851(+) CTGGTC/TCCCAG 3 -- us2k10--------
    rs1386299571,2
    --53459853(+) GGTCCC/GCAGTC 3 -- us2k10--------
    rs37558161,2
    C,F--53459897(+) GACTAG/CTGTGT 3 -- us2k1 tfbs31Minor allele frequency- C:0.14EA 120
    rs1501014711,2
    C--53460515(+) CCCAA-/CCCCCC 3 -- us2k10--------
    rs1417394081,2
    --53460633(+) CTACCA/GCCCGC 3 -- us2k10--------

    HapMap Linkage Disequilibrium report for CACNA1D (53528683 - 53778683 bp, first 250kb of CACNA1D)

    Structural Variations
         Database of Genomic Variants (DGV) 8 variations for CACNA1D:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2725284CNV Deletion23290073
    esv2673204CNV Deletion23128226
    nsv3826CNV Insertion18451855
    nsv520027CNV Loss19592680
    nsv876803CNV Loss21882294
    nsv521276CNV Loss19592680
    dgv283n21CNV Loss19592680
    nsv876804CNV Gain21882294

    Human Gene Mutation Database (HGMD): CACNA1D
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing CACNA1D
    DNA2.0 Custom Variant and Variant Library Synthesis for CACNA1D

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 114206   
    OMIM disorders: 614896  615474  
    UniProtKB/Swiss-Prot: CAC1D_HUMAN, Q01668
  • Sinoatrial node dysfunction and deafness (SANDD) [MIM:614896]: A disease characterized by congenital
    severe to profound deafness without vestibular dysfunction, associated with episodic syncope due to intermittent
    pronounced bradycardia. Note=The disease is caused by mutations affecting the gene represented in this entry

  • Selected diseases for CACNA1D (see all 28):    
    About MalaCards
    sinoatrial node dysfunction and deafness    primary aldosteronism, seizures, and neurologic abnormalities    hypokalemic periodic paralysis    congenital heart block
    lambert-eaton myasthenic syndrome    congenital stationary night blindness    night blindness    refractive error
    blindness    insulinoma    maturity-onset diabetes of the young    hypertrophic cardiomyopathy
    myopia    hyperparathyroidism    sinusitis    dilated cardiomyopathy
    insulin resistance    diabetes mellitus    cerebritis    neuroblastoma


    CACNA1D for disorders           About GeneDecksing

    1 Novoseek inferred disease relationship for CACNA1D gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    insulinoma 48.5 2 8529524 (1), 7760845 (1)

    Genetic Association Database (GAD): CACNA1D
    Human Genome Epidemiology (HuGE) Navigator: CACNA1D (5 documents)

    Export disorders for CACNA1D gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for CACNA1D gene, integrated from 10 sources (see all 84):
    (articles sorted by number of sources associating them with CACNA1D)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. The structures of the human calcium channel alpha 1 subunit (CACNL1A2) and beta subunit (CACNLB3) genes. (PubMed id 7557998)1, 2, 9 Yamada Y.... Seino Y. (Genomics 1995)
    2. A brain L-type calcium channel alpha 1 subunit gene (CCHL1A2) maps to mouse chromosome 14 and human chromosome 3. (PubMed id 1664412)1, 3, 9 Chin H.M....McBride O.W. (Genomics 1991)
    3. Genetic polymorphisms of L-type calcium channel alpha1C and alpha1D subunit genes are associated with sensitivity to the antihypertensive effects of L-type dihydropyridine calcium-channel blockers. (PubMed id 19225208)1, 4, 9 Kamide K....Kawano Y. (Circ. J. 2009)
    4. Loss of Ca(v)1.3 (CACNA1D) function in a human channelopathy with bradycardia and congenital deafness. (PubMed id 21131953)1, 2 Baig S.M....Bolz H.J. (Nat. Neurosci. 2011)
    5. Genome-wide detection of allele specific copy number variation associated with insulin resistance in African Americans from the HyperGEN study. (PubMed id 21901158)1, 4 Irvin M.R....Arnett D.K. (PLoS ONE 2011)
    6. L-type voltage-dependent calcium channel alpha subunit 1C is a novel candidate gene associated with secondary hyperparathyroidism: an application of haplotype-based analysis for multiple linked single nucleotide polymorphisms. (PubMed id 20424473)1, 4 Yokoyama K....Hosoya T. (Nephron Clin Pract 2010)
    7. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PubMed id 20379614)1, 4 Rose J.E....Uhl G.R. (Mol. Med. 2010)
    8. Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling. (PubMed id 19240061)1, 4 Trynka G....Wijmenga C. (Gut 2009)
    9. Modulation of voltage- and Ca2+-dependent gating of CaV1.3 L-type calcium channels by alternative splicing of a C-terminal regulatory domain. (PubMed id 18482979)1, 2 Singh A.... Koschak A. (J. Biol. Chem. 2008)
    10. alpha 1D (Cav1.3) subunits can form l-type Ca2+ channels activating at negative voltages. (PubMed id 11285265)1, 7 Koschak A....Striessnig J. (J. Biol. Chem. 2001)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 776 HGNC: 1391 AceView: CACNA1D Ensembl:ENSG00000157388 euGenes: HUgn776
    ECgene: CACNA1D Kegg: 776 H-InvDB: CACNA1D

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for CACNA1D Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section

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    Patent Information for CACNA1D gene:
    Search GeneIP for patents involving CACNA1D

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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