Property Summary

NCBI Gene PubMed Count 57
PubMed Score 153.27
PubTator Score 218.75

Knowledge Summary

Patent (3,154)

Expression

  Differential Expression (2)

Disease log2 FC p
acute quadriplegic myopathy -1.020 8.5e-04
psoriasis -1.200 6.6e-05

MLP Assay (10)

AID Type Active / Inconclusive / Inactive Description
686924 other 0 / 0 / 1 ML347 Eurofin Panel Assay for BMP Inhibitor (Probe Compound)
686925 other 0 / 0 / 1 ML352 Eurofin Panel Assay for Choline Transporter Inhibitor (Probe Compound)
686926 other 0 / 0 / 1 ML354 Eurofin Panel Assay for PAR4 Antagonists Inhibitor (Probe Compound)
686927 other 0 / 0 / 1 ML353 Eurofin Panel Assay for mGlu5 SAM Inhibitor (Probe Compound)
743249 screening 1 / 0 / 0 Development of the First Potent, Selective and CNS penetrant M5 Negative Allosteric Modulator (NAM)
743250 screening 1 / 0 / 0 Discovery and characterization of a small molecule allosteric agonists of mas-related G-Protein coupled receptor X1 ( MrgX1)
743251 screening 1 / 0 / 0 Development of a novel orthosteric Muscarinic 5 (M5) antagonist possessing a hig degree of muscarinic subtype selectivity
743252 screening 1 / 0 / 0 Development of the first CNS penetrant Muscarinic 5 (M5) Positive Allosteric Modulator based on a novel non-isatin core
743435 other 0 / 0 / 0 Development of inhibitors for Dopamine D4 Receptors: Eurofin Panel Assay Results
743437 other 0 / 0 / 0 Development of inhibitors for PLD2 (Eurofin Panel Assay Results)

Gene RIF (30)

PMID Text
26252573 CACNA1S and SCN4A mutations are relatively rare in patients with hypokalemic periodic paralysis
25735680 Defects in the genes coding for the skeletal muscle ryanodine receptor and alpha 1 subunit of the dihydropyridine receptor (CACNA1S) have been identified as causative for malignant hyperthermia.
25658027 The authors found one and three rare variants of unknown significance in CACNA1S in the Malignant Hyperthermia and Exertional Heat cohorts
24013571 Exome sequencing revealed one rare cacna1s nonsynonymous variant in a family with malignant hyperthermia
23888875 Aberrant splicing of Cav 1.1 may alter intracellular Ca(2+) signalling in myotonic dystrophy 1 and 2 myotubes. The differing dysregulation of intracellular Ca(2+) handling in DM1 and DM2 may explain their distinct sarcolemmal hyperexcitabilities.
22927026 Data indicate that the presence of either one of these JP-45 variants decreased the sensitivity of the dihydropyridine receptor DHPR to activation.
22140091 Misregulated splicing and altered gating of Ca(V)1.1 calcium channel is associated with muscle weakness in myotonic dystrophy.
21855088 A novel mutation in the CACNA1S gene--p.Arg900Gly--is found in a patient with hypokalemic periodic paralysis; this mutation is subsequently found to affect some of the patient's other family members.
21845430 Affected members of a 5-generation Chinese family with hypokalemic periodic paralysis patients had a novel His916Gln mutation in all male HypoPP patients of the family. Penetrance of the mutation was complete in male carriers, but not female carriers.
21841462 All familial periodic paralysis patients studied have mutations in either CACNA1S or SCN4A, but only 4 sporadic periodic paralysis patients have de novo mutations in CACNA1S (R1239H) and SCN4A (R669x2, R1135H).
21774221 Three SNPs of CACNA1S gene exon 11 were found but could not be associated with thyrotoxic hypokalemic periodic paralysis in people of Han Nationality in Sichuan.
21262876 Expression of transgenic variants of dihydropyridine receptor (alpha1DHPR) subunit leads to replacement of native channels interacting with ryanodine receptor 1 (RyR1), demonstrating molecular remodelling in adult skeletal muscle fibers.
21248738 Mutations in the affected genes cause Malignant Hyperthermia.
20861472 All individuals in the Italian family with malignant hyperthermia showed cosegregation of informative markers close to the voltage-dependent Ca2+ channel alpha-1S-subunit gene. Sequence analysis showed a c.4060A>T transversion.
20424473 Observational study of gene-disease association. (HuGE Navigator)
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
19825159 The study identified a single potentially pathogenic change in CACNA1S (p.Arg174Trp), and highlights that the haplotype structure across CACNA1S is diverse, with a high degree of variability
19825159 Observational study of gene-disease association. (HuGE Navigator)
19779499 Results identify a new mutation in CACNA1S and expand the spectrum of CACNA1S mutations associated with HypoPP.
19191329 Observational study of gene-disease association. (HuGE Navigator)
19187971 A novel method to detect autoantibodies to dihydropyridine receptor (DHPR), found increased DHPR antibody in myasthenia gravis patients compared to controls.
19134469 Ca(V)1.1 Delta 29 splice variant revealed the structural bases underlying the specific gating properties of skeletal muscle Ca(2+) channels, and suggests the existence of a distinct mode of excitation-contraction coupling in developing muscle
19118277 All mutations affected CACNA1S arginine residues, consistent with the gating pore cation leak hypothesis of hypokalemic periodic paralysis. Arginine mutations in S4 segments underlie 90% of hypokalemic periodic paralysis cases.
18229654 A Polish three-generation family with hypokalemic periodic paralysis and a mutation in CACNA1S is investigated.
17587224 We propose that CACNA1S mutations may comprise a previously unrecognized genetic risk factor in a greater spectrum of motor unit disorders including amyotrophic lateral sclerosis.
15726306 a novel Arg528Gly mutation in the CACNA1S gene that causes Hypokalemic periodic paralysis in a Chinese family
15716625 a mutation of the CACNA1S gene may have a role in hypokalemic periodic paralysis
15711422 Observational study of gene-disease association. (HuGE Navigator)
15072700 Observational study of gene-disease association. (HuGE Navigator)
12636044 polymorphisms in the CACNA1S gene is associated with Malignant Hyperthermia

AA Sequence

MEPSSPQDEGLRKKQPKKPVPEILPRPPRALFCLTLENPLRKACISIVEWKPFETIILLTIFANCVALAV      1 - 70
YLPMPEDDNNSLNLGLEKLEYFFLIVFSIEAAMKIIAYGFLFHQDAYLRSGWNVLDFTIVFLGVFTVILE     71 - 140
QVNVIQSHTAPMSSKGAGLDVKALRAFRVLRPLRLVSGVPSLQVVLNSIFKAMLPLFHIALLVLFMVIIY    141 - 210
AIIGLELFKGKMHKTCYFIGTDIVATVENEEPSPCARTGSGRRCTINGSECRGGWPGPNHGITHFDNFGF    211 - 280
SMLTVYQCITMEGWTDVLYWVNDAIGNEWPWIYFVTLILLGSFFILNLVLGVLSGEFTKEREKAKSRGTF    281 - 350
QKLREKQQLDEDLRGYMSWITQGEVMDVEDFREGKLSLDEGGSDTESLYEIAGLNKIIQFIRHWRQWNRI    351 - 420
FRWKCHDIVKSKVFYWLVILIVALNTLSIASEHHNQPLWLTRLQDIANRVLLSLFTTEMLMKMYGLGLRQ    421 - 490
YFMSIFNRFDCFVVCSGILEILLVESGAMTPLGISVLRCIRLLRIFKITKYWTSLSNLVASLLNSIRSIA    491 - 560
SLLLLLFLFIVIFALLGMQLFGGRYDFEDTEVRRSNFDNFPQALISVFQVLTGEDWTSMMYNGIMAYGGP    561 - 630
SYPGMLVCIYFIILFVCGNYILLNVFLAIAVDNLAEAESLTSAQKAKAEEKKRRKMSKGLPDKSEEEKST    631 - 700
MAKKLEQKPKGEGIPTTAKLKIDEFESNVNEVKDPYPSADFPGDDEEDEPEIPLSPRPRPLAELQLKEKA    701 - 770
VPIPEASSFFIFSPTNKIRVLCHRIVNATWFTNFILLFILLSSAALAAEDPIRADSMRNQILKHFDIGFT    771 - 840
SVFTVEIVLKMTTYGAFLHKGSFCRNYFNMLDLLVVAVSLISMGLESSAISVVKILRVLRVLRPLRAINR    841 - 910
AKGLKHVVQCMFVAISTIGNIVLVTTLLQFMFACIGVQLFKGKFFRCTDLSKMTEEECRGYYYVYKDGDP    911 - 980
MQIELRHREWVHSDFHFDNVLSAMMSLFTVSTFEGWPQLLYKAIDSNAEDVGPIYNNRVEMAIFFIIYII    981 - 1050
LIAFFMMNIFVGFVIVTFQEQGETEYKNCELDKNQRQCVQYALKARPLRCYIPKNPYQYQVWYIVTSSYF   1051 - 1120
EYLMFALIMLNTICLGMQHYNQSEQMNHISDILNVAFTIIFTLEMILKLMAFKARGYFGDPWNVFDFLIV   1121 - 1190
IGSIIDVILSEIDTFLASSGGLYCLGGGCGNVDPDESARISSAFFRLFRVMRLIKLLSRAEGVRTLLWTF   1191 - 1260
IKSFQALPYVALLIVMLFFIYAVIGMQMFGKIALVDGTQINRNNNFQTFPQAVLLLFRCATGEAWQEILL   1261 - 1330
ACSYGKLCDPESDYAPGEEYTCGTNFAYYYFISFYMLCAFLVINLFVAVIMDNFDYLTRDWSILGPHHLD   1331 - 1400
EFKAIWAEYDPEAKGRIKHLDVVTLLRRIQPPLGFGKFCPHRVACKRLVGMNMPLNSDGTVTFNATLFAL   1401 - 1470
VRTALKIKTEGNFEQANEELRAIIKKIWKRTSMKLLDQVIPPIGDDEVTVGKFYATFLIQEHFRKFMKRQ   1471 - 1540
EEYYGYRPKKDIVQIQAGLRTIEEEAAPEICRTVSGDLAAEEELERAMVEAAMEEGIFRRTGGLFGQVDN   1541 - 1610
FLERTNSLPPVMANQRPLQFAEIEMEEMESPVFLEDFPQDPRTNPLARANTNNANANVAYGNSNHSNSHV   1611 - 1680
FSSVHYEREFPEETETPATRGRALGQPCRVLGPHSKPCVEMLKGLLTQRAMPRGQAPPAPCQCPRVESSM   1681 - 1750
PEDRKSSTPGSLHEETPHSRSTRENTSRCSAPATALLIQKALVRGGLGTLAADANFIMATGQALADACQM   1751 - 1820
EPEEVEIMATELLKGREAPEGMASSLGCLNLGSSLGSLDQHQGSQETLIPPRL                    1821 - 1873
//

Text Mined References (59)

PMID Year Title
26252573 2015 Mutation analysis of CACNA1S and SCN4A in patients with hypokalemic periodic paralysis.
25735680 2015 Analysis of the entire ryanodine receptor type 1 and alpha 1 subunit of the dihydropyridine receptor (CACNA1S) coding regions for variants associated with malignant hyperthermia in Australian families.
25658027 2015 Next-generation Sequencing of RYR1 and CACNA1S in Malignant Hyperthermia and Exertional Heat Illness.
25416956 2014 A proteome-scale map of the human interactome network.
24013571 2013 Exome sequencing reveals novel rare variants in the ryanodine receptor and calcium channel genes in malignant hyperthermia families.
23888875 2014 Alternative splicing alterations of Ca2+ handling genes are associated with Ca2+ signal dysregulation in myotonic dystrophy type 1 (DM1) and type 2 (DM2) myotubes.
22927026 2013 JP-45/JSRP1 variants affect skeletal muscle excitation-contraction coupling by decreasing the sensitivity of the dihydropyridine receptor.
22140091 2012 Muscle weakness in myotonic dystrophy associated with misregulated splicing and altered gating of Ca(V)1.1 calcium channel.
21931568 2011 Genome-wide association study identifies four loci associated with eruption of permanent teeth.
21855088 2011 A novel mutation in the calcium channel gene in a family with hypokalemic periodic paralysis.
21845430 2012 A novel mutation in CACNA1S gene associated with hypokalemic periodic paralysis which has a gender difference in the penetrance.
21841462 2012 Genotype and phenotype analysis of patients with sporadic periodic paralysis.
21774221 2011 [The relationships between the single nueleotide polymorphisms of CACNA1S gene 11 exon and thyrotoxic hypokalemic periodic paralysis in the people of Han Nationality in Sichuan Province, China].
21262876 2011 Functional expression of transgenic 1sDHPR channels in adult mammalian skeletal muscle fibres.
21248738 2011 Clinical utility gene card for: malignant hyperthermia.
20861472 2010 Identification and functional characterization of malignant hyperthermia mutation T1354S in the outer pore of the Cavalpha1S-subunit.
20424473 2010 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.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
19825159 2009 The role of CACNA1S in predisposition to malignant hyperthermia.
19779499 2009 Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a South American family.
19191329 2009 Increasing the number of diagnostic mutations in malignant hyperthermia.
19187971 2009 Autoantibody to dihydropyridine receptor in myasthenia gravis.
19134469 2009 A CaV1.1 Ca2+ channel splice variant with high conductance and voltage-sensitivity alters EC coupling in developing skeletal muscle.
19118277 2009 Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis.
18229654 2007 Myopathy as the first symptom of hypokalemic periodic paralysis--case report of a girl from a Polish family with CACNA1S (R1239G) mutation.
18162704 2007 The genotype and clinical phenotype of Korean patients with familial hypokalemic periodic paralysis.
17587224 2008 Progressive muscle atrophy with hypokalemic periodic paralysis and calcium channel mutation.
17418573 2007 Hypokalaemic periodic paralysis due to the CACNA1S R1239H mutation in a large African family.
17204937 2007 Abnormal distribution of calcium-handling proteins: a novel distinctive marker in core myopathies.
16710414 2006 The DNA sequence and biological annotation of human chromosome 1.
16382099 2005 International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels.
15726306 2005 Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a Chinese family.
15716625 2005 A Korean family of hypokalemic periodic paralysis with mutation in a voltage-gated calcium channel (R1239G).
15711422 2005 Skeletal muscle dihydropyridine-sensitive calcium channel (CACNA1S) gene mutations in chinese patients with hypokalemic periodic paralysis.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15072700 2004 Absence of ion channels CACN1AS and SCN4A mutations in thyrotoxic hypokalemic periodic paralysis.
15001631 2004 Association of novel single nucleotide polymorphisms in the calcium channel alpha 1 subunit gene (Ca(v)1.1) and thyrotoxic periodic paralysis.
14660679 2004 Interaction of ATP sensor, cAMP sensor, Ca2+ sensor, and voltage-dependent Ca2+ channel in insulin granule exocytosis.
12636044 2003 Identification of new polymorphisms in the CACNA1S gene.
12496092 2002 Multiple regions of RyR1 mediate functional and structural interactions with alpha(1S)-dihydropyridine receptors in skeletal muscle.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11206130 2000 Triad proteins and intracellular Ca2+ transients during development of human skeletal muscle cells in aneural and innervated cultures.
9852570 1998 Gating of the L-type Ca channel in human skeletal myotubes: an activation defect caused by the hypokalemic periodic paralysis mutation R528H.
9668070 1998 Sorcin associates with the pore-forming subunit of voltage-dependent L-type Ca2+ channels.
9199552 1997 Malignant-hyperthermia susceptibility is associated with a mutation of the alpha 1-subunit of the human dihydropyridine-sensitive L-type voltage-dependent calcium-channel receptor in skeletal muscle.
9175745 1997 A genome wide search for susceptibility loci in three European malignant hyperthermia pedigrees.
8838325 1996 The structure of the gene encoding the human skeletal muscle alpha 1 subunit of the dihydropyridine-sensitive L-type calcium channel (CACNL1A3).
8592342 1995 Exclusion of defects in the skeletal muscle specific regions of the DHPR alpha 1 subunit as frequent causes of malignant hyperthermia.
8188298 1994 Refined localization of the alpha 1-subunit of the skeletal muscle L-type voltage-dependent calcium channel (CACNL1A3) to human chromosome 1q32 by in situ hybridization.
8118099 1993 The gene coding for the alpha 1 subunit of the skeletal dihydropyridine receptor (Cchl1a3 = mdg) maps to mouse chromosome 1 and human 1q32.
8004673 1994 Dihydropyridine receptor mutations cause hypokalemic periodic paralysis.
7987325 1994 A calcium channel mutation causing hypokalemic periodic paralysis.
7916735 1993 Assignment of the human gene for the alpha 1 subunit of the skeletal muscle DHP-sensitive Ca2+ channel (CACNL1A3) to chromosome 1q31-q32.
7897626 1995 Mutation in DHP receptor alpha 1 subunit (CACLN1A3) gene in a Dutch family with hypokalaemic periodic paralysis.
7847370 1995 Hypokalemic periodic paralysis and the dihydropyridine receptor (CACNL1A3): genotype/phenotype correlations for two predominant mutations and evidence for the absence of a founder effect in 16 caucasian families.
7713519 1994 Cloning of the human skeletal muscle alpha 1 subunit of the dihydropyridine-sensitive L-type calcium channel (CACNL1A3).
3037387 1987 Primary structure of the receptor for calcium channel blockers from skeletal muscle.
2844809 1988 cAMP-dependent protein kinase rapidly phosphorylates serine- 687 of the skeletal muscle receptor for calcium channel blockers.
1322891 1992 Specific phosphorylation of a COOH-terminal site on the full-length form of the alpha 1 subunit of the skeletal muscle calcium channel by cAMP-dependent protein kinase.