TS
MCID: TMT001
MIFTS: 52

Timothy Syndrome (TS) malady

Genetic diseases, Rare diseases categories

Summaries for Timothy Syndrome

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Sources:
9Disease Ontology, 22Genetics Home Reference, 66Wikipedia, 48OMIM, 20GeneReviews, 34MalaCards
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Disease Ontology:9 An autosomal dominant disease that is characterized by cardiac, hand/foot, facial, and neurodevelopmental features. the two forms are type 1 (classic) and type 2, a rare form caused by mutations in a transcript variant of cacna1c.

MalaCards: Timothy Syndrome, also known as long qt syndrome with syndactyly, is related to long qt syndrome and colorectal cancer. An important gene associated with Timothy Syndrome is CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), and among its related pathways are Post NMDA receptor activation events and Amphetamine addiction. The compounds (+-)-bay k 8644 and nnc 55-0396 dihydrochloride have been mentioned in the context of this disorder. Affiliated tissues include heart, and related mouse phenotypes are cardiovascular system and nervous system.

Genetics Home Reference:22 Timothy syndrome is a rare disorder that affects many parts of the body including the heart, digits (fingers and toes), and the nervous system.

Wikipedia:66 Timothy syndrome is a rare autosomal dominant disorder characterized by physical malformations, as well... more...

Description from OMIM:48 601005

GeneReviews summary for timothy

Aliases & Classifications for Timothy Syndrome

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Sources:
9Disease Ontology, 10diseasecard, 20GeneReviews, 21GeneTests, 23GTR, 22Genetics Home Reference, 48OMIM, 11DISEASES, 50Orphanet, 63UMLS, 37MESH via Orphanet, 27ICD10 via Orphanet, 64UMLS via Orphanet
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Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Genetic diseases, Rare diseases


Characteristics (Orphanet epidemiological data):

50
timothy syndrome:
Inheritance: Autosomal dominant; Prevalence: <1/1000000


Aliases & Descriptions:

timothy syndrome 9 10 20 21 23 22 48 11 50 63
long qt syndrome with syndactyly 20 22
lqt8 22 50
long qt syndrome - syndactyly 50
long qt syndrome type 8 50
ts 22


External Ids:

Disease Ontology9 DOID:0060173
OMIM48 601005
MESH via Orphanet37 C536962
ICD10 via Orphanet27 I45.8
UMLS via Orphanet64 C1832916

Related Diseases for Timothy Syndrome

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18GeneCards, 19GeneDecks
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Graphical network of the top 20 diseases related to Timothy Syndrome:



Diseases related to timothy syndrome

Symptoms for Timothy Syndrome

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48OMIM
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Symptoms by clinical synopsis from OMIM:

601005

Clinical features from OMIM:

601005

Drugs & Therapeutics for Timothy Syndrome

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Sources:
6CenterWatch, 43NIH Clinical Center, 7ClinicalTrials
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Approved drugs:

Search CenterWatch for Timothy Syndrome

Drug clinical trials:

Search ClinicalTrials for Timothy Syndrome

Search NIH Clinical Center for Timothy Syndrome

Search CenterWatch for Timothy Syndrome

Genetic Tests for Timothy Syndrome

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Sources:
21GeneTests, 23GTR
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Genetic tests related to Timothy Syndrome:

id Genetic test Affiliating Genes
1 Timothy Syndrome21 23 CACNA1C

Anatomical Context for Timothy Syndrome

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34MalaCards
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MalaCards organs/tissues related to Timothy Syndrome:

34
Heart

Animal Models for Timothy Syndrome or affiliated genes

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38MGI
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MGI Mouse Phenotypes related to Timothy Syndrome:

38
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053858.1KCNE1, CACNA2D1, CACNB2, CACNA1C, CACNA1H
2MP:00036317.0KCNE1, PSMC4, CACNA2D1, CACNB2, CACNA1C, CACNA1H

Publications for Timothy Syndrome

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Sources:
53PubMed
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Articles related to Timothy Syndrome:

(show all 29)
idTitleAuthorsYear
1
Cellular mechanisms of ventricular arrhythmias in a mouse model of Timothy syndrome (long QT syndrome 8). (24215710)
2014
2
Maternal mosaicism confounds the neonatal diagnosis of type 1 Timothy syndrome. (23690510)
2013
3
Modeling Timothy syndrome with iPS cells. (23299782)
2013
4
Inhibition of late sodium current by mexiletine: a novel pharmotherapeutical approach in timothy syndrome. (23580742)
2013
5
Sudden cardiac arrest during anesthesia in a 30-month-old boy with syndactyly: a case of genetically proven Timothy syndrome. (23678275)
2013
6
Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons. (23313911)
2013
7
Case scenario: anesthesia-related cardiac arrest in a child with Timothy syndrome. (23011317)
2012
8
Ca(V)1.2 I-II linker structure and Timothy syndrome. (22990809)
2012
9
Ranolazine safely decreases ventricular and atrial fibrillation in Timothy syndrome (LQT8). (20883512)
2012
10
Long QT, syndactyly, joint contractures, stroke and novel CACNA1C mutation: expanding the spectrum of Timothy syndrome. (22106044)
2012
11
L-type Ca2+ channel function during Timothy syndrome. (22999068)
2012
12
A Mouse Model of Timothy Syndrome: a Complex Autistic Disorder Resulting from a Point Mutation in Cav1.2. (24371506)
2012
13
Two mechanistically distinct effects of dihydropyridine nifedipine on CaV1.2 L-type CaA^a8_ channels revealed by Timothy syndrome mutation. (22554770)
2012
14
Mouse model of Timothy syndrome recapitulates triad of autistic traits. (21878566)
2011
15
A rare association of long QT syndrome and syndactyly: Timothy syndrome (LQT 8). (21915623)
2011
16
Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. (22120178)
2011
17
Somatic mosaicism contributes to phenotypic variation in Timothy syndrome. (21910241)
2011
18
Restoration of normal L-type Ca2+ channel function during Timothy syndrome by ablation of an anchoring protein. (21700933)
2011
19
Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. (21307850)
2011
20
Increased coupled gating of L-type Ca2+ channels during hypertension and Timothy syndrome. (20110531)
2010
21
The Timothy syndrome mutation of cardiac CaV1.2 (L-type) channels: multiple altered gating mechanisms and pharmacological restoration of inactivation. (19074970)
2009
22
The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels. (18250309)
2008
23
Introduction into Ca(v)2.1 of the homologous mutation of Ca(v)1.2 causing the Timothy syndrome questions the role of V421 in the phenotypic definition of P-type Ca(2+) channel. (18536931)
2008
24
Proarrhythmic defects in Timothy syndrome require calmodulin kinase II. (19001023)
2008
25
A life-threatening complication of the arterial tourniquet in Timothy syndrome. (17474959)
2007
26
Cellular basis for the electrocardiographic and arrhythmic manifestations of Timothy syndrome: effects of ranolazine. (17467634)
2007
27
Cyclosporin and Timothy syndrome increase mode 2 gating of CaV1.2 calcium channels through aberrant phosphorylation of S6 helices. (16537462)
2006
28
Verapamil decreases ventricular tachyarrhythmias in a patient with Timothy syndrome (LQT8). (16876748)
2006
29
Timothy Syndrome (20301577)
1993

Variations for Timothy Syndrome

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Sources:
65UniProtKB/Swiss-Prot, 1 National Center for Biotechnology Information (Clinvar)
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UniProtKB/Swiss-Prot genetic disease variations for Timothy Syndrome:

65
id Symbol AA change Variation ID SNP ID
1CACNA1Cp.Gly402SerVAR_026741
2CACNA1Cp.Gly406ArgVAR_026742

Clinvar genetic disease variations for Timothy Syndrome:

1
id Gene Name Type Significance SNP ID Assembly Location
1CACNA1CNM_000719.6(CACNA1C): c.1216G> A (p.Gly406Arg)single nucleotide variantPathogenicrs79891110GRCh37Chr 12, 2614110: 2614110
2CACNA1CNM_000719.6(CACNA1C): c.1204G> A (p.Gly402Ser)single nucleotide variantPathogenicrs80315385GRCh37Chr 12, 2614098: 2614098

Expression for genes affiliated with Timothy Syndrome

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Sources:
2BioGPS, 16Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Timothy Syndrome

Search GEO for disease gene expression data for Timothy Syndrome.

Pathways for genes affiliated with Timothy Syndrome

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Sources:
51PathCards, 56Reactome, 31KEGG, 61Thomson Reuters, 13EMD Millipore, 39NCBI BioSystems Database, 54QIAGEN, 52PharmGKB
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Pathways related to Timothy Syndrome according to GeneCards/GeneDecks:

(show all 38)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
9.8CACNA1C, CAMK2G
2
Show member pathways
9.8CACNA1C, CAMK2G
3
Show member pathways
9.8CAMK2G, CACNA1C
4
Show member pathways
Development Activation of ERK by Alpha 1 adrenergic receptors61
9.8CAMK2G, CACNA1C
59.7CACNA1H, CACNA1C
69.7CACNA1H, CACNA1C
7
Show member pathways
9.5CACNA1C, CACNB2
8
Show member pathways
9.3CAMK2G, CACNA1C, CACNA1H
99.3CAMK2G, CACNA1C, CACNA1H
10
Show member pathways
9.2CAMK2G, CACNA2D1, SCN4B
119.1KCNE1, CACNA1C, CACNB2
12
Show member pathways
9.1CACNA1C, CACNA1H, CACNB2
13
Show member pathways
9.1CACNB2, CACNA1H, CACNA1C
149.0CACNA2D1, CACNB2, CACNA1C
15
Show member pathways
Arrhythmogenic right ventricular cardiomyopathy39
9.0CACNA2D1, CACNA1C, CACNB2
169.0CACNB2, CACNA1C, CACNA2D1
17
Show member pathways
9.0CACNA2D1, CAMK2G, CACNB2
18
Show member pathways
8.6CAMK2G, CACNA2D1, CACNA1C, CACNB2
19
Show member pathways
MAPK signaling pathway39
8.6CACNA1H, CACNA1C, CACNB2, CACNA2D1
20
Show member pathways
8.6CACNA1H, CACNA1C, CACNA2D1, CACNB2
21
Show member pathways
8.6CACNA2D1, CACNB2, CACNA1C, CACNA1H
22
Show member pathways
8.6CACNB2, CACNA1H, CACNA2D1, CACNA1C
23
Show member pathways
8.6CACNB2, CACNA1C, CACNA1H, CACNA2D1
24
Show member pathways
8.6CACNB2, CACNA2D1, CACNA1C, CACNA1H
258.6CACNA1C, CACNB2, CACNA2D1, CACNA1H
268.3KCNE1, SCN4B, CACNA1C, CACNA1H, CACNB2
27
Show member pathways
8.2CACNB2, SCN4B, CACNA2D1, CACNA1C, CACNA1H
28
Show member pathways
Development Ligand independent activation of ESR1 and ESR261
8.2CAMK2G, CACNA1C, CACNA1H, CACNB2, CACNA2D1
29
Show member pathways
8.2CACNA2D1, CACNB2, CAMK2G, CACNA1C, CACNA1H
30
Show member pathways
8.2CAMK2G, CACNB2, CACNA2D1, CACNA1C, CACNA1H
31
Show member pathways
8.2CACNA1C, CACNA1H, CACNB2, CACNA2D1, CAMK2G
32
Show member pathways
8.2CACNA1H, CACNA2D1, CACNA1C, CAMK2G, CACNB2
33
Show member pathways
8.2CACNA1H, CACNA1C, CAMK2G, CACNB2, CACNA2D1
34
Show member pathways
8.2CAMK2G, CACNA1C, CACNB2, CACNA2D1, CACNA1H
357.9CAMK2G, SCN4B, CACNA2D1, CACNB2, CACNA1C, KCNE1
36
Show member pathways
7.8CACNA1H, CACNA1C, SCN4B, CACNA2D1, CACNB2, CAMK2G
37
Show member pathways
7.7CACNA2D1, CACNA1C, PSMC4, CACNA1H, CACNB2
387.7CACNA1H, CACNB2, CACNA2D1, PSMC4, CACNA1C

Compounds for genes affiliated with Timothy Syndrome

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Sources:
62Tocris Bioscience, 46Novoseek, 12DrugBank, 30IUPHAR, 52PharmGKB, 25HMDB
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Compounds related to Timothy Syndrome according to GeneCards/GeneDecks:

(show all 23)
idCompoundScoreTop Affiliating Genes
1(+-)-bay k 8644629.9CACNA1C, CACNA1H
2nnc 55-0396 dihydrochloride629.9CACNA1C, CACNA1H
3ibutilide46 1210.9CACNA2D1, CACNA1C
4mibefradil dihydrochloride629.9CACNA1C, CACNA1H
5omega-conotoxin gvia62 3010.9CACNA1C, CACNA1H
6pregabalin62 46 1211.8CACNA1H, CACNA1C
7zonisamide46 52 1211.7SCN4B, CACNA1H
8tetrodotoxin46 62 3011.7SCN4B, CAMK2G
9nimodipine46 30 1211.6CACNA1C, CACNB2
10verapamil46 30 52 25 1213.5CACNA1C, CACNB2
11nisoldipine30 46 1211.3CACNA1C, CACNB2, CACNA2D1
12nilvadipine46 1210.3CACNA2D1, CACNB2, CACNA1C
13amlodipine46 52 25 1212.3CACNA1C, CACNB2, CACNA2D1
14nicardipine46 30 1211.3CACNA1C, CACNB2, CACNA2D1
15anisomycin46 1210.0CAMK2G, PSMC4
16isradipine46 30 1210.9CACNA1H, CACNA1C, CACNB2, CACNA2D1
17nitrendipine46 52 30 1211.9CACNA2D1, CACNB2, CACNA1C, CACNA1H
18felodipine46 30 1210.9CACNA2D1, CACNB2, CACNA1C, CACNA1H
19potassium46 25 1210.9CAMK2G, PSMC4, KCNE1
20sodium46 259.8CAMK2G, PSMC4, SCN4B, KCNE1
21mibefradil46 30 1210.6CACNA1H, CACNA1C, CACNB2, PSMC4
22nifedipine46 30 52 1211.5CACNA2D1, CACNB2, CAMK2G, CACNA1C, CACNA1H
23calcium46 52 25 1210.6PSMC4, CACNA2D1, CACNB2, CAMK2G, CACNA1C, CACNA1H

GO Terms for genes affiliated with Timothy Syndrome

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17Gene Ontology
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Cellular components related to Timothy Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1Z discGO:0300189.7CACNA1C, KCNE1
2sarcolemmaGO:0423839.1CACNA1H, CACNB2
3voltage-gated calcium channel complexGO:0058918.5CACNA1H, CACNA1C, CACNB2, CACNA2D1

Biological processes related to Timothy Syndrome according to GeneCards/GeneDecks:

(show all 9)
idNameGO IDScoreTop Affiliating Genes
1cardiac muscle cell action potential involved in contractionGO:0860029.9SCN4B, KCNE1
2regulation of ventricular cardiac muscle cell membrane repolarizationGO:0603079.9SCN4B, KCNE1
3regulation of heart rate by cardiac conductionGO:0860919.8SCN4B, KCNE1
4insulin secretionGO:0300739.8CAMK2G, CACNA1C
5regulation of calcium ion transportGO:0519249.6CAMK2G, CACNA2D1
6calcium ion transportGO:0068169.6CAMK2G, CACNA2D1
7calcium ion importGO:0705099.5CACNB2, CACNA1H
8axon guidanceGO:0074119.0CACNA1H, CACNA1C, CACNB2
9synaptic transmissionGO:0072688.9CACNA1C, CAMK2G, CACNB2

Molecular functions related to Timothy Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1high voltage-gated calcium channel activityGO:0083319.5CACNA1C, CACNB2
2voltage-gated calcium channel activityGO:0052458.7CACNA1C, CACNB2, CACNA2D1

Products for genes affiliated with Timothy Syndrome

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Sources for Timothy Syndrome

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4CDC
14ExPASy
15FMA
23GTR
24HGMD
25HMDB
26ICD10
27ICD10 via Orphanet
28ICD9CM
30IUPHAR
31KEGG
36MeSH
37MESH via Orphanet
38MGI
41NCIt
42NDF-RT
45NINDS
46Novoseek
48OMIM
49OMIM via Orphanet
53PubMed
54QIAGEN
60SNOMED-CT via Orphanet
63UMLS
64UMLS via Orphanet