Aliases & Classifications for Timothy Syndrome

MalaCards integrated aliases for Timothy Syndrome:

Name: Timothy Syndrome 54 12 23 50 24 25 56 71 29 13 14 69
Long Qt Syndrome with Syndactyly 23 50 24 25 71
Lqt8 50 24 25 56 71
Long Qt Syndrome 8 50 24 71
Long Qt Syndrome Type 8 23 56
Ts 25 71
Long Qt Syndrome-Syndactyly Syndrome 56

Characteristics:

Orphanet epidemiological data:

56
timothy syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide);

OMIM:

54
Inheritance:
autosomal dominant

Miscellaneous:
de novo mutation, most patients have a gly406arg mutation in cacna1c
some patients with milder phenotypes exhibit somatic mosaicism


HPO:

32
timothy syndrome:
Mortality/Aging sudden death


GeneReviews:

23
Penetrance No study has specifically investigated the issue of the penetrance of ts. of note, however, penetrance was 100% in the 18 affected individuals with timothy syndrome reported to date [splawski et al 2004, lo-a-njoe et al 2005, splawski et al 2005] and it has remained very high (22 of 23 individuals with pathogenic variants had clearly abnormal electrocardiogram) in the two reports of gain-of-function cacn1c pathogenic variants in association with qt prolongation without extracardiac abnormalities [fukuyama et al 2014, wemhöner et al 2015]...

Classifications:



External Ids:

OMIM 54 601005
Disease Ontology 12 DOID:0060173
ICD10 33 G72.3
Orphanet 56 ORPHA65283
MESH via Orphanet 43 C536962
UMLS via Orphanet 70 C1832916
ICD10 via Orphanet 34 I45.8
MedGen 40 C1832916

Summaries for Timothy Syndrome

NIH Rare Diseases : 50 timothy syndromeis a disorder that affects the heart, digits (toes and fingers), and nervous system (brain and nerves). it is a type of long qt syndrome. long qt syndrome refers to a prolonged qt interval measurement seen on the electrocardiogram. symptoms of timothy syndrome include fusion of the skin between fingers or toes (syndactyly), distinctive facial features, and congenital heart defects. additional symptoms may include developmental delay, intellectual disability, and autism spectrum disorders. there are two forms of timothy syndrome, classified based on signs and symptoms. type 1, known as classic type, includes all of the symptoms described above. type 2, or atypical type, causes a more severe form of long qt syndrome and does not appear to include syndactyly. both types are caused by mutations in the cacna1c gene and are inherited in an autosomal dominant manner. treatment is focused on managing cardiac symptoms. this might include medications such as beta-blockers, placement of defibrillators, and pacemakers. last updated: 6/21/2016

MalaCards based summary : Timothy Syndrome, also known as long qt syndrome with syndactyly, is related to timothy syndrome type 1 and timothy syndrome type 2, and has symptoms including syndactyly and prolonged qt interval. An important gene associated with Timothy Syndrome is CACNA1C (Calcium Voltage-Gated Channel Subunit Alpha1 C), and among its related pathways/superpathways are CREB Pathway and Sweet Taste Signaling. The drugs Efavirenz and Suvorexant have been mentioned in the context of this disorder. Affiliated tissues include heart, skin and brain, and related phenotype is cardiovascular system.

UniProtKB/Swiss-Prot : 71 Timothy syndrome: Disorder characterized by multiorgan dysfunction including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities and autism.

Genetics Home Reference : 25 Timothy syndrome is a rare disorder that affects many parts of the body including the heart, digits (fingers and toes), and the nervous system.

OMIM : 54
Timothy syndrome is characterized by multiorgan dysfunction, including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities, and autism (Splawski et al., 2004). (601005)

Disease Ontology : 12 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 that has material basis in mutations in a transcript variant of CACNA1C on chromosome 12p13.33.

Wikipedia : 72 Timothy syndrome is a rare autosomal dominant disorder characterized by physical malformations, as well... more...

GeneReviews: NBK1403

Related Diseases for Timothy Syndrome

Diseases in the Timothy Syndrome family:

Timothy Syndrome Type 1 Timothy Syndrome Type 2

Diseases related to Timothy Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 71)
id Related Disease Score Top Affiliating Genes
1 timothy syndrome type 1 11.9
2 timothy syndrome type 2 11.9
3 gilles de la tourette syndrome 11.7
4 turner syndrome 11.6
5 virus-associated trichodysplasia spinulosa 11.5
6 trichostasis spinulosa 10.9
7 tuberous sclerosis-1 10.9
8 albinism, oculocutaneous, type ib 10.7
9 tsc2 angiomyolipomas, renal, modifier of 10.7
10 sclerotylosis 10.7
11 colorectal cancer 10.2
12 cardiac arrest 10.0
13 neuronitis 10.0
14 long qt syndrome 10.0
15 breast cancer 9.9
16 lung cancer 9.9
17 adenocarcinoma 9.8
18 squamous cell carcinoma 9.8
19 hepatitis 9.7
20 pancreatitis 9.7
21 esophagitis 9.7
22 pancreatic cancer 9.7
23 autistic disorder 9.7
24 atrial fibrillation 9.7
25 uterine fibroid 9.7 CACNA1C CACNB2
26 cardiac conduction disease with or without dilated cardiomyopathy 9.6 KCNH2 KCNQ1
27 acute lymphocytic leukemia 9.6
28 antiphospholipid syndrome 9.6
29 alcoholic hepatitis 9.6
30 glioblastoma multiforme 9.6
31 vaccinia 9.6
32 leukemia 9.6
33 liver disease 9.6
34 tricuspid valve stenosis 9.6
35 thrombocytopenia 9.6
36 angiosarcoma 9.6
37 malignant pleural mesothelioma 9.6
38 esophageal cancer 9.6
39 glioblastoma 9.6
40 sarcoma 9.6
41 granulocytopenia 9.6
42 growth hormone deficiency 9.6
43 cushing's syndrome 9.6
44 heparin-induced thrombocytopenia 9.6
45 neuroendocrine tumor 9.6
46 mutagen sensitivity 9.6
47 tendinopathy 9.6
48 hyperaldosteronism, familial, type iii 9.6 KCNH2 KCNQ1
49 ventricular tachycardia, catecholaminergic polymorphic, 1 9.5 KCNH2 KCNQ1
50 acute poisoning by drugs with membrane-stabilizing effect 9.4 CACNA2D1 KCNH2 KCNQ1

Graphical network of the top 20 diseases related to Timothy Syndrome:



Diseases related to Timothy Syndrome

Symptoms & Phenotypes for Timothy Syndrome

Symptoms via clinical synopsis from OMIM:

54

Head And Neck- Nose:
flat nasal bridge

Immunology:
recurrent infections

Head And Neck- Teeth:
small teeth

Muscle Soft Tissue:
hypotonia (in some patients)

Endocrine Features:
hypothyroidism (in some patients)

Skeletal- Feet:
cutaneous syndactyly

Respiratory- Airways:
bronchitis (in some patients)

Skin Nails & Hair- Hair:
no hair at birth

Neurologic- Central Nervous System:
seizures (in some patients)
developmental delay
mental retardation (in some patients)
autism or autism spectrum disorder

Head And Neck- Face:
round face

Head And Neck- Mouth:
thin upper lip
receding upper jaw

Cardiovascular- Vascular:
patent ductus arteriosus (in some patients)
pulmonary hypertension (in some patients)

Cardiovascular- Heart:
tetralogy of fallot (rare)
cardiac arrhythmias resulting in sudden death
long qt interval, severe
ventricular tachyarrhythmia
bradycardia, atrioventricular block
more
Skeletal- Hands:
cutaneous syndactyly

Respiratory- Lung:
pneumonia (in some patients)

Laboratory- Abnormalities:
hypocalcemia (in some patients)
hypoglycemia (in some patients)


Clinical features from OMIM:

601005

Human phenotypes related to Timothy Syndrome:

32
id Description HPO Frequency HPO Source Accession
1 syndactyly 32 HP:0001159
2 prolonged qt interval 32 HP:0001657

MGI Mouse Phenotypes related to Timothy Syndrome:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.02 CACNA1C CACNA2D1 CACNB2 KCNH2 KCNQ1

Drugs & Therapeutics for Timothy Syndrome

Drugs for Timothy Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 188)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Efavirenz Approved, Investigational Phase 4 154598-52-4 64139
2
Suvorexant Approved Phase 4 1030377-33-3
3 Anti-Infective Agents Phase 4,Phase 3,Phase 2,Phase 1,Early Phase 1
4 Anti-Retroviral Agents Phase 4,Phase 2
5 Antiviral Agents Phase 4,Phase 2,Phase 1,Early Phase 1
6 Cytochrome P-450 CYP3A Inducers Phase 4,Phase 3,Phase 2
7 Nucleic Acid Synthesis Inhibitors Phase 4,Phase 3,Phase 2,Phase 1
8 Reverse Transcriptase Inhibitors Phase 4,Phase 2
9 Cytochrome P-450 CYP2C9 Inhibitors Phase 4
10 Cytochrome P-450 Enzyme Inhibitors Phase 4
11 Neurotransmitter Agents Phase 4,Phase 3
12
Estradiol Approved, Investigational, Vet_approved Phase 3 50-28-2 5757
13
Ethambutol Approved Phase 3 74-55-5 3279 14052
14
Ethinyl Estradiol Approved Phase 3 57-63-6 5991
15
Isoniazid Approved Phase 3 54-85-3 3767
16
Moxifloxacin Approved, Investigational Phase 3 354812-41-2, 151096-09-2 152946
17
Norgestimate Approved Phase 3 35189-28-7 6540478
18
Pyrazinamide Approved Phase 3 98-96-4 1046
19
Rifampin Approved Phase 3 13292-46-1 5458213 5381226
20
Dopamine Approved Phase 3 51-61-6, 62-31-7 681
21
Haloperidol Approved Phase 3 52-86-8 3559
22
Ziprasidone Approved Phase 3 146939-27-7 60854
23
4-Aminopyridine Approved Phase 3 504-24-5 1727
24
Fluorouracil Approved Phase 3 51-21-8 3385
25
Imiquimod Approved, Investigational Phase 3 99011-02-6 57469
26 Antimetabolites Phase 3,Phase 2,Phase 1,Early Phase 1
27 Anti-Bacterial Agents Phase 3,Phase 2,Phase 1
28 Antibiotics, Antitubercular Phase 3,Phase 2,Phase 1
29 Antitubercular Agents Phase 3
30 Contraceptive Agents Phase 3
31 Contraceptives, Oral Phase 3
32 Contraceptives, Oral, Combined Phase 3
33 Estradiol 17 beta-cypionate Phase 3
34 Estradiol 3-benzoate Phase 3
35 Estradiol valerate Phase 3 979-32-8
36 Fluoroquinolones Phase 3
37 Hypolipidemic Agents Phase 3
38 Lipid Regulating Agents Phase 3
39 Norgestimate, ethinyl estradiol drug combination Phase 3
40 Polyestradiol phosphate Phase 3
41 Topoisomerase Inhibitors Phase 3
42 Adjuvants, Immunologic Phase 3,Phase 2
43 Immunosuppressive Agents Phase 3,Phase 2,Phase 1,Early Phase 1
44 interferons Phase 3,Phase 1,Phase 2
45 Antiemetics Phase 3,Phase 2
46 Antipsychotic Agents Phase 3
47 Autonomic Agents Phase 3,Phase 2
48 Central Nervous System Depressants Phase 3
49 decanoic acid Phase 3
50 Dopamine Agents Phase 3

Interventional clinical trials:

(show top 50) (show all 63)

id Name Status NCT ID Phase Drugs
1 Sustiva Levels With Use of a Gel Capsule Completed NCT01087814 Phase 4 Efavirenz;Over-encapsulated efavirenz
2 Suvorexant in Insomnia Co-morbid With Fibromyalgia Recruiting NCT02684136 Phase 4 suvorexant;placebo
3 Controlled Comparison of Two Moxifloxacin Containing Treatment Shortening Regimens in Pulmonary Tuberculosis Completed NCT00864383 Phase 3 Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin
4 The Modifying the Impact of ICU-Associated Neurological Dysfunction-USA (MIND-USA) Study Recruiting NCT01211522 Phase 3 Haloperidol;Ziprasidone;Placebo
5 Amifampridine Phosphate for the Treatment of Congenital Myasthenic Syndromes Recruiting NCT02562066 Phase 3 amifampridine phosphate;Placebo
6 Imiquimod, Fluorouracil, or Observation in Treating HIV-Positive Patients With High-Grade Anal Squamous Skin Lesions Recruiting NCT02059499 Phase 3 imiquimod;fluorouracil
7 A Study of Zidovudine/Lamivudine and Either Nevirapine or Nelfinavir for Reduction of Mother-to-child HIV Transmission During Breastfeeding Unknown status NCT00146380 Phase 2 Zidovudine/Lamivudine and either Nevirapine or Nelfinavir
8 Tretinoin in Treating Patients With Mycosis Fungoides or Sezary Syndrome Completed NCT00002479 Phase 2 tretinoin
9 A Safety Study of NNZ-2566 in Patients With Rett Syndrome Completed NCT01703533 Phase 2 NNZ-2566;Placebo
10 Comparison of Rituximab Induction Therapy Followed by Glatiramer Acetate Therapy to Glatiramer Acetate Monotherapy for MS Completed NCT01569451 Phase 2 Rituximab;Glatiramer Acetate
11 A Safety Study of NNZ-2566 in Pediatric Rett Syndrome Completed NCT02715115 Phase 2 NNZ-2566;Placebo
12 Safety, Tolerability and Preliminary Efficacy of FP-1201 in ALI and ARDS. Phase I/II Completed NCT00789685 Phase 1, Phase 2 Interferon Beta
13 Sorafenib Tosylate in Treating Patients With Progressive Metastatic Neuroendocrine Tumors Completed NCT00131911 Phase 2 sorafenib tosylate
14 Gefitinib in Treating Patients With Progressive Metastatic Neuroendocrine Tumors Completed NCT00075439 Phase 2 gefitinib
15 CPI-613 in Treating Patients With Myelodysplastic Syndromes Who Failed Previous Therapy Recruiting NCT01902381 Phase 2 6,8-bis(benzylthio)octanoic acid
16 QUILT-3.035: Relapse Prophylaxis With ALT-803 for AML and MDS Pts Following Allo HSCT Recruiting NCT02989844 Phase 2 ALT-803
17 Non-Myeloablative Conditioning for Unrelated Donor Umbilical Cord Blood Transplant Recruiting NCT00305682 Phase 2 cyclophosphamide;Fludarabine;mycophenolate mofetil;Sirolimus
18 Allo HSCT Using RIC for Hematological Diseases Recruiting NCT02661035 Phase 2 Allopurinol;Fludarabine;Cyclophosphamide;ATG;Tacrolimus;MMF
19 UCB Transplant for Hematological Diseases Using a Non Myeloablative Prep Recruiting NCT02722668 Phase 2 Fludarabine;Cyclophosphamide;MMF;Sirolimus
20 Treg Cell With IL-2 to Suppress aGVHD Umbilical Cord Blood Transplantation Recruiting NCT02991898 Phase 2
21 Reduced Intensity (RIC) Conditioning And Transplantation of HLA-Haploidentical Related Hematopoietic Recruiting NCT02988466 Phase 2 GVHD Prophylaxis
22 Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia Recruiting NCT00258427 Phase 2 busulfan;cyclophosphamide;fludarabine phosphate;methylprednisolone
23 Lenalidomide in Treating Patients With Relapsed Mycosis Fungoides/Sezary Syndrome Active, not recruiting NCT00466921 Phase 2 lenalidomide
24 Alemtuzumab in Treating Patients With Relapsed or Refractory Advanced Mycosis Fungoides or Sézary Syndrome Active, not recruiting NCT00057967 Phase 2
25 Reversing Tissue Fibrosis to Improve Immune Reconstitution in HIV Active, not recruiting NCT01852942 Phase 2 Losartan;Placebo
26 CD16/IL-15/CD33 Tri-Specific Killer Engagers (TriKes) for CD33+ Hem Malignancies Not yet recruiting NCT03214666 Phase 1, Phase 2 161533 with Bolus Test Dose;161533 Only
27 Temozolomide in Treating Patients With Mycosis Fungoides or Sezary Syndrome Terminated NCT00004106 Phase 2 temozolomide
28 Interleukin-2 in Treating Patients With Mycosis Fungoides or Sezary Syndrome Terminated NCT00005788 Phase 2
29 KL₄Surfactant Treatment in Patients With ARDS Terminated NCT00215553 Phase 2 Lucinactant
30 Safety Study of Recombinant Vaccinia Virus to Treat Refractory Solid Tumors in Pediatric Patients Completed NCT01169584 Phase 1 Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594)
31 Safety Study of Autologous Umbilical Cord Blood Cells for Treatment of Hypoplastic Left Heart Syndrome Recruiting NCT01883076 Phase 1
32 Dose-Escalation Trial of Carfilzomib With and Without Romidepsin in Cutaneous T-Cell Lymphoma Recruiting NCT01738594 Phase 1 carfilzomib;romidepsin
33 HSV1716 in Patients With Non-Central Nervous System (Non-CNS) Solid Tumors Recruiting NCT00931931 Phase 1
34 Gemcitabine and Pemetrexed Disodium in Treating Patients With Advanced Mycosis Fungoides or Sézary Syndrome Terminated NCT00369629 Phase 1 Gemcitabine;Pemetrexed
35 Fetoscopic Selective Laser Photocoagulation in Twin-Twin Transfusion Syndrome Unknown status NCT00345852
36 An Assessment of Cognitive Function in Irritable Bowel Syndrome Unknown status NCT01304355
37 Left Ventricular Pacing to Prevent Iatrogenic TR Pilot Study Unknown status NCT02314897
38 Analysis of the Prevalence and Characteristics of Concomitant Sleep and Headache Disorders, and the Efficacy of CPAP Treatment for Headache Among Those Patients Diagnosed With Obstructive Sleep Apnea Unknown status NCT00520156
39 Comparing Rehabilitation Programs for Patellofemoral Pain Syndrome Completed NCT00445224
40 Early Risk Stratification in ED Chest Pain Patients Completed NCT02364271
41 Sensory Processing in Subjects With Painful Bladder Syndrome Completed NCT00903643
42 Complex Sleep Apnea Syndrome (CompSAS) Resolution Study Completed NCT00915499
43 Quality of Life in Patients With Refractory Angina Completed NCT00840437
44 Tissue Drug Levels of HIV Medications Completed NCT01490346 Initiation of anti-retroviral therapy
45 Problems With Immune Recovery in the Gut Tissue Completed NCT01460433
46 Fludarabine Based RIC for Bone Marrow Failure Syndromes Recruiting NCT02928991 Early Phase 1
47 A Prospective Study of Patients With Hypoplastic Left Heart Syndrome (HLHS) Following Stage II Surgical Palliation Recruiting NCT01708863
48 Unrelated And Partially Matched Related Donor PSCT w/ TCR αβ Depletion for Patients With BMF Recruiting NCT03047746
49 Gamma Globulin Observations and Outcomes Database for Patients With Primary Immunodeficiency Disease (GOOD-SHEPARD-PI) Recruiting NCT01883921
50 VitalScan MCG Rule-out Multi-centre Pivotal Study - UK Recruiting NCT02921438

Search NIH Clinical Center for Timothy Syndrome

Genetic Tests for Timothy Syndrome

Genetic tests related to Timothy Syndrome:

id Genetic test Affiliating Genes
1 Timothy Syndrome 29 24 CACNA1C

Anatomical Context for Timothy Syndrome

MalaCards organs/tissues related to Timothy Syndrome:

39
Heart, Skin, Brain, Liver, Endothelial, T Cells, Bone Marrow

Publications for Timothy Syndrome

Articles related to Timothy Syndrome:

(show all 46)
id Title Authors Year
1
Altered Cav1.2 function in the Timothy syndrome mouse model produces ascending serotonergic abnormalities. ( 28921675 )
2017
2
Timothy syndrome 1 genotype without syndactyly and major extracardiac manifestations. ( 28211989 )
2017
3
A multicentre study of patients with Timothy syndrome. ( 28371864 )
2017
4
Inhibition of CDK5 Alleviates the Cardiac Phenotypes in Timothy Syndrome. ( 28648896 )
2017
5
Incomplete Timothy syndrome secondary to a mosaic mutation of the CACNA1C gene diagnosed using next-generation sequencing. ( 27868338 )
2017
6
A case of Timothy syndrome with adrenal medullary dystrophy. ( 27593853 )
2016
7
Arrhythmogenesis in Timothy Syndrome is associated with defects in Ca(2+)-dependent inactivation. ( 26822303 )
2016
8
Cardiac arrest refractory to standard intervention in atypical Timothy syndrome (LQT8 type 2). ( 27034553 )
2016
9
Gain-of-function mutations in the calcium channel CACNA1C (Cav1.2) cause non-syndromic long-QT but not Timothy syndrome. ( 25633834 )
2015
10
Unusual retrospective prenatal findings in a male newborn with Timothy syndrome type 1. ( 25882468 )
2015
11
Expanding the phenotype of Timothy syndrome type 2: an adolescent with ventricular fibrillation but normal development. ( 25691416 )
2015
12
Long QT syndrome with craniofacial, digital, and neurologic features: Is it useful to distinguish between timothy syndrome types 1 and 2? ( 26227324 )
2015
13
A rare association with suffered cardiac arrest, long QT interval, and syndactyly: Timothy syndrome (LQT-8). ( 26301350 )
2015
14
Exome sequencing helped the fine diagnosis of two siblings afflicted with atypical Timothy syndrome (TS2). ( 24773605 )
2014
15
Alteration in basal and depolarization induced transcriptional network in iPSC derived neurons from Timothy syndrome. ( 25360157 )
2014
16
Cellular mechanisms of ventricular arrhythmias in a mouse model of Timothy syndrome (long QT syndrome 8). ( 24215710 )
2014
17
Novel Timothy syndrome mutation leading to increase in CACNA1C window current. ( 25260352 )
2014
18
Dentition abnormalities in a Timothy syndrome patient with a novel genetic mutation: a case report. ( 24960393 )
2014
19
Modeling Timothy syndrome with iPS cells. ( 23299782 )
2013
20
Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons. ( 23313911 )
2013
21
Inhibition of late sodium current by mexiletine: a novel pharmotherapeutical approach in timothy syndrome. ( 23580742 )
2013
22
Sudden cardiac arrest during anesthesia in a 30-month-old boy with syndactyly: a case of genetically proven Timothy syndrome. ( 23678275 )
2013
23
Maternal mosaicism confounds the neonatal diagnosis of type 1 Timothy syndrome. ( 23690510 )
2013
24
Case scenario: anesthesia-related cardiac arrest in a child with Timothy syndrome. ( 23011317 )
2012
25
A Mouse Model of Timothy Syndrome: a Complex Autistic Disorder Resulting from a Point Mutation in Cav1.2. ( 24371506 )
2012
26
Ca(V)1.2 I-II linker structure and Timothy syndrome. ( 22990809 )
2012
27
L-type Ca2+ channel function during Timothy syndrome. ( 22999068 )
2012
28
Ranolazine safely decreases ventricular and atrial fibrillation in Timothy syndrome (LQT8). ( 20883512 )
2012
29
Two mechanistically distinct effects of dihydropyridine nifedipine on CaV1.2 L-type CaA^a8_ channels revealed by Timothy syndrome mutation. ( 22554770 )
2012
30
Long QT, syndactyly, joint contractures, stroke and novel CACNA1C mutation: expanding the spectrum of Timothy syndrome. ( 22106044 )
2012
31
Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. ( 21307850 )
2011
32
Somatic mosaicism contributes to phenotypic variation in Timothy syndrome. ( 21910241 )
2011
33
Mouse model of Timothy syndrome recapitulates triad of autistic traits. ( 21878566 )
2011
34
A rare association of long QT syndrome and syndactyly: Timothy syndrome (LQT 8). ( 21915623 )
2011
35
Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. ( 22120178 )
2011
36
Restoration of normal L-type Ca2+ channel function during Timothy syndrome by ablation of an anchoring protein. ( 21700933 )
2011
37
Increased coupled gating of L-type Ca2+ channels during hypertension and Timothy syndrome. ( 20110531 )
2010
38
The Timothy syndrome mutation of cardiac CaV1.2 (L-type) channels: multiple altered gating mechanisms and pharmacological restoration of inactivation. ( 19074970 )
2009
39
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
40
Proarrhythmic defects in Timothy syndrome require calmodulin kinase II. ( 19001023 )
2008
41
The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels. ( 18250309 )
2008
42
Cellular basis for the electrocardiographic and arrhythmic manifestations of Timothy syndrome: effects of ranolazine. ( 17467634 )
2007
43
A life-threatening complication of the arterial tourniquet in Timothy syndrome. ( 17474959 )
2007
44
Verapamil decreases ventricular tachyarrhythmias in a patient with Timothy syndrome (LQT8). ( 16876748 )
2006
45
Cyclosporin and Timothy syndrome increase mode 2 gating of CaV1.2 calcium channels through aberrant phosphorylation of S6 helices. ( 16537462 )
2006
46
Timothy Syndrome ( 20301577 )
1993

Variations for Timothy Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Timothy Syndrome:

71 (show all 11)
id Symbol AA change Variation ID SNP ID
1 CACNA1C p.Gly402Ser VAR_026741
2 CACNA1C p.Gly406Arg VAR_026742
3 CACNA1C p.Ile1186Thr VAR_072381
4 CACNA1C p.Arg518Cys VAR_075154
5 CACNA1C p.Arg518His VAR_075155
6 CACNA1C p.Ala582Asp VAR_075156
7 CACNA1C p.Arg858His VAR_075158
8 CACNA1C p.Arg860Gly VAR_075159
9 CACNA1C p.Ile1186Val VAR_075160
10 CACNA1C p.Ile1523Met VAR_075162
11 CACNA1C p.Glu1544Lys VAR_075163

ClinVar genetic disease variations for Timothy Syndrome:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 CACNA1C NM_000719.6(CACNA1C): c.1216G> A (p.Gly406Arg) single nucleotide variant Pathogenic rs79891110 GRCh37 Chromosome 12, 2614110: 2614110
2 CACNA1C NM_000719.6(CACNA1C): c.1204G> A (p.Gly402Ser) single nucleotide variant Pathogenic rs80315385 GRCh37 Chromosome 12, 2614098: 2614098
3 CACNA1C NM_001167625.1(CACNA1C): c.1216G> A (p.Gly406Arg) single nucleotide variant Pathogenic rs786205745 GRCh37 Chromosome 12, 2613704: 2613704
4 CACNA1C NM_001167623.1(CACNA1C): c.1216G> C (p.Gly406Arg) single nucleotide variant Pathogenic rs786205745 GRCh37 Chromosome 12, 2613704: 2613704
5 CACNA1C NM_000719.6(CACNA1C): c.4418C> G (p.Ala1473Gly) single nucleotide variant Pathogenic/Likely pathogenic rs794727587 GRCh37 Chromosome 12, 2774766: 2774766

Expression for Timothy Syndrome

Search GEO for disease gene expression data for Timothy Syndrome.

Pathways for Timothy Syndrome

Pathways related to Timothy Syndrome according to GeneCards Suite gene sharing:

(show all 23)
id Super pathways Score Top Affiliating Genes
1
Show member pathways
12.99 CACNA1C CACNA2D1 CACNB2 CAMK2G
2
Show member pathways
12.75 CACNA1C CACNA2D1 CACNB2 CAMK2G
3
Show member pathways
12.71 CACNA2D1 CACNB2 CAMK2G KCNH2 KCNQ1
4
Show member pathways
12.63 CACNA1C CACNA2D1 CACNB2 CAMK2G
5
Show member pathways
12.56 CACNA1C CACNA2D1 CACNB2 CAMK2G
6
Show member pathways
12.56 CACNA1C CACNA2D1 CACNB2 CAMK2G KCNE1 KCNQ1
7
Show member pathways
12.45 CACNA1C CAMK2G KCNQ1
8
Show member pathways
12.43 CACNA1C CACNA2D1 CACNB2 CAMK2G KCNE1 KCNH2
9 12.4 CACNA1C CACNA2D1 CACNB2
10
Show member pathways
12.27 CACNA1C CACNB2 CAMK2G
11
Show member pathways
12.15 CACNA1C CACNA2D1 CACNB2
12 12.12 CACNA1C CACNB2 KCNE1 KCNH2 KCNQ1
13
Show member pathways
12.03 CACNA1C CACNA2D1 CACNB2 CAMK2G
14 11.84 CACNA1C CACNA2D1 CACNB2
15
Show member pathways
11.78 CACNA1C CACNA2D1 CACNB2
16 11.55 CACNA1C CACNA2D1 CACNB2
17 11.45 CACNA1C CACNA2D1 CACNB2
18 11.32 CACNA1C CACNA2D1 CACNB2 KCNQ1
19 11.3 CACNA1C CACNA2D1 CACNB2
20 11.14 CACNA1C CACNB2
21 11.1 CACNA1C CACNB2 KCNE1 KCNH2 KCNQ1
22
Show member pathways
10.98 CACNA1C CACNA2D1 CACNB2 CAMK2G KCNE1 KCNQ1
23 10.82 KCNE1 KCNQ1

GO Terms for Timothy Syndrome

Cellular components related to Timothy Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 plasma membrane GO:0005886 9.8 CACNA1C CACNA2D1 CACNB2 CAMK2G KCNE1 KCNH2
2 voltage-gated potassium channel complex GO:0008076 9.33 KCNE1 KCNH2 KCNQ1
3 sarcoplasmic reticulum GO:0016529 9.32 CACNA2D1 CAMK2G
4 voltage-gated calcium channel complex GO:0005891 9.13 CACNA1C CACNA2D1 CACNB2
5 L-type voltage-gated calcium channel complex GO:1990454 8.8 CACNA1C CACNA2D1 CACNB2

Biological processes related to Timothy Syndrome according to GeneCards Suite gene sharing:

(show all 30)
id Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.95 CACNA1C CACNA2D1 CACNB2 KCNE1 KCNH2 KCNQ1
2 calcium ion transport GO:0006816 9.84 CACNA1C CACNA2D1 CACNB2 CAMK2G
3 potassium ion transmembrane transport GO:0071805 9.8 KCNE1 KCNH2 KCNQ1
4 potassium ion transport GO:0006813 9.79 KCNE1 KCNH2 KCNQ1
5 calcium ion transmembrane transport GO:0070588 9.78 CACNA1C CACNA2D1 CACNB2
6 cardiac muscle cell action potential involved in contraction GO:0086002 9.7 CACNA1C CACNA2D1 KCNE1
7 positive regulation of potassium ion transmembrane transport GO:1901381 9.69 KCNE1 KCNH2 KCNQ1
8 ventricular cardiac muscle cell action potential GO:0086005 9.67 KCNE1 KCNH2 KCNQ1
9 cellular response to drug GO:0035690 9.65 KCNH2 KCNQ1
10 cellular response to cAMP GO:0071320 9.64 KCNE1 KCNQ1
11 cardiac muscle contraction GO:0060048 9.64 KCNH2 KCNQ1
12 regulation of calcium ion transport GO:0051924 9.63 CACNA2D1 CAMK2G
13 regulation of potassium ion transmembrane transport GO:1901379 9.63 KCNE1 KCNH2
14 regulation of ion transmembrane transport GO:0034765 9.63 CACNA1C CACNA2D1 CACNB2 KCNE1 KCNH2 KCNQ1
15 calcium ion transport into cytosol GO:0060402 9.61 CACNA1C CACNA2D1
16 membrane repolarization during cardiac muscle cell action potential GO:0086013 9.61 KCNE1 KCNH2 KCNQ1
17 regulation of membrane repolarization GO:0060306 9.6 KCNH2 KCNQ1
18 membrane depolarization during AV node cell action potential GO:0086045 9.58 CACNA1C CACNB2
19 positive regulation of high voltage-gated calcium channel activity GO:1901843 9.58 CACNA2D1 CACNB2
20 potassium ion export GO:0071435 9.58 KCNE1 KCNH2 KCNQ1
21 potassium ion export across plasma membrane GO:0097623 9.57 KCNH2 KCNQ1
22 membrane depolarization during atrial cardiac muscle cell action potential GO:0098912 9.56 CACNA1C CACNB2
23 regulation of ventricular cardiac muscle cell membrane repolarization GO:0060307 9.56 CACNA2D1 KCNE1 KCNH2 KCNQ1
24 calcium ion transmembrane transport via high voltage-gated calcium channel GO:0061577 9.55 CACNA1C CACNA2D1
25 membrane repolarization during ventricular cardiac muscle cell action potential GO:0098915 9.54 KCNE1 KCNH2 KCNQ1
26 membrane repolarization during action potential GO:0086011 9.5 KCNE1 KCNH2 KCNQ1
27 membrane repolarization GO:0086009 9.46 KCNE1 KCNQ1
28 cardiac conduction GO:0061337 9.43 CACNA1C CACNA2D1 CACNB2 KCNE1 KCNH2 KCNQ1
29 regulation of heart rate by cardiac conduction GO:0086091 9.1 CACNA1C CACNA2D1 CACNB2 KCNE1 KCNH2 KCNQ1
30 transport GO:0006810 10.07 CACNA1C CACNA2D1 CACNB2 KCNE1 KCNH2 KCNQ1

Molecular functions related to Timothy Syndrome according to GeneCards Suite gene sharing:

(show all 13)
id Name GO ID Score Top Affiliating Genes
1 calmodulin binding GO:0005516 9.69 CACNA1C CAMK2G KCNQ1
2 voltage-gated ion channel activity GO:0005244 9.67 CACNA1C KCNH2 KCNQ1
3 calcium channel activity GO:0005262 9.63 CACNA1C CACNA2D1 CACNB2
4 potassium channel activity GO:0005267 9.61 KCNE1 KCNH2 KCNQ1
5 voltage-gated potassium channel activity GO:0005249 9.58 KCNE1 KCNH2 KCNQ1
6 scaffold protein binding GO:0097110 9.52 KCNH2 KCNQ1
7 voltage-gated calcium channel activity GO:0005245 9.5 CACNA1C CACNA2D1 CACNB2
8 high voltage-gated calcium channel activity GO:0008331 9.48 CACNA1C CACNB2
9 delayed rectifier potassium channel activity GO:0005251 9.43 KCNE1 KCNH2 KCNQ1
10 voltage-gated calcium channel activity involved in AV node cell action potential GO:0086056 9.37 CACNA1C CACNB2
11 voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization GO:1902282 9.33 KCNE1 KCNH2 KCNQ1
12 voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization GO:0086008 9.13 KCNE1 KCNH2 KCNQ1
13 voltage-gated calcium channel activity involved in cardiac muscle cell action potential GO:0086007 8.8 CACNA1C CACNA2D1 CACNB2

Sources for Timothy Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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