DRD
MCID: DYS192
MIFTS: 56

Dystonia, Dopa-Responsive (DRD)

Categories: Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Dystonia, Dopa-Responsive

MalaCards integrated aliases for Dystonia, Dopa-Responsive:

Name: Dystonia, Dopa-Responsive 56 73 29 6
Dystonia 5 56 12 73 29 54 6 15
Dopa-Responsive Dystonia 52 25 58 71
Drd 56 25 73
Dystonia, Dopa-Responsive, with or Without Hyperphenylalaninemia 56 13
Hereditary Progressive Dystonia with Marked Diurnal Fluctuation 25 58
Hereditary Progressive Dystonia with Diurnal Fluctuation 52 58
Dystonia-Parkinsonism with Diurnal Fluctuation 56 73
Autosomal Dominant Dopa-Responsive Dystonia 58 73
Autosomal Dominant Segawa Syndrome 58 73
Hpd with Diurnal Fluctuation 52 58
Dyt5 56 73
Dystonia, Progressive, with Diurnal Variation 56
Dystonia, Dopa-Responsive, Autosomal Dominant 56
Progressive Dystonia with Diurnal Fluctuation 73
Dopa-Responsive Dystonia, Autosomal Dominant 56
Gtpch1-Deficient Dopa-Responsive Dystonia 58
Dystonia, Type 5, Dopa-Responsive Type 39
Segawa Syndrome, Autosomal Dominant 56
Hpd with Marked Diurnal Fluctuation 58
Dystonia 5, Dopa-Responsive Type 25
Gtpch1-Deficient Drd 58
Dystonia 5; Dyt5 56
Dystonia-5 73
Dyt-Gch1 52
Dyt-Spr 52
Dyt-Th 52
Dyt5a 58

Characteristics:

Orphanet epidemiological data:

58
dopa-responsive dystonia
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Prevalence: 1-9/1000000 (Europe),1-9/1000000 (Worldwide); Age of onset: Childhood;
autosomal dominant dopa-responsive dystonia
Inheritance: Autosomal dominant,Not applicable; Prevalence: 1-9/1000000 (Europe); Age of onset: Childhood; Age of death: normal life expectancy;

OMIM:

56
Inheritance:
autosomal dominant
autosomal recessive (rare)

Miscellaneous:
genetic heterogeneity (see )
onset in childhood (6-7 years)
defect in tetrahydrobiopterin (bh4) synthesis
favorable response to l-dopa without side effects
favorable response to bh4
diurnal fluctuation, more apparent in earlier years, later subsides
symptoms worsen with fatigue and exercise
age-related clinical course
female predominance (4:1)
clinical heterogeneity
autosomal recessive inheritance with earlier onset has been reported in 3 patients
see also autosomal recessive bh4-dependent hyperphenylalaninemia , an allelic disorder with a more severe phenotype


HPO:

31
dystonia, dopa-responsive:
Inheritance autosomal dominant inheritance autosomal recessive inheritance heterogeneous
Onset and clinical course childhood onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Dystonia, Dopa-Responsive

Genetics Home Reference : 25 Dopa-responsive dystonia is a disorder that involves involuntary muscle contractions, tremors, and other uncontrolled movements (dystonia). The features of this condition range from mild to severe. This form of dystonia is called dopa-responsive dystonia because the signs and symptoms typically improve with sustained use of a medication known as L-Dopa. Signs and symptoms of dopa-responsive dystonia usually appear during childhood, most commonly around age 6. The first signs of the condition are typically the development of inward- and upward-turning feet (clubfeet) and dystonia in the lower limbs. The dystonia spreads to the upper limbs over time; beginning in adolescence, the whole body is typically involved. Affected individuals may have unusual limb positioning and a lack of coordination when walking or running. Some people with this condition have sleep problems or episodes of depression more frequently than would normally be expected. Over time, affected individuals often develop a group of movement abnormalities called parkinsonism. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, tremors, and an inability to hold the body upright and balanced (postural instability). The movement difficulties associated with dopa-responsive dystonia usually worsen with age but stabilize around age 30. A characteristic feature of dopa-responsive dystonia is worsening of movement problems later in the day and an improvement of symptoms in the morning, after sleep (diurnal fluctuation). Rarely, the movement problems associated with dopa-responsive dystonia do not appear until adulthood. In these adult-onset cases, parkinsonism usually develops before dystonia, and movement problems are slow to worsen and do not show diurnal fluctuations.

MalaCards based summary : Dystonia, Dopa-Responsive, also known as dystonia 5, is related to segawa syndrome, autosomal recessive and hyperphenylalaninemia, bh4-deficient, a, and has symptoms including gait ataxia, torticollis and dystonia, diurnal. An important gene associated with Dystonia, Dopa-Responsive is GCH1 (GTP Cyclohydrolase 1), and among its related pathways/superpathways are Dopaminergic Neurogenesis and Alpha-synuclein signaling. The drugs Iron and Dihydroxyphenylalanine have been mentioned in the context of this disorder. Affiliated tissues include testes, brain and cerebellum, and related phenotypes are gait disturbance and spasticity

Disease Ontology : 12 A dystonia characterized by childhood-onset dystonia that responds to low doses of levodopa (L-dopa) and may be associated with parkinsonism at an older age and has material basis in autosomal dominant inheritance of heterozygous mutation in the gene enconding GTP cyclohydrolase 1 (GCH1) on chromosome 14q13.

NIH Rare Diseases : 52 Dopa-responsive dystonia (DRD) is an inherited type of dystonia that typically begins during childhood but may begin in adolescence or adulthood. Depending on the specific type of DRD, specific symptoms can vary. Features can range from mild to severe. In most cases, dystonia begins in the lower limbs and spreads to the upper limbs over time. Symptoms may include unusual limb positioning; a lack of coordination when walking or running; sleep problems; and episodes of depression. Affected people also often develop a group of movement abnormalities called parkinsonism . Although movement difficulties usually worsen with age, they often stabilize around age 30. DRD may be caused by mutations in the GCH1 , TH or SPR genes , or the cause may be unknown. Depending on the genetic cause, DRD may be inherited in an autosomal dominant (most commonly) or autosomal recessive manner. This form of dystonia is called 'dopa-responsive' dystonia because the symptoms typically improve during treatment with levodopa and carbidopa .

OMIM : 56 Autosomal dominant dopa-responsive dystonia (DRD) is characterized by generalized dystonia, diurnal fluctuation of symptoms, and a dramatic therapeutic response to L-dopa. The clinical spectrum can range from subtle neurologic signs and symptoms (e.g., abnormal writing tests) to orthopedic signs (e.g., pes equinovarus), parkinsonism, and even psychiatric manifestations (summary by Steinberger et al., 2007). (128230)

UniProtKB/Swiss-Prot : 73 Dystonia, dopa-responsive: A form of dystonia that responds to L-DOPA treatment without side effects. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DRD typically presents in childhood with walking problems due to dystonia of the lower limbs and worsening of the dystonia towards the evening. It is characterized by postural and motor disturbances showing marked diurnal fluctuation. Torsion of the trunk is unusual. Symptoms are alleviated after sleep and aggravated by fatigue and exercise.

Related Diseases for Dystonia, Dopa-Responsive

Diseases related to Dystonia, Dopa-Responsive via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 140)
# Related Disease Score Top Affiliating Genes
1 segawa syndrome, autosomal recessive 34.0 TH GCH1
2 hyperphenylalaninemia, bh4-deficient, a 32.5 SPR GCH1
3 hyperphenylalaninemia, bh4-deficient, b 31.2 TH GCH1
4 dystonia 11, myoclonic 31.0 TOR1A THAP1 SGCE PNKD GCH1 ATP1A3
5 hereditary dystonia 30.8 TH GCH1 ATP1A3
6 phenylketonuria 30.6 TH SLC6A3 GCH1
7 hyperphenylalaninemia 30.4 TH SPR GCH1
8 gilles de la tourette syndrome 30.4 TH SLC6A3 SGCE
9 spasmodic dysphonia 30.2 TOR1A THAP1
10 dystonia 1, torsion, autosomal dominant 30.1 TOR1A THAP1 SGCE GCH1
11 torticollis 30.0 TOR1A PRRT2
12 basal ganglia disease 29.9 TOR1A THAP1 GCH1
13 choreatic disease 29.9 SGCE PRRT2 PNKD GCH1
14 obsessive-compulsive disorder 29.7 TOR1A SLC6A3 SGCE GCH1
15 migraine with or without aura 1 29.7 SLC6A3 PRRT2 PNKD ATP1A3
16 dystonia 3, torsion, x-linked 29.5 TOR1A THAP1 TAF1L TAF1 SGCE PRKRA
17 dystonia 12 28.6 TOR1A THAP1 TAF1L TAF1 SLC2A1 SGCE
18 parkinson disease, late-onset 28.4 TOR1A TH TAF1L TAF1 SPR SLC6A3
19 cervical dystonia 28.3 TOR1A THAP1 TH SPR SGCE PRKRA
20 segmental dystonia 27.6 TOR1A THAP1 TAF1L TAF1 SGCE PRKRA
21 focal dystonia 27.6 TOR1A THAP1 TAF1L TAF1 SGCE PRKRA
22 multifocal dystonia 27.2 TOR1A THAP1 TAF1L TAF1 SPR SGCE
23 dystonia 26.8 TOR1A THAP1 TH TAF1 SPR SLC6A3
24 movement disease 26.6 TOR1A THAP1 TH TAF1 SLC6A3 SLC2A1
25 dystonia, dopa-responsive, due to sepiapterin reductase deficiency 13.0
26 paraplegia 10.4
27 gtp cyclohydrolase 1-deficient dopa-responsive dystonia 10.4
28 ataxia-telangiectasia 10.4
29 parkinson disease 15, autosomal recessive early-onset 10.4
30 ataxia and polyneuropathy, adult-onset 10.4
31 telangiectasis 10.4
32 autosomal dominant cerebellar ataxia 10.4
33 myoclonus 10.4
34 hereditary spastic paraplegia 10.4
35 conversion disorder 10.3 PNKD GCH1
36 postencephalitic parkinson disease 10.3 TH SLC6A3
37 early-onset parkinson's disease 10.3
38 spastic diplegia 10.3
39 tremor 10.3
40 familial paroxysmal nonkinesigenic dyskinesia 10.3 PRRT2 PNKD
41 tetrahydrobiopterin deficiency 10.3 TH SPR GCH1
42 delusional disorder 10.2 TH SLC6A3
43 paroxysmal nonkinesigenic dyskinesia 1 10.2 PRRT2 PNKD
44 episodic kinesigenic dyskinesia 2 10.2 PRRT2 PNKD
45 hyperphenylalaninemia, bh4-deficient, c 10.2
46 scoliosis 10.2
47 paroxysmal dyskinesia 10.2 PRRT2 PNKD
48 mental depression 10.2
49 depression 10.2
50 reflex epilepsy 10.2 PRRT2 PNKD

Graphical network of the top 20 diseases related to Dystonia, Dopa-Responsive:



Diseases related to Dystonia, Dopa-Responsive

Symptoms & Phenotypes for Dystonia, Dopa-Responsive

Human phenotypes related to Dystonia, Dopa-Responsive:

58 31 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 gait disturbance 58 31 hallmark (90%) Very frequent (99-80%) HP:0001288
2 spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0001257
3 hearing impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000365
4 sleep disturbance 58 31 frequent (33%) Frequent (79-30%) HP:0002360
5 fatigue 58 31 frequent (33%) Frequent (79-30%) HP:0012378
6 anxiety 58 31 frequent (33%) Frequent (79-30%) HP:0000739
7 depressivity 58 31 frequent (33%) Frequent (79-30%) HP:0000716
8 talipes equinovarus 58 31 frequent (33%) Frequent (79-30%) HP:0001762
9 pes cavus 58 31 frequent (33%) Frequent (79-30%) HP:0001761
10 gait ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0002066
11 babinski sign 58 31 frequent (33%) Frequent (79-30%) HP:0003487
12 torticollis 58 31 frequent (33%) Frequent (79-30%) HP:0000473
13 rigidity 58 31 frequent (33%) Frequent (79-30%) HP:0002063
14 limb dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0002451
15 brisk reflexes 58 31 frequent (33%) Frequent (79-30%) HP:0001348
16 parkinsonism 58 31 frequent (33%) Frequent (79-30%) HP:0001300
17 postural tremor 58 31 frequent (33%) Frequent (79-30%) HP:0002174
18 lower limb hyperreflexia 58 31 frequent (33%) Frequent (79-30%) HP:0002395
19 abnormality of the substantia nigra 58 31 frequent (33%) Frequent (79-30%) HP:0045007
20 decreased csf homovanillic acid 58 31 frequent (33%) Frequent (79-30%) HP:0003785
21 transient hyperphenylalaninemia 58 31 frequent (33%) Frequent (79-30%) HP:0008297
22 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
23 hypothyroidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000821
24 hypertension 58 31 occasional (7.5%) Occasional (29-5%) HP:0000822
25 obsessive-compulsive behavior 58 31 occasional (7.5%) Occasional (29-5%) HP:0000722
26 generalized dystonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0007325
27 progressive flexion contractures 58 31 occasional (7.5%) Occasional (29-5%) HP:0005876
28 horizontal nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000666
29 rheumatoid arthritis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001370
30 bradykinesia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002067
31 impaired vibration sensation in the lower limbs 58 31 occasional (7.5%) Occasional (29-5%) HP:0002166
32 paresis of extensor muscles of the big toe 58 31 occasional (7.5%) Occasional (29-5%) HP:0002601
33 intellectual disability 58 Excluded (0%)
34 ataxia 58 Frequent (79-30%)
35 abnormality of movement 58 Very frequent (99-80%)
36 hyperreflexia 31 HP:0001347
37 abnormality of extrapyramidal motor function 58 Frequent (79-30%)
38 writer's cramp 31 HP:0002356
39 focal dystonia 58 Frequent (79-30%)
40 parkinsonism with favorable response to dopaminergic medication 31 HP:0002548

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
hyperreflexia
gait ataxia
parkinsonism
extensor plantar responses
gait abnormalities
more
Head And Neck Neck:
torticollis

Laboratory Abnormalities:
decreased tetrahydrobiopterin (bh4) in csf
decreased homovanillic acid (hva) in csf
5-hiaa csf may be normal or decreased
decreased gtp cyclohydrolase i activity (about 20% of normal)
transient hyperphenylalaninemia occurs on oral loading test with phenylalanine

Skeletal Limbs:
talipes equinovarus
pes cavus

Skeletal Spine:
scoliosis (rare)

Clinical features from OMIM:

128230

UMLS symptoms related to Dystonia, Dopa-Responsive:


gait ataxia, torticollis, dystonia, diurnal

MGI Mouse Phenotypes related to Dystonia, Dopa-Responsive:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.9 ATP1A3 PNKD PRKRA PRRT2 SGCE SLC2A1
2 homeostasis/metabolism MP:0005376 9.73 ATP1A3 GCH1 PNKD PRKRA PRRT2 SGCE
3 nervous system MP:0003631 9.4 ATP1A3 GCH1 PNKD PRKRA PRRT2 SGCE

Drugs & Therapeutics for Dystonia, Dopa-Responsive

Drugs for Dystonia, Dopa-Responsive (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Iron Approved, Experimental 15438-31-0, 7439-89-6 27284 23925
2 Dihydroxyphenylalanine

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 GENomic Biomarkers for PARKinson's Disease Completed NCT00465790
2 Natural History and Biospecimen Repository for Dystonia; Comprehensive Rating Tools for Cervical Dystonia; Validity & Reliability of Diagnostic Methods & Measures of Spasmodic Dysphonia Recruiting NCT01373424
3 Imaging Neuromelanin and Iron in Dystonia/Parkinsonism Not yet recruiting NCT03572114

Search NIH Clinical Center for Dystonia, Dopa-Responsive

Genetic Tests for Dystonia, Dopa-Responsive

Genetic tests related to Dystonia, Dopa-Responsive:

# Genetic test Affiliating Genes
1 Dystonia 5 29 GCH1
2 Dystonia, Dopa-Responsive 29

Anatomical Context for Dystonia, Dopa-Responsive

MalaCards organs/tissues related to Dystonia, Dopa-Responsive:

40
Testes, Brain, Cerebellum, Cortex

Publications for Dystonia, Dopa-Responsive

Articles related to Dystonia, Dopa-Responsive:

(show top 50) (show all 83)
# Title Authors PMID Year
1
Utility of MLPA in deletion analysis of GCH1 in dopa-responsive dystonia. 6 56
17111153 2007
2
A new GTP-cyclohydrolase I mutation in an unusual dopa-responsive dystonia, familial form. 6 56
10208576 1999
3
Dystonia with motor delay in compound heterozygotes for GTP-cyclohydrolase I gene mutations. 61 6
9667588 1998
4
Gender-related penetrance and de novo GTP-cyclohydrolase I gene mutations in dopa-responsive dystonia. 61 56
9566388 1998
5
EFNS guidelines on diagnosis and treatment of primary dystonias. 6
20482602 2011
6
Study of a Swiss dopa-responsive dystonia family with a deletion in GCH1: redefining DYT14 as DYT5. 56
17804835 2008
7
Broadening the phenotype of childhood-onset dopa-responsive dystonia. 56
16908750 2006
8
High mutation rate in dopa-responsive dystonia: detection with comprehensive GCHI screening. 56
15753436 2005
9
Hereditary Dystonia Overview 6
20301334 2003
10
Autosomal dominant guanosine triphosphate cyclohydrolase I deficiency (Segawa disease). 56
12891652 2003
11
Autosomal dominant GTP-CH deficiency presenting as a dopa-responsive myoclonus-dystonia syndrome. 6
12391354 2002
12
Neuropathology of a case of dopa-responsive dystonia associated with a new genetic locus, DYT14. 56
12084887 2002
13
GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia 6
20301681 2002
14
A splice mutation in the GTP cyclohydrolase I gene causes dopa-responsive dystonia by exon skipping. 6
11486899 2001
15
Neurologic and psychiatric manifestations in a family with a mutation in exon 2 of the guanosine triphosphate-cyclohydrolase gene. 56
11346370 2001
16
A novel nonsense mutation of the GTP cyclohydrolase I gene in a family with dopa-responsive dystonia. 6
11359069 2001
17
Dopa-responsive dystonia: mutation analysis of GCH1 and analysis of therapeutic doses of L-dopa. German Dystonia Study Group. 56
11113234 2000
18
Dopa-responsive dystonia is induced by a dominant-negative mechanism. 6
11026444 2000
19
Striatal biopterin and tyrosine hydroxylase protein reduction in dopa-responsive dystonia. 56
10496263 1999
20
Oral phenylalanine loading profiles in symptomatic and asymptomatic gene carriers with dopa-responsive dystonia due to dominantly inherited GTP cyclohydrolase deficiency. 56
10384370 1999
21
GCH1 mutation in a patient with adult-onset oromandibular dystonia. 6
10078749 1999
22
High penetrance and pronounced variation in expressivity of GCH1 mutations in five families with dopa-responsive dystonia. 56
9585358 1998
23
Clinical similarities of hereditary progressive/dopa responsive dystonia caused by different types of mutations in the GTP cyclohydrolase I gene. 6
9576537 1998
24
Two previously unrecognized splicing mutations of GCH1 in Dopa-responsive dystonia: exon skipping and one base insertion. 6
10732814 1997
25
Oral phenylalanine loading in dopa-responsive dystonia: a possible diagnostic test. 56
9153460 1997
26
Characterization of mouse and human GTP cyclohydrolase I genes. Mutations in patients with GTP cyclohydrolase I deficiency. 6
7730309 1995
27
Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene. 56
7874165 1994
28
Lessons from a remarkable family with dopa-responsive dystonia. 56
8163996 1994
29
Dopa-responsive dystonia: pathological and biochemical observations in a case. 56
7908789 1994
30
Linkage mapping of dopa-responsive dystonia (DRD) to chromosome 14q. 56
8298648 1993
31
Dopamine beta-hydroxylase gene excluded in four subtypes of hereditary dystonia. 56
1677923 1991
32
Dopa-responsive dystonia: long-term treatment response and prognosis. 56
1899474 1991
33
Identification of a highly polymorphic microsatellite VNTR within the argininosuccinate synthetase locus: exclusion of the dystonia gene on 9q32-34 as the cause of dopa-responsive dystonia in a large kindred. 56
1985454 1991
34
Biochemical and neurophysiological investigations in two forms of Segawa's disease. 56
1969123 1990
35
Tyrosine hydroxylase and levodopa responsive dystonia. 56
2565377 1989
36
Dopa-responsive dystonia. 56
3041760 1988
37
Long-term treatment with levodopa in a family with autosomal dominant torsion dystonia. 56
3400489 1988
38
Hereditary dystonia-parkinsonism syndrome of juvenile onset. 56
3762960 1986
39
Idiopathic dystonia-parkinsonism with marked diurnal fluctuation of symptoms. 56
3985584 1985
40
Hereditary progressive dystonia with marked diurnal fluctuation. 56
945938 1976
41
Hereditary Parkinsonism-dystonia with sustained control by L-DOPA and anticholinergic medication. 56
942621 1976
42
Abnormal patterns of corticomuscular and intermuscular coherence in childhood dystonia. 61
32067914 2020
43
Quality of life outcomes after deep brain stimulation in dystonia: A systematic review. 61
31767450 2020
44
Rescue Sedation When Treating Acute Agitation in the Emergency Department With Intramuscular Antipsychotics. 61
30745194 2019
45
Sensory trick splint as a multimodal therapy for oromandibular dystonia. 61
29126810 2018
46
Movement disorders in genetically confirmed mitochondrial disease and the putative role of the cerebellum. 61
28901595 2018
47
Dystonia in Patients with Spinocerebellar Ataxia 3 - Machado-Joseph disease: An Underestimated Diagnosis? 61
30008965 2018
48
Anodal transcranial direct current stimulation to the cerebellum improves handwriting and cyclic drawing kinematics in focal hand dystonia. 61
26042019 2015
49
Dystonia: an update on phenomenology, classification, pathogenesis and treatment. 61
24978640 2014
50
Haloperidol versus placebo for schizophrenia. 61
24242360 2013

Variations for Dystonia, Dopa-Responsive

ClinVar genetic disease variations for Dystonia, Dopa-Responsive:

6 (show top 50) (show all 141) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GCH1 NM_000161.3(GCH1):c.541+1G>CSNV Pathogenic 465762 rs1555358599 14:55313816-55313816 14:54847098-54847098
2 GCH1 NC_000014.9:g.(?_54865307)_(54865456_?)deldeletion Pathogenic 465757 14:55332025-55332174 14:54865307-54865456
3 GCH1 NM_000161.3(GCH1):c.344-1G>CSNV Pathogenic 465761 rs1555360050 14:55332155-55332155 14:54865437-54865437
4 GCH1 NM_000161.3(GCH1):c.278dup (p.Thr94fs)duplication Pathogenic 465759 rs1555362835 14:55369103-55369104 14:54902385-54902386
5 GCH1 NM_000161.3(GCH1):c.1A>T (p.Met1Leu)SNV Pathogenic 465758 rs1555362907 14:55369381-55369381 14:54902663-54902663
6 GCH1 NC_000014.9:g.(?_54902301)_(54902683_?)deldeletion Pathogenic 529416 14:55369019-55369401 14:54902301-54902683
7 GCH1 NM_000161.3(GCH1):c.626+1G>ASNV Pathogenic 529415 rs1555358507 14:55312485-55312485 14:54845767-54845767
8 GCH1 NM_000161.3(GCH1):c.344-1G>ASNV Pathogenic 529413 rs1555360050 14:55332155-55332155 14:54865437-54865437
9 GCH1 NM_000161.3(GCH1):c.186_197delinsA (p.Asp63fs)indel Pathogenic 529414 rs1555362845 14:55369185-55369196 14:54902467-54902478
10 GCH1 NM_000161.3(GCH1):c.541+1G>TSNV Pathogenic 489338 rs1555358599 14:55313816-55313816 14:54847098-54847098
11 GCH1 NC_000014.9:g.(?_54865317)_(54865446_?)deldeletion Pathogenic 652965 14:55332035-55332164 14:54865317-54865446
12 GCH1 NM_000161.3(GCH1):c.509+1_509+3delinsTGTGAGindel Pathogenic 641360 14:55326396-55326398 14:54859678-54859680
13 GCH1 NC_000014.9:g.(?_54859671)_(54865446_?)deldeletion Pathogenic 832851 14:55326389-55332164
14 GCH1 NC_000014.9:g.(?_54902311)_(54902702_?)deldeletion Pathogenic 832331 14:55369029-55369420
15 GCH1 GCH1, IVS2, G-C, +1SNV Pathogenic 9279
16 GCH1 NM_000161.3(GCH1):c.262C>T (p.Arg88Trp)SNV Pathogenic 9271 rs104894433 14:55369120-55369120 14:54902402-54902402
17 GCH1 NM_000161.3(GCH1):c.401A>T (p.Asp134Val)SNV Pathogenic 9272 rs104894437 14:55332097-55332097 14:54865379-54865379
18 GCH1 GCH1, 2-BP INSinsertion Pathogenic 9273
19 GCH1 NM_000161.3(GCH1):c.602G>A (p.Gly201Glu)SNV Pathogenic 9274 rs104894438 14:55312510-55312510 14:54845792-54845792
20 GCH1 GCH1, IVS1, A-G, -2SNV Pathogenic 9275
21 GCH1 GCH1, IVS2, A-G, -2SNV Pathogenic 9276
22 GCH1 NM_000161.3(GCH1):c.3G>C (p.Met1Ile)SNV Pathogenic 9277 rs104894439 14:55369379-55369379 14:54902661-54902661
23 GCH1 NM_000161.3(GCH1):c.431A>C (p.His144Pro)SNV Pathogenic 9278 rs104894440 14:55332067-55332067 14:54865349-54865349
24 GCH1 NM_000161.3(GCH1):c.323G>A (p.Gly108Asp)SNV Pathogenic 9282 rs104894435 14:55369059-55369059 14:54902341-54902341
25 GCH1 NM_000161.3(GCH1):c.404T>A (p.Ile135Lys)SNV Pathogenic 9285 rs104894441 14:55332094-55332094 14:54865376-54865376
26 GCH1 NM_000161.3(GCH1):c.142C>T (p.Gln48Ter)SNV Pathogenic 9288 rs104894444 14:55369240-55369240 14:54902522-54902522
27 GCH1 GCH1, IVS5, G-A, +1SNV Pathogenic 9289
28 GCH1 GCH1, DELdeletion Pathogenic 9291
29 GCH1 NM_000161.3(GCH1):c.607G>A (p.Gly203Arg)SNV Pathogenic 381665 rs988395114 14:55312505-55312505 14:54845787-54845787
30 GCH1 NM_000161.3(GCH1):c.1A>G (p.Met1Val)SNV Pathogenic 642685 14:55369381-55369381 14:54902663-54902663
31 GCH1 NM_000161.3(GCH1):c.76del (p.Asp26fs)deletion Pathogenic 647643 14:55369306-55369306 14:54902588-54902588
32 GCH1 NM_000161.3(GCH1):c.127_130dup (p.Ala44fs)duplication Pathogenic 641586 14:55369251-55369252 14:54902533-54902534
33 GCH1 NM_000161.3(GCH1):c.473del (p.Pro158fs)deletion Pathogenic 848233 14:55326435-55326435 14:54859717-54859717
34 GCH1 NM_000161.3(GCH1):c.248dup (p.Glu84fs)duplication Pathogenic 640887 14:55369133-55369134 14:54902415-54902416
35 GCH1 NM_000161.3(GCH1):c.532A>T (p.Arg178Ter)SNV Pathogenic 640160 14:55313826-55313826 14:54847108-54847108
36 GCH1 NM_000161.3(GCH1):c.220_223del (p.Ala74fs)deletion Pathogenic 573159 rs1566687321 14:55369159-55369162 14:54902441-54902444
37 GCH1 NM_000161.3(GCH1):c.281C>A (p.Thr94Lys)SNV Likely pathogenic 568970 rs1566687244 14:55369101-55369101 14:54902383-54902383
38 GCH1 NM_000161.3(GCH1):c.614T>A (p.Val205Glu)SNV Likely pathogenic 574828 rs1418922853 14:55312498-55312498 14:54845780-54845780
39 GCH1 NM_000161.3(GCH1):c.212T>C (p.Leu71Pro)SNV Likely pathogenic 651184 14:55369170-55369170 14:54902452-54902452
40 GCH1 NM_000161.3(GCH1):c.281C>T (p.Thr94Met)SNV Likely pathogenic 813311 14:55369101-55369101 14:54902383-54902383
41 GCH1 NM_000161.3(GCH1):c.195G>A (p.Glu65=)SNV Conflicting interpretations of pathogenicity 623842 rs139350456 14:55369187-55369187 14:54902469-54902469
42 GCH1 NM_000161.3(GCH1):c.400G>A (p.Asp134Asn)SNV Conflicting interpretations of pathogenicity 459899 rs1353623780 14:55332098-55332098 14:54865380-54865380
43 GCH1 NM_000161.3(GCH1):c.297C>T (p.Ala99=)SNV Conflicting interpretations of pathogenicity 313396 rs776450369 14:55369085-55369085 14:54902367-54902367
44 GCH1 NM_000161.3(GCH1):c.*93G>ASNV Conflicting interpretations of pathogenicity 881768 14:55310642-55310642 14:54843924-54843924
45 GCH1 NM_000161.3(GCH1):c.610G>A (p.Val204Ile)SNV Conflicting interpretations of pathogenicity 161248 rs200891969 14:55312502-55312502 14:54845784-54845784
46 GCH1 NM_000161.3(GCH1):c.206C>T (p.Pro69Leu)SNV Conflicting interpretations of pathogenicity 161247 rs56127440 14:55369176-55369176 14:54902458-54902458
47 GCH1 NM_000161.3(GCH1):c.671A>G (p.Lys224Arg)SNV Conflicting interpretations of pathogenicity 9283 rs41298442 14:55310817-55310817 14:54844099-54844099
48 GCH1 NM_000161.3(GCH1):c.*1044G>ASNV Conflicting interpretations of pathogenicity 883618 14:55309691-55309691 14:54842973-54842973
49 GCH1 NM_000161.3(GCH1):c.543T>G (p.Val181=)SNV Conflicting interpretations of pathogenicity 313393 rs765670568 14:55312569-55312569 14:54845851-54845851
50 GCH1 NM_000161.3(GCH1):c.626+9G>TSNV Conflicting interpretations of pathogenicity 313391 rs374007793 14:55312477-55312477 14:54845759-54845759

UniProtKB/Swiss-Prot genetic disease variations for Dystonia, Dopa-Responsive:

73 (show all 33)
# Symbol AA change Variation ID SNP ID
1 GCH1 p.Pro23Leu VAR_002633 rs41298432
2 GCH1 p.Leu79Pro VAR_002634
3 GCH1 p.Arg88Pro VAR_002635
4 GCH1 p.Arg88Trp VAR_002636 rs104894433
5 GCH1 p.Met102Lys VAR_002637
6 GCH1 p.Asp134Val VAR_002638 rs104894437
7 GCH1 p.Cys141Trp VAR_002639
8 GCH1 p.His144Pro VAR_002640 rs104894440
9 GCH1 p.His153Pro VAR_002641
10 GCH1 p.Arg178Ser VAR_002642
11 GCH1 p.Thr186Lys VAR_002644
12 GCH1 p.Gly201Glu VAR_002645 rs104894438
13 GCH1 p.Gly203Arg VAR_002646 rs988395114
14 GCH1 p.Lys224Arg VAR_002648 rs41298442
15 GCH1 p.Phe234Ser VAR_002649
16 GCH1 p.Leu71Gln VAR_016888
17 GCH1 p.Ala74Val VAR_016889
18 GCH1 p.Gly83Ala VAR_016890
19 GCH1 p.Gly90Val VAR_016892
20 GCH1 p.Met102Arg VAR_016893
21 GCH1 p.Asp115Asn VAR_016895 rs139309517
22 GCH1 p.Ile135Lys VAR_016896 rs104894441
23 GCH1 p.Cys141Arg VAR_016897
24 GCH1 p.Leu163Arg VAR_016898
25 GCH1 p.Ser176Thr VAR_016899
26 GCH1 p.Gln180Arg VAR_016900
27 GCH1 p.Val191Ile VAR_016901 rs762208304
28 GCH1 p.Pro199Leu VAR_016902
29 GCH1 p.Met211Val VAR_016903
30 GCH1 p.Met213Val VAR_016904 rs134856249
31 GCH1 p.Arg241Trp VAR_016906 rs137520979
32 GCH1 p.Arg249Ser VAR_016907 rs104894442
33 GCH1 p.Thr106Ile VAR_054112

Expression for Dystonia, Dopa-Responsive

Search GEO for disease gene expression data for Dystonia, Dopa-Responsive.

Pathways for Dystonia, Dopa-Responsive

Pathways related to Dystonia, Dopa-Responsive according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.73 TH SLC6A3
2 10.64 TOR1A TH SLC6A3
3
Show member pathways
10.52 TH SLC6A3
4
Show member pathways
10.26 TH SPR GCH1

GO Terms for Dystonia, Dopa-Responsive

Cellular components related to Dystonia, Dopa-Responsive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 neuron projection GO:0043005 9.46 TOR1A TH SLC6A3 PRRT2
2 neuronal cell body membrane GO:0032809 9.26 SLC6A3 ATP1A3
3 synaptic vesicle GO:0008021 9.13 TOR1A TH PRRT2
4 axon GO:0030424 8.92 TH SLC6A3 PRRT2 ATP1A3

Biological processes related to Dystonia, Dopa-Responsive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 neurotransmitter biosynthetic process GO:0042136 9.43 TH SLC6A3
2 nitric oxide biosynthetic process GO:0006809 9.4 SPR GCH1
3 cofactor metabolic process GO:0051186 9.37 SPR GCH1
4 regulation of dopamine metabolic process GO:0042053 9.32 SLC6A3 PNKD
5 hyaloid vascular plexus regression GO:1990384 9.26 TH SLC6A3
6 tetrahydrobiopterin biosynthetic process GO:0006729 9.16 SPR GCH1
7 neuromuscular process controlling posture GO:0050884 9.13 PRRT2 PNKD GCH1
8 dopamine biosynthetic process GO:0042416 8.8 TH SLC6A3 GCH1

Molecular functions related to Dystonia, Dopa-Responsive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 TBP-class protein binding GO:0017025 9.26 TAF1L TAF1
2 lysine-acetylated histone binding GO:0070577 9.16 TAF1L TAF1
3 dopamine binding GO:0035240 8.96 TH SLC6A3
4 steroid hormone binding GO:1990239 8.62 SULT2B1 ATP1A3

Sources for Dystonia, Dopa-Responsive

3 CDC
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11 DGIdb
17 EFO
18 ExPASy
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68 SNOMED-CT via HPO
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