MCID: PRK092
MIFTS: 44

Parkinson Disease 6, Autosomal Recessive Early-Onset

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

Aliases & Classifications for Parkinson Disease 6, Autosomal Recessive Early-Onset

MalaCards integrated aliases for Parkinson Disease 6, Autosomal Recessive Early-Onset:

Name: Parkinson Disease 6, Autosomal Recessive Early-Onset 53 28 69
Parkinson Disease 6, Early Onset 53 13
Parkinson Disease 6 71 28
Park6 53 71
Parkinson Disease, Autosomal Recessive Early-Onset, Digenic, Pink1/dj1 28
Parkinson Disease Autosomal Recessive Early-Onset Digenic Pink1/dj1 71
Autosomal Recessive Early-Onset Parkinson Disease Type 6 71
Autosomal Recessive Early-Onset Parkinson Disease 6 12
Parkinson Disease 6 Late-Onset Susceptibility to 71
Parkinson Disease 6, Early-Onset; Park6 53
Parkinson Disease 6, Early-Onset 53
Early-Onset Parkinson Disease 6 12
Parkinson Disease 6 Early-Onset 71
Parkinsonism Young Adult Onset 71

Characteristics:

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
slow progression
levodopa-responsive
early onset (9-48 years, but reported up to 68 years)
diurnal fluctuation
levodopa-induced dyskinesias
a subset of patients have heterozygous mutations, which may predispose to disease development


HPO:

31
parkinson disease 6, autosomal recessive early-onset:
Onset and clinical course infantile onset slow progression
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Parkinson Disease 6, Autosomal Recessive Early-Onset

UniProtKB/Swiss-Prot : 71 Parkinson disease 6: An early-onset form of Parkinson disease, a neurodegenerative disorder characterized by parkinsonian signs such as rigidity, resting tremor and bradykinesia. A subset of patients manifest additional symptoms including hyperreflexia, autonomic instability, dementia and psychiatric disturbances. Symptoms show diurnal fluctuation and can improve after sleep. PARK6 pathogenesis involves respiratory complex I deficiency causing mitochondrial depolarization and dysfunction. Inheritance is autosomal recessive.

MalaCards based summary : Parkinson Disease 6, Autosomal Recessive Early-Onset, also known as parkinson disease 6, early onset, is related to parkinson disease, late-onset and parkinson disease 2, autosomal recessive juvenile, and has symptoms including dystonia, bradykinesia and hyperreflexia. An important gene associated with Parkinson Disease 6, Autosomal Recessive Early-Onset is PINK1 (PTEN Induced Putative Kinase 1), and among its related pathways/superpathways are Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. and Parkinsons Disease Pathway. The drug Fluorodeoxyglucose F18 has been mentioned in the context of this disorder.

Disease Ontology : 12 A Parkinson's disease that has material basis in mutations in the PINK1 gene on chromosome 1p36.12.

Description from OMIM: 605909

Related Diseases for Parkinson Disease 6, Autosomal Recessive Early-Onset

Diseases in the Parkinson Disease, Late-Onset family:

Parkinson Disease 1, Autosomal Dominant Parkinson Disease 15, Autosomal Recessive Early-Onset
Parkinson Disease 12 Parkinson Disease 2, Autosomal Recessive Juvenile
Parkinson Disease 3, Autosomal Dominant Parkinson Disease 4, Autosomal Dominant
Parkinson Disease 6, Autosomal Recessive Early-Onset Parkinson Disease 7, Autosomal Recessive Early-Onset
Parkinson Disease 10 Parkinson Disease 8, Autosomal Dominant
Parkinson Disease 11, Autosomal Dominant Parkinson Disease 13, Autosomal Dominant
Parkinson Disease 14, Autosomal Recessive Parkinson Disease 16
Parkinson Disease 5, Autosomal Dominant Parkinson Disease 17
Parkinson Disease 18, Autosomal Dominant Parkinson Disease 19a, Juvenile-Onset
Parkinson Disease 20, Early-Onset Parkinson Disease 21
Parkinson Disease 22, Autosomal Dominant Parkinson Disease 23, Autosomal Recessive Early-Onset
Juvenile-Onset Parkinson Disease Early-Onset Parkinson Disease
Parkinson Disease Type 9 Hereditary Late-Onset Parkinson Disease

Diseases related to Parkinson Disease 6, Autosomal Recessive Early-Onset via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 23)
# Related Disease Score Top Affiliating Genes
1 parkinson disease, late-onset 31.3 MT-ND5 PARK7 PINK1
2 parkinson disease 2, autosomal recessive juvenile 29.8 PARK7 PINK1
3 parkinson disease 10 10.0 PARK7 PINK1
4 early-onset parkinson disease 10.0 PARK7 PINK1
5 parkinson disease 15, autosomal recessive early-onset 10.0 PARK7 PINK1
6 movement disease 9.9 PARK7 PINK1
7 synucleinopathy 9.9 PARK7 PINK1
8 parkinson disease 7, autosomal recessive early-onset 9.9
9 leber optic atrophy 9.8 MT-ND5 MT-ND6
10 mitochondrial dna-associated leigh syndrome and narp 9.8 MT-ND5 MT-ND6
11 encephalomyopathy 9.8 MT-ND5 MT-ND6
12 nervous system disease 9.8 PARK7 PINK1
13 cranial nerve disease 9.8 MT-ND5 MT-ND6
14 optic nerve disease 9.8 MT-ND5 MT-ND6
15 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 9.8 MT-ND5 MT-ND6
16 mitochondrial encephalomyopathy 9.7 MT-ND5 MT-ND6
17 kearns-sayre syndrome 9.7 MT-ND5 MT-ND6
18 mitochondrial metabolism disease 9.7 MT-ND5 MT-ND6
19 lactic acidosis 9.7 MT-ND5 MT-ND6
20 mitochondrial disorders 9.6 MT-ND5 MT-ND6
21 leber hereditary optic neuropathy 9.6 MT-ND5 MT-ND6
22 neuropathy 9.5 MT-ND5 MT-ND6
23 mitochondrial complex i deficiency 9.4 MT-ND5 MT-ND6

Graphical network of the top 20 diseases related to Parkinson Disease 6, Autosomal Recessive Early-Onset:



Diseases related to Parkinson Disease 6, Autosomal Recessive Early-Onset

Symptoms & Phenotypes for Parkinson Disease 6, Autosomal Recessive Early-Onset

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
bradykinesia
rigidity
parkinsonism
resting tremor
asymmetry at onset (74%)
more
Genitourinary Bladder:
urinary urgency (in 44% of patients)

Neurologic Behavioral Psychiatric Manifestations:
depression
anxiety
psychiatric disturbances (25%)


Clinical features from OMIM:

605909

Human phenotypes related to Parkinson Disease 6, Autosomal Recessive Early-Onset:

31 (show all 11)
# Description HPO Frequency HPO Source Accession
1 dystonia 31 HP:0001332
2 bradykinesia 31 HP:0002067
3 hyperreflexia 31 HP:0001347
4 anxiety 31 HP:0000739
5 rigidity 31 HP:0002063
6 dementia 31 HP:0000726
7 parkinsonism 31 HP:0001300
8 postural instability 31 HP:0002172
9 urinary urgency 31 HP:0000012
10 resting tremor 31 HP:0002322
11 depressivity 31 HP:0000716

UMLS symptoms related to Parkinson Disease 6, Autosomal Recessive Early-Onset:


resting tremor, bradykinesia, muscle rigidity

Drugs & Therapeutics for Parkinson Disease 6, Autosomal Recessive Early-Onset

Drugs for Parkinson Disease 6, Autosomal Recessive Early-Onset (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Fluorodeoxyglucose F18 Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Development of a Novel 18F-DTBZ PET Imaging as a Biomarker to Monitor Neurodegeneration of PARK6 and PARK8 Parkinsonism Completed NCT01759888 Phase 2 18F-DTBZ
2 Genetic Study in Young Onset Parkinson's Disease Unknown status NCT01529970

Search NIH Clinical Center for Parkinson Disease 6, Autosomal Recessive Early-Onset

Genetic Tests for Parkinson Disease 6, Autosomal Recessive Early-Onset

Genetic tests related to Parkinson Disease 6, Autosomal Recessive Early-Onset:

# Genetic test Affiliating Genes
1 Parkinson Disease 6, Autosomal Recessive Early-Onset 28 PINK1
2 Parkinson Disease 6 28
3 Parkinson Disease, Autosomal Recessive Early-Onset, Digenic, Pink1/dj1 28

Anatomical Context for Parkinson Disease 6, Autosomal Recessive Early-Onset

Publications for Parkinson Disease 6, Autosomal Recessive Early-Onset

Articles related to Parkinson Disease 6, Autosomal Recessive Early-Onset:

(show all 13)
# Title Authors Year
1
PTEN-inducible kinase 1 (PINK1)/Park6 is indispensable for normal heart function. ( 21606348 )
2011
2
Enhanced vulnerability of PARK6 patient skin fibroblasts to apoptosis induced by proteasomal stress. ( 20045449 )
2010
3
FOXO3a-dependent regulation of Pink1 (Park6) mediates survival signaling in response to cytokine deprivation. ( 19276113 )
2009
4
Sleep quality in a family with hereditary parkinsonism (PARK6). ( 17766179 )
2008
5
[Case of a 30-year history of PARK6 --findings from functional imaging of the brain]. ( 19048950 )
2008
6
Mitochondrial dysfunction, peroxidation damage and changes in glutathione metabolism in PARK6. ( 17141510 )
2007
7
Assessment of PINK1 (PARK6) polymorphisms in Finnish PD. ( 16046032 )
2006
8
Dopaminergic function in a family with the PARK6 form of autosomal recessive Parkinson's syndrome. ( 15785866 )
2005
9
The gene responsible for PARK6 Parkinson's disease, PINK1, does not influence common forms of parkinsonism. ( 15349859 )
2004
10
PINK1 (PARK6) associated Parkinson disease in Ireland. ( 15505171 )
2004
11
PARK6 is a common cause of familial parkinsonism. ( 12548371 )
2002
12
Autosomal recessive early onset parkinsonism is linked to three loci: PARK2, PARK6, and PARK7. ( 12548343 )
2002
13
Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35-p36. ( 11254447 )
2001

Variations for Parkinson Disease 6, Autosomal Recessive Early-Onset

UniProtKB/Swiss-Prot genetic disease variations for Parkinson Disease 6, Autosomal Recessive Early-Onset:

71 (show all 23)
# Symbol AA change Variation ID SNP ID
1 PINK1 p.Gly309Asp VAR_018994 rs74315355
2 PINK1 p.Cys92Phe VAR_046568
3 PINK1 p.Ala168Pro VAR_046575 rs768091663
4 PINK1 p.Pro196Leu VAR_046577 rs138302371
5 PINK1 p.Ala217Asp VAR_046578 rs74315360
6 PINK1 p.Glu240Lys VAR_046581 rs573931674
7 PINK1 p.Leu268Val VAR_046584 rs372280083
8 PINK1 p.His271Gln VAR_046585 rs28940284
9 PINK1 p.Arg279His VAR_046587 rs74315358
10 PINK1 p.Thr313Met VAR_046589 rs74315359
11 PINK1 p.Leu347Pro VAR_046593 rs28940285
12 PINK1 p.Cys388Arg VAR_046596
13 PINK1 p.Glu417Gly VAR_046599
14 PINK1 p.Arg464His VAR_046605 rs764328076
15 PINK1 p.Leu489Pro VAR_046607
16 PINK1 p.Cys125Gly VAR_062773
17 PINK1 p.Ala280Thr VAR_062774 rs772510148
18 PINK1 p.Leu369Pro VAR_062775
19 PINK1 p.Gly386Ala VAR_062776
20 PINK1 p.Arg407Gln VAR_062778 rs556540177
21 PINK1 p.Gly409Val VAR_062779
22 PINK1 p.Gln126Pro VAR_064344
23 PINK1 p.Val170Gly VAR_078934

ClinVar genetic disease variations for Parkinson Disease 6, Autosomal Recessive Early-Onset:

6 (show all 16)
# Gene Variation Type Significance SNP ID Assembly Location
1 MT-ND6 m.14319T> C single nucleotide variant risk factor rs199476110 GRCh37 Chromosome MT, 14319: 14319
2 MT-ND5 m.12397A> G single nucleotide variant risk factor rs200890363 GRCh37 Chromosome MT, 12397: 12397
3 PINK1 NM_032409.2(PINK1): c.620delG (p.Arg207Glnfs) deletion Pathogenic rs756677845 GRCh37 Chromosome 1, 20964567: 20964567
4 PINK1 NM_032409.2(PINK1): c.926G> A (p.Gly309Asp) single nucleotide variant Pathogenic rs74315355 GRCh37 Chromosome 1, 20971132: 20971132
5 PINK1 NM_032409.2(PINK1): c.813C> A (p.His271Gln) single nucleotide variant Pathogenic rs28940284 GRCh37 Chromosome 1, 20971019: 20971019
6 PINK1 NM_032409.2(PINK1): c.1311G> A (p.Trp437Ter) single nucleotide variant Pathogenic rs74315356 GRCh37 Chromosome 1, 20975547: 20975547
7 PINK1 NM_032409.2(PINK1): c.736C> T (p.Arg246Ter) single nucleotide variant Pathogenic rs74315357 GRCh37 Chromosome 1, 20966445: 20966445
8 PINK1 NM_032409.2(PINK1): c.1040T> C (p.Leu347Pro) single nucleotide variant Pathogenic rs28940285 GRCh37 Chromosome 1, 20972133: 20972133
9 PINK1 NM_032409.2(PINK1): c.1570_1573dupTTAG (p.Asp525Valfs) duplication Pathogenic rs730880302 GRCh37 Chromosome 1, 20977008: 20977011
10 PINK1 PINK1, 3-BP INS, 1602CAA insertion Pathogenic
11 PINK1 NM_032409.2(PINK1): c.836G> A (p.Arg279His) single nucleotide variant Pathogenic rs74315358 GRCh37 Chromosome 1, 20971042: 20971042
12 PINK1 NM_005216.4(DDOST): c.*807_*5409del deletion Pathogenic GRCh38 Chromosome 1, 20646970: 20651572
13 PINK1 NM_032409.2(PINK1): c.938C> T (p.Thr313Met) single nucleotide variant Pathogenic rs74315359 GRCh37 Chromosome 1, 20971144: 20971144
14 PINK1 NM_032409.2(PINK1): c.650C> A (p.Ala217Asp) single nucleotide variant Pathogenic rs74315360 GRCh37 Chromosome 1, 20964597: 20964597
15 PINK1 NM_032409.2(PINK1): c.1366C> T (p.Gln456Ter) single nucleotide variant Pathogenic rs45539432 GRCh37 Chromosome 1, 20975602: 20975602
16 PARK7 NM_007262.4(PARK7): c.115G> T (p.Ala39Ser) single nucleotide variant Pathogenic rs137853051 GRCh37 Chromosome 1, 8025408: 8025408

Expression for Parkinson Disease 6, Autosomal Recessive Early-Onset

Search GEO for disease gene expression data for Parkinson Disease 6, Autosomal Recessive Early-Onset.

Pathways for Parkinson Disease 6, Autosomal Recessive Early-Onset

GO Terms for Parkinson Disease 6, Autosomal Recessive Early-Onset

Cellular components related to Parkinson Disease 6, Autosomal Recessive Early-Onset according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin GO:0000785 9.4 PARK7 PINK1
2 cell body GO:0044297 9.37 PARK7 PINK1
3 mitochondrial inner membrane GO:0005743 9.33 MT-ND5 MT-ND6 PINK1
4 mitochondrial intermembrane space GO:0005758 9.32 PARK7 PINK1
5 respiratory chain GO:0070469 9.26 MT-ND5 MT-ND6
6 mitochondrial respiratory chain complex I GO:0005747 8.96 MT-ND5 PARK7
7 mitochondrion GO:0005739 8.92 MT-ND5 MT-ND6 PARK7 PINK1

Biological processes related to Parkinson Disease 6, Autosomal Recessive Early-Onset according to GeneCards Suite gene sharing:

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of gene expression GO:0010629 9.58 PARK7 PINK1
2 autophagy GO:0006914 9.58 PARK7 PINK1
3 protein stabilization GO:0050821 9.57 PARK7 PINK1
4 positive regulation of protein kinase B signaling GO:0051897 9.56 PARK7 PINK1
5 negative regulation of neuron apoptotic process GO:0043524 9.55 PARK7 PINK1
6 positive regulation of DNA binding transcription factor activity GO:0051091 9.54 PARK7 PINK1
7 cellular response to oxidative stress GO:0034599 9.52 PARK7 PINK1
8 mitochondrion organization GO:0007005 9.51 PARK7 PINK1
9 positive regulation of peptidyl-serine phosphorylation GO:0033138 9.49 PARK7 PINK1
10 mitochondrial respiratory chain complex I assembly GO:0032981 9.48 MT-ND5 MT-ND6
11 mitochondrial electron transport, NADH to ubiquinone GO:0006120 9.46 MT-ND5 MT-ND6
12 activation of protein kinase B activity GO:0032148 9.43 PARK7 PINK1
13 regulation of mitochondrial membrane potential GO:0051881 9.4 PARK7 PINK1
14 regulation of neuron apoptotic process GO:0043523 9.37 PARK7 PINK1
15 response to hydrogen peroxide GO:0042542 9.33 MT-ND5 MT-ND6 PARK7
16 negative regulation of oxidative stress-induced neuron death GO:1903204 9.32 PARK7 PINK1
17 negative regulation of oxidative stress-induced cell death GO:1903202 9.26 PARK7 PINK1
18 positive regulation of mitochondrial electron transport, NADH to ubiquinone GO:1902958 8.96 PARK7 PINK1
19 negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway GO:1903384 8.62 PARK7 PINK1

Molecular functions related to Parkinson Disease 6, Autosomal Recessive Early-Onset according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 NADH dehydrogenase (ubiquinone) activity GO:0008137 8.62 MT-ND5 MT-ND6

Sources for Parkinson Disease 6, Autosomal Recessive Early-Onset

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
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29 HGMD
30 HMDB
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35 IUPHAR
36 KEGG
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42 MESH via Orphanet
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58 PubMed
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65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
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70 UMLS via Orphanet
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