Details of Disease

Disease Name

Autosomal recessive juvenile Parkinson disease 2

Parkinson disease 2; Parkinson disease, juvenile, autosomal recessive; Parkinson disease 2, autosomal recessive juvenile; autosomal recessive juvenile Parkinson's disease 2; JP; autosomal recessive juvenile Parkinson disease; Parkinsonism, early-onset, with diurnal fluctuation; Parkinson disease autosomal recessive, early onset; Parkinsonism, early onset, with diurnal fluctuation; PDJ; juvenile parkinsonism; PARK2; autosomal recessive juvenile Parkinson disease 2; autosomal recessive juvenile Parkinson disease type 2; Parkinson disease, juvenile, type 2; young-onset Parkinson disease caused by mutation in PRKN; PRKN young-onset Parkinson disease

Definition

A group of disorders which feature impaired motor control characterized by bradykinesia, muscle rigidity; tremor; and postural instability. Parkinsonian diseases are generally divided into primary parkinsonism (see parkinson disease), secondary parkinsonism (see parkinson disease, secondary) and inherited forms. These conditions are associated with dysfunction of dopaminergic or closely related motor integration neuronal pathways in the basal ganglia.

Disease Hierarchy

DIS05LFS: Young-onset Parkinson disease

DISNSTD1: Autosomal recessive juvenile Parkinson disease 2

Disease Identifiers

MONDO ID

MONDO_0010820

MESH ID

D020734

UMLS CUI

C1868675

OMIM ID

600116

MedGen ID

401500

General Information of Disease (ID: DISNSTD1)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 15 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GSR	TTEP6RV	Limited	Therapeutic	[1]
NGF	TTDN3LF	Limited	Therapeutic	[2]
PRKCD	TT7A1BO	Limited	Therapeutic	[3]
PRL	TTJ2TSA	Limited	Biomarker	[4]
SNCA	TT08OSU	Limited	Biomarker	[5]
LRRK2	TTK0FEA	moderate	Biomarker	[6]
DDC	TTN451K	Strong	Therapeutic	[7]
DRD2	TTEX248	Strong	Biomarker	[8]
GBA	TT1B5PU	Strong	Biomarker	[9]
GDNF	TTF23ML	Strong	Therapeutic	[10]
MAPT	TTS87KH	Strong	Biomarker	[11]
PARP1	TTVDSZ0	Strong	Biomarker	[12]
SLC18A2	TTNZRI3	Strong	Therapeutic	[7]
TH	TTUHP71	Strong	Biomarker	[13]
UBE2E2	TTXJEOF	Strong	Biomarker	[14]
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⏷ Show the Full List of 15 DTT(s)

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC30A10	DTYBI73	Strong	Biomarker	[15]
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This Disease Is Related to 3 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
ALDH1A1	DE2JP1Y	Limited	Biomarker	[16]
ALDH1A2	DEKN1H4	Limited	Biomarker	[16]
PARK7	DEPOVCH	Strong	Biomarker	[6]
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This Disease Is Related to 25 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ATP13A2	OTKWBUGK	Limited	Biomarker	[17]
CBLL2	OTB4AD3V	Limited	Altered Expression	[18]
MUL1	OT2JC9YR	Limited	Altered Expression	[18]
PDYN	OTEJ6430	Limited	Biomarker	[19]
PNOC	OTJEAADN	Limited	Biomarker	[20]
PRKRA	OTUTVZZU	Disputed	Biomarker	[21]
DCTN1	OT5B51FJ	moderate	Biomarker	[22]
PODXL	OTPNQXF3	moderate	Genetic Variation	[23]
ATP1A3	OTM8EG6H	Strong	Biomarker	[24]
CNTN5	OTWU5FLZ	Strong	Biomarker	[23]
CNTN6	OTXVGVOR	Strong	Biomarker	[23]
DAB1	OTPL9MA3	Strong	Altered Expression	[25]
DNAJC6	OT1P6ZIE	Strong	Genetic Variation	[26]
FBXO7	OTGTN8TJ	Strong	Genetic Variation	[27]
GPR37	OTIMDDI3	Strong	Biomarker	[28]
HTRA2	OTC7616F	Strong	Biomarker	[6]
POLG	OTDUCT04	Strong	Biomarker	[29]
PTRHD1	OTN0GYY8	Strong	Genetic Variation	[30]
RNF41	OTN1DQOY	Strong	Biomarker	[31]
SBNO1	OTNX3RL0	Strong	Biomarker	[32]
SBNO2	OT1C6J3K	Strong	Biomarker	[32]
SEPTIN5	OT6JTJBO	Strong	Biomarker	[33]
SKIL	OTNBXH32	Strong	Biomarker	[32]
SYNJ1	OTTE02XC	Strong	Genetic Variation	[34]
PRKN	OTJBN41W	Definitive	Autosomal recessive	[35]
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⏷ Show the Full List of 25 DOT(s)

References

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2	Brain targeting of nerve growth factor using poly(butyl cyanoacrylate) nanoparticles.J Drug Target. 2009 Sep;17(8):564-74. doi: 10.1080/10611860903112842.
3	Blockade of PKCdelta proteolytic activation by loss of function mutants rescues mesencephalic dopaminergic neurons from methylcyclopentadienyl manganese tricarbonyl (MMT)-induced apoptotic cell death.Ann N Y Acad Sci. 2004 Dec;1035:271-89. doi: 10.1196/annals.1332.017.
4	Correlation between plasma levels of prolactin and chlorpromazine in psychiatric patients.Psychol Med. 1975 May;5(2):214-6. doi: 10.1017/s0033291700056488.
5	Glucose Metabolism and AMPK Signaling Regulate Dopaminergic Cell Death Induced by Gene (-Synuclein)-Environment (Paraquat) Interactions.Mol Neurobiol. 2017 Jul;54(5):3825-3842. doi: 10.1007/s12035-016-9906-2. Epub 2016 Jun 20.
6	Methylmercury can induce Parkinson's-like neurotoxicity similar to 1-methyl-4- phenylpyridinium: a genomic and proteomic analysis on MN9D dopaminergic neuron cells.J Toxicol Sci. 2015 Dec;40(6):817-28. doi: 10.2131/jts.40.817.
7	Vesicular monoamine transporter-2 and aromatic L-amino acid decarboxylase gene therapy prevents development of motor complications in parkinsonian rats after chronic intermittent L-3,4-dihydroxyphenylalanine administration.Exp Neurol. 2006 Jan;197(1):215-24. doi: 10.1016/j.expneurol.2005.09.012. Epub 2005 Nov 2.
8	Thiethylperazine-induced parkinsonism: in vivo demonstration of dopamine D2 receptors blockade.Eur J Neurol. 2004 Oct;11(10):709-10. doi: 10.1111/j.1468-1331.2004.00844.x.
9	Selective loss of glucocerebrosidase activity in sporadic Parkinson's disease and dementia with Lewy bodies.Mol Neurodegener. 2015 Mar 27;10:15. doi: 10.1186/s13024-015-0010-2.
10	Behavioral improvement and dopamine release in a Parkinsonian rat model. Neurosci Lett. 2002 Sep 13;330(1):5-8. doi: 10.1016/s0304-3940(02)00672-9.
11	Familial aggregation of parkinsonism in progressive supranuclear palsy.Neurology. 2009 Jul 14;73(2):98-105. doi: 10.1212/WNL.0b013e3181a92bcc. Epub 2009 May 20.
12	Spatial and functional relationship between poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in the brain.Neuroscience. 2007 Aug 10;148(1):198-211. doi: 10.1016/j.neuroscience.2007.04.062. Epub 2007 Jul 19.
13	Four novel mutations in the tyrosine hydroxylase gene in patients with infantile parkinsonism.Ann Hum Genet. 2000 Jan;64(Pt 1):25-31. doi: 10.1017/S0003480000007922.
14	Parkin is linked to the ubiquitin pathway.J Mol Med (Berl). 2001 Sep;79(9):482-94. doi: 10.1007/s001090100242.
15	Manganese-Induced Parkinsonism Is Not Idiopathic Parkinson's Disease: Environmental and Genetic Evidence.Toxicol Sci. 2015 Aug;146(2):204-12. doi: 10.1093/toxsci/kfv099.
16	Benomyl, aldehyde dehydrogenase, DOPAL, and the catecholaldehyde hypothesis for the pathogenesis of Parkinson's disease.Chem Res Toxicol. 2014 Aug 18;27(8):1359-61. doi: 10.1021/tx5002223. Epub 2014 Jul 24.
17	Low doses of paraquat and polyphenols prolong life span and locomotor activity in knock-down parkin Drosophila melanogaster exposed to oxidative stress stimuli: implication in autosomal recessive juvenile parkinsonism.Gene. 2013 Jan 10;512(2):355-63. doi: 10.1016/j.gene.2012.09.120. Epub 2012 Oct 6.
18	Post-translational modification of Parkin and its research progress in cancer.Cancer Commun (Lond). 2019 Nov 21;39(1):77. doi: 10.1186/s40880-019-0421-5.
19	Differential regulation of striatal preproenkephalin and preprotachykinin mRNA levels in MPTP-lesioned monkeys chronically treated with dopamine D1 or D2 receptor agonists.J Neurochem. 1999 Feb;72(2):682-92. doi: 10.1046/j.1471-4159.1999.0720682.x.
20	Nociceptin/Orphanin FQ Inhibits the Survival and Axon Growth of Midbrain Dopaminergic Neurons Through a p38-MAPK Dependent Mechanism.Mol Neurobiol. 2016 Dec;53(10):7284-7297. doi: 10.1007/s12035-015-9611-6. Epub 2015 Dec 21.
21	DYT16, a novel young-onset dystonia-parkinsonism disorder: identification of a segregating mutation in the stress-response protein PRKRA. Lancet Neurol. 2008 Mar;7(3):207-15. doi: 10.1016/S1474-4422(08)70022-X. Epub 2008 Feb 1.
22	DCTN1 mutations in Perry syndrome.Nat Genet. 2009 Feb;41(2):163-5. doi: 10.1038/ng.293. Epub 2009 Jan 11.
23	Discovery of a frameshift mutation in podocalyxin-like (PODXL) gene, coding for a neural adhesion molecule, as causal for autosomal-recessive juvenile Parkinsonism. J Med Genet. 2016 Jul;53(7):450-6. doi: 10.1136/jmedgenet-2015-103459. Epub 2016 Feb 10.
24	Mutations in the Na+/K+ -ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism. Neuron. 2004 Jul 22;43(2):169-75. doi: 10.1016/j.neuron.2004.06.028.
25	Disabled-1 is a large common fragile site gene, inactivated in multiple cancers.Genes Chromosomes Cancer. 2008 Feb;47(2):165-74. doi: 10.1002/gcc.20519.
26	DNAJC6 Mutations Associated With Early-Onset Parkinson's Disease. Ann Neurol. 2016 Feb;79(2):244-56. doi: 10.1002/ana.24553. Epub 2016 Jan 14.
27	Pathophysiological mechanisms linking F-box only protein 7 (FBXO7) and Parkinson's disease (PD).Mutat Res Rev Mutat Res. 2018 Oct-Dec;778:72-78. doi: 10.1016/j.mrrev.2018.10.001. Epub 2018 Oct 17.
28	Folding Underlies Bidirectional Role of GPR37/Pael-R in Parkinson Disease.Trends Pharmacol Sci. 2017 Aug;38(8):749-760. doi: 10.1016/j.tips.2017.05.006. Epub 2017 Jun 16.
29	Alpers syndrome with prominent white matter changes.Brain Dev. 2008 Apr;30(4):295-300. doi: 10.1016/j.braindev.2007.08.009. Epub 2007 Oct 17.
30	PTRHD1 Loss-of-function mutation in an african family with juvenile-onset Parkinsonism and intellectual disability.Mov Disord. 2018 Nov;33(11):1814-1819. doi: 10.1002/mds.27501. Epub 2018 Nov 6.
31	Suppression of Nrdp1 toxicity by Parkin in Drosophila models.Biochem Biophys Res Commun. 2011 Dec 9;416(1-2):18-23. doi: 10.1016/j.bbrc.2011.10.104. Epub 2011 Nov 6.
32	S-Nitrosylation of PINK1 Attenuates PINK1/Parkin-Dependent Mitophagy in hiPSC-Based Parkinson's Disease Models.Cell Rep. 2017 Nov 21;21(8):2171-2182. doi: 10.1016/j.celrep.2017.10.068.
33	Dopamine-dependent neurodegeneration in rats induced by viral vector-mediated overexpression of the parkin target protein, CDCrel-1.Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12438-43. doi: 10.1073/pnas.2132992100. Epub 2003 Oct 6.
34	Identification of a novel homozygous mutation Arg459Pro in SYNJ1 gene of an Indian family with autosomal recessive juvenile Parkinsonism.Parkinsonism Relat Disord. 2016 Oct;31:124-128. doi: 10.1016/j.parkreldis.2016.07.014. Epub 2016 Jul 26.
35	The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.