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Table 1 Genes implicated in Parkinson disease and atypical parkinsonian syndromes

From: Genetic perspective on the synergistic connection between vesicular transport, lysosomal and mitochondrial pathways associated with Parkinson’s disease pathogenesis

GeneMOIMutation spectrumMutation mechanismClinical phenotypeLevodopa responsePathologyProtein productPathwayReferences
ATP10BARMissense and splice site mutationsLOFEOPD/LOPDLimited, levodopa-induced dyskinesiaUnknownPhospholipid transporting ATPase 10BEndo-lysosome[213]
ATP13A2ARMissense and PTC mutationsLOFJuvenile APS called Kufor-Rakeb syndrome with pyramidal signs, supranuclear gaze palsy and cognitive impairment; NCL; HSPGoodLipofuscinosisCation transporting ATPase 13A2Endo-lysosome[37, 90, 257, 277]
ATP6AP2XRp.Ser115Ser and
p.Asp107Asp
LOFJuvenile APS with slow disease progression and considerable phenotypic variability including spasticity, intellectual disability and epilepsyLimited, levodopa-induced dyskinesiaLB-, tau+bRenin/prorenin receptorEndo-lysosome[176, 279]
DJ-1ARDeletions, PTC and missense mutationsLOFEOPD with slow disease progression and rarely autonomic dysfunctions or cognitive impairmentLimited, levodopa-induced dyskinesiaLB + bDJ-1Mitochondria[3, 31, 163, 334].
DNAJC6ARc.802-2A > G, p.Thr741Thr, p.Gln791b, p.Gln846b,
p.Arg927Gly
LOFJuvenile and early-onset APS with rapidly disease progression and possible intellectual disability, seizures and pyramidal signs.Limited, levodopa-induced dyskinesia and psychiatric featuresUnknownAuxilinVesicular transport[85, 175, 240]
FBXO7ARPTC and missense mutationsLOFRanging from classic EOPD to juvenile APS with pyramidal signs (spasticity, impaired fine movements and increased reflexes)Limited, levodopa-induced dyskinesia and psychiatric featuresUnknownF-box protein 7Mitochondria[76, 125, 149, 204, 311, 369]
PARK2ARDeletions, PTC and missense mutationsLOFEOPD with slow disease progression and rarely autonomic dysfunctions or cognitive impairmentLimited, levodopa-induced dyskinesiaMost LB-ParkinMitochondria[1, 156, 160, 264]
PINK1ARDeletions, PTC and missense mutationsLOFEOPD with slow disease progression and rarely autonomic dysfunctions or cognitive impairmentLimited, levodopa-induced dyskinesiaLB + bPTEN-induced kinase 1Mitochondria[156, 293]
PLA2G6ARCNV, PTC and missense mutationsLOFEarly-onset APS called dystonia-parkinsonism with cognitive decline, autonomic dysfunction and psychiatric manifestations; INAD; atypical NADLimited, levodopa-induced dyskinesiaAxonal spheroid,
iron deposits
Phospholipase A2Endo-lysosome[126, 139, 157, 161, 184, 249, 316, 370]
LRRK2ADMissense mutationsGOFLOPD with slow disease progression and rarely cognitive impairmentGoodMost LB+, rarely tau+Leucine-rich repeat kinase 2Vesicular transport[132, 251, 285, 346, 379]
SNCAADMultiplications, p.Ala30Pro, p.Glu46Lys, p.Gly51Asp, p.Ala53Glu and p.Ala53ThraGOFEOPD/LOPD with severe, rapidly disease progression and cognitive impairment; DLB; MSAGoodLB+α-SynucleinVesicular transport[6, 28, 162, 181, 191, 263, 272, 284, 295, 317, 372]
SYNJ1ARp.Arg258Gln, p.Arg459ProLOFJuvenile APS with possible cognitive impairment, epilepsy and dystoniaLimited, levodopa-induced dyskinesiaLB-, tau+bSynaptojanin 1Vesicular transport[168, 180, 239, 273]
VPS13CARDeletions and PTC mutationsLOFEOPD/DLB with severe, rapidly disease progression and cognitive declineGoodLB+Vacuolar protein sorting 13CEndo-lysosome[69, 183, 193, 297]
VPS35ADp.Asp620AsnLOFLOPD with slow disease progression and rarely cognitive impairment or neuropsychiatric symptomsGoodUnknownVacuolar protein sorting 35Vesicular transport[275, 364]
  1. aPathogenicity of the SNCA p.His50Gln is uncertain [28]. bNeuropathological report of a single carrier. Abbreviations: MOI, mode of inheritance; AR autosomal recessive, AD autosomal dominant, XR X-linked recessive, EOPD early-onset Parkinson disease; LOPD, late-onset Parkinson disease, APS atypical parkinsonian syndrome; MSA multiple system atrophy, DLB dementia with Lewy bodies; NCL neuronal ceroid-lipofuscinosis, HSP hereditary spastic paraplegia, INAD infantile neuroaxonal dystrophy, NAD neuroaxonal dystrophy, PTC premature termination codon, CNV copy number variation, LB+ positive for Lewy body pathology, LB- negative for Lewy body pathology; tau+, positive for tau pathology
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