TABLE 1.
Summary of PD-linked and SVE-associated genes information in this article.
| Gene | Location | Protein | Function | Mutation | Animal model involved in the pathogenesis of PD |
| SNCA | (Human) Chromosome 4, 4q22.1 (Mouse) Chromosome 6, 6 B3| 6 29.15 cM | α-Synuclein | The major protein component of the Lewy body in the brain of patients with PD. | A30P, E46K, H50Q, G51D, and A53T | Mice expressing mutant α-synuclein, or overexpression of wild-type α-synuclein, SNCA knockout model, acute injection of virus encoding wild-type or mutant α-synuclein, or α-synuclein pre-formed fibrils |
| LRRK2 | (Human) Chromosome 12, 12q12 (Mouse) Chromosome 15, 15| 15 E3 | Leucine-rich repeat kinase 2 | LRRK2 is a kinase that is located largely in the cytoplasm but also associates with the mitochondrial outer membrane. LRRK2 interacts with the C-terminal R2 ring finger domain of Parkin | R1396G, R1441C, Y1654C, Y1699C, I1122V, I2020T, and G2019S. | Mice with G2019S R1441C mutant. Chemical inhibition of LRRK2. LRRK2 knockout mice |
| PRKN | (Human) Chromosome 6, 6q26 (Mouse) Chromosome 17, 17A1| 17 7.8 cM | Parkin | Parkin is a 465-residue E3 ubiquitin ligase that plays a critical role in ubiquitination- the process whereby molecules are covalently labeled with ubiquitin and directed toward degradation in proteasomes or lysosomes. | R256C, R275W, G328E, A398T, and T415N; heterozygous mutation | Parkin knockout mice |
| PIKN1 | (Human) Chromosome 1, 1p36.12 (Mouse) Chromosome 4, 4| 4 D3 | PTEN-induced kinase 1 | PINK1 is a mitochondrial serine/threonine-protein kinase, which is thought to protect cells from stress-induced mitochondrial dysfunction. PINK1 activity causes the parkin protein to bind to depolarized mitochondria to induce autophagy of those mitochondria. PINK1 is processed by healthy mitochondria and released to trigger neuron differentiation | R246X, H271Q, E417G, L347P, and Q239X/R492X heterozygous PINK1 mutations | PINK1 knockout mice, PINK1-deficient mouse and lack of PINK1 in Drosophila |
| DJ-1 | (Human) Chromosome 1, 1p36.23 (Mouse) Chromosome 4, 4| 4 E2 | human protein deglycase DJ-1 | DJ-1 protects neurons against oxidative stress and cell death. DJ-1 acts as a positive regulator of androgen receptor-dependent transcription. | M26I, E64D, and L166P | DJ-1 knockout mice |
| DNAJC6 | (Human) Chromosome 1, 1p31.3 (Mouse) Chromosome 4, 4| 4 C6 | Auxilin | Auxilin regulates molecular chaperone activity by stimulating ATPase activity. Auxilin is a putative tyrosine-protein phosphatase. | Q734X, R927G, and T741T | DNAJC6 knockout mouse Auxilin knockout Drosophila |
| SYNJ1 | (Human) Chromosome 21, 21q22.2 (Mouse) Chromosome 16, 16| 16 52.18 cM | Synaptojanin 1 | Synaptojanin 1 is a protein involved in vesicle uncoating in neurons. This is an important regulatory lipid phosphatase. | R258Q and R459P Homozygous R258Q mutation | SYNJ1 R258Q knock-in mice SYNJ1 knockout SYNJ1 heterozygote and triploid |
| SH3GL2 | (Human) Chromosome 9, 9p22.2 (Mouse) Chromosome 4, 4 C4| 4 40.23 cM | Endophilin A1 | Endophilin A1 is a member of the BAR protein family involved in membrane deformation, and its SH3 domain in the carboxyl-terminal is capable of recruiting dynamin and synaptojanin 1 | F10E, A66D, and A63S/A66S/M70Q (or called “SSQ”) heterozygous mutation | EndoA triple knockout (TKO) mice Endophilin knockout mice heterozygous mutation of endophilin in Drosophila |