Table 1.

Monogenic Parkinson's disease genes. GWAS, genome-wide association studies; JOPD, juvenile-onset PD; YOPD, young-onset PD; MOPD, middle-onset PD; LOPD, late-onset PD; AD, autosomal-dominant; AR, autosomal-recessive; GOF, gain-of-function; LOF, loss-of-function; probable, higher likelihood/orthologue evidence; possible, high likelihood/associative evidence; ER, endoplasmic reticulum, EGFR, epidermal growth factor receptor. *Same PRKN locus.

no.	gene symbol	gene name	age of onset	inheritance pattern	GWAS hit	confidence as PD gene	mechanism	proposed cellular functions
1	SNCA	synuclein-alpha	YOPD or MOPD	AD	yes	very high	LOF/GOF	synaptic vesicle trafficking, molecular chaperone activity [32,33]
2	LRRK2	leucine-rich repeat kinase 2	LOPD	AD	yes	very high	GOF	vesicle trafficking [34]
3	GBA1	glucosylceramidase-beta 1	YOPD	AR	yes	very high	LOF/GOF?	lysosomal ceramide metabolism [35]
4	VPS13C	vacuolar protein sorting 13 homologue C	YOPD	AR	yes	very high	LOF	lipid transfer from ER to lysosomes [36]
5	VPS35	VPS35 retromer complex component	LOPD	AD	no	very high	LOF	endo-lysosomal sorting [37]
6	ATP13A2	ATPase cation transporting 13A2	YOPD	AR	no	very high	LOF	lysosomal polyamine transporter [38]
7	PRKN	Parkin RBR E3 ubiquitin-protein ligase	YOPD or JOPD	AR	no	very high	LOF	mitochondrial quality control [39]
8	PINK1	PTEN-induced kinase 1	YOPD	AR	no	very high	LOF	mitochondrial quality control [39]
9	DJ-1	parkinsonism associated deglycase	YOPD	AR	no	very high	LOF	involved in oxidative stress, mitochondrial quality control [40]
10	PLA2G6	phospholipase A2 group VI	YOPD	AR	no	very high	LOF	membrane lipid biosynthesis [41,42]
11	FBXO7	F-box protein 7	YOPD	AR	no	very high	LOF	E3 ubiquitin-protein ligase [43]
12	CHCHD2	coiled-coil–helix–coiled-coil–helix domain-containing 2	LOPD	AD	no	very high	both	hypoxia-responsive transcription factor; mitochondrial electron transport [44]
13	GCH1	GTP cyclohydrolase 1	YOPD	AD	yes	very high	LOF	involved in neurotransmitter synthesis, nitric oxide synthesis, GTP binding [45,46]
19	LRP10	LDL receptor-related protein 10	YOPD or MOPD	AD	no	very high	LOF	lipoprotein uptake and endosomal sorting [47,48]
14	DNAJC6	DnaJ heat shock protein family (Hsp40) member C6	YOPD	AR	no	high	LOF	uncoating of clathrin-coated vesicles [49]
15	SYNJ1	synaptojanin 1	YOPD	AR	no	high	LOF	synaptic vesicle phosphoinositide metabolism [50]
16	ATP10B	ATPase phospholipid-transporting 10B	YOPD	AR	no	high	LOF	lipid transfer from ER to lysosomes [51]
17	DCTN1	dynactin subunit 1	YOPD or MOPD	AD	no	high	LOF	transport along microtubules [52]
18	POLG	DNA polymerase-gamma, catalytic subunit	YOPD	AR and AR	no	high	LOF?	replication of mitochondrial DNA [53]
20	TMEM230*	transmembrane protein 230	LOPD	AD	no	low	LOF	involved in trafficking and recycling of synaptic vesicles [54]
21	DNAJC13*	DnaJ heat shock protein family (Hsp40) member C13	LOPD	AD	no	low	GOF	endosomal membrane tubulation and trafficking [55]
22	PSAP	prosaposin	MOPD or LOPD	AD	no	low	LOF?	lysosomal sphingolipid metabolism [56]
23	HTRA2	HtrA serine peptidase 2	YOPD or LOPD	AD	no	low	LOF	serine protease activity, response to oxidative stress, apoptosis [57]
24	EIF4G1	eukaryotic translation initiation factor 4 gamma 1	LOPD	AD	no	low	LOF	ER stress-dependent translation [58]
25	GIGYF2	GRB10-interacting GYF protein 2	LOPD	AD	no	low	undetermined	component of translation initiation repressor complex [59]
26	SCA2	ataxin 2	YOPD or MOPD	AD	no	undetermined	LOF?/GOF?	involved in EGFR trafficking, stress granule formation, regulation of translation [60]