Parkinson disease

Summary

Parkinson disease (MONDO:0005180) is a disease (an umbrella term covering 6 Mondo subtypes) caused by variants in GBA1, LRRK2, PARK7, and 4 other genes, with 74 cohort genes (792 GWAS associations across 112 studies) and 4,025 clinical trials. The dominant Reactome pathway is Defective B3GALTL causes PpS (4 cohort genes). Top therapeutic interventions include carbidopa anhydrous, rasagiline, and levodopa.

At a glance

• Causal genes: GBA1 (GenCC Definitive), LRRK2 (GenCC Definitive), PARK7 (GenCC Definitive), PINK1 (GenCC Definitive) (+3 more)
• Umbrella term: 6 Mondo subtypes
• Cohort genes: 74
• GWAS associations: 792
• ClinVar variants: 33
• Clinical trials: 4,025

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Parkinson disease
Mondo ID	MONDO:0005180
MeSH	D010300
OMIM	168600
Orphanet	319705
DOID	DOID:14330
ICD-10-CM	G20
ICD-11	296066191
NCIT	C26845
SNOMED CT	49049000
UMLS	C0030567
MedGen	10590
Is cancer (heuristic)	no

Also known as: paralysis agitans · Parkinson disease · Parkinson’s disease · PD

Data availability: 33 ClinVar variants · 792 GWAS associations (112 studies) · 13 GenCC gene-disease records · 3,044 cell lines.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › basal ganglia disorder › parkinsonian disorder › Parkinson disease

Related subtypes (20): postencephalitic Parkinson disease, dystonia 12, Perry syndrome, X-linked parkinsonism-spasticity syndrome, early-onset parkinsonism-intellectual disability syndrome, X-linked dystonia-parkinsonism, autosomal dominant striatal neurodegeneration type 1, dystonia 16, parkinsonism-dystonia, infantile, cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome, hemiparkinsonism-hemiatrophy syndrome, carbon monoxide-induced parkinsonism, cyanide-induced parkinsonism, atypical juvenile parkinsonism, primary progressive freezing gait, encephalitis lethargica, parkinsonism with dementia of Guadeloupe, multiple system atrophy, parkinsonian type, parkinsonism with polyneuropathy, vascular parkinsonism

Subtypes (6): late-onset Parkinson disease, parkinsonian-pyramidal syndrome, Parkinson disease, mitochondrial, Parkinson disease 16, young-onset Parkinson disease, Parkinson disease 25, autosomal recessive early-onset, with impaired intellectual development

Genetics & variants

GWAS landscape

792 GWAS associations across 112 studies. Top hits map to 25 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs356182	4e-170	SNCA	A
rs356203	5e-149	SNCA	T	0.25
rs34637584	4e-148	LRRK2	A	2.43
rs76763715	3e-90	GBA1	?	4.11
rs1372518	2e-79	SNCA	A
rs35682329	1e-75	HMGN2P18	A
rs34311866	5e-75	TMEM175	T
rs35749011	2e-70	HMGN2P18 - KRTCAP2	A	0.61
rs62053943	1e-69	LINC02210-CRHR1	T
rs17649553	1e-68	MAPT	C	1.28
rs12734374	4e-68	ASH1L	A
rs199453	9e-67	NSF	T	0.2
rs356219	6e-65	SNCA	?	1.29
rs114525519	9e-60	TRIM46	?	2.56
rs116540837	2e-53	ASH1L	?	2.38
H1H2	8e-52		?	1.28
rs10513789	6e-50	MCCC1	T
rs356228	1e-48	GPRIN3 - SNCA	C	0.15
rs12987123	4e-42	STK39 - RN7SL813P	A
rs10847864	2e-41	HIP1R	T
rs7225002	2e-40	KANSL1	A	0.14
rs28903073	1e-39	LRRK2	?	3.12
rs116114495	2e-39	PBXIP1	?	2.13
rs1474055	3e-39	STK39 - RN7SL813P	T	0.18
rs713522	1e-38	MAPT	T
rs7221167	1e-37	MAPT-AS1	T	0.14
rs1630500	1e-37	KCNN3 - PMVK	?	2.07
rs6826785	2e-37	SNCA	?
rs34806123	4e-37	SNCA	?
rs5019538	1e-36	SNCA	A	0.16

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST010990	Smeland OB	2020	34,875	440,781	Genome-wide Association Analysis of Parkinson’s Disease and Schizophrenia Reveals Shared Genetic Architecture and Identifies Novel Risk Loci.
GCST010991	Smeland OB	2020	20,184	397,324	Genome-wide Association Analysis of Parkinson’s Disease and Schizophrenia Reveals Shared Genetic Architecture and Identifies Novel Risk Loci.
GCST004902	Chang D	2017	20,184	397,324	A meta-analysis of genome-wide association studies identifies 17 new Parkinson’s disease risk loci.
GCST009324	Nalls MA	2019	15,056	12,637	Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies.
GCST009325	Nalls MA	2019	15,056	449,056	Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies.
GCST002544	Nalls MA	2014	13,708	95,282	Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease.
GCST90042668	Jiang L	2021	9,960	383,719	A generalized linear mixed model association tool for biobank-scale data.
GCST003984	Pickrell JK	2016	9,619	324,522	Detection and interpretation of shared genetic influences on 42 human traits.
GCST90042681	Jiang L	2021	6,877	409,676	A generalized linear mixed model association tool for biobank-scale data.
GCST010049	Foo JN	2020	6,724	24,851	Identification of Risk Loci for Parkinson Disease in Asians and Comparison of Risk Between Asians and Europeans: A Genome-Wide Association Study.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	4
Tier 2: splice/UTR	2
Tier 3: regulatory	0
Tier 4: intronic/intergenic	44

MAF distribution

Bucket	Variants
common (>=0.05)	42
low_freq (0.01-0.05)	3
rare (<0.01)	1
unknown	4

Functional consequences

Consequence	Count
intron_variant	37
intergenic_variant	5
missense_variant	4
splice_region_variant	2
non_coding_transcript_exon_variant	1
unknown	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs356182	4	89704960	G>A,C,T	0.05	intron_variant	SNCA	4e-170	Tier 4: intronic/intergenic
rs356203	4	89744890	C>A,G,T	0.385	intron_variant	SNCA	5e-149	Tier 4: intronic/intergenic
rs34637584	12	40340400	G>A	0.002	missense_variant	LRRK2	4e-148	Tier 1: coding
rs76763715	1	155235843	T>C,G		missense_variant	GBA1	3e-90	Tier 1: coding
rs1372518	4	89836143	A>C,G,T	0.05	intron_variant	SNCA	2e-79	Tier 4: intronic/intergenic
rs35682329	1	155148667	A>G	0.05	non_coding_transcript_exon_variant	HMGN2P18	1e-75	Tier 4: intronic/intergenic
rs34311866	4	958159	T>C	0.05	missense_variant	TMEM175	5e-75	Tier 1: coding
rs35749011	1	155162560	G>A,T	0.017	intergenic_variant	HMGN2P18 - KRTCAP2	2e-70	Tier 4: intronic/intergenic
rs62053943	17	45666837	C>T	0.05	intron_variant	LINC02210-CRHR1	1e-69	Tier 4: intronic/intergenic
rs17649553	17	45917282	C>G,T	0.221	intron_variant	MAPT	1e-68	Tier 4: intronic/intergenic
rs12734374	1	155419060	A>T	0.05	intron_variant	ASH1L	4e-68	Tier 4: intronic/intergenic
rs199453	17	46723580	C>A,G,T	0.231	intron_variant	NSF	9e-67	Tier 4: intronic/intergenic
rs356219	4	89716450	G>A	0.41	intron_variant	SNCA	6e-65	Tier 4: intronic/intergenic
rs114525519	1	155179361	G>T	0.05	intron_variant	TRIM46	9e-60	Tier 4: intronic/intergenic
rs116540837	1	155432750	T>C,G	0.05	intron_variant	ASH1L	2e-53	Tier 4: intronic/intergenic
H1H2				0.2			8e-52	Tier 4: intronic/intergenic
rs10513789	3	183042285	T>C,G	0.05	intron_variant	MCCC1	6e-50	Tier 4: intronic/intergenic
rs356228	4	89685975	C>G	0.459	intron_variant	GPRIN3 - SNCA	1e-48	Tier 4: intronic/intergenic
rs12987123	2	168264031	A>C,T	0.05	intron_variant	STK39 - RN7SL813P	4e-42	Tier 4: intronic/intergenic
rs10847864	12	122842051	G>A,C,T	0.05	intron_variant	HIP1R	2e-41	Tier 4: intronic/intergenic
rs7225002	17	46111701	A>C,G	0.391	intron_variant	KANSL1	2e-40	Tier 4: intronic/intergenic
rs28903073	12	40259708	G>A		intron_variant	LRRK2	1e-39	Tier 4: intronic/intergenic
rs116114495	1	154951539	C>A,T	0.05	splice_region_variant	PBXIP1	2e-39	Tier 2: splice/UTR
rs1474055	2	168253884	C>T	0.131	intron_variant	STK39 - RN7SL813P	3e-39	Tier 4: intronic/intergenic
rs713522	17	45987897	T>A,C	0.05	intron_variant	MAPT	1e-38	Tier 4: intronic/intergenic
rs7221167	17	45855941	T>A,C	0.419	intron_variant	MAPT-AS1	1e-37	Tier 4: intronic/intergenic
rs1630500	1	154882579	G>A,C	0.05	intergenic_variant	KCNN3 - PMVK	1e-37	Tier 4: intronic/intergenic
rs6826785	4	89761323	T>C	0.05	intron_variant	SNCA	2e-37	Tier 4: intronic/intergenic
rs34806123	4	89762971	A>G,T	0.05	intron_variant	SNCA	4e-37	Tier 4: intronic/intergenic
rs5019538	4	89715479	G>A	0.321	intron_variant	SNCA	1e-36	Tier 4: intronic/intergenic

ClinVar germline variants

33 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 9 conflicting classifications of pathogenicity, 5 pathogenic, 3 benign/likely benign, 2 pathogenic/likely pathogenic; risk factor, 1 conflicting classifications of pathogenicity; risk factor, 1 pathogenic/likely pathogenic, 1 likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
4290	NM_000157.4(GBA1):c.1226A>G (p.Asn409Ser)	GBA1	Pathogenic/Likely pathogenic; risk factor	criteria provided, multiple submitters, no conflicts
1940	NM_198578.4(LRRK2):c.6055G>A (p.Gly2019Ser)	LRRK2	Pathogenic/Likely pathogenic; risk factor	criteria provided, multiple submitters, no conflicts
1809808	NC_000004.11:g.39350045_39350099delinsAAGGG[(141_831)]	RFC1	Pathogenic	no assertion criteria provided
222067	NM_020821.3(VPS13C):c.8445+2T>G	VPS13C	Pathogenic	criteria provided, single submitter
222068	NM_020821.3(VPS13C):c.806_807insCAGA (p.Arg269fs)	VPS13C	Pathogenic	criteria provided, single submitter
222069	NM_020821.3(VPS13C):c.9568G>T (p.Glu3190Ter)	VPS13C	Pathogenic	criteria provided, single submitter
222070	NM_020821.3(VPS13C):c.4165G>C (p.Gly1389Arg)	VPS13C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
222071	NM_020821.3(VPS13C):c.4777del (p.Gln1593fs)	VPS13C	Pathogenic	criteria provided, single submitter
3773765	NM_004562.3(PRKN):c.1014_1028delinsGAGCCAGGCTGTG (p.Ala339fs)	PRKN	Likely pathogenic	criteria provided, single submitter
18398	NM_181840.1(KCNK18):c.414_415del (p.Phe139fs)	KCNK18	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1943	NM_198578.4(LRRK2):c.7153G>A (p.Gly2385Arg)	LRRK2	Conflicting classifications of pathogenicity; risk factor	criteria provided, conflicting classifications
3571549	NM_198578.4(LRRK2):c.2300G>A (p.Arg767His)	LRRK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
39198	NM_198578.4(LRRK2):c.4883G>C (p.Arg1628Pro)	LRRK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
872630	NM_198578.4(LRRK2):c.4310A>G (p.Asn1437Ser)	LRRK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
224859	NM_001382273.1(TNK2):c.2675G>A (p.Arg892His)	TNK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
88849	NM_001382273.1(TNK2):c.1957G>A (p.Val653Met)	TNK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
224861	NM_003285.3(TNR):c.1774A>G (p.Thr592Ala)	TNR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
224863	NM_003285.3(TNR):c.538A>C (p.Asn180His)	TNR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
224864	NM_003285.3(TNR):c.496A>G (p.Thr166Ala)	TNR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4075748	NM_003458.4(BSN):c.9862G>A (p.Glu3288Lys)	BSN	Uncertain significance	criteria provided, single submitter
1793311	NM_198578.4(LRRK2):c.2576G>T (p.Gly859Val)	LRRK2	Uncertain significance	criteria provided, single submitter
3068560	NM_198578.4(LRRK2):c.1147A>C (p.Ser383Arg)	LRRK2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2150544	NM_003560.4(PLA2G6):c.1028C>T (p.Ala343Val)	PLA2G6	Uncertain significance	criteria provided, multiple submitters, no conflicts
1434096	NM_032242.4(PLXNA1):c.3368C>T (p.Pro1123Leu)	PLXNA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3015387	NM_198994.3(TGM6):c.1076C>T (p.Pro359Leu)	TGM6	Uncertain significance	criteria provided, multiple submitters, no conflicts
224858	NM_001382273.1(TNK2):c.2981C>T (p.Ala994Val)	TNK2	Uncertain significance	criteria provided, single submitter
224860	NM_001382273.1(TNK2):c.1088T>C (p.Val363Ala)	TNK2	Uncertain significance	criteria provided, single submitter
224862	NM_003285.3(TNR):c.1732C>T (p.Arg578Ter)	TNR	Uncertain significance	criteria provided, single submitter
224865	NM_003285.3(TNR):c.463T>A (p.Cys155Ser)	TNR	Uncertain significance	criteria provided, single submitter
39221	NM_198578.4(LRRK2):c.6241A>G (p.Asn2081Asp)	LRRK2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 59 · Orphanet: 50 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 5

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
LRRK2	LRRK2	GWAS, GenCC, Orphanet
GBA1	GBA1	GWAS, GenCC, Orphanet
PRKN	PRKN	GWAS, GenCC, Orphanet
SNCA	SNCA	GWAS, GenCC, Orphanet
VPS13C	VPS13C	GWAS, Orphanet

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
GBA1	Definitive	Autosomal dominant	Parkinson disease	17
LRRK2	Definitive	Autosomal dominant	Parkinson disease	5
PARK7	Definitive	Autosomal recessive	Parkinson disease	5
PINK1	Definitive	Autosomal recessive	autosomal recessive early-onset Parkinson disease 6	6
PRKN	Definitive	Autosomal recessive	Parkinson disease	4
SNCA	Definitive	Autosomal dominant	Parkinson disease	10
VPS35	Definitive	Autosomal dominant	Parkinson disease	7
TMEM230	Moderate	Semidominant	Parkinson disease	2
RIC3	Limited	Autosomal dominant	Parkinson disease	2
WASL	Limited	Autosomal recessive	Parkinson disease

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LRRK2	Orphanet:2828	Young-onset Parkinson disease
LRRK2	Orphanet:411602	Hereditary late-onset Parkinson disease
GBA1	Orphanet:2072	Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome
GBA1	Orphanet:411602	Hereditary late-onset Parkinson disease
GBA1	Orphanet:77259	Gaucher disease type 1
GBA1	Orphanet:77260	Gaucher disease type 2
GBA1	Orphanet:77261	Gaucher disease type 3
GBA1	Orphanet:85212	Fetal Gaucher disease
PRKN	Orphanet:2828	Young-onset Parkinson disease
SNCA	Orphanet:171695	Parkinsonian-pyramidal syndrome
SNCA	Orphanet:2828	Young-onset Parkinson disease
SNCA	Orphanet:411602	Hereditary late-onset Parkinson disease
VPS35	Orphanet:411602	Hereditary late-onset Parkinson disease
VPS13C	Orphanet:2828	Young-onset Parkinson disease
PINK1	Orphanet:2828	Young-onset Parkinson disease
PARK7	Orphanet:2828	Young-onset Parkinson disease
PARK7	Orphanet:90020	Parkinson-dementia complex of Guam
CNNM2	Orphanet:620363	Primary hypomagnesemia-generalized seizures-intellectual disability-obesity syndrome
SATB1	Orphanet:684232	Intellectual disability-epilepsy-dental anomalies-facial dysmorphism syndrome
SCN3A	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
SCN3A	Orphanet:98820	Familial focal epilepsy with variable foci
BMP4	Orphanet:139471	Microphthalmia with brain and digit anomalies
BMP4	Orphanet:199306	Cleft lip/palate
BMP4	Orphanet:828	Stickler syndrome
BMP4	Orphanet:93100	Renal agenesis, unilateral
SEMA4A	Orphanet:1872	Cone rod dystrophy
SEMA4A	Orphanet:440437	Familial colorectal cancer Type X
SEMA4A	Orphanet:791	Retinitis pigmentosa
SEMA5A	Orphanet:281	Monosomy 5p syndrome
SLCO1B3	Orphanet:3111	Rotor syndrome
SMARCA2	Orphanet:3051	Nicolaides-Baraitser syndrome
SMARCA2	Orphanet:637013	SMARCA2-related blepharophimosis-intellectual disability syndrome
SREBF1	Orphanet:388	Hirschsprung disease
TPM1	Orphanet:154	Familial isolated dilated cardiomyopathy
TPM1	Orphanet:54260	Left ventricular noncompaction
TRPS1	Orphanet:502	Trichorhinophalangeal syndrome type 2
TRPS1	Orphanet:77258	Trichorhinophalangeal syndrome type 1
UBTF	Orphanet:500180	Childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder
WNT3	Orphanet:3301	Tetraamelia-multiple malformations syndrome
ZP3	Orphanet:404466	Female infertility due to zona pellucida defect
CA8	Orphanet:1766	Dysequilibrium syndrome
CACNA1B	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
SLC44A4	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
KLHL7	Orphanet:157820	Cold-induced sweating syndrome
KLHL7	Orphanet:603684	KLHL7-related Bohring-Opitz-like and Crisponi/Cold-induced sweating-like overlap syndrome
KLHL7	Orphanet:603689	KLHL7-related Bohring-Opitz-like syndrome
KLHL7	Orphanet:603694	KLHL7-related Crisponi/cold-induced sweating-like syndrome
KLHL7	Orphanet:791	Retinitis pigmentosa
MED12L	Orphanet:528084	Non-specific syndromic intellectual disability
DDRGK1	Orphanet:93352	Spondyloepimetaphyseal dysplasia, Shohat type

Cohort genes → proteins

74 cohort genes, 73 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	61
gwas_and_gencc	1
gwas_and_clinvar	1
multi_evidence	11

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LRRK2	HGNC:18618	ENSG00000188906	Q5S007	Leucine-rich repeat serine/threonine-protein kinase 2	gwas,gencc,clinvar
GBA1	HGNC:4177	ENSG00000177628	P04062	Lysosomal acid glucosylceramidase	gwas,gencc,clinvar
PRKN	HGNC:8607	ENSG00000185345	O60260	E3 ubiquitin-protein ligase parkin	gwas,gencc,clinvar
SNCA	HGNC:11138	ENSG00000145335	P37840	Alpha-synuclein	gwas,gencc
VPS35	HGNC:13487	ENSG00000069329	Q96QK1	Vacuolar protein sorting-associated protein 35	gencc,clinvar
VPS13C	HGNC:23594	ENSG00000129003	Q709C8	Intermembrane lipid transfer protein VPS13C	gwas,clinvar
WASL	HGNC:12735	ENSG00000106299	O00401	Actin nucleation-promoting factor WASL	gencc
PINK1	HGNC:14581	ENSG00000158828	Q9BXM7	Serine/threonine-protein kinase PINK1, mitochondrial	gencc
TMEM230	HGNC:15876	ENSG00000089063	Q96A57	Transmembrane protein 230	gencc
PARK7	HGNC:16369	ENSG00000116288	Q99497	Parkinson disease protein 7	gencc
RIC3	HGNC:30338	ENSG00000166405	Q7Z5B4	Protein RIC-3	gencc
RIT2	HGNC:10017	ENSG00000152214	Q99578	GTP-binding protein Rit2	gwas
CNNM2	HGNC:103	ENSG00000148842	Q9H8M5	Metal transporter CNNM2	gwas
RPS12	HGNC:10385	ENSG00000112306	P25398	Small ribosomal subunit protein eS12	gwas
BICD1	HGNC:1049	ENSG00000151746	Q96G01	Protein bicaudal D homolog 1	gwas
BIN3	HGNC:1054	ENSG00000147439	Q9NQY0	Bridging integrator 3	gwas
SATB1	HGNC:10541	ENSG00000182568	Q01826	DNA-binding protein SATB1	gwas
SCN3A	HGNC:10590	ENSG00000153253	Q9NY46	Sodium channel protein type 3 subunit alpha	gwas
BMP4	HGNC:1071	ENSG00000125378	P12644	Bone morphogenetic protein 4	gwas
SEMA4A	HGNC:10729	ENSG00000196189	Q9H3S1	Semaphorin-4A	gwas
SEMA5A	HGNC:10736	ENSG00000112902	Q13591	Semaphorin-5A	gwas
SCAF11	HGNC:10784	ENSG00000139218	Q99590	Protein SCAF11	gwas
SH3GL2	HGNC:10831	ENSG00000107295	Q99962	Endophilin-A1	gwas
SLCO1B3	HGNC:10961	ENSG00000111700	Q9NPD5	Solute carrier organic anion transporter family member 1B3	gwas
SMARCA2	HGNC:11098	ENSG00000080503	P51531	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2	gwas
BSN	HGNC:1117	ENSG00000164061	Q9UPA5	Protein bassoon	clinvar
SP1	HGNC:11205	ENSG00000185591	P08047	Transcription factor Sp1	gwas
SREBF1	HGNC:11289	ENSG00000072310	P36956	Sterol regulatory element-binding protein 1	gwas
DENND2B	HGNC:11350	ENSG00000166444	P78524	DENN domain-containing protein 2B	gwas
SULT1C2	HGNC:11456	ENSG00000198203	O00338	Sulfotransferase 1C2	gwas
SYT4	HGNC:11512	ENSG00000132872	Q9H2B2	Synaptotagmin-4	gwas
TIAL1	HGNC:11804	ENSG00000151923	Q01085	Nucleolysin TIAR	gwas
ANO2	HGNC:1183	ENSG00000047617	Q9NQ90	Anoctamin-2	gwas
TNR	HGNC:11953	ENSG00000116147	Q92752	Tenascin-R	clinvar
TOX3	HGNC:11972	ENSG00000103460	O15405	TOX high mobility group box family member 3	gwas
TPM1	HGNC:12010	ENSG00000140416	P09493	Tropomyosin alpha-1 chain	gwas
LDLRAD4	HGNC:1224	ENSG00000168675	O15165	Low-density lipoprotein receptor class A domain-containing protein 4	gwas
TRPM2	HGNC:12339	ENSG00000142185	O94759	Transient receptor potential cation channel subfamily M member 2	gwas
TRPS1	HGNC:12340	ENSG00000104447	Q9UHF7	Zinc finger transcription factor Trps1	gwas
TMEM59	HGNC:1239	ENSG00000116209	Q9BXS4	Transmembrane protein 59	gwas
UBTF	HGNC:12511	ENSG00000108312	P17480	Nucleolar transcription factor 1	gwas
UNC13B	HGNC:12566	ENSG00000198722	O14795	Protein unc-13 homolog B	gwas
USP25	HGNC:12624	ENSG00000155313	Q9UHP3	Ubiquitin carboxyl-terminal hydrolase 25	gwas
VAMP4	HGNC:12645	ENSG00000117533	O75379	Vesicle-associated membrane protein 4	gwas
WNT9A	HGNC:12778	ENSG00000143816	O14904	Protein Wnt-9a	gwas
WNT3	HGNC:12782	ENSG00000108379	P56703	Proto-oncogene Wnt-3	gwas
ZNF184	HGNC:12975	ENSG00000096654	Q99676	Zinc finger protein 184	gwas
TSHZ2	HGNC:13010	ENSG00000182463	Q9NRE2	Teashirt homolog 2	gwas
ZP3	HGNC:13189	ENSG00000188372	P21754	Zona pellucida sperm-binding protein 3	gwas
TCIM	HGNC:1357	ENSG00000176907	Q9NR00	Transcriptional and immune response regulator	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LRRK2	Leucine-rich repeat serine/threonine-protein kinase 2	Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking.
GBA1	Lysosomal acid glucosylceramidase	Glucosylceramidase that catalyzes, within the lysosomal compartment, the hydrolysis of glucosylceramides/GlcCers (such as beta-D-glucosyl-(1<->1’)-N-acylsphing-4-enine) into free ceramides (such as N-acylsphing-4-enine) and glucose.
PRKN	E3 ubiquitin-protein ligase parkin	Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.
SNCA	Alpha-synuclein	Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release.
VPS35	Vacuolar protein sorting-associated protein 35	Acts as a component of the retromer cargo-selective complex (CSC).
VPS13C	Intermembrane lipid transfer protein VPS13C	Mediates the transfer of lipids between membranes at organelle contact sites.
WASL	Actin nucleation-promoting factor WASL	Regulates actin polymerization by stimulating the actin-nucleating activity of the Arp2/3 complex.
PINK1	Serine/threonine-protein kinase PINK1, mitochondrial	Serine/threonine-protein kinase which acts as a sensor of mitochondrial damage and protects against mitochondrial dysfunction during cellular stress.
TMEM230	Transmembrane protein 230	Involved in trafficking and recycling of synaptic vesicles.
PARK7	Parkinson disease protein 7	Multifunctional protein with controversial molecular function which plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease.
RIC3	Protein RIC-3	Molecular chaperone which facilitates proper subunit assembly and surface trafficking of alpha-7 (CHRNA7) and alpha-8 (CHRNA8) nicotinic acetylcholine receptors.
RIT2	GTP-binding protein Rit2	Binds and exchanges GTP and GDP.
CNNM2	Metal transporter CNNM2	Divalent metal cation transporter.
RPS12	Small ribosomal subunit protein eS12	Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit.
BICD1	Protein bicaudal D homolog 1	Regulates coat complex coatomer protein I (COPI)-independent Golgi-endoplasmic reticulum transport by recruiting the dynein-dynactin motor complex.
BIN3	Bridging integrator 3	Involved in cytokinesis and septation where it has a role in the localization of F-actin.
SATB1	DNA-binding protein SATB1	Crucial silencing factor contributing to the initiation of X inactivation mediated by Xist RNA that occurs during embryogenesis and in lymphoma.
SCN3A	Sodium channel protein type 3 subunit alpha	Pore-forming subunit of Nav1.3, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
BMP4	Bone morphogenetic protein 4	Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including neurogenesis, vascular development, angiogenesis and osteogenesis.
SEMA4A	Semaphorin-4A	Cell surface receptor for PLXNB1, PLXNB2, PLXNB3 and PLXND1 that plays an important role in cell-cell signaling.
SEMA5A	Semaphorin-5A	Bifunctional axonal guidance cue regulated by sulfated proteoglycans; attractive effects result from interactions with heparan sulfate proteoglycans (HSPGs), while the inhibitory effects depend on interactions with chondroitin sulfate prot…
SCAF11	Protein SCAF11	Plays a role in pre-mRNA alternative splicing by regulating spliceosome assembly.
SH3GL2	Endophilin-A1	Implicated in synaptic vesicle endocytosis.
SLCO1B3	Solute carrier organic anion transporter family member 1B3	Mediates the Na(+)-independent uptake of organic anions.
SMARCA2	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
BSN	Protein bassoon	Scaffold protein of the presynaptic cytomatrix at the active zone (CAZ) which is the place in the synapse where neurotransmitter is released.
SP1	Transcription factor Sp1	Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli.
SREBF1	Sterol regulatory element-binding protein 1	Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane.
DENND2B	DENN domain-containing protein 2B	May be involved in cytoskeletal organization and tumorogenicity.
SULT1C2	Sulfotransferase 1C2	Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) to catalyze the sulfate conjugation of phenolic compounds.
SYT4	Synaptotagmin-4	Synaptotagmin family member which does not bind Ca(2+).
TIAL1	Nucleolysin TIAR	RNA-binding protein involved in alternative pre-RNA splicing and in cytoplasmic stress granules formation.
ANO2	Anoctamin-2	Calcium-activated chloride channel (CaCC) which may play a role in olfactory signal transduction.
TNR	Tenascin-R	Neural extracellular matrix (ECM) protein involved in interactions with different cells and matrix components.
TOX3	TOX high mobility group box family member 3	Transcriptional coactivator of the p300/CBP-mediated transcription complex.
TPM1	Tropomyosin alpha-1 chain	Binds to actin filaments in muscle and non-muscle cells.
LDLRAD4	Low-density lipoprotein receptor class A domain-containing protein 4	Functions as a negative regulator of TGF-beta signaling and thereby probably plays a role in cell proliferation, differentiation, apoptosis, motility, extracellular matrix production and immunosuppression.
TRPM2	Transient receptor potential cation channel subfamily M member 2	Nonselective, voltage-independent cation channel that mediates Na(+) and Ca(2+) influx, leading to increased cytoplasmic Ca(2+) levels.
TRPS1	Zinc finger transcription factor Trps1	Transcriptional repressor.
TMEM59	Transmembrane protein 59	Acts as a regulator of autophagy in response to S.aureus infection by promoting activation of LC3 (MAP1LC3A, MAP1LC3B or MAP1LC3C).
UBTF	Nucleolar transcription factor 1	Recognizes the ribosomal RNA gene promoter and activates transcription mediated by RNA polymerase I (Pol I) through cooperative interactions with the transcription factor SL1/TIF-IB complex.
UNC13B	Protein unc-13 homolog B	Plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway.
USP25	Ubiquitin carboxyl-terminal hydrolase 25	Deubiquitinating enzyme that hydrolyzes ubiquitin moieties conjugated to substrates and thus, functions in various biological processes including inflammation and immune response.
VAMP4	Vesicle-associated membrane protein 4	Involved in the pathway that functions to remove an inhibitor (probably synaptotagmin-4) of calcium-triggered exocytosis during the maturation of secretory granules.
WNT9A	Protein Wnt-9a	Ligand for members of the frizzled family of seven transmembrane receptors.
WNT3	Proto-oncogene Wnt-3	Ligand for members of the frizzled family of seven transmembrane receptors.
ZNF184	Zinc finger protein 184	May be involved in transcriptional regulation.
TSHZ2	Teashirt homolog 2	Probable transcriptional regulator involved in developmental processes.
ZP3	Zona pellucida sperm-binding protein 3	Component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy.
TCIM	Transcriptional and immune response regulator	Seems to be involved in the regulation of cell growth an differentiation, may play different and opposite roles depending on the tissue or cell type.

Protein-family classification

Druggable: 15 · Difficult: 18 · Unknown: 41 · Druggable fraction: 0.2

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Ion channel	3	4.5×	0.289
Transporter	2	2.1×	0.640
Scaffold/PPI	6	1.4×	0.640
Transcription factor	12	1.3×	0.640
Kinase	3	1.1×	0.952
Other/Unknown	41	1.0×	0.952
GPCR	2	0.7×	0.952
Enzyme (other)	3	0.5×	0.952
Protease	1	0.5×	0.952
Antibody/Immunoglobulin	1	0.4×	0.952

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LRRK2	Kinase	yes		Prot_kinase_dom, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
GBA1	Enzyme (other)	yes	3.2.1.45	Glyco_hydro_30, GH_hydrolase_sf, GH30_C
PRKN	Transcription factor	no	2.3.2.27	Ubiquitin-like_dom, IBR_dom, Parkin
SNCA	Other/Unknown	no		Synuclein, Synuclein_alpha
VPS35	Other/Unknown	no		Vps35, ARM-type_fold, Vps35_C
VPS13C	Other/Unknown	no		VPS13_VAB, VPS13, VPS13_N
WASL	Other/Unknown	no		CRIB_dom, WH1/EVH1_dom, WH2_dom
PINK1	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TMEM230	Other/Unknown	no		TMEM_230/134, TMEM230
PARK7	Enzyme (other)	yes	3.5.1.124	DJ-1/PfpI, DJ-1, Class_I_gatase-like
RIC3	Other/Unknown	no		Ric3, RIC3_N
RIT2	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
CNNM2	Other/Unknown	no		CBS_dom, CNNM, RmlC-like_jellyroll
RPS12	Other/Unknown	no		Ribosomal_eS12, Ribosomal_eL8/eL30/eS12/Gad45, Ribosomal_eL30-like_sf
BICD1	Other/Unknown	no		BICD
BIN3	Scaffold/PPI	no		BAR_dom, AH/BAR_dom_sf, Bin3_BAR
SATB1	Transcription factor	no		HD, CUT_dom, Homeodomain-like_sf
SCN3A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_trans_assoc_dom
BMP4	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like
SEMA4A	Scaffold/PPI	no		Semap_dom, Plexin_repeat, WD40/YVTN_repeat-like_dom_sf
SEMA5A	Scaffold/PPI	no		TSP1_rpt, Semap_dom, Plexin_repeat
SCAF11	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
SH3GL2	Scaffold/PPI	no		SH3_domain, BAR_dom, AH/BAR_dom_sf
SLCO1B3	Transporter	yes		Kazal_dom, OATP, MFS_dom
SMARCA2	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
BSN	Transcription factor	no		Znf_piccolo, Znf_FYVE_PHD, Znf_RING/FYVE/PHD
SP1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
SREBF1	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf
DENND2B	Other/Unknown	no		cDENN_dom, dDENN_dom, uDENN_dom
SULT1C2	Other/Unknown	no		Sulfotransferase_dom, P-loop_NTPase
SYT4	Other/Unknown	no		C2_dom, Synaptotagmin, C2_domain_sf
TIAL1	Other/Unknown	no		RRM_dom, RRM_euk-type, Nucleotide-bd_a/b_plait_sf
ANO2	Other/Unknown	no		Anoctamin, Anoct_dimer, Anoctamin_TM
TNR	Antibody/Immunoglobulin	yes		EGF, Fibrinogen_a/b/g_C_dom, FN3_dom
TOX3	Other/Unknown	no		HMG_box_dom, HMG_box_dom_sf, TOX_HMG-box_domain
TPM1	Other/Unknown	no		Tropomyosin
LDLRAD4	Other/Unknown	no		LDrepeatLR_classA_rpt, LDLR_class-A_CS, LDL_receptor-like_sf
TRPM2	Ion channel	yes		NUDIX_hydrolase_dom, Ion_trans_dom, NUDIX_hydrolase-like_dom_sf
TRPS1	Transcription factor	no		Znf_GATA, Znf_C2H2_type, Znf_NHR/GATA
TMEM59	Other/Unknown	no		Uncharacterised_TMEM59
UBTF	Other/Unknown	no		HMG_box_dom, HMG_box_5, HMG_box_dom_sf
UNC13B	Other/Unknown	no		C2_dom, PKC_DAG/PE, MUN_dom
USP25	Protease	yes		Peptidase_C19_UCH, UIM_dom, UBA-like_sf
VAMP4	Other/Unknown	no		Synaptobrevin-like, V_SNARE_CC, VAMP4
WNT9A	Other/Unknown	no		Wnt, Wnt9a, Wnt_CS
WNT3	Other/Unknown	no		Wnt, Wnt3, Wnt_CS
ZNF184	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
TSHZ2	Transcription factor	no		HD, Znf_C2H2_type, Teashirt_fam
ZP3	Other/Unknown	no		ZP_dom, ZP_dom_CS, ZP-C_dom
TCIM	Other/Unknown	no		Avpi1/C8orf4_dom, Tcim

Expression context

Cohort genes with no expression data: 0.

66 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	2
moderate (6-20)	0
broad (>20)	72
unknown	0

Top tissues across cohort

Tissue	Cohort genes
sural nerve	8
middle temporal gyrus	7
calcaneal tendon	6
primordial germ cell in gonad	5
endothelial cell	5
monocyte	4
male germ line stem cell (sensu Vertebrata) in testis	4
right adrenal gland	4
secondary oocyte	4
cortical plate	4
Brodmann (1909) area 23	4
pancreatic ductal cell	4
sperm	4
buccal mucosa cell	3
leukocyte	3
stromal cell of endometrium	3
adrenal tissue	3
ventricular zone	3
lateral nuclear group of thalamus	3
tendon of biceps brachii	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LRRK2	220	broad	marker	buccal mucosa cell, monocyte, leukocyte
GBA1	134	ubiquitous	marker	stromal cell of endometrium, islet of Langerhans, placenta
PRKN	174	ubiquitous	marker	sural nerve, male germ line stem cell (sensu Vertebrata) in testis, hindlimb stylopod muscle
SNCA	280	ubiquitous	marker	trabecular bone tissue, orbitofrontal cortex, pons
VPS35	149	ubiquitous	marker	ventricular zone, adrenal tissue, corpus callosum
VPS13C	291	ubiquitous	marker	calcaneal tendon, upper leg skin, epithelium of nasopharynx
WASL	290	ubiquitous	marker	middle temporal gyrus, lateral nuclear group of thalamus, jejunal mucosa
PINK1	295	ubiquitous	marker	tendon of biceps brachii, gastrocnemius, gluteal muscle
TMEM230	145	ubiquitous	marker	gall bladder, C1 segment of cervical spinal cord, right adrenal gland cortex
PARK7	294	ubiquitous	marker	adult organism, tibia, deltoid
RIC3	178	broad	marker	adenohypophysis, left lobe of thyroid gland, right lobe of thyroid gland
RIT2	128	tissue_specific	marker	cerebellar cortex, cerebellar hemisphere, cerebellum
CNNM2	234	ubiquitous	marker	secondary oocyte, oocyte, right adrenal gland
RPS12	153	ubiquitous	marker	left ovary, primordial germ cell in gonad, ovary
BICD1	259	ubiquitous	marker	ventricular zone, sural nerve, ganglionic eminence
BIN3	259	ubiquitous	marker	sural nerve, right adrenal gland cortex, right adrenal gland
SATB1	294	ubiquitous	marker	orbitofrontal cortex, frontal pole, thymus
SCN3A	221	broad	marker	endothelial cell, cortical plate, middle temporal gyrus
BMP4	189	ubiquitous	marker	pigmented layer of retina, retina, rectum
SEMA4A	219	broad	marker	monocyte, mononuclear cell, leukocyte
SEMA5A	262	ubiquitous	marker	metanephric glomerulus, renal glomerulus, stromal cell of endometrium
SCAF11	295	ubiquitous	marker	buccal mucosa cell, colonic epithelium, tendon of biceps brachii
SH3GL2	193	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, endothelial cell
SLCO1B3	106	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
SMARCA2	301	ubiquitous	marker	calcaneal tendon, colonic epithelium, cortical plate
BSN	156	broad	marker	frontal pole, paraflocculus, middle temporal gyrus
SP1	264	ubiquitous	marker	nipple, trabecular bone tissue, skin of hip
SREBF1	172	ubiquitous	marker	left adrenal gland, right adrenal gland, left adrenal gland cortex
DENND2B	278	ubiquitous	marker	body of uterus, left uterine tube, right uterine tube
SULT1C2	191	broad	marker	pylorus, nephron tubule, renal medulla

Protein interactions among cohort

Intra-cohort edges: 35.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRKN	10,281
LRRK2	7,628
SNCA	7,615
PARK7	5,722
UBAP2	4,661
RPS12	4,627
BMP4	4,425
SP1	4,275
SMARCA2	4,237
PINK1	4,175

Intra-cohort edges

A	B	Sources
BSN	TNR	string_interaction
CA8	TMEM59	string_interaction
DDRGK1	VPS13C	string_interaction
GBA1	LRRK2	string_interaction
GBA1	PRKN	string_interaction
GBA1	SNCA	biogrid_interaction, string_interaction
GBA1	VPS13C	string_interaction
LAMP3	SFXN2	intact
LRRK2	PARK7	string_interaction
LRRK2	PINK1	string_interaction
LRRK2	PRKN	string_interaction
LRRK2	SH3GL2	string_interaction
LRRK2	SNCA	string_interaction
LRRK2	TMEM230	string_interaction
LRRK2	VPS13C	string_interaction
LRRK2	VPS35	string_interaction
NCKIPSD	WASL	string_interaction
PARK7	PINK1	string_interaction
PARK7	PRKN	biogrid_interaction, string_interaction
PARK7	SNCA	string_interaction
PINK1	PRKN	intact, string_interaction
PINK1	SNCA	string_interaction
PINK1	VPS13C	string_interaction
PRKN	SH3GL2	string_interaction
PRKN	SNCA	string_interaction
PRKN	VPS13C	string_interaction
PRKN	VPS35	string_interaction
RIC3	TMEM230	string_interaction
RIT2	SYT4	string_interaction
SYT4	VAMP4	string_interaction
TMEM230	VPS13C	string_interaction
TMEM230	VPS35	string_interaction
TRPS1	ZFP64	string_interaction
TSHZ2	ZFP64	string_interaction
VPS13C	VPS35	string_interaction

Structural data

PDB: 42 · AlphaFold-only: 31 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SNCA	P37840	232
RPS12	P25398	198
PARK7	Q99497	88
GBA1	P04062	58
LRRK2	Q5S007	44
SMARCA2	P51531	32
TAS1R2	Q8TE23	25
PRKN	O60260	21
TRPM2	O94759	15
TPM1	P09493	14
VPS35	Q96QK1	13
SP1	P08047	11
CAMK2D	Q13557	9
WASL	O00401	8
SATB1	Q01826	8
DDRGK1	Q96HY6	8
CNNM2	Q9H8M5	7
USP25	Q9UHP3	7
CACNA1B	Q00975	7
PINK1	Q9BXM7	6
NCKIPSD	Q9NZQ3	6
SEMA5A	Q13591	4
SH3GL2	Q99962	4
UBTF	P17480	4
TIAL1	Q01085	3
TLR9	Q9NR96	3
SCN3A	Q9NY46	2
TNR	Q92752	2
PDLIM2	Q96JY6	2
ZFP64	Q9NTW7	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BIN3	Q9NQY0	92.83
RIT2	Q99578	88.46
SFXN2	Q96NB2	85.11
SEMA4A	Q9H3S1	85.05
OR9Q1	Q8NGQ5	84.62
SLC44A4	Q53GD3	83.79
WNT9A	O14904	83.18
TMEM230	Q96A57	81.46
VAMP4	O75379	81.23
SLC2A13	Q96QE2	80.34
BMP4	P12644	79.12
TCIM	Q9NR00	79.01
ZP3	P21754	77.32
UNC13B	O14795	75.85
ANO2	Q9NQ90	74.81
ZNF184	Q99676	72.56
BICD1	Q96G01	72.36
TMEM59	Q9BXS4	66.53
MED12L	Q86YW9	66.04
TOX3	O15405	60.22
DENND2B	P78524	58.86
RIC3	Q7Z5B4	58.55
LDLRAD4	O15165	58.44
PRDM15	P57071	56.66
DIRC1	Q969H9	55.23
TSHZ2	Q9NRE2	54.88
TRPS1	Q9UHF7	49.12
UBAP2	Q5T6F2	43.47
SCAF11	Q99590	42.56
VPS13C	Q709C8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 588. Enrichment computed across 250 evidence-associated genes (138 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 138 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective B3GALTL causes PpS	4	8.9×	0.232	SEMA5A, ADAMTS16, ADAMTS20, THSD4
O-glycosylation of TSR domain-containing proteins	4	8.7×	0.232	SEMA5A, ADAMTS16, ADAMTS20, THSD4
Clathrin-mediated endocytosis	7	4.3×	0.232	SH3GL2, VAMP4, WASL, SCARB2, HIP1R, SYT11, AAK1
Phase 1 - inactivation of fast Na+ channels	2	23.6×	0.300	KCNIP3, KCNIP4
Neurotoxicity of clostridium toxins	2	20.7×	0.300	STX1B, SV2C
WNT ligand biogenesis and trafficking	3	9.2×	0.300	VPS35, WNT9A, WNT3
Diseases associated with O-glycosylation of proteins	4	6.2×	0.300	SEMA5A, ADAMTS16, ADAMTS20, THSD4
O-linked glycosylation	5	5.2×	0.300	SEMA5A, ADAMTS16, ADAMTS20, ST6GALNAC3, THSD4
TWIK-related spinal cord K+ channel (TRESK)	1	82.8×	0.395	KCNK18
Synthesis of CL	1	82.8×	0.395	CRLS1
Defective CYP1B1 causes Glaucoma	1	82.8×	0.395	CYP1B1
Defective CYP17A1 causes AH5	1	82.8×	0.395	CYP17A1
Defective SLCO1B3 causes hyperbilirubinemia, Rotor type (HBLRR)	1	82.8×	0.395	SLCO1B3
Trafficking and processing of endosomal TLR	2	11.8×	0.395	TLR9, CTSB
Uptake and actions of bacterial toxins	2	11.8×	0.395	STX1B, SV2C
Bacterial Infection Pathways	3	7.3×	0.395	SH3GL2, STX1B, SV2C
Collagen degradation	4	5.1×	0.395	COL13A1, COL3A1, COL5A2, CTSB
Cargo recognition for clathrin-mediated endocytosis	5	3.8×	0.395	SH3GL2, VAMP4, SCARB2, SYT11, AAK1
Formation of WDR5-containing histone-modifying complexes	3	5.8×	0.446	KAT8, KANSL1, SETD1A
Activation of gene expression by SREBF (SREBP)	3	5.6×	0.446	SP1, SREBF1, CHD9
Collagen chain trimerization	3	5.6×	0.446	COL13A1, COL3A1, COL5A2
Acetylcholine Neurotransmitter Release Cycle	2	9.7×	0.468	UNC13B, RIMS1
Serotonin Neurotransmitter Release Cycle	2	9.2×	0.472	UNC13B, RIMS1
Norepinephrine Neurotransmitter Release Cycle	2	9.2×	0.472	UNC13B, RIMS1
Other semaphorin interactions	2	8.7×	0.472	SEMA4A, SEMA5A
Metal ion SLC transporters	2	8.7×	0.472	SLC41A1, SLC39A8
Diseases of glycosylation	4	3.8×	0.472	SEMA5A, ADAMTS16, ADAMTS20, THSD4
Oleoyl-phe metabolism	1	41.4×	0.487	PM20D1
Fibronectin matrix formation	2	8.3×	0.487	COL3A1, COL5A2
Chromatin organization	5	3.0×	0.536	SMARCA2, KAT8, ASH1L, KANSL1, SETD1A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 218 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of synaptic vesicle endocytosis	6	24.4×	2e-04	LRRK2, PRKN, VAMP4, PARK7, SYT11, DGKQ
mitochondrion to lysosome vesicle-mediated transport	3	77.3×	0.001	PRKN, VPS35, PINK1
regulation of synaptic vesicle transport	3	77.3×	0.001	LRRK2, PRKN, PINK1
regulation of reactive oxygen species metabolic process	5	16.8×	0.004	LRRK2, PRKN, PINK1, COQ7, CYP1B1
negative regulation of neuron projection development	7	7.6×	0.012	LRRK2, RIT2, TNR, CD38, STX1B, PRAG1, PAQR3
regulation of calcium ion-dependent exocytosis	4	17.2×	0.020	SYT4, SYT11, SYT10, SYT17
negative regulation of late endosome to lysosome transport	2	77.3×	0.025	LRRK2, VPS35
positive regulation of dopamine biosynthetic process	2	77.3×	0.025	VPS35, PARK7
obsolete regulation of protein targeting to mitochondrion	3	29.0×	0.025	PRKN, SREBF1, PINK1
positive regulation of neurotransmitter secretion	3	25.8×	0.025	SNCA, STX1B, MICU3
dopamine uptake involved in synaptic transmission	3	25.8×	0.025	PRKN, SNCA, PARK7
positive regulation of dendrite extension	4	13.4×	0.027	PRKN, SYT4, RIMS1, SYT17
response to hydroperoxide	3	23.2×	0.028	SP1, TRPM2, CD38
regulation of clathrin-dependent endocytosis	3	23.2×	0.028	HIP1R, TNK2, AAK1
positive regulation of type 2 mitophagy	3	21.1×	0.035	GBA1, PRKN, PINK1
regulation of protein stability	8	4.6×	0.036	LRRK2, PRKN, VPS35, SREBF1, USP25, DDRGK1, CCAR2, DSG3
positive regulation of mitochondrial electron transport, NADH to ubiquinone	2	51.5×	0.039	PINK1, PARK7
negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway	2	51.5×	0.039	PINK1, PARK7
cellular response to hydrogen sulfide	2	51.5×	0.039	PRKN, PINK1
mitochondrial fragmentation involved in apoptotic process	3	19.3×	0.039	PRKN, VPS35, CCAR2
obsolete synaptic vesicle docking	3	17.8×	0.039	UNC13B, RIMS1, STX1B
negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	3	17.8×	0.039	PRKN, PINK1, PARK7
positive regulation of canonical Wnt signaling pathway	7	5.0×	0.039	LRRK2, VPS35, RPS12, SEMA5A, PRDM15, CCAR2, FGF10
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	6	5.8×	0.040	LRRK2, GBA1, PRKN, DDRGK1, PRICKLE1, PAQR3
regulation of dopamine secretion	3	16.6×	0.046	PRKN, SNCA, SYT4
adult locomotory behavior	5	6.9×	0.048	PRKN, SNCA, PARK7, INPP5F, CLCN3
autophagy	8	4.0×	0.052	LRRK2, GBA1, TMEM59, PARK7, SCARB2, TBC1D5, SYT11, WDR41
positive regulation of dopamine receptor signaling pathway	2	38.6×	0.053	LRRK2, VPS35
prostatic bud formation	2	38.6×	0.053	BMP4, FGF10
tear secretion	2	38.6×	0.053	PRICKLE1, FGF10

Therapeutics

Drugs indicated for this disease

24 approved, 34 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Amantadine	Approved (phase 4)
Apomorphine	Approved (phase 4)
Benztropine	Approved (phase 4)
Biperiden	Approved (phase 4)
Bromocriptine	Approved (phase 4)
Cabergoline	Approved (phase 4)
Entacapone	Approved (phase 4)
Ethopropazine	Approved (phase 4)
Istradefylline	Approved (phase 4)
Levodopa	Approved (phase 4)
Methixene	Approved (phase 4)
Opicapone	Approved (phase 4)
Pergolide	Approved (phase 4)
Piribedil	Approved (phase 4)
Pramipexole	Approved (phase 4)
Procyclidine	Approved (phase 4)
Rasagiline	Approved (phase 4)
Rivastigmine	Approved (phase 4)
Ropinirole	Approved (phase 4)
Rotigotine	Approved (phase 4)
Safinamide	Approved (phase 4)
Selegiline	Approved (phase 4)
Tolcapone	Approved (phase 4)
Trihexyphenidyl	Approved (phase 4)
Ambroxol	Phase 3 (in late-stage trials)
Ampreloxetine	Phase 3 (in late-stage trials)
Benserazide	Phase 3 (in late-stage trials)
Buntanetap	Phase 3 (in late-stage trials)
Buspirone	Phase 3 (in late-stage trials)
Caffeine	Phase 3 (in late-stage trials)
Creatine	Phase 3 (in late-stage trials)
Donepezil	Phase 3 (in late-stage trials)
Dopamine	Phase 3 (in late-stage trials)
Duloxetine	Phase 3 (in late-stage trials)
Exenatide	Phase 3 (in late-stage trials)
Foslevodopa	Phase 3 (in late-stage trials)
Incobotulinumtoxina	Phase 3 (in late-stage trials)
Inosine	Phase 3 (in late-stage trials)
Isradipine	Phase 3 (in late-stage trials)
Lactobacillus Acidophilus	Phase 3 (in late-stage trials)
Lisuride	Phase 3 (in late-stage trials)
Memantine	Phase 3 (in late-stage trials)
Nabilone	Phase 3 (in late-stage trials)
Naloxone	Phase 3 (in late-stage trials)
Nicotinamide Riboside	Phase 3 (in late-stage trials)
Oxycodone	Phase 3 (in late-stage trials)
Pardoprunox	Phase 3 (in late-stage trials)
Paroxetine	Phase 3 (in late-stage trials)
Perampanel	Phase 3 (in late-stage trials)
Pitolisant	Phase 3 (in late-stage trials)
Preladenant	Phase 3 (in late-stage trials)
Rifaximin	Phase 3 (in late-stage trials)
Sumanirole	Phase 3 (in late-stage trials)
Tavapadon	Phase 3 (in late-stage trials)
Tozadenant	Phase 3 (in late-stage trials)
Tyramine	Phase 3 (in late-stage trials)
Ubidecarenone	Phase 3 (in late-stage trials)
Vitamin E	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Acetylcysteine, CEP-1347, Calcium, Cannabidiol, Cannabinol, Ceftriaxone, Cholecalciferol, Citalopram, Deferiprone, Dextromethorphan, Domperidone, Droxidopa, Epigalocatechin Gallate, Filgrastim, Fludrocortisone Acetate, Folic Acid, Gemfibrozil, Ginkgo, Glutathione, Insulin Human, Insulin Pork, Ketamine, Levetiracetam, Liraglutide, Lixisenatide, Lovastatin, Maltodextrin, Melatonin, Metformin, Methylphenidate, Minocycline, Modafinil, Montelukast, Moxifloxacin, Nicotine, Nilotinib, Onabotulinumtoxina, Pentoxifylline, Pimavanserin, Pioglitazone, Pridopidine, Quetiapine, Radotinib, Remimazolam, Semaglutide, Sildenafil, Simvastatin, Sodium Chloride, Sulforaphane, Topiramate, Tropicamide, Ursodiol, Varenicline, Vatiquinone, Venglustat, Verdiperstat, Zolpidem, Zonisamide, Zuranolone.

Drug target analysis

Approved (phase 4): 12 · Phase ≥3: 12 · Phased (≥1): 18 · Undrugged: 56

Druggability breadth: 79 of 250 evidence-associated genes (32%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
LRRK2	PONATINIB
GBA1	MIGALASTAT
SNCA	ESTRADIOL
RPS12	GENTAMICIN SULFATE
SCN3A	BEPRIDIL
SLCO1B3	CANDESARTAN CILEXETIL
SREBF1	CALCIFEDIOL ANHYDROUS
TRPM2	CLOTRIMAZOLE
CACNA1B	NIFEDIPINE
CAMK2D	MOMELOTINIB
TLR9	HYDROXYCHLOROQUINE
CCNT2	PALBOCICLIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN3A	93	4
SLCO1B3	50	4
LRRK2	42	4
CAMK2D	40	4
SNCA	31	4
CACNA1B	23	4
GBA1	12	4
TRPM2	5	4
TLR9	5	4
CCNT2	3	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	LRRK2
FEDRATINIB	4	CAMK2D, LRRK2
AXITINIB	4	LRRK2
RUXOLITINIB	4	CAMK2D, LRRK2
PALBOCICLIB	4	CAMK2D, CCNT2, LRRK2
ENTRECTINIB	4	LRRK2
TOFACITINIB CITRATE	4	CAMK2D, LRRK2
TOFACITINIB	4	CAMK2D, LRRK2
VANDETANIB	4	LRRK2
BOSUTINIB	4	LRRK2
BRIGATINIB	4	CAMK2D, LRRK2
NINTEDANIB	4	LRRK2
SUNITINIB	4	CAMK2D, LRRK2
ERLOTINIB	4	CAMK2D, LRRK2, SLCO1B3
MIDOSTAURIN	4	CAMK2D, LRRK2
MIGALASTAT	4	GBA1
GLUCONOLACTONE	4	GBA1
MIGLITOL	4	GBA1
MEXILETINE	4	GBA1, SCN3A
GENTIAN VIOLET	4	GBA1, SNCA
CHLORHEXIDINE	4	GBA1
TAMOXIFEN	4	GBA1
ESTRADIOL	4	SNCA
ESTRONE	4	SNCA
TETRACYCLINE	4	SNCA
PHYTONADIONE	4	SNCA
CEFTRIAXONE	4	SNCA
FLORBETAPIR	4	SNCA
ESTRIOL	4	SNCA
RIFAMPIN	4	SLCO1B3, SNCA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
LRRK2	809	Binding:799, ADMET:7, Functional:3
SNCA	459	Binding:458, Functional:1
GBA1	436	Binding:403, Functional:33
CAMK2D	338	Binding:337, Functional:1
SMARCA2	311	Binding:274, Functional:25, ADMET:12
SLCO1B3	136	ADMET:79, Binding:30, Functional:27
CACNA1B	135	Binding:110, Functional:25
TLR9	132	Binding:125, Functional:7
SCN3A	102	Binding:79, Functional:18, ADMET:4, Toxicity:1
RPS12	90	Binding:90
PARK7	62	Binding:62
TRPM2	59	Binding:58, Functional:1
TAS1R2	30	Functional:15, Binding:15
PINK1	24	Binding:24
USP25	19	Binding:19
SREBF1	17	Binding:17
CCNT2	16	Binding:16
VPS35	11	Binding:11
SP1	10	Binding:8, ADMET:2
ANO2	8	Binding:5, ADMET:3
UBTF	7	Binding:7
WNT3	5	Functional:3, Binding:2
TPM1	3	Binding:3
BMP4	2	Binding:2
BIN3	1	Binding:1
SULT1C2	1	ADMET:1
TIAL1	1	Binding:1
UBAP2	1	Binding:1
KLHL7	1	Binding:1
DDRGK1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GBA1	3.2.1.45	glucosylceramidase
PRKN	2.3.2.27, 2.3.2.31	RING-type E3 ubiquitin transferase, RBR-type E3 ubiquitin transferase
PARK7	3.5.1.124, 4.2.1.130	protein deglycase, D-lactate dehydratase
CA8	4.2.1.1	carbonic anhydrase
CAMK2D	2.7.11.17	Ca2+/calmodulin-dependent protein kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
LRRK2	809
GBA1	436
SNCA	459
SCN3A	102
SLCO1B3	136
SMARCA2	311
CACNA1B	135
CAMK2D	338
TLR9	132

Pharmacogenomics

Cohort genes with a PharmGKB record: 73; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
PONATINIB	4	LRRK2
FEDRATINIB	4	CAMK2D, LRRK2
AXITINIB	4	LRRK2
RUXOLITINIB	4	CAMK2D, LRRK2
PALBOCICLIB	4	CAMK2D, CCNT2, LRRK2
ENTRECTINIB	4	LRRK2
TOFACITINIB CITRATE	4	CAMK2D, LRRK2
TOFACITINIB	4	CAMK2D, LRRK2
VANDETANIB	4	LRRK2
BOSUTINIB	4	LRRK2
BRIGATINIB	4	CAMK2D, LRRK2
NINTEDANIB	4	LRRK2
SUNITINIB	4	CAMK2D, LRRK2
ERLOTINIB	4	CAMK2D, LRRK2, SLCO1B3
MIDOSTAURIN	4	CAMK2D, LRRK2
MIGALASTAT	4	GBA1
GLUCONOLACTONE	4	GBA1
MIGLITOL	4	GBA1
MEXILETINE	4	GBA1, SCN3A
GENTIAN VIOLET	4	GBA1, SNCA
CHLORHEXIDINE	4	GBA1
TAMOXIFEN	4	GBA1
ESTRADIOL	4	SNCA
ESTRONE	4	SNCA
TETRACYCLINE	4	SNCA
PHYTONADIONE	4	SNCA
CEFTRIAXONE	4	SNCA
FLORBETAPIR	4	SNCA
ESTRIOL	4	SNCA
RIFAMPIN	4	SLCO1B3, SNCA

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	12	LRRK2, GBA1, SNCA, RPS12, SCN3A, SLCO1B3, SREBF1, TRPM2, CACNA1B, CAMK2D (+2 more)
B	Phased (≥1) drug, not yet approved	6	VPS35, PARK7, SMARCA2, SP1, UBTF, TAS1R2
C	Druggable family + PDB, no drug	4	PINK1, TNR, USP25, CA8
D	Druggable family + AlphaFold only, no drug	2	OR9Q1, SLC2A13
E	Difficult family or no structure, no drug	50	PRKN, VPS13C, WASL, TMEM230, RIC3, RIT2, CNNM2, BICD1, BIN3, SATB1 (+40 more)

Undrugged target profiles

56 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PRKN	0	SNCA, PARK7, LRRK2
VPS13C	0	VPS35
PINK1	24	PARK7
TMEM230	0	VPS35
WASL	0	—
RIC3	0	—
RIT2	0	—
CNNM2	0	—
BICD1	0	—
BIN3	1	—
SATB1	0	—
BMP4	2	—
SEMA4A	0	—
SEMA5A	0	—
SCAF11	0	—
SH3GL2	0	—
BSN	0	—
DENND2B	0	—
SULT1C2	1	—
SYT4	0	—
TIAL1	1	—
ANO2	8	—
TNR	0	—
TOX3	0	—
TPM1	3	—
LDLRAD4	0	—
TRPS1	0	—
TMEM59	0	—
UNC13B	0	—
USP25	19	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4,025.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	420
PHASE3	221
PHASE4	150
PHASE1	149
PHASE1/PHASE2	95
PHASE2/PHASE3	51
EARLY_PHASE1	14

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03924414	PHASE4	ACTIVE_NOT_RECRUITING	Trial of Parkinson’s And Zoledronic Acid
NCT05357612	PHASE4	RECRUITING	Characterization of the Serotonin 2A Receptor Selective PET Tracer [18F]MH.MZ in Patients With Neurodegenerative Diseases
NCT05855577	PHASE4	NOT_YET_RECRUITING	Motor Function Efficacy of Pharmacological Treatments Targeting Energy Metabolism, in Parkinson’s Patients
NCT06013956	PHASE4	RECRUITING	Personalized Real-Time DBS and PD Mechanisms
NCT06234995	PHASE4	RECRUITING	Cortical Electrophysiology of Response Inhibition in Parkinson’s Disease
NCT06316232	PHASE4	RECRUITING	DBS and Levodopa for Treating Freezing of Gait in Parkinson’s Disease
NCT06710574	PHASE4	RECRUITING	Multimodal Image Technologies Investigate the Role and Mechanism of Probiotics in Improving RBD with Parkinson’s Disease
NCT06765668	PHASE4	RECRUITING	A Study of CREXONT (Carbidopa and Levodopa) Extended-Release Capsules in Participants With Parkinson’s Disease
NCT07138560	PHASE4	RECRUITING	BOOST-PD A Naturalistic Study on IPX-203 for Parkinson’s Disease
NCT07187466	PHASE4	NOT_YET_RECRUITING	Behavioral and/or Mirabegron to Treat Urinary Symptoms in Parkinson Disease
NCT07384429	PHASE4	RECRUITING	Effects of Lemborexant on Motor-sleep Comorbidity in Parkinson’s Disease
NCT00030979	PHASE4	COMPLETED	Donepezil to Treat Dementia in Parkinson’s Disease
NCT00043849	PHASE4	COMPLETED	Treatment of Agitation/Psychosis in Dementia/Parkinsonism (TAP/DAP)
NCT00095810	PHASE4	COMPLETED	Aripiprazole in Patients With Psychosis Associated With Parkinson’s Disease
NCT00125567	PHASE4	COMPLETED	Stalevo in Early Wearing-Off Patients
NCT00143026	PHASE4	COMPLETED	Study to Compare the Effect of Treatment With Carbidopa/Levodopa/Entacapone on the Quality of Life of Patients With Parkinson’s Disease. This Study is Not Recruiting in the United States
NCT00144300	PHASE4	COMPLETED	Ophthalmologic Safety Study of Pramipexole Immediate Release (IR) Versus Ropinirole in Early Parkinson’s Disease (PD) Patients
NCT00153972	PHASE4	COMPLETED	Dopamine Turnover Rate as Surrogate Parameter for Diagnosis of Early Parkinson’s Disease
NCT00174239	PHASE4	TERMINATED	Study Of Cabaser and Sinemet CR For The Treatment Of Nighttime Symptoms Associated With Parkinson’s Disease.
NCT00215904	PHASE4	COMPLETED	D-serine Adjuvant Treatment for Parkinson’s Disease
NCT00247247	PHASE4	COMPLETED	Comtess® Versus Cabaseril® as Add-on to Levodopa in the Treatment of Parkinsonian Patients Suffering From Wearing- Off.
NCT00272688	PHASE4	COMPLETED	Continuous Delivery of Levodopa in Patients With Advanced Idiopathic Parkinsons Disease - Cost-benefit
NCT00297778	PHASE4	COMPLETED	Pramipexole Versus Placebo in Parkinson’s Disease (PD) Patients With Depressive Symptoms
NCT00304161	PHASE4	COMPLETED	Effectiveness of Antidepressant Treatment for Depression in People With Parkinson’s Disease
NCT00307450	PHASE4	COMPLETED	Efficacy and Safety of Levetiracetam Versus Placebo on Levodopa-induced Dyskinesias in Advanced Parkinson’s Disease
NCT00321854	PHASE4	COMPLETED	Study of (Mirapex) Pramipexole for the Early Treatment of Parkinsons Disease (PD)
NCT00354133	PHASE4	UNKNOWN	Controlled Trial With Deep Brain Stimulation in Patients With Early Parkinson’s Disease
NCT00373087	PHASE4	COMPLETED	COMT Polymorphism and Entacapone Efficacy
NCT00391898	PHASE4	COMPLETED	Efficacy of Levodopa/Carbidopa/Entacapone vs Levodopa/Carbidopa in Parkinson’s Disease Patients With Early Wearing-off
NCT00399477	PHASE4	COMPLETED	A Non-Blinded Study Demonstrating the Effectiveness and Safety of Azilect Alone or in Combination Therapy in Parkinson’s Disease
NCT00402233	PHASE4	COMPLETED	A Randomized, Double-blind, Active (Pramipexole 0.5 mg Tid) and Placebo Controlled, Study of Pramipexole Given 0.5 mg and 0.75 mg Bid Over 12-week Treatment in Early Parkinson’s Disease (PD) Patients
NCT00437125	PHASE4	COMPLETED	Study on the Tolerability of Duloxetine in Depressed Patients With Parkinson’s Disease
NCT00443872	PHASE4	COMPLETED	Efficacy of Orally Disintegrating Selegiline in Parkinson’s Patients Experiencing Adverse Effects With Dopamine Agonists
NCT00455143	PHASE4	TERMINATED	Cognitive Protection - Dexmedetomidine and Cognitive Reserve
NCT00462007	PHASE4	COMPLETED	Study to Evaluate Initiation of Stalevo in Early Wearing-off
NCT00462254	PHASE4	TERMINATED	Ramelteon (ROZEREM) in the Treatment of Sleep Disturbances Associated With Parkinson’s Disease
NCT00477802	PHASE4	TERMINATED	Botulinum Toxin Type A (Botox) in the Management of Levodopa-Induced Peak-Dose Dyskinesias in Parkinson’s Disease
NCT00485069	PHASE4	COMPLETED	REQUIP (Ropinirole Hydrochloride) IR Long-Term Phase 4 Study
NCT00489255	PHASE4	COMPLETED	Safety/Efficacy of Tigan® to Control Nausea/Vomiting Experienced During Apokyn® Initiation and Treatment
NCT00526630	PHASE4	COMPLETED	Methylphenidate for the Treatment of Gait Impairment in Parkinson’s Disease

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CARBIDOPA ANHYDROUS	4	132
RASAGILINE	4	70
LEVODOPA	4	61
APOMORPHINE	4	48
PRAMIPEXOLE	4	36
ROTIGOTINE	4	36
OPICAPONE	4	29
ROPINIROLE	4	29
SAFINAMIDE	4	25
AMANTADINE	4	19
ISTRADEFYLLINE	4	19
ENTACAPONE	4	18
RIVASTIGMINE	4	15
BROMOCRIPTINE	4	12
DEXMEDETOMIDINE	4	11
DROXIDOPA	4	11
PERAMPANEL	4	11
DONEPEZIL	4	10
TERAZOSIN	4	10
ATOMOXETINE	4	9
DOPAMINE	4	7
FOSLEVODOPA	4	5
DEFERIPRONE	4	4
RIFAXIMIN	4	4
DOMPERIDONE	4	3
ESCITALOPRAM	4	3
MELATONIN	4	3
MEMANTINE	4	3
METHYLPHENIDATE	4	3
MIRABEGRON	4	3