young-onset Parkinson disease
diseaseOn this page
Also known as early-onset Parkinson diseaseYOPD
Summary
young-onset Parkinson disease (MONDO:0017279) is a disease (an umbrella term covering 9 Mondo subtypes) with 14 cohort genes and 3 clinical trials.
At a glance
- Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
- Umbrella term: 9 Mondo subtypes
- Cohort genes: 14
- ClinVar variants: 33
- Phenotypes (HPO): 34
- Clinical trials: 3
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Point prevalence | 1-5 / 10 000 | 15 | Europe | Validated |
| Point prevalence | 1-5 / 10 000 | Worldwide | Not yet validated |
Signs & symptoms
Clinical features (HPO)
34 HPO clinical features (Orphanet curated; top 34 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0002063 | Rigidity | Very frequent (80-99%) |
| HP:0000716 | Depression | Frequent (30-79%) |
| HP:0000738 | Hallucinations | Frequent (30-79%) |
| HP:0000741 | Apathy | Frequent (30-79%) |
| HP:0001337 | Tremor | Frequent (30-79%) |
| HP:0002172 | Postural instability | Frequent (30-79%) |
| HP:0100660 | Dyskinesia | Frequent (30-79%) |
| HP:0012760 | Reduced social responsiveness | Occasional (5-29%) |
| HP:0000551 | Color vision defect | Occasional (5-29%) |
| HP:0000726 | Dementia | Occasional (5-29%) |
| HP:0000736 | Short attention span | Occasional (5-29%) |
| HP:0000739 | Anxiety | Occasional (5-29%) |
| HP:0001257 | Spasticity | Occasional (5-29%) |
| HP:0001332 | Dystonia | Occasional (5-29%) |
| HP:0001347 | Hyperreflexia | Occasional (5-29%) |
| HP:0002014 | Diarrhea | Occasional (5-29%) |
| HP:0002018 | Nausea | Occasional (5-29%) |
| HP:0002019 | Constipation | Occasional (5-29%) |
| HP:0002067 | Bradykinesia | Occasional (5-29%) |
| HP:0002141 | Gait imbalance | Occasional (5-29%) |
| HP:0002578 | Gastroparesis | Occasional (5-29%) |
| HP:0003394 | Muscle spasm | Occasional (5-29%) |
| HP:0004409 | Hyposmia | Occasional (5-29%) |
| HP:0012332 | Abnormal autonomic nervous system physiology | Occasional (5-29%) |
| HP:0012452 | Restless legs | Occasional (5-29%) |
| HP:0025269 | Panic attack | Occasional (5-29%) |
| HP:0030014 | Female sexual dysfunction | Occasional (5-29%) |
| HP:0040307 | Male sexual dysfunction | Occasional (5-29%) |
| HP:0100543 | Cognitive impairment | Occasional (5-29%) |
| HP:0100785 | Insomnia | Occasional (5-29%) |
| HP:0000651 | Diplopia | Very rare (<1-4%) |
| HP:0000713 | Agitation | Very rare (<1-4%) |
| HP:0000727 | Frontal lobe dementia | Very rare (<1-4%) |
| HP:0100710 | Impulsivity | Very rare (<1-4%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | young-onset Parkinson disease |
| Mondo ID | MONDO:0017279 |
| Orphanet | 2828 |
| DOID | DOID:0060894 |
| SNOMED CT | 715345007 |
| UMLS | C4275179 |
| MedGen | 907947 |
| GARD | 0016610 |
| Is cancer (heuristic) | no |
Also known as: early-onset Parkinson disease · YOPD
Data availability: 33 ClinVar variants · 7 GenCC gene-disease records · 222 cell lines.
Disease family
An umbrella term covering 9 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 › young-onset Parkinson disease
Related subtypes (5): late-onset Parkinson disease, parkinsonian-pyramidal syndrome, Parkinson disease, mitochondrial, Parkinson disease 16, Parkinson disease 25, autosomal recessive early-onset, with impaired intellectual development
Subtypes (9): juvenile-onset Parkinson disease, Parkinson disease 12, autosomal recessive juvenile Parkinson disease 2, Parkinson disease 3, autosomal dominant, autosomal recessive early-onset Parkinson disease 6, autosomal recessive early-onset Parkinson disease 7, Parkinson disease 10, early-onset Parkinson disease 20, autosomal recessive early-onset Parkinson disease 23
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
33 retrieved; paginated sample, class counts are floors:
12 likely pathogenic, 8 pathogenic, 6 pathogenic/likely pathogenic, 3 conflicting classifications of pathogenicity, 3 uncertain significance, 1 pathogenic/likely pathogenic; risk factor
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 93445 | NM_000157.4(GBA1):c.115+1G>A | GBA1 | Pathogenic/Likely pathogenic | 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 |
| 493448 | NM_004562.3(PRKN):c.1A>G (p.Met1Val) | PACRG | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1119999 | GRCh37/hg19 6q26(chr6:162622150-162683772) | PRKN | Pathogenic | criteria provided, single submitter |
| 1120002 | GRCh37/hg19 6q26(chr6:162622150-162622256) | PRKN | Pathogenic | criteria provided, single submitter |
| 1120005 | GRCh37/hg19 6q26(chr6:162864400-162864441) | PRKN | Pathogenic | criteria provided, single submitter |
| 1120006 | GRCh37/hg19 6q26(chr6:162394320-162475157) | PRKN | Pathogenic | criteria provided, single submitter |
| 1120009 | GRCh37/hg19 6q26(chr6:161969922-161990424) | PRKN | Pathogenic | criteria provided, single submitter |
| 356016 | NM_004562.3(PRKN):c.1289G>A (p.Gly430Asp) | PRKN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 425403 | NM_004562.3(PRKN):c.101_102del (p.Gln34fs) | PRKN | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 7050 | NM_004562.3(PRKN):c.823C>T (p.Arg275Trp) | PRKN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1120010 | GRCh37/hg19 4q22.1(chr4:90647764-90758128) | SNCA | Pathogenic | criteria provided, single submitter |
| 88844 | NM_203446.3(SYNJ1):c.656G>A (p.Arg219Gln) | SYNJ1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 222070 | NM_020821.3(VPS13C):c.4165G>C (p.Gly1389Arg) | VPS13C | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 982938 | NM_020821.3(VPS13C):c.1111C>T (p.Arg371Ter) | VPS13C | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1119998 | NM_007262.5(PARK7):c.460A>G (p.Thr154Ala) | PARK7 | Likely pathogenic | criteria provided, single submitter |
| 1120000 | GRCh37/hg19 6q26(chr6:162864400-162864441) | PRKN | Likely pathogenic | criteria provided, single submitter |
| 1120001 | GRCh37/hg19 6q26(chr6:162683576-162683772) | PRKN | Likely pathogenic | criteria provided, single submitter |
| 1120003 | GRCh37/hg19 6q26(chr6:162475128-162475157) | PRKN | Likely pathogenic | criteria provided, single submitter |
| 1120004 | GRCh37/hg19 6q26(chr6:162475128-162475157) | PRKN | Likely pathogenic | criteria provided, single submitter |
| 1120008 | GRCh37/hg19 6q26(chr6:162206818-162206900) | PRKN | Likely pathogenic | criteria provided, single submitter |
| 3075760 | NM_020821.3(VPS13C):c.3908+2T>C | VPS13C | Likely pathogenic | criteria provided, single submitter |
| 3075761 | NM_020821.3(VPS13C):c.2408+1G>A | VPS13C | Likely pathogenic | criteria provided, single submitter |
| 3075762 | NM_020821.3(VPS13C):c.3331G>T (p.Gly1111Ter) | VPS13C | Likely pathogenic | criteria provided, single submitter |
| 3075763 | NM_020821.3(VPS13C):c.5462T>A (p.Leu1821Ter) | VPS13C | Likely pathogenic | criteria provided, single submitter |
| 3075814 | NM_020821.3(VPS13C):c.5698C>T (p.Gln1900Ter) | VPS13C | Likely pathogenic | criteria provided, single submitter |
| 3075815 | NM_020821.3(VPS13C):c.1119G>A (p.Trp373Ter) | VPS13C | Likely pathogenic | criteria provided, single submitter |
| 334317 | NM_015488.5(PNKD):c.466-3C>A | CATIP-AS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1120007 | NM_004562.3(PRKN):c.1288G>A (p.Gly430Ser) | PRKN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 7054 | NM_004562.3(PRKN):c.719C>T (p.Thr240Met) | PRKN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 42 · Orphanet: 28 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
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 |
|---|---|---|---|---|
| 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 |
| DNAJC6 | Strong | Autosomal recessive | juvenile onset Parkinson disease 19A | 7 |
| SYNJ1 | Strong | Autosomal recessive | early-onset Parkinson disease 20 | 10 |
| VPS13C | Strong | Autosomal recessive | autosomal recessive early-onset Parkinson disease 23 | 5 |
| PODXL | Supportive | Autosomal recessive | young-onset Parkinson disease | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| SYNJ1 | Orphanet:2828 | Young-onset Parkinson disease |
| SYNJ1 | Orphanet:391411 | Atypical juvenile parkinsonism |
| SYNJ1 | Orphanet:442835 | Non-specific early-onset epileptic encephalopathy |
| PARK7 | Orphanet:2828 | Young-onset Parkinson disease |
| PARK7 | Orphanet:90020 | Parkinson-dementia complex of Guam |
| VPS13C | Orphanet:2828 | Young-onset Parkinson disease |
| PRKN | Orphanet:2828 | Young-onset Parkinson disease |
| PODXL | Orphanet:2828 | Young-onset Parkinson disease |
| PODXL | Orphanet:391411 | Atypical juvenile parkinsonism |
| PINK1 | Orphanet:2828 | Young-onset Parkinson disease |
| DNAJC6 | Orphanet:2828 | Young-onset Parkinson disease |
| DNAJC6 | Orphanet:391411 | Atypical juvenile parkinsonism |
| SNCA | Orphanet:171695 | Parkinsonian-pyramidal syndrome |
| SNCA | Orphanet:2828 | Young-onset Parkinson disease |
| SNCA | Orphanet:411602 | Hereditary late-onset Parkinson disease |
| BSCL2 | Orphanet:100998 | Autosomal dominant spastic paraplegia type 17 |
| BSCL2 | Orphanet:139536 | Distal hereditary motor neuropathy type 5 |
| BSCL2 | Orphanet:363400 | Progressive encephalopathy-severe neurodegeneration-lipodystrophy syndrome |
| BSCL2 | Orphanet:696289 | Congenital generalized lipodystrophy type 2 |
| LRRK2 | Orphanet:2828 | Young-onset Parkinson disease |
| LRRK2 | Orphanet:411602 | Hereditary late-onset Parkinson disease |
| THAP1 | Orphanet:98806 | Primary dystonia, DYT6 type |
| 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 |
Cohort genes → proteins
14 cohort genes, 13 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 14 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| SYNJ1 | HGNC:11503 | ENSG00000159082 | O43426 | Synaptojanin-1 | gencc,clinvar |
| PARK7 | HGNC:16369 | ENSG00000116288 | Q99497 | Parkinson disease protein 7 | gencc,clinvar |
| VPS13C | HGNC:23594 | ENSG00000129003 | Q709C8 | Intermembrane lipid transfer protein VPS13C | gencc,clinvar |
| PRKN | HGNC:8607 | ENSG00000185345 | O60260 | E3 ubiquitin-protein ligase parkin | gencc,clinvar |
| PODXL | HGNC:9171 | ENSG00000128567 | O00592 | Podocalyxin | gencc,clinvar |
| PINK1 | HGNC:14581 | ENSG00000158828 | Q9BXM7 | Serine/threonine-protein kinase PINK1, mitochondrial | gencc |
| DNAJC6 | HGNC:15469 | ENSG00000116675 | O75061 | Auxilin | gencc |
| SNCA | HGNC:11138 | ENSG00000145335 | P37840 | Alpha-synuclein | clinvar |
| BSCL2 | HGNC:15832 | ENSG00000168000 | Q96G97 | Seipin | clinvar |
| LRRK2 | HGNC:18618 | ENSG00000188906 | Q5S007 | Leucine-rich repeat serine/threonine-protein kinase 2 | clinvar |
| PACRG | HGNC:19152 | ENSG00000112530 | Q96M98 | Parkin coregulated gene protein | clinvar |
| THAP1 | HGNC:20856 | ENSG00000131931 | Q9NVV9 | THAP domain-containing protein 1 | clinvar |
| CATIP-AS2 | HGNC:41079 | ENSG00000237281 | CATIP antisense RNA 2 | clinvar | |
| GBA1 | HGNC:4177 | ENSG00000177628 | P04062 | Lysosomal acid glucosylceramidase | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| SYNJ1 | Synaptojanin-1 | Phosphatase that acts on various phosphoinositides, including phosphatidylinositol 4-phosphate, phosphatidylinositol (4,5)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate. |
| 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. |
| VPS13C | Intermembrane lipid transfer protein VPS13C | Mediates the transfer of lipids between membranes at organelle contact sites. |
| PRKN | E3 ubiquitin-protein ligase parkin | Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. |
| PODXL | Podocalyxin | Involved in the regulation of both adhesion and cell morphology and cancer progression. |
| 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. |
| DNAJC6 | Auxilin | May act as a protein phosphatase and/or a lipid phosphatase. |
| SNCA | Alpha-synuclein | Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release. |
| BSCL2 | Seipin | Plays a crucial role in the formation of lipid droplets (LDs) which are storage organelles at the center of lipid and energy homeostasis. |
| 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. |
| PACRG | Parkin coregulated gene protein | Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating. |
| THAP1 | THAP domain-containing protein 1 | DNA-binding transcription regulator that regulates endothelial cell proliferation and G1/S cell-cycle progression. |
| 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. |
Protein-family classification
Druggable: 5 · Difficult: 2 · Unknown: 7 · Druggable fraction: 0.36
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 |
|---|---|---|---|
| Phosphatase | 1 | 6.0× | 0.386 |
| Kinase | 2 | 4.0× | 0.386 |
| Enzyme (other) | 2 | 1.7× | 0.547 |
| Transcription factor | 2 | 1.2× | 0.649 |
| Other/Unknown | 7 | 0.9× | 0.761 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| SYNJ1 | Other/Unknown | no | IPPc, RRM_dom, SAC_dom | |
| PARK7 | Enzyme (other) | yes | 3.5.1.124 | DJ-1/PfpI, DJ-1, Class_I_gatase-like |
| VPS13C | Other/Unknown | no | VPS13_VAB, VPS13, VPS13_N | |
| PRKN | Transcription factor | no | 2.3.2.27 | Ubiquitin-like_dom, IBR_dom, Parkin |
| PODXL | Other/Unknown | no | CD34/Podocalyxin, PODXL | |
| PINK1 | Kinase | yes | Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf | |
| DNAJC6 | Phosphatase | yes | Tyr_Pase_dom, DnaJ_domain, Tensin_C2-dom | |
| SNCA | Other/Unknown | no | Synuclein, Synuclein_alpha | |
| BSCL2 | Other/Unknown | no | Seipin | |
| LRRK2 | Kinase | yes | Prot_kinase_dom, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp | |
| PACRG | Other/Unknown | no | Parkin_co-regulated_protein | |
| THAP1 | Transcription factor | no | THAP_Znf, THAP1/10, THAP_Znf_sf | |
| CATIP-AS2 | Other/Unknown | no | ||
| GBA1 | Enzyme (other) | yes | 3.2.1.45 | Glyco_hydro_30, GH_hydrolase_sf, GH30_C |
Expression context
Cohort genes with no expression data: 0.
11 cohort genes are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 14 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| male germ line stem cell (sensu Vertebrata) in testis | 3 |
| Brodmann (1909) area 23 | 2 |
| pons | 2 |
| lateral nuclear group of thalamus | 1 |
| adult organism | 1 |
| deltoid | 1 |
| tibia | 1 |
| calcaneal tendon | 1 |
| epithelium of nasopharynx | 1 |
| upper leg skin | 1 |
| hindlimb stylopod muscle | 1 |
| sural nerve | 1 |
| germinal epithelium of ovary | 1 |
| metanephric glomerulus | 1 |
| renal glomerulus | 1 |
| gastrocnemius | 1 |
| gluteal muscle | 1 |
| tendon of biceps brachii | 1 |
| endothelial cell | 1 |
| substantia nigra pars compacta | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| SYNJ1 | 278 | ubiquitous | yes | Brodmann (1909) area 23, lateral nuclear group of thalamus, pons |
| PARK7 | 294 | ubiquitous | marker | adult organism, tibia, deltoid |
| VPS13C | 291 | ubiquitous | marker | calcaneal tendon, upper leg skin, epithelium of nasopharynx |
| PRKN | 174 | ubiquitous | marker | sural nerve, male germ line stem cell (sensu Vertebrata) in testis, hindlimb stylopod muscle |
| PODXL | 276 | ubiquitous | marker | renal glomerulus, metanephric glomerulus, germinal epithelium of ovary |
| PINK1 | 295 | ubiquitous | marker | tendon of biceps brachii, gastrocnemius, gluteal muscle |
| DNAJC6 | 227 | ubiquitous | marker | endothelial cell, Brodmann (1909) area 23, substantia nigra pars compacta |
| SNCA | 280 | ubiquitous | marker | trabecular bone tissue, orbitofrontal cortex, pons |
| BSCL2 | 149 | ubiquitous | marker | superior frontal gyrus, primary visual cortex, pituitary gland |
| LRRK2 | 220 | broad | marker | buccal mucosa cell, monocyte, leukocyte |
| PACRG | 197 | broad | marker | bronchial epithelial cell, right uterine tube, epithelium of bronchus |
| THAP1 | 260 | ubiquitous | yes | secondary oocyte, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis |
| CATIP-AS2 | 108 | yes | male germ line stem cell (sensu Vertebrata) in testis, bone marrow cell, tonsil | |
| GBA1 | 134 | ubiquitous | marker | stromal cell of endometrium, islet of Langerhans, placenta |
Protein interactions among cohort
Intra-cohort edges: 23.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| PRKN | 10,281 |
| LRRK2 | 7,628 |
| SNCA | 7,615 |
| PARK7 | 5,722 |
| PINK1 | 4,175 |
| DNAJC6 | 3,784 |
| PODXL | 2,741 |
| GBA1 | 2,568 |
| PACRG | 2,520 |
| SYNJ1 | 2,177 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| DNAJC6 | PINK1 | string_interaction |
| DNAJC6 | PRKN | string_interaction |
| DNAJC6 | SYNJ1 | string_interaction |
| DNAJC6 | VPS13C | string_interaction |
| GBA1 | LRRK2 | string_interaction |
| GBA1 | PRKN | string_interaction |
| GBA1 | SNCA | biogrid_interaction, string_interaction |
| GBA1 | VPS13C | string_interaction |
| LRRK2 | PARK7 | string_interaction |
| LRRK2 | PINK1 | string_interaction |
| LRRK2 | PRKN | string_interaction |
| LRRK2 | SNCA | string_interaction |
| LRRK2 | VPS13C | string_interaction |
| PACRG | PRKN | 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 | SNCA | string_interaction |
| PRKN | VPS13C | string_interaction |
| SYNJ1 | VPS13C | string_interaction |
Structural data
PDB: 10 · AlphaFold-only: 3 · No structure: 1
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| SNCA | P37840 | 232 |
| PARK7 | Q99497 | 88 |
| GBA1 | P04062 | 58 |
| LRRK2 | Q5S007 | 44 |
| PRKN | O60260 | 21 |
| PINK1 | Q9BXM7 | 6 |
| SYNJ1 | O43426 | 5 |
| PACRG | Q96M98 | 5 |
| THAP1 | Q9NVV9 | 3 |
| BSCL2 | Q96G97 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| DNAJC6 | O75061 | 64.29 |
| PODXL | O00592 | 53.66 |
| VPS13C | Q709C8 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 36. Enrichment computed across 14 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| PINK1-PRKN Mediated Mitophagy | 2 | 89.2× | 0.008 | PRKN, PINK1 |
| Aggrephagy | 2 | 62.1× | 0.008 | PARK7, PRKN |
| Amyloid fiber formation | 2 | 25.7× | 0.030 | PRKN, SNCA |
| Clathrin-mediated endocytosis | 2 | 21.3× | 0.033 | SYNJ1, DNAJC6 |
| PTK6 promotes HIF1A stabilization | 1 | 203.9× | 0.035 | LRRK2 |
| Josephin domain DUBs | 1 | 119.0× | 0.045 | PRKN |
| Synthesis of IP2, IP, and Ins in the cytosol | 1 | 95.2× | 0.045 | SYNJ1 |
| FOXO-mediated transcription of cell death genes | 1 | 89.2× | 0.045 | PINK1 |
| Signaling by PTK6 | 1 | 68.0× | 0.045 | LRRK2 |
| Signaling by Non-Receptor Tyrosine Kinases | 1 | 68.0× | 0.045 | LRRK2 |
| Chaperone Mediated Autophagy | 1 | 62.1× | 0.045 | PARK7 |
| Inositol phosphate metabolism | 1 | 59.5× | 0.045 | SYNJ1 |
| Regulation of necroptotic cell death | 1 | 54.9× | 0.045 | PRKN |
| Synthesis of IP3 and IP4 in the cytosol | 1 | 52.9× | 0.045 | SYNJ1 |
| Membrane Trafficking | 2 | 9.3× | 0.045 | SYNJ1, DNAJC6 |
| PI Metabolism | 1 | 44.6× | 0.046 | SYNJ1 |
| Lysosome Vesicle Biogenesis | 1 | 40.8× | 0.046 | DNAJC6 |
| Late endosomal microautophagy | 1 | 40.8× | 0.046 | PARK7 |
| Vesicle-mediated transport | 2 | 8.7× | 0.046 | SYNJ1, DNAJC6 |
| Association of TriC/CCT with target proteins during biosynthesis | 1 | 36.6× | 0.046 | GBA1 |
| Glycosphingolipid catabolism | 1 | 36.6× | 0.046 | GBA1 |
| trans-Golgi Network Vesicle Budding | 1 | 31.7× | 0.051 | DNAJC6 |
| SUMOylation of transcription cofactors | 1 | 30.4× | 0.051 | PARK7 |
| Synthesis of PIPs at the plasma membrane | 1 | 26.4× | 0.053 | SYNJ1 |
| Phospholipid metabolism | 1 | 25.0× | 0.053 | SYNJ1 |
| Golgi Associated Vesicle Biogenesis | 1 | 25.0× | 0.053 | DNAJC6 |
| Antimicrobial mechanism of IFN-stimulated genes | 1 | 24.6× | 0.053 | SNCA |
| PKR-mediated signaling | 1 | 17.6× | 0.071 | SNCA |
| Interferon Signaling | 1 | 15.0× | 0.080 | SNCA |
| Cytokine Signaling in Immune system | 1 | 5.1× | 0.216 | SNCA |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 13 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 transport | 3 | 1296.3× | 1e-07 | PRKN, PINK1, LRRK2 |
| cellular response to oxidative stress | 5 | 59.5× | 2e-06 | PARK7, PRKN, SNCA, PINK1, LRRK2 |
| mitochondrion organization | 5 | 58.4× | 2e-06 | PARK7, VPS13C, PRKN, PINK1, LRRK2 |
| dopamine uptake involved in synaptic transmission | 3 | 432.1× | 3e-06 | PARK7, PRKN, SNCA |
| positive regulation of type 2 mitophagy | 3 | 353.5× | 5e-06 | PRKN, PINK1, GBA1 |
| negative regulation of neuron apoptotic process | 5 | 42.6× | 5e-06 | PARK7, PRKN, SNCA, PINK1, GBA1 |
| negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway | 3 | 299.1× | 6e-06 | PARK7, PRKN, PINK1 |
| regulation of synaptic vesicle endocytosis | 3 | 204.7× | 2e-05 | PARK7, PRKN, LRRK2 |
| negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway | 3 | 194.4× | 2e-05 | PARK7, PRKN, LRRK2 |
| regulation of reactive oxygen species metabolic process | 3 | 169.1× | 3e-05 | PRKN, PINK1, LRRK2 |
| synaptic vesicle uncoating | 2 | 864.2× | 5e-05 | SYNJ1, DNAJC6 |
| mitochondrion to lysosome vesicle-mediated transport | 2 | 864.2× | 5e-05 | PRKN, PINK1 |
| positive regulation of mitochondrial electron transport, NADH to ubiquinone | 2 | 864.2× | 5e-05 | PARK7, PINK1 |
| negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway | 2 | 864.2× | 5e-05 | PARK7, PINK1 |
| cellular response to hydrogen sulfide | 2 | 864.2× | 5e-05 | PRKN, PINK1 |
| response to oxidative stress | 4 | 40.2× | 6e-05 | PARK7, PRKN, PINK1, LRRK2 |
| negative regulation of mitochondrial fission | 2 | 518.5× | 1e-04 | PRKN, PINK1 |
| negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide | 2 | 518.5× | 1e-04 | PARK7, PINK1 |
| regulation of locomotion | 2 | 432.1× | 2e-04 | SNCA, LRRK2 |
| mitophagy | 3 | 73.4× | 2e-04 | PRKN, PINK1, GBA1 |
| adult locomotory behavior | 3 | 69.5× | 2e-04 | PARK7, PRKN, SNCA |
| cellular response to manganese ion | 2 | 370.4× | 2e-04 | PRKN, LRRK2 |
| cellular response to dopamine | 2 | 370.4× | 2e-04 | PRKN, LRRK2 |
| obsolete regulation of protein targeting to mitochondrion | 2 | 324.1× | 3e-04 | PRKN, PINK1 |
| mitochondrion localization | 2 | 259.3× | 4e-04 | PRKN, LRRK2 |
| positive regulation of proteasomal ubiquitin-dependent protein catabolic process | 3 | 48.6× | 5e-04 | PRKN, LRRK2, GBA1 |
| cellular response to toxic substance | 2 | 216.1× | 6e-04 | PRKN, PINK1 |
| protein localization to mitochondrion | 2 | 199.4× | 6e-04 | PRKN, LRRK2 |
| negative regulation of excitatory postsynaptic potential | 2 | 199.4× | 6e-04 | PRKN, LRRK2 |
| regulation of cellular response to oxidative stress | 2 | 199.4× | 6e-04 | PRKN, PINK1 |
Therapeutics
Drug target analysis
Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 5 · Undrugged: 9
Druggability breadth: 6 of 14 evidence-associated genes (43%) 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 |
|---|---|
| SYNJ1 | PYRVINIUM |
| SNCA | ESTRADIOL |
| LRRK2 | PONATINIB |
| GBA1 | MIGALASTAT |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| LRRK2 | 42 | 4 |
| SNCA | 31 | 4 |
| GBA1 | 12 | 4 |
| SYNJ1 | 1 | 4 |
| PARK7 | 1 | 2 |
| VPS13C | 0 | 0 |
| PRKN | 0 | 0 |
| PODXL | 0 | 0 |
| PINK1 | 0 | 0 |
| DNAJC6 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| PYRVINIUM | 4 | SYNJ1 |
| ESTRADIOL | 4 | SNCA |
| ESTRONE | 4 | SNCA |
| TETRACYCLINE | 4 | SNCA |
| PHYTONADIONE | 4 | SNCA |
| CEFTRIAXONE | 4 | SNCA |
| FLORBETAPIR | 4 | SNCA |
| ESTRIOL | 4 | SNCA |
| RIFAMPIN | 4 | SNCA |
| TRETINOIN | 4 | SNCA |
| TESTOSTERONE | 4 | SNCA |
| BRILLIANT BLUE G | 4 | SNCA |
| BROMOCRIPTINE | 4 | SNCA |
| PERGOLIDE | 4 | SNCA |
| DOPAMINE | 4 | SNCA |
| MENADIONE | 4 | SNCA |
| GENTIAN VIOLET | 4 | GBA1, SNCA |
| SELEGILINE | 4 | SNCA |
| RETINOL | 4 | SNCA |
| PONATINIB | 4 | LRRK2 |
| FEDRATINIB | 4 | LRRK2 |
| AXITINIB | 4 | LRRK2 |
| RUXOLITINIB | 4 | LRRK2 |
| PALBOCICLIB | 4 | LRRK2 |
| ENTRECTINIB | 4 | LRRK2 |
| TOFACITINIB CITRATE | 4 | LRRK2 |
| TOFACITINIB | 4 | LRRK2 |
| VANDETANIB | 4 | LRRK2 |
| BOSUTINIB | 4 | LRRK2 |
| BRIGATINIB | 4 | LRRK2 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 3.
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 |
| PARK7 | 62 | Binding:62 |
| PINK1 | 24 | Binding:24 |
| SYNJ1 | 2 | Binding:2 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| PARK7 | 3.5.1.124, 4.2.1.130 | protein deglycase, D-lactate dehydratase |
| PRKN | 2.3.2.27, 2.3.2.31 | RING-type E3 ubiquitin transferase, RBR-type E3 ubiquitin transferase |
| GBA1 | 3.2.1.45 | glucosylceramidase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| SNCA | 459 |
| LRRK2 | 809 |
| GBA1 | 436 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 13; 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) |
|---|---|---|
| PYRVINIUM | 4 | SYNJ1 |
| ESTRADIOL | 4 | SNCA |
| ESTRONE | 4 | SNCA |
| TETRACYCLINE | 4 | SNCA |
| PHYTONADIONE | 4 | SNCA |
| CEFTRIAXONE | 4 | SNCA |
| FLORBETAPIR | 4 | SNCA |
| ESTRIOL | 4 | SNCA |
| RIFAMPIN | 4 | SNCA |
| TRETINOIN | 4 | SNCA |
| TESTOSTERONE | 4 | SNCA |
| BRILLIANT BLUE G | 4 | SNCA |
| BROMOCRIPTINE | 4 | SNCA |
| PERGOLIDE | 4 | SNCA |
| DOPAMINE | 4 | SNCA |
| MENADIONE | 4 | SNCA |
| GENTIAN VIOLET | 4 | GBA1, SNCA |
| SELEGILINE | 4 | SNCA |
| RETINOL | 4 | SNCA |
| PONATINIB | 4 | LRRK2 |
| FEDRATINIB | 4 | LRRK2 |
| AXITINIB | 4 | LRRK2 |
| RUXOLITINIB | 4 | LRRK2 |
| PALBOCICLIB | 4 | LRRK2 |
| ENTRECTINIB | 4 | LRRK2 |
| TOFACITINIB CITRATE | 4 | LRRK2 |
| TOFACITINIB | 4 | LRRK2 |
| VANDETANIB | 4 | LRRK2 |
| BOSUTINIB | 4 | LRRK2 |
| BRIGATINIB | 4 | LRRK2 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 4 | SYNJ1, SNCA, LRRK2, GBA1 |
| B | Phased (≥1) drug, not yet approved | 1 | PARK7 |
| C | Druggable family + PDB, no drug | 1 | PINK1 |
| D | Druggable family + AlphaFold only, no drug | 1 | DNAJC6 |
| E | Difficult family or no structure, no drug | 7 | VPS13C, PRKN, PODXL, BSCL2, PACRG, THAP1, CATIP-AS2 |
Undrugged target profiles
9 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 |
| PINK1 | 24 | PARK7 |
| DNAJC6 | 0 | SYNJ1 |
| VPS13C | 0 | — |
| PODXL | 0 | — |
| BSCL2 | 0 | — |
| PACRG | 0 | — |
| THAP1 | 0 | — |
| CATIP-AS2 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 3.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 2 |
| PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT07267065 | PHASE1 | NOT_YET_RECRUITING | AAV2-hAADC for Parkinson’s Disease (PDCS-01) |
| NCT04033393 | Not specified | UNKNOWN | Dual-task Performance in Young-onset PD |
| NCT04722198 | Not specified | UNKNOWN | Effects of Lactobacillus Plantarum PS128 on Symptoms of Early-onset Parkinson’s Disease: a Pilot Study |