Parkinsonian disorder

disease
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Summary

Parkinsonian disorder (MONDO:0021095) is a disease (an umbrella term covering 21 Mondo subtypes) with 21 cohort genes and 33 clinical trials. Top therapeutic interventions include preladenant, mavoglurant, and isoxaflutole.

At a glance

  • Umbrella term: 21 Mondo subtypes
  • Cohort genes: 21
  • ClinVar variants: 31
  • Clinical trials: 33

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameparkinsonian disorder
Mondo IDMONDO:0021095
MeSHD020734
DOIDDOID:0080855
UMLSC0242422
MedGen66079
Is cancer (heuristic)no

Data availability: 31 ClinVar variants.

Disease family

An umbrella term covering 21 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disordercentral nervous system disorderbrain disorderbasal ganglia disorderparkinsonian disorder

Related subtypes (3): basal ganglia cerebrovascular disorder, bilateral striopallidodentate calcinosis, biotin-responsive basal ganglia disease

Subtypes (21): postencephalitic Parkinson disease, 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

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

31 retrieved; paginated sample, class counts are floors:

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

ClinVarVariant (HGVS)GeneClassificationReview
1687738NM_002087.4(GRN):c.52A>G (p.Thr18Ala)GRNPathogenicno assertion criteria provided
375734NM_001013663.2(PTRHD1):c.155G>A (p.Cys52Tyr)LOC129933272Pathogeniccriteria provided, single submitter
374038NM_001288705.3(CSF1R):c.647G>A (p.Arg216Gln)CSF1RConflicting classifications of pathogenicitycriteria provided, conflicting classifications
453052NM_004082.5(DCTN1):c.673C>T (p.Arg225Trp)DCTN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
1680932NM_002047.4(GARS1):c.1268C>T (p.Ser423Phe)GARS1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
199044NM_000157.4(GBA1):c.1093G>A (p.Glu365Lys)GBA1Conflicting classifications of pathogenicity; risk factorcriteria provided, conflicting classifications
4288NM_000157.4(GBA1):c.1448T>C (p.Leu483Pro)GBA1Conflicting classifications of pathogenicity; risk factorcriteria provided, conflicting classifications
18398NM_181840.1(KCNK18):c.414_415del (p.Phe139fs)KCNK18Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
3571549NM_198578.4(LRRK2):c.2300G>A (p.Arg767His)LRRK2Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
127974NM_005591.4(MRE11):c.1727G>A (p.Arg576Gln)MRE11Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
198195NM_006516.4(SLC2A1):c.790C>T (p.Arg264Cys)SLC2A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
21481NM_007375.4(TARDBP):c.269C>T (p.Ala90Val)TARDBPConflicting classifications of pathogenicitycriteria provided, conflicting classifications
375707NM_001199107.2(TBC1D24):c.1078C>T (p.Arg360Cys)TBC1D24Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
375708NM_001199107.2(TBC1D24):c.404C>T (p.Pro135Leu)TBC1D24Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
373900NM_183357.3(ADCY5):c.649del (p.Arg217fs)ADCY5Uncertain significanceno assertion criteria provided
4075748NM_003458.4(BSN):c.9862G>A (p.Glu3288Lys)BSNUncertain significancecriteria provided, single submitter
1037550NM_014043.4(CHMP2B):c.613C>T (p.Arg205Trp)CHMP2BUncertain significancecriteria provided, multiple submitters, no conflicts
493050NM_000157.4(GBA1):c.1279G>A (p.Glu427Lys)GBA1Uncertain significancecriteria provided, multiple submitters, no conflicts
373908NM_198578.4(LRRK2):c.5647T>C (p.Phe1883Leu)LRRK2Uncertain significancecriteria provided, single submitter
2502848NM_001377265.1(MAPT):c.416A>G (p.Lys139Arg)MAPTUncertain significanceno assertion criteria provided
481777NM_005591.4(MRE11):c.229G>A (p.Glu77Lys)MRE11Uncertain significancecriteria provided, multiple submitters, no conflicts
374080NC_012920.1(MT-ND6):m.14598T>CMT-ND6Uncertain significancereviewed by expert panel
523454NM_002609.4(PDGFRB):c.3241G>A (p.Glu1081Lys)PDGFRBUncertain significancecriteria provided, single submitter
2150544NM_003560.4(PLA2G6):c.1028C>T (p.Ala343Val)PLA2G6Uncertain significancecriteria provided, multiple submitters, no conflicts
1434096NM_032242.4(PLXNA1):c.3368C>T (p.Pro1123Leu)PLXNA1Uncertain significancecriteria provided, multiple submitters, no conflicts
3015387NM_198994.3(TGM6):c.1076C>T (p.Pro359Leu)TGM6Uncertain significancecriteria provided, multiple submitters, no conflicts
523569NM_198994.3(TGM6):c.76C>T (p.Pro26Ser)TGM6Uncertain significancecriteria provided, single submitter
374122NM_003332.4(TYROBP):c.94G>A (p.Asp32Asn)TYROBPUncertain significancecriteria provided, multiple submitters, no conflicts
39221NM_198578.4(LRRK2):c.6241A>G (p.Asn2081Asp)LRRK2Benign/Likely benigncriteria provided, multiple submitters, no conflicts
159725NM_003560.4(PLA2G6):c.1027G>A (p.Ala343Thr)PLA2G6Benign/Likely benigncriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 71 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SLC2A1Orphanet:168577Hereditary cryohydrocytosis with reduced stomatin
SLC2A1Orphanet:1942Epilepsy with myoclonic-atonic seizures
SLC2A1Orphanet:2131Alternating hemiplegia of childhood
SLC2A1Orphanet:53583Paroxysmal dystonic choreathetosis with episodic ataxia and spasticity
SLC2A1Orphanet:71277Classic glucose transporter type 1 deficiency syndrome
SLC2A1Orphanet:86911Epilepsy with myoclonic absences
SLC2A1Orphanet:98811Paroxysmal exertion-induced dyskinesia
TARDBPOrphanet:275872Frontotemporal dementia with motor neuron disease
TARDBPOrphanet:700154TARDBP-related predominantly upper-limb distal myopathy
TARDBPOrphanet:803Amyotrophic lateral sclerosis
TYROBPOrphanet:2770Nasu-Hakola disease
TGM6Orphanet:276193Spinocerebellar ataxia type 35
TGM6Orphanet:319465Inherited acute myeloid leukemia
LRRK2Orphanet:2828Young-onset Parkinson disease
LRRK2Orphanet:411602Hereditary late-onset Parkinson disease
ADCY5Orphanet:1429Benign hereditary chorea
ADCY5Orphanet:324588Familial dyskinesia and facial myokymia
CSF1ROrphanet:313808Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia
CSF1ROrphanet:556985Early-onset calcifying leukoencephalopathy-skeletal dysplasia
CHMP2BOrphanet:100069Semantic dementia
CHMP2BOrphanet:100070Progressive non-fluent aphasia
CHMP2BOrphanet:275864Behavioral variant of frontotemporal dementia
CHMP2BOrphanet:803Amyotrophic lateral sclerosis
DCTN1Orphanet:139589Distal hereditary motor neuropathy type 7
DCTN1Orphanet:178509Perry syndrome
DCTN1Orphanet:803Amyotrophic lateral sclerosis
TBC1D24Orphanet:163727Rolandic epilepsy-paroxysmal exercise-induced dystonia-writer’s cramp syndrome
TBC1D24Orphanet:293181Epilepsy of infancy with migrating focal seizures
TBC1D24Orphanet:352582Familial infantile myoclonic epilepsy
TBC1D24Orphanet:352587Focal epilepsy-intellectual disability-cerebro-cerebellar malformation
TBC1D24Orphanet:352596Progressive myoclonic epilepsy with dystonia
TBC1D24Orphanet:79500DOORS syndrome
TBC1D24Orphanet:90635Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
TBC1D24Orphanet:90636Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
GARS1Orphanet:139536Distal hereditary motor neuropathy type 5
GARS1Orphanet:99938Autosomal dominant Charcot-Marie-Tooth disease type 2D
GBA1Orphanet:2072Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome
GBA1Orphanet:411602Hereditary late-onset Parkinson disease
GBA1Orphanet:77259Gaucher disease type 1
GBA1Orphanet:77260Gaucher disease type 2
GBA1Orphanet:77261Gaucher disease type 3
GBA1Orphanet:85212Fetal Gaucher disease
GRNOrphanet:100069Semantic dementia
GRNOrphanet:100070Progressive non-fluent aphasia
GRNOrphanet:275864Behavioral variant of frontotemporal dementia
GRNOrphanet:314629CLN11 disease
MAPTOrphanet:100069Semantic dementia
MAPTOrphanet:100070Progressive non-fluent aphasia
MAPTOrphanet:240071Classic progressive supranuclear palsy syndrome
MAPTOrphanet:240085Progressive supranuclear palsy-predominant parkinsonism syndrome

Cohort genes → proteins

21 cohort genes, 21 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence21

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SLC2A1HGNC:11005ENSG00000117394P11166Solute carrier family 2, facilitated glucose transporter member 1clinvar
BSNHGNC:1117ENSG00000164061Q9UPA5Protein bassoonclinvar
TARDBPHGNC:11571ENSG00000120948Q13148TAR DNA-binding protein 43clinvar
TYROBPHGNC:12449ENSG00000011600O43914TYRO protein tyrosine kinase-binding proteinclinvar
TGM6HGNC:16255ENSG00000166948O95932Protein-glutamine gamma-glutamyltransferase 6clinvar
LRRK2HGNC:18618ENSG00000188906Q5S007Leucine-rich repeat serine/threonine-protein kinase 2clinvar
KCNK18HGNC:19439ENSG00000186795Q7Z418Potassium channel subfamily K member 18clinvar
ADCY5HGNC:236ENSG00000173175O95622Adenylate cyclase type 5clinvar
CSF1RHGNC:2433ENSG00000182578P07333Macrophage colony-stimulating factor 1 receptorclinvar
CHMP2BHGNC:24537ENSG00000083937Q9UQN3Charged multivesicular body protein 2bclinvar
DCTN1HGNC:2711ENSG00000204843Q14203Dynactin subunit 1clinvar
TBC1D24HGNC:29203ENSG00000162065Q9ULP9TBC1 domain family member 24clinvar
GARS1HGNC:4162ENSG00000106105P41250Glycine–tRNA ligaseclinvar
GBA1HGNC:4177ENSG00000177628P04062Lysosomal acid glucosylceramidaseclinvar
GRNHGNC:4601ENSG00000030582P28799Progranulinclinvar
MAPTHGNC:6893ENSG00000186868P10636Microtubule-associated protein tauclinvar
MRE11HGNC:7230ENSG00000020922P49959Double-strand break repair protein MRE11clinvar
MT-ND6HGNC:7462ENSG00000198695P03923NADH-ubiquinone oxidoreductase chain 6clinvar
PDGFRBHGNC:8804ENSG00000113721P09619Platelet-derived growth factor receptor betaclinvar
PLA2G6HGNC:9039ENSG00000184381O6073385/88 kDa calcium-independent phospholipase A2clinvar
PLXNA1HGNC:9099ENSG00000114554Q9UIW2Plexin-A1clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SLC2A1Solute carrier family 2, facilitated glucose transporter member 1Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake.
BSNProtein bassoonScaffold protein of the presynaptic cytomatrix at the active zone (CAZ) which is the place in the synapse where neurotransmitter is released.
TARDBPTAR DNA-binding protein 43RNA-binding protein that is involved in various steps of RNA biogenesis and processing.
TYROBPTYRO protein tyrosine kinase-binding proteinAdapter protein which non-covalently associates with activating receptors found on the surface of a variety of immune cells to mediate signaling and cell activation following ligand binding by the receptors.
TGM6Protein-glutamine gamma-glutamyltransferase 6Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins.
LRRK2Leucine-rich repeat serine/threonine-protein kinase 2Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking.
KCNK18Potassium channel subfamily K member 18K(+) channel that conducts outward and inward rectifying currents at depolarized and hyperpolarized membrane potentials, respectively.
ADCY5Adenylate cyclase type 5Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.
CSF1RMacrophage colony-stimulating factor 1 receptorTyrosine-protein kinase that acts as a cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes…
CHMP2BCharged multivesicular body protein 2bProbable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs.
DCTN1Dynactin subunit 1Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules.
TBC1D24TBC1 domain family member 24May act as a GTPase-activating protein for Rab family protein(s).
GARS1Glycine–tRNA ligaseCatalyzes the ATP-dependent ligation of glycine to the 3’-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (Gly-AMP).
GBA1Lysosomal acid glucosylceramidaseGlucosylceramidase 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.
GRNProgranulinSecreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation.
MAPTMicrotubule-associated protein tauPromotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity.
MRE11Double-strand break repair protein MRE11Core component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.
MT-ND6NADH-ubiquinone oxidoreductase chain 6Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor.
PDGFRBPlatelet-derived growth factor receptor betaTyrosine-protein kinase that acts as a cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, surviv…
PLA2G685/88 kDa calcium-independent phospholipase A2Calcium-independent phospholipase involved in phospholipid remodeling with implications in cellular membrane homeostasis, mitochondrial integrity and signal transduction.
PLXNA1Plexin-A1Coreceptor for SEMA3A, SEMA3C, SEMA3F and SEMA6D.

Protein-family classification

Druggable: 10 · Difficult: 2 · Unknown: 9 · Druggable fraction: 0.48

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.

FamilyGenesFoldFDR
Kinase34.0×0.307
Ion channel15.3×0.405
Transporter13.7×0.405
Antibody/Immunoglobulin22.8×0.405
Enzyme (other)31.7×0.405
Scaffold/PPI10.8×0.934
Other/Unknown90.8×0.934
Transcription factor10.4×0.934

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SLC2A1TransporteryesGlu_transpt_1, Sugar/inositol_transpt, MFS_sugar_transport-like
BSNTranscription factornoZnf_piccolo, Znf_FYVE_PHD, Znf_RING/FYVE/PHD
TARDBPOther/UnknownnoRRM_dom, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf
TYROBPOther/UnknownnoTyrobp
TGM6Antibody/Immunoglobulinyes2.3.2.13Transglutaminase_N, Transglutaminase-like, Transglutaminase_C
LRRK2KinaseyesProt_kinase_dom, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
KCNK18Ion channelyes2pore_dom_K_chnl, K_chnl_dom
ADCY5Enzyme (other)yes4.6.1.1A/G_cyclase, Adcy_conserved_dom, A/G_cyclase_CS
CSF1RKinaseyes2.7.10.1Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
CHMP2BOther/UnknownnoSnf7_fam
DCTN1Other/UnknownnoCAP-Gly_domain, Dynactin, CAP-Gly_dom_sf
TBC1D24Other/UnknownnoRab-GAP-TBC_dom, TLDc_dom, Rab-GAP_TBC_sf
GARS1Enzyme (other)yes6.1.1.14WHEP-TRS_dom, aa-tRNA-synt_IIb, tRNA-synt_gly
GBA1Enzyme (other)yes3.2.1.45Glyco_hydro_30, GH_hydrolase_sf, GH30_C
GRNOther/UnknownnoGranulin, Granulin_sf, Granulin_fam
MAPTOther/UnknownnoMAP_tubulin-bd_rpt, Tau, MAP2/MAP4/Tau
MRE11Other/UnknownnoMre11, Calcineurin-like_PHP, Mre11_DNA-bd
MT-ND6Other/UnknownnoNADH_UbQ/plastoQ_OxRdtase_su6, ComplexI_Subunit6
PDGFRBKinaseyes2.7.10.1Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
PLA2G6Scaffold/PPIno3.1.1.4Ankyrin_rpt, PNPLA_dom, Acyl_Trfase/lysoPLipase
PLXNA1Antibody/ImmunoglobulinyesSemap_dom, Plexin_repeat, IPT_dom

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)1
broad (>20)20
unknown0

Top tissues across cohort

TissueCohort genes
monocyte4
stromal cell of endometrium4
middle temporal gyrus3
secondary oocyte3
leukocyte3
colonic epithelium2
granulocyte2
prefrontal cortex2
cortical plate2
right uterine tube2
skin of abdomen1
sural nerve1
tibial nerve1
frontal pole1
paraflocculus1
ganglionic eminence1
ventricular zone1
mononuclear cell1
bone marrow cell1
kidney epithelium1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SLC2A1250ubiquitousmarkertibial nerve, sural nerve, skin of abdomen
BSN156broadmarkerfrontal pole, paraflocculus, middle temporal gyrus
TARDBP301ubiquitousmarkersecondary oocyte, ventricular zone, ganglionic eminence
TYROBP271broadmarkermonocyte, mononuclear cell, leukocyte
TGM639tissue_specificmarkercolonic epithelium, bone marrow cell, kidney epithelium
LRRK2220broadmarkerbuccal mucosa cell, monocyte, leukocyte
KCNK1811yesnucleus accumbens, caudate nucleus, colonic epithelium
ADCY5193broadmarkerapex of heart, lower esophagus muscularis layer, lower esophagus
CSF1R245broadmarkergranulocyte, monocyte, leukocyte
CHMP2B300ubiquitousmarkermedial globus pallidus, amniotic fluid, mucosa of sigmoid colon
DCTN1275ubiquitousmarkerright frontal lobe, prefrontal cortex, right hemisphere of cerebellum
TBC1D24227ubiquitousmarkerparotid gland, Brodmann (1909) area 23, middle temporal gyrus
GARS1293ubiquitousmarkersecondary oocyte, cartilage tissue, lateral nuclear group of thalamus
GBA1134ubiquitousmarkerstromal cell of endometrium, islet of Langerhans, placenta
GRN301ubiquitousmarkermonocyte, granulocyte, stromal cell of endometrium
MAPT141broadmarkercortical plate, superior frontal gyrus, prefrontal cortex
MRE11254ubiquitousmarkercalcaneal tendon, oocyte, secondary oocyte
MT-ND6134ubiquitousmarkermucosa of stomach, left uterine tube, right uterine tube
PDGFRB270ubiquitousmarkerstromal cell of endometrium, right coronary artery, endocervix
PLA2G6232ubiquitousmarkerright uterine tube, right lobe of thyroid gland, left lobe of thyroid gland
PLXNA1279tissue_specificmarkermiddle temporal gyrus, cortical plate, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 9.

Hub genes (top 10 by interactor count)

SymbolInteractor count
LRRK27,628
MAPT7,289
TARDBP7,245
SLC2A15,711
PDGFRB5,111
CSF1R4,392
MRE113,932
DCTN13,654
TYROBP2,723
GBA12,568

Intra-cohort edges

ABSources
CHMP2BTARDBPstring_interaction
CSF1RTYROBPstring_interaction
DCTN1MAPTbiogrid_interaction
GBA1LRRK2string_interaction
GBA1PLA2G6string_interaction
LRRK2MAPTstring_interaction
MAPTTARDBPstring_interaction
MAPTTBC1D24intact
PLXNA1TYROBPstring_interaction

Structural data

PDB: 16 · AlphaFold-only: 5 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
MAPTP10636293
GBA1P0406258
TARDBPQ1314844
LRRK2Q5S00744
CSF1RP0733326
GARS1P4125014
DCTN1Q1420313
MRE11P4995910
GRNP287998
PDGFRBP096198
SLC2A1P111665
TYROBPO439145
MT-ND6P039235
PLXNA1Q9UIW23
ADCY5O956222
CHMP2BQ9UQN31

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
TGM6O9593290.95
PLA2G6O6073386.16
TBC1D24Q9ULP984.46
KCNK18Q7Z41870.04
BSNQ9UPA5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 177. Enrichment computed across 21 evidence-associated genes (19 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 19 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Other semaphorin interactions263.3×0.078TYROBP, PLXNA1
TWIK-related spinal cord K+ channel (TRESK)1601.0×0.098KCNK18
Defective SLC2A1 causes GLUT1 deficiency syndrome 1 (GLUT1DS1)1601.0×0.098SLC2A1
Lactose synthesis1200.3×0.130SLC2A1
Acyl chain remodeling of CL1100.2×0.130PLA2G6
Sensing of DNA Double Strand Breaks1100.2×0.130MRE11
PTK6 promotes HIF1A stabilization185.9×0.130LRRK2
Vitamin C (ascorbate) metabolism175.1×0.130SLC2A1
Adenylate cyclase activating pathway160.1×0.130ADCY5
STING mediated induction of host immune responses154.6×0.130MRE11
Tandem pore domain potassium channels150.1×0.130KCNK18
Caspase-mediated cleavage of cytoskeletal proteins150.1×0.130MAPT
Defective homologous recombination repair (HRR) due to PALB2 loss of function150.1×0.130MRE11
HDR through MMEJ (alt-NHEJ)146.2×0.130MRE11
Translation of Replicase and Assembly of the Replication Transcription Complex146.2×0.130CHMP2B
IRF3-mediated induction of type I IFN142.9×0.130MRE11
Diseases of DNA Double-Strand Break Repair142.9×0.130MRE11
Translation of Replicase and Assembly of the Replication Transcription Complex142.9×0.130CHMP2B
Defective homologous recombination repair (HRR) due to BRCA2 loss of function142.9×0.130MRE11
Adenylate cyclase inhibitory pathway140.1×0.130ADCY5
SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion140.1×0.130PLXNA1
PKA activation in glucagon signalling135.4×0.130ADCY5
Signal regulatory protein family interactions135.4×0.130TYROBP
Sema3A PAK dependent Axon repulsion135.4×0.130PLXNA1
PKA activation133.4×0.130ADCY5
CRMPs in Sema3A signaling133.4×0.130PLXNA1
Resolution of D-Loop Structures133.4×0.130MRE11
Phase 4 - resting membrane potential131.6×0.130KCNK18
Activation of GABAB receptors131.6×0.130ADCY5
PKA-mediated phosphorylation of CREB130.1×0.130ADCY5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 20 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
microglial cell activation involved in immune response2337.0×0.003TYROBP, GRN
intracellular distribution of mitochondria2240.7×0.003LRRK2, MAPT
T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell2210.7×0.003TYROBP, PLXNA1
regulation of mitochondrial fission2210.7×0.003LRRK2, MAPT
lysosome organization346.0×0.003LRRK2, GBA1, GRN
microglial cell proliferation2187.2×0.004CSF1R, GBA1
maintenance of synapse structure2153.2×0.005DCTN1, GRN
lysosomal protein catabolic process2105.3×0.009GBA1, GRN
locomotory exploration behavior299.1×0.009LRRK2, GRN
positive regulation of superoxide anion generation288.7×0.010TYROBP, MAPT
olfactory bulb development276.6×0.013LRRK2, CSF1R
protein autophosphorylation321.8×0.013LRRK2, CSF1R, PDGFRB
positive regulation of microtubule polymerization267.4×0.014DCTN1, MAPT
myeloid leukocyte activation1842.6×0.016TYROBP
regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation1842.6×0.016KCNK18
cell migration involved in coronary angiogenesis1842.6×0.016PDGFRB
nuclear inner membrane organization1842.6×0.016TARDBP
metanephric glomerular mesangial cell proliferation involved in metanephros development1842.6×0.016PDGFRB
plus-end-directed organelle transport along microtubule1842.6×0.016MAPT
mitochondrial double-strand break repair via homologous recombination1842.6×0.016MRE11
positive regulation of neuronal action potential1842.6×0.016GBA1
cellular response to curcumin1842.6×0.016LRRK2
Wnt signalosome assembly1842.6×0.016LRRK2
positive regulation of aspartic-type peptidase activity1842.6×0.016GRN
amyloid fibril formation260.2×0.016TARDBP, MAPT
motor behavior256.2×0.016DCTN1, GBA1
neuromuscular junction development252.7×0.016LRRK2, DCTN1
neuromuscular process252.7×0.016DCTN1, GBA1
axon development245.5×0.016TBC1D24, MAPT
neuron cellular homeostasis245.5×0.016CHMP2B, DCTN1

Therapeutics

Drug target analysis

Approved (phase 4): 7 · Phase ≥3: 8 · Phased (≥1): 9 · Undrugged: 12

Druggability breadth: 16 of 21 evidence-associated genes (76%) 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.

SymbolExample approved molecule
SLC2A1EMETINE
TARDBPMITOXANTRONE
LRRK2PONATINIB
CSF1RPONATINIB
GBA1MIGALASTAT
MAPTBEPRIDIL
PDGFRBPONATINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
MAPT4494
PDGFRB1024
CSF1R794
LRRK2424
GBA1124
SLC2A174
TARDBP14
GARS113
PLA2G612
BSN00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
EMETINE4SLC2A1
MITOXANTRONE4TARDBP
PONATINIB4CSF1R, LRRK2, PDGFRB
FEDRATINIB4CSF1R, LRRK2, PDGFRB
AXITINIB4CSF1R, LRRK2, PDGFRB
RUXOLITINIB4LRRK2
PALBOCICLIB4LRRK2
ENTRECTINIB4CSF1R, LRRK2
TOFACITINIB CITRATE4LRRK2
TOFACITINIB4LRRK2
VANDETANIB4CSF1R, LRRK2, PDGFRB
BOSUTINIB4CSF1R, LRRK2, PDGFRB
BRIGATINIB4CSF1R, LRRK2
NINTEDANIB4CSF1R, LRRK2, PDGFRB
SUNITINIB4CSF1R, LRRK2, PDGFRB
ERLOTINIB4LRRK2, PDGFRB
MIDOSTAURIN4CSF1R, LRRK2, PDGFRB
SORAFENIB4CSF1R, PDGFRB
DASATINIB ANHYDROUS4CSF1R
SUNITINIB MALATE4CSF1R, PDGFRB
NERATINIB4CSF1R
IBRUTINIB4CSF1R
PACRITINIB4CSF1R, PDGFRB
NILOTINIB4CSF1R, PDGFRB
FILGOTINIB4CSF1R
PEXIDARTINIB4CSF1R, PDGFRB
PAZOPANIB4CSF1R, PDGFRB
DASATINIB4CSF1R, PDGFRB
QUIZARTINIB4CSF1R, PDGFRB
CRIZOTINIB4CSF1R

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

SymbolAssaysType breakdown
PDGFRB1,237Binding:1213, Functional:16, ADMET:8
CSF1R897Binding:879, Functional:17, ADMET:1
LRRK2809Binding:799, ADMET:7, Functional:3
GBA1436Binding:403, Functional:33
MAPT184Binding:180, Functional:4
SLC2A1158Binding:130, ADMET:24, Functional:4
PLA2G647Binding:47
ADCY543Binding:33, Functional:9, ADMET:1
MRE1136Binding:36
KCNK189Binding:7, ADMET:2
TARDBP8Binding:7, Functional:1
TGM68Binding:8
GARS18Binding:8
MT-ND64Binding:4
GRN2Binding:2
DCTN11Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
TGM62.3.2.13protein-glutamine gamma-glutamyltransferase
ADCY54.6.1.1adenylate cyclase
CSF1R2.7.10.1receptor protein-tyrosine kinase
GARS16.1.1.14glycine-tRNA ligase
GBA13.2.1.45glucosylceramidase
PDGFRB2.7.10.1receptor protein-tyrosine kinase
PLA2G63.1.1.4phospholipase A2

Cohort genes with high screening signal

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

SymbolChEMBL assays
SLC2A1158
LRRK2809
CSF1R897
GBA1436
MAPT184
PDGFRB1,237

Pharmacogenomics

Cohort genes with a PharmGKB record: 20; 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.

CompoundMax phaseCohort target (bioactivity)
EMETINE4SLC2A1
MITOXANTRONE4TARDBP
PONATINIB4CSF1R, LRRK2, PDGFRB
FEDRATINIB4CSF1R, LRRK2, PDGFRB
AXITINIB4CSF1R, LRRK2, PDGFRB
RUXOLITINIB4LRRK2
PALBOCICLIB4LRRK2
ENTRECTINIB4CSF1R, LRRK2
TOFACITINIB CITRATE4LRRK2
TOFACITINIB4LRRK2
VANDETANIB4CSF1R, LRRK2, PDGFRB
BOSUTINIB4CSF1R, LRRK2, PDGFRB
BRIGATINIB4CSF1R, LRRK2
NINTEDANIB4CSF1R, LRRK2, PDGFRB
SUNITINIB4CSF1R, LRRK2, PDGFRB
ERLOTINIB4LRRK2, PDGFRB
MIDOSTAURIN4CSF1R, LRRK2, PDGFRB
SORAFENIB4CSF1R, PDGFRB
DASATINIB ANHYDROUS4CSF1R
SUNITINIB MALATE4CSF1R, PDGFRB
NERATINIB4CSF1R
IBRUTINIB4CSF1R
PACRITINIB4CSF1R, PDGFRB
NILOTINIB4CSF1R, PDGFRB
FILGOTINIB4CSF1R
PEXIDARTINIB4CSF1R, PDGFRB
PAZOPANIB4CSF1R, PDGFRB
DASATINIB4CSF1R, PDGFRB
QUIZARTINIB4CSF1R, PDGFRB
CRIZOTINIB4CSF1R

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)7SLC2A1, TARDBP, LRRK2, CSF1R, GBA1, MAPT, PDGFRB
BPhased (≥1) drug, not yet approved2GARS1, PLA2G6
CDruggable family + PDB, no drug2ADCY5, PLXNA1
DDruggable family + AlphaFold only, no drug2TGM6, KCNK18
EDifficult family or no structure, no drug8BSN, TYROBP, CHMP2B, DCTN1, TBC1D24, GRN, MRE11, MT-ND6

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
BSN0
TYROBP0
TGM68
KCNK189
ADCY543
CHMP2B0
DCTN11
TBC1D240
GRN2
MRE1136
MT-ND64
PLXNA10

Clinical trials & evidence

Clinical trials

Clinical trials: 33.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified25
PHASE25
PHASE42
PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT01662414PHASE4COMPLETEDEffect of Undenatured Cysteine-Rich Whey Protein Isolate (HMS 90®) in Patients With Parkinson’s Disease
NCT04871464PHASE4UNKNOWNRole and Mechanism of Probiotics in Improving Motor Symptoms in Mild to Moderate Parkinson’s Disease
NCT00686699PHASE2TERMINATEDStudy of Preladenant for the Treatment of Antipsychotic Induced Movement Disorders in Participants With Schizophrenia (Study P04628)
NCT01385592PHASE2COMPLETEDEvaluation of the Efficacy and Safety of AFQ056 in Parkinson’s Patients With L-dopa Induced Dyskinesias
NCT01491529PHASE2COMPLETEDEvaluation of the Efficacy and Safety of Modified Release AFQ056 in Parkinson’s Patients With L-dopa Induced Dyskinesias
NCT01491932PHASE2COMPLETEDOpen-label, Long-term Safety Extension Study of AFQ056 in Parkinson’s Patients With L-dopa Induced Dyskinesias
NCT04727658PHASE2TERMINATEDLinac FRACtionated Radiosurgical THALamotomie in Tremors (FRACTHAL)
NCT03065192PHASE1COMPLETEDSafety and Efficacy Study of VY-AADC01 for Advanced Parkinson’s Disease
NCT02696603Not specifiedACTIVE_NOT_RECRUITINGMobile Parkinson Observatory for Worldwide, Evidence-based Research (mPower)
NCT02994719Not specifiedRECRUITINGGait Analysis in Neurological Disease
NCT03130595Not specifiedACTIVE_NOT_RECRUITINGWest Sweden Parkinson Objective Measurement Registry Study
NCT03649503Not specifiedRECRUITINGThe National Registry Study For the Real-world Patients With Parkinsonian Disorders in China
NCT04985539Not specifiedACTIVE_NOT_RECRUITINGThe Personalized Parkinson Project De Novo Cohort
NCT06193252Not specifiedRECRUITINGSlow-SPEED-NL: Slowing Parkinson’s Early Through Exercise Dosage-Netherlands
NCT06875739Not specifiedENROLLING_BY_INVITATIONAn Innovative Method in SAliva Samples for the Early Differential Diagnosis of High-impact NeuroDegenerative Diseases Through Raman Spectroscopy
NCT06993142Not specifiedNOT_YET_RECRUITINGSlow-SPEED: Slowing Parkinson’s Early Through Exercise Dosage
NCT07187843Not specifiedRECRUITINGStudy of Axial and Cognitive Symptoms and Biomarkers of Neurodegeneration in Brain-first and Body-first PD
NCT07324330Not specifiedRECRUITINGSlowing Cognitive Decline in Alpha-synucleinopathies by Enhancing Physical Activity
NCT00355927Not specifiedUNKNOWNSedation During Microelectrode Recordings Before Deep Brain Stimulation for Movement Disorders.
NCT01380899Not specifiedCOMPLETEDUsefulness of α-synuclein as a Marker for Early Diagnosis of Parkinson’s Disease in Skin Biopsy.
NCT01853150Not specifiedCOMPLETEDRepetitive Transcranial Magnetic Stimulation for Freezing of Gait
NCT02021903Not specifiedCOMPLETEDPost-prandial Hypotension and Sleepiness in Parkinson’s Disease and Other Synucleinopathies
NCT03156647Not specifiedCOMPLETEDAlpha-synuclein Level in Saliva to Differentiate Between Idiopathic Parkinson Disease and Iatrogenic Parkinsonian Syndrome
NCT04237948Not specifiedCOMPLETEDtDCS Plus Physical Therapy for Progressive Supranuclear Palsy
NCT04704349Not specifiedCOMPLETEDLatest Imaging SPECT System Evaluation Phase 1
NCT04847609Not specifiedWITHDRAWNGentleCath Air (Urinary Self-catheterization) - Pain in Female Patients With Neurological Vesico-sphincter Disorders
NCT04925622Not specifiedCOMPLETEDComplex Eye Movements in Parkinson’s Disease and Related Movement Disorders
NCT04974034Not specifiedCOMPLETEDMovement Disorders Analysis Using a Deep Learning Approach
NCT05356845Not specifiedCOMPLETEDOral Health, Orofacial Function and Oral Health Care in Patients With Parkinson’s Disease
NCT05452655Not specifiedUNKNOWNIntensive Multidisciplinary Rehabilitation and Biomarkers in Parkinson’s Disease
NCT05608915Not specifiedCOMPLETEDExternal vs Internal-triggered Augmented-reality Visual Cues to Treat Freezing of Gait
NCT05906719Not specifiedUNKNOWNMachine Vision Based MDS-UPDRS III Machine Rating
NCT06283043Not specifiedUNKNOWNEffect of Motor Function, Depression and Sleep Quality on Attention in Parkinson’s Disease

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
PRELADENANT31
MAVOGLURANT23
ISOXAFLUTOLE21