PINK1

Summary

PINK1 (PTEN induced kinase 1, HGNC:14581) is a protein-coding gene on chromosome 1p36.12, encoding Serine/threonine-protein kinase PINK1, mitochondrial (Q9BXM7). Serine/threonine-protein kinase which acts as a sensor of mitochondrial damage and protects against mitochondrial dysfunction during cellular stress.

This gene encodes a serine/threonine protein kinase that localizes to mitochondria. It is thought to protect cells from stress-induced mitochondrial dysfunction. Mutations in this gene cause one form of autosomal recessive early-onset Parkinson disease.

Source: NCBI Gene 65018 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Parkinson disease (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 425 total — 32 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 40
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_032409

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14581
Approved symbol	PINK1
Name	PTEN induced kinase 1
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Aliases	BRPK
Ensembl gene	ENSG00000158828
Ensembl biotype	protein_coding
OMIM	608309
Entrez	65018

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000321556, ENST00000400490, ENST00000492302, ENST00000878739, ENST00000878740, ENST00000878741, ENST00000878742, ENST00000878743, ENST00000878744, ENST00000878745, ENST00000878746, ENST00000878747, ENST00000878748, ENST00000878749, ENST00000940631, ENST00000940632, ENST00000945624

RefSeq mRNA: 1 — MANE Select: NM_032409 NM_032409

CCDS: CCDS211

Canonical transcript exons

ENST00000321556 — 8 exons

Exon	Start	End
ENSE00001041273	20639892	20639992
ENSE00001041274	20637842	20638129
ENSE00001465660	20633458	20633935
ENSE00001543152	20650434	20651511
ENSE00003524815	20648995	20649231
ENSE00003577628	20644490	20644672
ENSE00003662034	20648505	20648632
ENSE00003693654	20645560	20645723

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.5742 / max 235.8858, expressed in 1802 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1132	26.1595	1800
1133	0.3055	156
1131	0.1092	37

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.35	gold quality
gastrocnemius	UBERON:0001388	98.98	gold quality
gluteal muscle	UBERON:0002000	98.98	gold quality
right frontal lobe	UBERON:0002810	98.95	gold quality
prefrontal cortex	UBERON:0000451	98.92	gold quality
amygdala	UBERON:0001876	98.89	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.88	gold quality
muscle of leg	UBERON:0001383	98.86	gold quality
apex of heart	UBERON:0002098	98.81	gold quality
putamen	UBERON:0001874	98.79	gold quality
nucleus accumbens	UBERON:0001882	98.76	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.75	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.74	gold quality
cingulate cortex	UBERON:0003027	98.68	gold quality
right adrenal gland cortex	UBERON:0035827	98.64	gold quality
anterior cingulate cortex	UBERON:0009835	98.63	gold quality
right adrenal gland	UBERON:0001233	98.61	gold quality
triceps brachii	UBERON:0001509	98.61	gold quality
caudate nucleus	UBERON:0001873	98.60	gold quality
muscle organ	UBERON:0001630	98.57	gold quality
left adrenal gland	UBERON:0001234	98.53	gold quality
medial globus pallidus	UBERON:0002477	98.53	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.50	gold quality
left adrenal gland cortex	UBERON:0035825	98.50	gold quality
spinal cord	UBERON:0002240	98.43	gold quality
hypothalamus	UBERON:0001898	98.40	gold quality
frontal cortex	UBERON:0001870	98.39	gold quality
adrenal cortex	UBERON:0001235	98.34	gold quality
heart left ventricle	UBERON:0002084	98.34	gold quality
substantia nigra	UBERON:0002038	98.32	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6308	yes	286.35
E-ANND-3	yes	6.10

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
BAG5	Repression

Upstream regulators (CollecTRI, top): EED, FOXO3, PTEN

miRNA regulators (miRDB)

31 targeting PINK1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-6807-3P	99.15	69.23	1275
HSA-MIR-4723-3P	97.67	65.91	1017
HSA-MIR-6511A-3P	97.60	66.61	713
HSA-MIR-6511B-3P	97.60	66.61	713
HSA-MIR-96-3P	97.47	68.03	839
HSA-MIR-6769B-3P	97.41	65.53	1036
HSA-MIR-3183	97.40	65.68	978
HSA-MIR-509-3-5P	97.21	67.74	1517
HSA-MIR-509-5P	97.21	67.90	1512
HSA-MIR-4418	97.04	67.16	1372
HSA-MIR-346	97.01	66.97	662
HSA-MIR-1180-3P	95.98	66.88	65
HSA-MIR-6789-5P	94.05	66.19	285

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• The subclinical loss of striatal dopamine storage capacity found in PARK6 carriers implies that the unidentified gene on the short arm of chromosome 1 exhibits either haploinsufficency or a dominant negative effect. (PMID:12447943)
• Autosomal recessive early onset parkinsonism is linked to three loci: PARK2, PARK6, and PARK7. (PMID:12548343)
• PARK6 appears to be an important locus for autosomal recessive juvenile parkinsonism in Europe. (PMID:12548371)
• mutations in PINK1 are associated with PARK6 a locus linked to a rare familial form of Parkinson disease; cell culture studies suggest that PINK1 is mitochondrially located and may exert a protective effect on the cell that is abrogated by the mutations (PMID:15087508)
• Strong evidence indicates that, although important in mendelian forms of Parkinson’s disease (PD), PINK1 does not influence the cause of sporadic nonmendelian forms of PD. (PMID:15349859)
• Six novel pathogenic PINK1 mutations suggest that PINK1 may be the second most common causative gene next to parkin in parkinsonism with the recessive mode of inheritance. (PMID:15349870)
• The results indicate worldwide distribution of PARK6-linked parkinsonism. (PMID:15505170)
• Overall, these data indicate that PINK1 mutations are a rare cause of PD in Ireland. (PMID:15505171)
• Autosomal recessive mutations in PINK1 are a rare cause of young-onset Parkinson disease. (PMID:15596610)
• These results show that PINK1 is processed at the N terminus in a manner consistent with mitochondrial import, but the mature protein also exists in the cytosol. (PMID:15824318)
• The G309D and W437OPA mutations in PINK1 gene probably do not represent common causes of familial or sporadic PD in a Caucasian population. (PMID:15876334)
• Thus, early-onset PD with dementia may be considered PINK1-linked parkinsonism. Furthermore, patients with PINK1 mutations form 8.9% of parkin- and DJ-1-negative ARPD families. (PMID:15955953)
• A patient homozygous for A PINK1 mutation was characterized clinically. All clinical and laboratory features, including SPECT and assessment of autonomic function, were indistinguishable from typical idiopathic Parkinson disease. (PMID:15955954)
• PINK1 homozygous mutations are a relevant cause of disease among Italian sporadic patients with early-onset parkinsonism. (PMID:16009891)
• PINK1 reduces the basal neuronal pro-apoptotic activity and protects neurons from staurosporine-induced apoptosis; loss of this protective function may underlie degeneration of nigral dopaminergic neurons in patients with PINK1 mutations (PMID:16079129)
• Both wild-type and mutant PINK1 proteins localize to mitochondria and prove that a short N-terminal part of PINK1 is sufficient for its mitochondrial targeting. (PMID:16207731)
• PINK1 participates in the protection of dopaminergic neurons (PMID:16226715)
• The phenotypic spectrum associated with PINK1-positive Parkinson disease patients may be wider than previously reported. (PMID:16482571)
• PINK1 mutations (homozygous nonsense and heterozygous missense) that highlight issues in Parkinson disease diagnosis. (PMID:16547921)
• PINK1 and DJ-1 may have a role in early-onset Parkinson’s disease and physically associate and collaborate to protect cells against stress via complex formation (PMID:16632486)
• Expression of human PINK1 in the Drosophila testes restores male fertility and normal mitochondrial morphology in a portion of pink1 mutants, demonstrating functional conservation between human and Drosophila Pink1 (PMID:16672981)
• A patient, heterozygote for W437X mutation, was affected by Parkinson’s disease and 3 further relatives were reported affected, according to an autosomal dominant transmission. (PMID:16700027)
• Heterozygous PINK1 mutations may predispose to PD, as was previously suggested by the presence of dopamine hypometabolism in asymptomatic mutation carriers. (PMID:16769864)
• This study extends the phenotypic and molecular spectrum of the PINK1 gene and the geographic origin of patients with PINK1 gene mutations. (PMID:16966503)
• PINK1 mutations mutations are a significant risk factor in the development of later onset Parkinson’s disease (PMID:16969854)
• Thus, in addition to the activation segment, the C-terminal tail of PINK1 also contains regulatory motifs capable of governing PINK1 kinase activity. (PMID:17000703)
• This finding suggests a role not only of homozygous but also of heterozygous PINK1 mutations in the development of parkinsonian signs and underlines the necessity to carefully investigate family members of affected mutation carriers. (PMID:17013904)
• PINK-1 encodes the PTEN induced kinase 1 and is located to provide a link between mitochondria and the pathogenesis of Parkinson disease–REVIEW (PMID:17017532)
• We genotyped eight known mutations in three clinic-based cohorts with Parkinsonism and found one homozygous p.L347P mutation in PINK1. (PMID:17055324)
• PINK1 A340T variant may contribute to the risk for late-onset PD in Chinese. (PMID:17084972)
• These data indicate that PINK1 function is critical to prevent oxidative damage and that peripheral cells may be useful for studies of progression and therapy of PARK6. (PMID:17141510)
• Deletion of the entire PINK1 gene and a splice site mutation (g.15445_15467del23) which produces several aberrant mRNAs in Parkinson disease. (PMID:17154281)
• PINK1 mutations are rare in Norwegian patients with EOP and familial Parkinson’s disease;however, the data suggest that some heterozygous mutations might increase the risk of developing Parkinson’s disease (PMID:17172567)
• affective and psychotic symptoms may be part of the phenotypic spectrum or even the sole manifestation of PINK1 mutations (PMID:17202228)
• Absence of correlation between PINK1 mRNA levels and clinical status in heterozygous mutation carriers suggests that other genetic or environmental factors play a role in determining the phenotypic variability in Parkinson disease. (PMID:17219214)
• a mammalian non-coding antisense molecule can positively influence the abundance of a cis-transcribed mRNA; dsRNA-mediated mechanism for stabilizing the expression of svPINK1 (PMID:17362513)
• possible association of IVS5-5G>A polymorphism, positioned in the upstream region of exon 5 of PINK1 gene with the risk for sporadic late onset Parkinson disease (LOPD) in Chinese (PMID:17557243)
• regulation of the PINK1 locus, linked to neurodegenerative disease, is altered in obesity, NIDDM and inactivity, while the combination of RNAi experiments and clinical data suggests a role for PINK1 in cell energetics (PMID:17567565)
• PINK1 protects against oxidative-stress-induced cell death by suppressing cytochrome c release from mitochondria, and this protective action of PINK1 depends on its kinase activity to phosphorylate TRAP1. (PMID:17579517)
• PINK1 exerts anti-apoptotic effect by inhibiting the opening of mPTP and that PARK6 mutant PINK1 loses its ability to prevent mPTP opening and cytochrome c release. (PMID:17707122)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pink1	ENSDARG00000001929
mus_musculus	Pink1	ENSMUSG00000028756
rattus_norvegicus	Pink1	ENSRNOG00000015385
drosophila_melanogaster	Pink1	FBGN0029891
caenorhabditis_elegans		WBGENE00017137

Paralogs (3): PEAK1 (ENSG00000173517), PEAK3 (ENSG00000188305), PRAG1 (ENSG00000275342)

Protein

Protein identifiers

Serine/threonine-protein kinase PINK1, mitochondrial — Q9BXM7 (reviewed: Q9BXM7)

Alternative names: BRPK, PTEN-induced putative kinase protein 1

All UniProt accessions (1): Q9BXM7

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase which acts as a sensor of mitochondrial damage and protects against mitochondrial dysfunction during cellular stress. It phosphorylates mitochondrial proteins to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components. In healthy mitochondria, PINK1 is translocated across the mitochondrial outer membrane (MOM) via the translocase of the outer membrane (TOM) complex, and inserted into the mitochondrial inner membrane (MIM) via the translocase of the inner membrane (TIM23) complex where it is cleaved and released into the cytosol. Depending on the severity of mitochondrial damage, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to eliminating severely damaged mitochondria via PINK1-PRKN-dependent mitophagy. When cellular stress results in irreversible mitochondrial damage, PINK1 accumulates at the outer mitochondrial membrane (OMM) where it phosphorylates pre-existing polyubiquitin chains at ‘Ser-65’, recruits PRKN from the cytosol to the OMM and activates PRKN by phosphorylation at ‘Ser-65’; activated PRKN then ubiquitinates VDAC1 and other OMM proteins to initiate mitophagy. The PINK1-PRKN pathway also promotes fission of damaged mitochondria through phosphorylation and PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2. This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes. Also promotes mitochondrial fission independently of PRKN and ATG7-mediated mitophagy, via the phosphorylation and activation of DNM1L. Regulates motility of damaged mitochondria by promoting the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma. Required for ubiquinone reduction by mitochondrial complex I by mediating phosphorylation of complex I subunit NDUFA10. Phosphorylates LETM1, positively regulating its mitochondrial calcium transport activity.

Subunit / interactions. Upon mitochondrial depolarization, associates with the TOM complex and the VDAC2 homodimer; its import into the mitochondria is stalled at the TOM complex. Upon mitochondrial depolarization, interacts with TIMM23. Forms a supercomplex with TOM and TIM23 complexes; PINK1-TOM-TIM23 supercomplex formation requires PINK1 interaction with TOMM20 and TOMM70. The interaction with TOM and TIM23 complexes is critical for PINK1 stabilization at the outer mitochondrial membrane, kinase activation and downstream mitophagy. Interacts with PRKN. Interacts with FBXO7. Forms a complex with PRKN and PARK7. Interacts with NENF.

Subcellular location. Mitochondrion outer membrane. Mitochondrion inner membrane. Cytoplasm. Cytosol.

Tissue specificity. Highly expressed in heart, skeletal muscle and testis, and at lower levels in brain, placenta, liver, kidney, pancreas, prostate, ovary and small intestine. Present in the embryonic testis from an early stage of development.

Post-translational modifications. Proteolytically cleaved. In healthy cells, the precursor is continuously imported into the inner mitochondrial membrane (IMM), where it is proteolytically cleaved by mitochondrial-processing peptidase (MPP) and then undergoes further proteolytic cleavage by PARL or AFG3L2 to give rise to the 52 kDa short form. The 52 kDa short form is then released into the cytosol where it rapidly undergoes proteasome-dependent degradation. In unhealthy cells, when cellular stress conditions lead to the loss of mitochondrial membrane potential, mitochondrial import is impaired leading to the precursor accumulating on the outer mitochondrial membrane (OMM). If accumulation at the OMM fails and it is imported into the depolarized mitochondria, it undergoes cleavage by the IMM protease OMA1, promoting its subsequent degradation by the proteasome. Autophosphorylated. Loss of mitochondrial membrane potential results in the precursor accumulating on the outer mitochondrial membrane (OMM) where it is activated by autophosphorylation. Autophosphorylation at Ser-228 and Ser-402 is sufficient and essential for selective recruitment of PRKN to depolarized mitochondria, via PINK1-dependent phosphorylation of ubiquitin and maybe PRKN.

Disease relevance. Parkinson disease 6 (PARK6) [MIM:605909] An early-onset form of Parkinson disease, a neurodegenerative disorder characterized by parkinsonian signs such as rigidity, resting tremor and bradykinesia. A subset of patients manifest additional symptoms including hyperreflexia, autonomic instability, dementia and psychiatric disturbances. Symptoms show diurnal fluctuation and can improve after sleep. PARK6 pathogenesis involves respiratory complex I deficiency causing mitochondrial depolarization and dysfunction. Inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BXM7-1	1	yes
Q9BXM7-2	2

RefSeq proteins (1): NP_115785* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR040110	PINK1_STKc	Domain
IPR051511	MitoQC_Scaffold_Kinases	Family

Pfam: PF00069

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (141 total): sequence variant 72, helix 22, mutagenesis site 15, strand 14, turn 4, splice variant 2, sequence conflict 2, region of interest 2, binding site 2, modified residue 2, transit peptide 1, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
9EII	ELECTRON MICROSCOPY	2.75
9KQN	ELECTRON MICROSCOPY	2.84
9KMR	ELECTRON MICROSCOPY	2.98
9EIH	ELECTRON MICROSCOPY	3.1
9EIJ	ELECTRON MICROSCOPY	3.3
9KOX	ELECTRON MICROSCOPY	4.43

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXM7-F1	77.82	0.54

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 362 (proton acceptor)

Ligand- & substrate-binding residues (2): 162–170; 186

Post-translational modifications (2): 228, 402

Mutagenesis-validated functional residues (15):

Position	Phenotype
112–117	in 3ea; impaired ability to localize to the outer mitochondrial membrane.
131	under depolarizing conditions, it results in loss of interaction with tomm20 and fails to support pink1-tom-tim23 comple
219	abolishes mfn2 phosphorylation and interaction with prkn; when associated with ala-362 and ala-384.
219	loss of enzyme activity and impaired localization of prkn to mitochondria; when associated with a-362 and a-384.
362	abolishes mfn2 phosphorylation and interaction with prkn; when associated with a-219 and a-384. loss of enzyme activity
384	abolishes mfn2 phosphorylation and interaction with prkn; when associated with a-219 and a-362. loss of enzyme activity
384	loss of activity. abolishes drp1 phosphorylation. no effect on localization to mitochondria.
532	under depolarizing conditions, it results in severely reduced autophosphorylation on s-228 and loss of kinase activation
536	under depolarizing conditions, it results in loss of interaction with tomm20 and fails to support pink1-tom-tim23 comple
536	under depolarizing conditions, it fails to support pink1-tom-tim23 complex assembly and mitophagy activation.
539	under depolarizing conditions, it results in severely reduced autophosphorylation on s-228 and loss of kinase activation
540	under depolarizing conditions, does not affect autophosphorylation on s-228 and kinase activation.
540	under depolarizing conditions, it results in loss of interaction with tomm20 and fails to support pink1-tom-tim23 comple
543	no effect on interaction with tomm20 and mitophagy activation under depolarizing conditions.
543	under depolarizing conditions, it fails to support pink1-tom-tim23 complex assembly and mitophagy activation.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5205685	PINK1-PRKN Mediated Mitophagy
R-HSA-9614657	FOXO-mediated transcription of cell death genes

MSigDB gene sets: 555 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_SYNAPTIC_VESICLE_LOCALIZATION, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_POSITIVE_REGULATION_OF_MITOCHONDRIAL_FISSION, GOBP_LYSOSOMAL_TRANSPORT, TGCGCANK_UNKNOWN, GOBP_VACUOLE_ORGANIZATION, GOBP_VESICLE_LOCALIZATION, GOBP_NEGATIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_PROTEIN_TARGETING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS

GO Biological Process (72): autophagy of mitochondrion (GO:0000422), mitophagy (GO:0000423), regulation of oxidative phosphorylation (GO:0002082), response to ischemia (GO:0002931), protein phosphorylation (GO:0006468), ubiquitin-dependent protein catabolic process (GO:0006511), response to oxidative stress (GO:0006979), mitochondrion organization (GO:0007005), regulation of hydrogen peroxide metabolic process (GO:0010310), negative regulation of gene expression (GO:0010629), regulation of mitochondrion organization (GO:0010821), dopamine secretion (GO:0014046), macroautophagy (GO:0016236), positive regulation of macroautophagy (GO:0016239), negative regulation of macroautophagy (GO:0016242), protein ubiquitination (GO:0016567), respiratory electron transport chain (GO:0022904), hemopoiesis (GO:0030097), positive regulation of cell migration (GO:0030335), regulation of protein ubiquitination (GO:0031396), positive regulation of protein ubiquitination (GO:0031398), positive regulation of synaptic transmission, dopaminergic (GO:0032226), positive regulation of dopamine secretion (GO:0033603), cellular response to oxidative stress (GO:0034599), intracellular signal transduction (GO:0035556), TORC2 signaling (GO:0038203), regulation of apoptotic process (GO:0042981), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), regulation of protein-containing complex assembly (GO:0043254), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of translation (GO:0045727), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of JNK cascade (GO:0046329), protein stabilization (GO:0050821), regulation of mitochondrial membrane potential (GO:0051881), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), regulation of proteasomal protein catabolic process (GO:0061136), cellular response to hypoxia (GO:0071456), obsolete establishment of protein localization to mitochondrion (GO:0072655), maintenance of protein location in mitochondrion (GO:0072656)

GO Molecular Function (17): magnesium ion binding (GO:0000287), protease binding (GO:0002020), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), kinase activity (GO:0016301), peptidase activator activity (GO:0016504), kinase binding (GO:0019900), ubiquitin protein ligase binding (GO:0031625), protein kinase B binding (GO:0043422), protein-containing complex binding (GO:0044877), C3HC4-type RING finger domain binding (GO:0055131), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (17): chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), cytoskeleton (GO:0005856), membrane (GO:0016020), axon (GO:0030424), growth cone (GO:0030426), cell body (GO:0044297), perinuclear region of cytoplasm (GO:0048471), Lewy body (GO:0097413), astrocyte projection (GO:0097449)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Mitophagy	1
FOXO-mediated transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoplasm	4
macroautophagy	3
intracellular membrane-bounded organelle	3
autophagy	2
response to stress	2
protein ubiquitination	2
regulation of macroautophagy	2
enzyme binding	2
protein kinase activity	2
binding	2
mitochondrial membrane	2
autophagy of mitochondrion	1
oxidative phosphorylation	1
regulation of aerobic respiration	1
phosphorylation	1
protein modification process	1
modification-dependent protein catabolic process	1
organelle organization	1
hydrogen peroxide metabolic process	1
regulation of reactive oxygen species metabolic process	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
mitochondrion organization	1
regulation of organelle organization	1
signal release	1
catecholamine secretion	1
autophagosome assembly	1
positive regulation of autophagy	1
negative regulation of autophagy	1
protein modification by small protein conjugation	1
electron transport chain	1
cellular respiration	1
cell development	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
regulation of protein modification by small protein conjugation or removal	1
metal ion binding	1

Protein interactions and networks

STRING

3211 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PINK1	PARK7	Q99497	999
PINK1	PRKN	O60260	999
PINK1	MFN2	O95140	992
PINK1	FBXO7	Q9Y3I1	990
PINK1	BECN1	Q14457	969
PINK1	LRRK2	Q5S007	955
PINK1	SNCA	P37840	947
PINK1	SQSTM1	Q13501	937
PINK1	TOMM20	Q15388	934
PINK1	MFN1	Q8IWA4	930
PINK1	PARL	Q9H300	928
PINK1	CALCOCO2	Q13137	924
PINK1	ATP13A2	Q9NQ11	923
PINK1	FIS1	Q9Y3D6	918
PINK1	HTRA2	O43464	915

IntAct

100 interactions, top by confidence:

A	B	Type	Score
	RAB8A	psi-mi:“MI:0217”(phosphorylation reaction)	0.820
	RAB8A	psi-mi:“MI:0217”(phosphorylation reaction)	0.790
PINK1	PRKN	psi-mi:“MI:0403”(colocalization)	0.750
PINK1	PRKN	psi-mi:“MI:0914”(association)	0.750
PRKN	PINK1	psi-mi:“MI:0914”(association)	0.750
PINK1	PRKN	psi-mi:“MI:0915”(physical association)	0.750
PRKN	PINK1	psi-mi:“MI:0915”(physical association)	0.750
FBXO7	PRKN	psi-mi:“MI:0914”(association)	0.620
FBXO7	PINK1	psi-mi:“MI:0915”(physical association)	0.580
PINK1	FBXO7	psi-mi:“MI:0915”(physical association)	0.580
SOCS4	PINK1	psi-mi:“MI:0915”(physical association)	0.570
	PINK1	psi-mi:“MI:0915”(physical association)	0.560
AP2B1	PINK1	psi-mi:“MI:0915”(physical association)	0.560
BIRC5	PINK1	psi-mi:“MI:0915”(physical association)	0.560
PNP	PINK1	psi-mi:“MI:0915”(physical association)	0.560
TEAD1	PINK1	psi-mi:“MI:0915”(physical association)	0.560
FEZ2	PINK1	psi-mi:“MI:0915”(physical association)	0.560
IQSEC1	PINK1	psi-mi:“MI:0915”(physical association)	0.560
PDZK1IP1	PINK1	psi-mi:“MI:0915”(physical association)	0.560
SPAG8	PINK1	psi-mi:“MI:0915”(physical association)	0.560
VPS29	PINK1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (864): RHOT2 (Affinity Capture-MS), IMMT (Affinity Capture-MS), RHOT2 (Affinity Capture-Western), IMMT (Affinity Capture-Western), PINK1 (Affinity Capture-Western), NAE1 (Affinity Capture-MS), PARK2 (Affinity Capture-Western), PARK2 (Affinity Capture-Western), UBC (Affinity Capture-MS), TGM2 (Biochemical Activity), TGM2 (Affinity Capture-Western), PINK1 (Affinity Capture-Western), TGM2 (Reconstituted Complex), PINK1 (Synthetic Lethality), PINK1 (Two-hybrid)

ESM2 similar proteins: A0JNQ6, A6NC42, A6NGQ2, A6NGR9, A6QP75, A7E3N7, A9X185, E1BDF2, E9PGG2, F6SZT2, P0C7A0, P85965, Q06VW1, Q0ZFW8, Q14DK4, Q3UK37, Q3UV16, Q3ZBN4, Q400G9, Q4VXA5, Q587J8, Q5JSQ8, Q60953, Q60I26, Q60I27, Q6NUI2, Q6ZUX3, Q810I0, Q8BH06, Q8C0R7, Q8IWB1, Q8IWY9, Q8IYX4, Q8K4C2, Q8N6L0, Q8N7F7, Q8NCV1, Q8TE82, Q91WA6, Q95JV3

Diamond homologs: A0A194W8T8, A0A8I5ZNK2, A7A1P0, A9SY39, B0XXN8, B5DFG1, B5VNQ3, C4YRB7, D4A280, D6WMX4, E0W1I1, F4JBP3, G4N7X0, G4NDR3, O14328, O22042, O35099, O88506, O95382, O95747, O96013, P0CY23, P0CY24, P22216, P23561, P28829, P54265, P83510, Q03497, Q04759, Q09013, Q09298, Q09792, Q0KHV6, Q10407, Q15835, Q21029, Q40541, Q4P5N0, Q4WHP3

SIGNOR signaling

36 interactions.

A	Effect	B	Mechanism
PINK1	up-regulates	HTRA2	phosphorylation
PINK1	up-regulates	PRKN	phosphorylation
PINK1	“up-regulates activity”	UBC	phosphorylation
PINK1	“down-regulates quantity”	CYCS
PTEN	“up-regulates quantity by expression”	PINK1	“transcriptional regulation”
PMPCB	“down-regulates quantity by destabilization”	PINK1	cleavage
PARL	“down-regulates quantity by destabilization”	PINK1	cleavage
PINK1	“down-regulates activity”	HIF3A	phosphorylation
PINK1	“down-regulates activity”	TUFM	phosphorylation
PINK1	“up-regulates activity”	PRKN	phosphorylation
PINK1	“down-regulates quantity by destabilization”	RHOT2	phosphorylation
PINK1	“down-regulates quantity by destabilization”	RHOT1	phosphorylation
PINK1	“down-regulates quantity by destabilization”	ZNF746	phosphorylation
PINK1	“down-regulates quantity”	MFN1	ubiquitination
PINK1	“down-regulates quantity”	MFN2	ubiquitination
PINK1	“down-regulates activity”	PTEN	phosphorylation
PINK1	“up-regulates activity”	TRAP1	phosphorylation
PINK1	“down-regulates quantity”	MFN2	phosphorylation
PINK1	“up-regulates activity”	ZNF746	phosphorylation
PINK1	“up-regulates activity”	TP53	phosphorylation
MARK2	“up-regulates activity”	PINK1	phosphorylation
PINK1	“up-regulates activity”	HDAC3	phosphorylation
PINK1	“down-regulates activity”	MAPT	phosphorylation
PINK1	“up-regulates activity”	DNM1L	phosphorylation
PINK1	“up-regulates activity”	MAP3K7	phosphorylation
PINK1	“down-regulates quantity”	CRLS1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

425 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	32
Likely pathogenic	15
Uncertain significance	184
Likely benign	107
Benign	35

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1074575	NC_000001.10:g.(?20972043)(20972226_?)del	Pathogenic
1398596	NM_032409.3(PINK1):c.666G>A (p.Trp222Ter)	Pathogenic
1399771	NM_032409.3(PINK1):c.1329del (p.Tyr444fs)	Pathogenic
1454290	NM_032409.3(PINK1):c.85_106del (p.Tyr29fs)	Pathogenic
189240	NM_032409.3(PINK1):c.620del (p.Arg207fs)	Pathogenic
2020503	NM_032409.3(PINK1):c.1600C>T (p.Gln534Ter)	Pathogenic
2043496	NM_032409.3(PINK1):c.710del (p.Met237fs)	Pathogenic
2404	NM_032409.3(PINK1):c.926G>A (p.Gly309Asp)	Pathogenic
2405	NM_032409.3(PINK1):c.813C>A (p.His271Gln)	Pathogenic
2406	NM_032409.3(PINK1):c.1311G>A (p.Trp437Ter)	Pathogenic
2407	NM_032409.3(PINK1):c.736C>T (p.Arg246Ter)	Pathogenic
2408	NM_032409.3(PINK1):c.1040T>C (p.Leu347Pro)	Pathogenic
2409	NM_032409.3(PINK1):c.1570_1573dup (p.Asp525fs)	Pathogenic
2410	NM_032409.3(PINK1):c.1597CAA[3] (p.Gln534dup)	Pathogenic
2412	NC_000001.11:g.20646973_20651575del	Pathogenic
2414	NM_032409.3(PINK1):c.650C>A (p.Ala217Asp)	Pathogenic
2415	NM_032409.3(PINK1):c.1366C>T (p.Gln456Ter)	Pathogenic
2417	NM_032409.3(PINK1):c.1196C>T (p.Pro399Leu)	Pathogenic
2427034	NC_000001.10:g.(?20972033)(20972236_?)del	Pathogenic
2854318	NM_032409.3(PINK1):c.1155_1156insTGCCCGCGTCCCTTTCTCCATAAAATTCTTCTTAGTAGCTA (p.Gly386delinsCysProArgProPheLeuHisLysIleLeuLeuSerSerTer)	Pathogenic
2918812	NM_032409.3(PINK1):c.309del (p.Phe104fs)	Pathogenic
3247755	NC_000001.10:g.(?20960807)(20964608_?)del	Pathogenic
3660782	NM_032409.3(PINK1):c.1396dup (p.Tyr466fs)	Pathogenic
431963	NM_032409.3(PINK1):c.1474C>T (p.Arg492Ter)	Pathogenic
4526585	NM_032409.3(PINK1):c.1557del (p.Lys520fs)	Pathogenic
4753796	NM_032409.3(PINK1):c.619C>T (p.Arg207Ter)	Pathogenic
581272	NM_032409.3(PINK1):c.599del (p.Ala200fs)	Pathogenic
631590	NM_032409.3(PINK1):c.665G>A (p.Trp222Ter)	Pathogenic
631591	NM_032409.3(PINK1):c.774C>A (p.Tyr258Ter)	Pathogenic
661098	NM_032409.3(PINK1):c.13C>T (p.Gln5Ter)	Pathogenic

SpliceAI

1661 predictions. Top by Δscore:

Variant	Effect	Δscore
1:20633933:CAGG:C	donor_loss	1.0000
1:20633936:G:GC	donor_loss	1.0000
1:20633937:T:G	donor_loss	1.0000
1:20644479:T:A	acceptor_gain	1.0000
1:20644673:G:GG	donor_gain	1.0000
1:20645559:GCT:G	acceptor_gain	1.0000
1:20645720:CCAG:C	donor_loss	1.0000
1:20645721:CAG:C	donor_loss	1.0000
1:20645722:AGGTA:A	donor_loss	1.0000
1:20645723:GGTAG:G	donor_loss	1.0000
1:20645724:GTA:G	donor_loss	1.0000
1:20648501:CCA:C	acceptor_loss	1.0000
1:20648502:CAG:C	acceptor_loss	1.0000
1:20648503:A:AG	acceptor_gain	1.0000
1:20648503:AGAC:A	acceptor_gain	1.0000
1:20648503:AGACG:A	acceptor_gain	1.0000
1:20648504:G:A	acceptor_loss	1.0000
1:20648504:G:GT	acceptor_gain	1.0000
1:20648504:GA:G	acceptor_gain	1.0000
1:20648504:GAC:G	acceptor_gain	1.0000
1:20648504:GACG:G	acceptor_gain	1.0000
1:20648504:GACGG:G	acceptor_gain	1.0000
1:20648630:GAG:G	donor_gain	1.0000
1:20648631:AGGTG:A	donor_loss	1.0000
1:20648632:GGTG:G	donor_loss	1.0000
1:20648633:G:C	donor_loss	1.0000
1:20648634:T:G	donor_loss	1.0000
1:20649229:AAG:A	donor_loss	1.0000
1:20649230:AG:A	donor_loss	1.0000
1:20649231:GG:G	donor_loss	1.0000

AlphaMissense

3699 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:20645682:G:T	R361I	0.997
1:20638111:G:C	K219N	0.996
1:20638111:G:T	K219N	0.996
1:20648532:A:T	D384V	0.996
1:20644554:T:C	F281L	0.995
1:20644556:C:A	F281L	0.995
1:20644556:C:G	F281L	0.995
1:20645682:G:C	R361T	0.995
1:20645691:A:T	K364I	0.995
1:20645685:A:C	D362A	0.993
1:20649052:T:A	W437R	0.993
1:20649052:T:C	W437R	0.993
1:20638118:T:A	W222R	0.992
1:20638118:T:C	W222R	0.992
1:20645683:A:C	R361S	0.992
1:20645683:A:T	R361S	0.992
1:20645685:A:T	D362V	0.992
1:20648533:T:A	D384E	0.992
1:20648533:T:G	D384E	0.992
1:20648545:C:G	C388W	0.991
1:20644555:T:C	F281S	0.990
1:20644656:T:C	F315L	0.990
1:20644658:C:A	F315L	0.990
1:20644658:C:G	F315L	0.990
1:20645658:T:C	L353P	0.990
1:20645692:A:C	K364N	0.990
1:20645692:A:T	K364N	0.990
1:20645686:C:A	D362E	0.989
1:20645686:C:G	D362E	0.989
1:20648532:A:C	D384A	0.989

dbSNP variants (sampled 300 via entrez): RS1000200110 (1:20650980 G>A), RS1000295586 (1:20651373 T>C,G), RS1000355480 (1:20639467 C>G), RS1000451915 (1:20646043 T>C), RS1000922751 (1:20644082 C>T), RS1001036726 (1:20640673 G>C), RS1001528077 (1:20646072 G>C), RS1001538071 (1:20645752 T>A), RS1001663088 (1:20641451 T>C), RS1001702223 (1:20634042 G>A,C), RS1001797485 (1:20641114 C>A), RS1002171599 (1:20640221 G>A,C), RS1002267965 (1:20638567 A>G), RS1002349413 (1:20650744 C>T), RS1002382724 (1:20634679 G>A)

Disease associations

OMIM: gene MIM:608309 | disease phenotypes: MIM:605909, MIM:609888, MIM:168600

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive early-onset Parkinson disease 6	Definitive	Autosomal recessive
Parkinson disease	Definitive	Autosomal recessive
young-onset Parkinson disease	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Parkinson disease	Definitive	AR

Mondo (6): autosomal recessive early-onset Parkinson disease 6 (MONDO:0011613), leprosy, susceptibility to, 1 (MONDO:0012358), neuroblastoma (MONDO:0005072), late-onset Parkinson disease (MONDO:0008199), Parkinson disease (MONDO:0005180), young-onset Parkinson disease (MONDO:0017279)

Orphanet (4): Young-onset Parkinson disease (Orphanet:2828), Leprosy (Orphanet:548), Neuroblastoma (Orphanet:635), Hereditary late-onset Parkinson disease (Orphanet:411602)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000012	Urinary urgency
HP:0000551	Color vision defect
HP:0000651	Diplopia
HP:0000713	Agitation
HP:0000716	Depression
HP:0000726	Dementia
HP:0000727	Frontal lobe dementia
HP:0000736	Short attention span
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0001257	Spasticity
HP:0001300	Parkinsonism
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0002014	Diarrhea
HP:0002018	Nausea
HP:0002019	Constipation
HP:0002063	Rigidity
HP:0002067	Bradykinesia
HP:0002141	Gait imbalance
HP:0002172	Postural instability
HP:0002322	Resting tremor
HP:0002578	Gastroparesis
HP:0003394	Muscle spasm
HP:0003593	Infantile onset
HP:0003677	Slowly progressive
HP:0004409	Hyposmia

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004862_162	Itch intensity from mosquito bite adjusted by bite size	6.000000e-06
GCST005352_14	Paclitaxel disposition in epithelial ovarian cancer	6.000000e-07
GCST009524_107	Household income (MTAG)	3.000000e-08
GCST009524_271	Household income (MTAG)	3.000000e-09
GCST010916_1	Proportion of activated microglia (inferior temporal cortex)	6.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0009695	household income

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009447	Neuroblastoma	C04.557.465.625.600.590.650.550; C04.557.470.670.590.650.550; C04.557.580.625.600.590.650.550
D010300	Parkinson Disease	C10.228.140.079.862.500; C10.228.662.600.400; C10.574.928.750
C565276	Parkinson Disease 6, Autosomal Recessive Early-Onset (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3337330 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — NKF2 family

ChEMBL bioactivities

7 potent at pChembl≥5 of 8 total, top 7 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.40	EC50	40	nM	CHEMBL6169465
6.82	EC50	150	nM	CHEMBL6174333
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.82	EC50	1500	nM	CHEMBL6147847
5.54	EC50	2900	nM	CHEMBL6144415

CTD chemical–gene interactions

118 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Carbonyl Cyanide m-Chlorophenyl Hydrazone	increases stability, increases activity, increases degradation, affects cotreatment, increases expression (+6 more)	7
Rotenone	decreases reaction, affects localization, increases cleavage, decreases response to substance, affects binding (+5 more)	6
1-Methyl-4-phenylpyridinium	increases expression, increases response to substance, affects reaction, affects response to substance	4
3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone	decreases reaction, increases expression, decreases expression	3
Paraquat	affects response to substance, affects cotreatment, affects reaction, increases expression, increases reaction (+2 more)	3
Valproic Acid	increases expression	3
Cyclosporine	decreases reaction, increases expression, decreases expression	3
Palmitic Acid	decreases reaction, increases expression, affects cotreatment, decreases expression	3
lead acetate	increases phosphorylation, affects cotreatment, decreases expression, increases abundance, increases reaction (+2 more)	2
sulforaphane	decreases expression, increases expression	2
sodium arsenite	affects methylation, increases expression	2
chromium hexavalent ion	increases expression, increases reaction	2
MitoTEMPO	decreases reaction, increases expression	2
Acetaminophen	increases expression	2
Acetylcysteine	increases expression, affects cotreatment, decreases reaction	2
Antimycin A	affects response to substance, affects expression, decreases expression, affects cotreatment, affects localization (+2 more)	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Hydrogen Peroxide	increases expression, affects reaction, decreases expression, decreases reaction, affects response to substance	2
Lead	increases abundance, increases reaction, affects expression, affects cotreatment, decreases expression	2
Melatonin	affects cotreatment, decreases reaction, increases expression, increases reaction, affects reaction	2
Silicon Dioxide	decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Oleic Acid	affects cotreatment, decreases expression, decreases reaction	2
aristolochic acid I	increases expression	1
afuresertib	increases expression	1
3-monochloropropane-1, 2 diol ester	increases expression, decreases reaction	1
quinone	decreases reaction, increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
titanium dioxide	increases expression	1

ChEMBL screening assays

24 unique, capped per target: 24 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3383262	Binding	Inhibition of PINK (unknown origin) assessed as remaining enzyme activity at 10 uM by radioactive [33P]-ATP filter binding assay	Synthesis and preliminary mechanistic evaluation of 5-(p-tolyl)-1-(quinolin-2-yl)pyrazole-3-carboxylic acid amides with potent antiproliferative activity on human cancer cell lines. — Eur J Med Chem

Cellosaurus cell lines

56 cell lines: 37 induced pluripotent stem cell, 7 cancer cell line, 5 embryonic stem cell, 4 finite cell line, 3 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_9S09	ESi040-A	Induced pluripotent stem cell	Female
CVCL_A8LT	LCSBi002-A	Induced pluripotent stem cell	Male
CVCL_A8LU	LCSBi002-B	Induced pluripotent stem cell	Male
CVCL_A8LV	LCSBi002-C	Induced pluripotent stem cell	Male
CVCL_B0YK	Abcam SH-SY5Y PINK1 KO	Cancer cell line	Female
CVCL_B3DW	Abcam HEK293T PINK1 KO	Transformed cell line	Female
CVCL_B9PU	Abcam A-549 PINK1 KO	Cancer cell line	Male
CVCL_C0K0	CBIGi001-A-2	Induced pluripotent stem cell	Male
CVCL_C0K1	CBIGi001-A-3	Induced pluripotent stem cell	Male
CVCL_C1TN	ICGi042-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

600 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
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
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NCT00571285	PHASE4	TERMINATED	Clinical Effects of Vitamin D Repletion in Patients With Parkinson’s Disease
NCT00584025	PHASE4	WITHDRAWN	Keppra IV for the Treatment of Motor Fluctuations in Parkinson’s Disease
NCT00584090	PHASE4	WITHDRAWN	Solifenacin Succinate (VESIcare) for the Treatment of Urinary Incontinence in Parkinson’s Disease
NCT00590122	PHASE4	COMPLETED	Parcopa Versus Carbidopa-levodopa in a Single Dose Cross-over Comparison Study
NCT00594464	PHASE4	COMPLETED	A Trial of Neupro® (Rotigotine Transdermal Patch) in Patients With Parkinson’s Disease Undergoing Surgery
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NCT00642356	PHASE4	TERMINATED	Carbidopa/Levodopa/Entacapone Versus Immediate Release (IR) Carbidopa/Levodopa on Non-motor Symptoms in Patients With Idiopathic Parkinson’s Disease and Demonstrating Non-motor Symptoms of Wearing Off
NCT00646204	PHASE4	COMPLETED	Namenda (Memantine) for Non-motor Symptoms in Parkinson’s Disease