PARK7

Summary

PARK7 (Parkinsonism associated deglycase, HGNC:16369) is a protein-coding gene on chromosome 1p36.23, encoding Parkinson disease protein 7 (Q99497). 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.

The product of this gene belongs to the peptidase C56 family of proteins. It acts as a positive regulator of androgen receptor-dependent transcription. It may also function as a redox-sensitive chaperone, as a sensor for oxidative stress, and it apparently protects neurons against oxidative stress and cell death. Defects in this gene are the cause of autosomal recessive early-onset Parkinson disease 7. Two transcript variants encoding the same protein have been identified for this gene.

Source: NCBI Gene 11315 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Parkinson disease (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 165 total — 12 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 44
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_007262

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16369
Approved symbol	PARK7
Name	Parkinsonism associated deglycase
Location	1p36.23
Locus type	gene with protein product
Status	Approved
Aliases	DJ-1, DJ1, GATD2
Ensembl gene	ENSG00000116288
Ensembl biotype	protein_coding
OMIM	602533
Entrez	11315

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 32 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000338639, ENST00000377488, ENST00000377491, ENST00000377493, ENST00000460192, ENST00000465354, ENST00000469225, ENST00000493373, ENST00000493678, ENST00000497113, ENST00000872623, ENST00000872624, ENST00000872625, ENST00000872626, ENST00000872627, ENST00000872628, ENST00000872629, ENST00000872630, ENST00000872631, ENST00000923297, ENST00000923298, ENST00000923299, ENST00000923300, ENST00000923301, ENST00000923302, ENST00000923303, ENST00000923304, ENST00000923305, ENST00000923306, ENST00000923307, ENST00000923308, ENST00000923309, ENST00000923310, ENST00000923312, ENST00000923313

RefSeq mRNA: 2 — MANE Select: NM_007262 NM_001123377, NM_007262

CCDS: CCDS93

Canonical transcript exons

ENST00000338639 — 7 exons

Exon	Start	End
ENSE00001049271	7961711	7961793
ENSE00001941967	7984894	7985505
ENSE00002898274	7977652	7977738
ENSE00003499981	7970894	7970963
ENSE00003584479	7969345	7969404
ENSE00003616908	7962763	7962875
ENSE00003623984	7965324	7965425

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 87.9159 / max 1263.1084, expressed in 1824 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
453	85.4455	1824
454	2.0647	1310
455	0.3434	118
452	0.0622	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adult organism	UBERON:0007023	99.56	gold quality
tibia	UBERON:0000979	99.55	gold quality
deltoid	UBERON:0001476	99.52	gold quality
endothelial cell	CL:0000115	99.51	gold quality
choroid plexus epithelium	UBERON:0003911	99.50	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.49	gold quality
tibialis anterior	UBERON:0001385	99.48	gold quality
biceps brachii	UBERON:0001507	99.47	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.47	gold quality
islet of Langerhans	UBERON:0000006	99.45	gold quality
vastus lateralis	UBERON:0001379	99.45	gold quality
heart right ventricle	UBERON:0002080	99.44	gold quality
quadriceps femoris	UBERON:0001377	99.43	gold quality
right adrenal gland	UBERON:0001233	99.42	gold quality
ganglionic eminence	UBERON:0004023	99.42	gold quality
cranial nerve II	UBERON:0000941	99.41	gold quality
pons	UBERON:0000988	99.41	gold quality
epithelium of nasopharynx	UBERON:0001951	99.41	gold quality
trigeminal ganglion	UBERON:0001675	99.40	gold quality
pituitary gland	UBERON:0000007	99.39	gold quality
left adrenal gland	UBERON:0001234	99.39	gold quality
myocardium	UBERON:0002349	99.39	gold quality
parietal pleura	UBERON:0002400	99.39	gold quality
right adrenal gland cortex	UBERON:0035827	99.39	gold quality
adrenal cortex	UBERON:0001235	99.37	gold quality
periodontal ligament	UBERON:0008266	99.36	gold quality
left adrenal gland cortex	UBERON:0035825	99.36	gold quality
nucleus accumbens	UBERON:0001882	99.35	gold quality
adenohypophysis	UBERON:0002196	99.35	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.35	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	55.38
E-HCAD-1	yes	14.81
E-CURD-122	yes	12.91
E-CURD-112	yes	10.52
E-CURD-46	yes	9.82
E-CURD-88	yes	5.06
E-MTAB-10042	yes	4.27
E-CURD-89	no	974.77
E-HCAD-6	no	677.26
E-HCAD-30	no	303.03
E-CURD-120	no	31.07
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

8 targets.

Target	Regulation
BBC3	Repression
CXCL8	Activation
GCLM	Activation
ICAM1	Activation
NQO1	Activation
SLC18A2	Activation
TH	Activation
TXN	Activation

Upstream regulators (CollecTRI, top): AR, CNBP, E2F4, ESR1, HIF1A, KLF17, SP1, SP3, STAT1, TCF23, TP53

miRNA regulators (miRDB)

12 targeting PARK7, 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-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-617	96.79	65.96	738
HSA-MIR-4703-3P	96.68	68.61	545
HSA-MIR-874-3P	95.02	65.66	806
HSA-MIR-1234-3P	86.70	58.45	109
HSA-MIR-7107-5P	86.70	59.28	110

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• show that DJ-1 mutations are associated with PARK7, a monogenic form of human parkinsonism (PMID:12446870)
• Autosomal recessive early onset parkinsonism is linked to three loci: PARK2, PARK6, and PARK7. (PMID:12548343)
• androgen receptor is positively regulated by DJ-1, which antagonizes the function of negative regulators, including DJBP, a novel DJ-1-binding protein (PMID:12612053)
• disease-causing L166P mutation has disrupted the C-terminal region and the dimerization of the protein. (PMID:12761214)
• DJ-1 contains an additional alpha-helix at the C-terminal region, which blocks the putative catalytic site of DJ-1 and appears to regulate the enzymatic activity. (PMID:12796482)
• We describe clinical and neuroimaging features of the 4 patients in the original PARK7-linked kindred. (PMID:12815653)
• mutant DJ-1, causative for recessive Parkinson’s disease, is degraded through the ubiquitin-proteasome system (PMID:12851414)
• crystal structure of DJ-1 at 1.6 A resolution locates Leu166 in the middle of a helix and thus predicts that the L166P mutation will bend the helix and impact the dimerization of DJ-1 (PMID:12914946)
• structural comparisons between DJ-1 protein, Hsp31, and an Archaea protease lead to the identification of the chaperone activity of DJ-1 (PMID:12939276)
• Whether a polymorphism (g.168_185del) within exon 1 of DJ-1 contributes to the risk of sporadic Parkinson disease in a Finnish case-control series was analyzed. This gene does not play a major role in genetic predisposition to PD in this population (PMID:14557580)
• localization in testis, sperm, and semen; DJ-1 may play an important and as yet uncharacterized role in spermatogenesis and fertilization in humans (PMID:14579415)
• By positional cloning within the refined PARK7 critical region we recently identified mutations in the DJ-1 gene in the two PARK7-linked families. (PMID:14598065)
• DJ-1 mutants are rich in beta-strand and alpha-helix conformation and have different suceptibilies to thermal denaturation (PMID:14607841)
• The PARK7 gene is not a common locus for early onset autosomal recessive parkinsonism. (PMID:14638971)
• These results suggest that loss of protective activity of DJ-1 from neuro-toxicity induced by these stresses contributes to neuronal cell death in AR-EOP with mutant DJ-1. (PMID:14652021)
• different neurodegenerative diseases may have similar pathological mechanisms, and that these processes likely include DJ-1 (PMID:14705119)
• DJ-1 has a role in neurodegeneration offers and progression of Parkinson’s disease (review) (PMID:14712351)
• L166P mutation may contribute to the loss of normal DJ-1 function and are likely to be the underlying cause of early onset PD in affected members of the Italian kindred. (PMID:14713311)
• Early-onset Parkinson disease is associated with single heterozygous loss-of-function DJ-1 mutations, including a heterozygous deletion of exons 5 to 7 and an 11-base pair deletion, removing the invariant donor splice site in intron 5. (PMID:14872018)
• DNA mutational analysis in patients with recessively-inherited early onset parkinsonism (PMID:14985393)
• DJ-1(A NEWLY DISCOVERED MUTANT GENE) IS LINKED TO A GENETICALLY ISOLATED POPULATION IN THE SOUTHWEST OF THE NETHERLANDS AND PRESENTS WITH EARLY-ONSET AUTOSOMAL-RECESSIVE PARKINSONISM. (SEE PAGE 80 UNDER PARK7(DJ-1) (PMID:15018843)
• analyzed other mutants of DJ-1 found in Parkinson’s disease patients, including M26I, R98Q, and D149A, as well as L166P (PMID:15219840)
• Mutations in the DJ-1 gene are rare in early-onset Parkinson’s disease in both sporadic and familial cases. (PMID:15254937)
• SNP1 (position 4,345 bp) & SNP3 (position 16,491 bp) were significantly associated with Parkinson disease in women. Because the DJ1 protein regulates the androgen receptor, these gender-specific findings may be genuine. (PMID:15304593)
• A new mutation, c.192G>C (p.E64D), associated with early-onset Parkinson disease was found in a Turkish patient. It does not alter the structure, but affects expression & nuclear localization of the protein. (PMID:15365989)
• DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation (PMID:15502874)
• DJ-1 is the third of four genes known to be definitively causal in familial Parkinson disease (PMID:15503154)
• DJ-1 positively regulates p53 through Topors-mediated sumoylation (PMID:15703819)
• linkage to six chromosomal regions and have identified three causative genes: PARK1 (alpha-synuclein), PARK2 (parkin), and PARK7 (DJ-1) in Parkinson disease (PMID:15717024)
• Data show that DJ-1 is a key negative regulator of PTEN that may be a useful prognostic marker for cancer. (PMID:15766664)
• Parkinson disease-associated PARK7 is a transcriptional co-activator that protects against neuronal apoptosis. (PMID:15790595)
• We confirmed the pathological co-localization of DJ-1 with other neurodegenerative disease-associated proteins, as well as the decrease in DJ-1 solubility in disease tissue. In addition, we report the presence of DJ-1 in a large molecular complex. (PMID:15935068)
• DJ-1 is an integral mitochondrial protein that may have important functions in regulating mitochondrial physiology. Our findings of DJ-1’s mitochondrial localization may have important implications for understanding the pathogenesis of Parkinson’s disease (PMID:15944198)
• DJ-1 was sumoylated on a lysine residue at K130 by PIASxalpha or PIASy. The K130 mutation abrogated all of the functions of DJ-1, including ras-dependent transformation, cell growth promotion and anti-UV-induced apoptosis activities. (PMID:15976810)
• DJ-1 sequesters Daxx in the nucleus, prevents it from gaining access to the cytoplasm, from binding to and activating its effector kinase apoptosis signal-regulating kinase 1, and therefore, from triggering the ensuing death pathway. (PMID:15983381)
• DJ-1 up-regulates glutathione synthesis during oxidative stress and inhibits A53T alpha-synuclein toxicity (PMID:16227205)
• A novel homozygous mutation in exon 7 (E163K) and a new homozygous mutation (g.168_185dup) in the promoter region of the gene of parkinsonism-dementia-amyotrophic lateral sclerosis complex. (PMID:16240358)
• distinct cysteine residues of DJ-1 harbor differential roles in relation to its structure and function (PMID:16316629)
• Data show that DJ1 mutations were rare in Chinese patients with autosomal recessive early-onset Parkinsonism. (PMID:16331561)
• Results suggest that DJ-1 may act as an oxidative-stress-induced chaperone to prevent alpha-synuclein fibrillation. (PMID:16403519)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	park7	ENSDARG00000116835
mus_musculus	Park7	ENSMUSG00000028964
rattus_norvegicus		ENSRNOG00000069013
drosophila_melanogaster	DJ-1alpha	FBGN0033885
drosophila_melanogaster	dj-1beta	FBGN0039802
caenorhabditis_elegans		WBGENE00015184
caenorhabditis_elegans		WBGENE00016789

Protein

Protein identifiers

Parkinson disease protein 7 — Q99497 (reviewed: Q99497)

Alternative names: Maillard deglycase, Oncogene DJ1, Parkinsonism-associated deglycase, Protein DJ-1, Protein/nucleic acid deglycase DJ-1

All UniProt accessions (4): Q99497, K7ELW0, K7EN27, V9HWC2

UniProt curated annotations — full annotation on UniProt →

Function. 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. It is involved in neuroprotective mechanisms like the stabilization of NFE2L2 and PINK1 proteins, male fertility as a positive regulator of androgen signaling pathway as well as cell growth and transformation through, for instance, the modulation of NF-kappa-B signaling pathway. Has been described as a protein and nucleotide deglycase that catalyzes the deglycation of the Maillard adducts formed between amino groups of proteins or nucleotides and reactive carbonyl groups of glyoxals. But this function is rebuted by other works. As a protein deglycase, repairs methylglyoxal- and glyoxal-glycated proteins, and releases repaired proteins and lactate or glycolate, respectively. Deglycates cysteine, arginine and lysine residues in proteins, and thus reactivates these proteins by reversing glycation by glyoxals. Acts on early glycation intermediates (hemithioacetals and aminocarbinols), preventing the formation of advanced glycation endproducts (AGE) that cause irreversible damage. Also functions as a nucleotide deglycase able to repair glycated guanine in the free nucleotide pool (GTP, GDP, GMP, dGTP) and in DNA and RNA. Is thus involved in a major nucleotide repair system named guanine glycation repair (GG repair), dedicated to reversing methylglyoxal and glyoxal damage via nucleotide sanitization and direct nucleic acid repair. Protects histones from adduction by methylglyoxal, controls the levels of methylglyoxal-derived argininine modifications on chromatin. Able to remove the glycations and restore histone 3, histone glycation disrupts both local and global chromatin architecture by altering histone-DNA interactions as well as histone acetylation and ubiquitination levels. Displays a very low glyoxalase activity that may reflect its deglycase activity. Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death. Required for correct mitochondrial morphology and function as well as for autophagy of dysfunctional mitochondria. Plays a role in regulating expression or stability of the mitochondrial uncoupling proteins SLC25A14 and SLC25A27 in dopaminergic neurons of the substantia nigra pars compacta and attenuates the oxidative stress induced by calcium entry into the neurons via L-type channels during pacemaking. Regulates astrocyte inflammatory responses, may modulate lipid rafts-dependent endocytosis in astrocytes and neuronal cells. In pancreatic islets, involved in the maintenance of mitochondrial reactive oxygen species (ROS) levels and glucose homeostasis in an age- and diet dependent manner. Protects pancreatic beta cells from cell death induced by inflammatory and cytotoxic setting. Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress. Metal-binding protein able to bind copper as well as toxic mercury ions, enhances the cell protection mechanism against induced metal toxicity. In macrophages, interacts with the NADPH oxidase subunit NCF1 to direct NADPH oxidase-dependent ROS production, and protects against sepsis.

Subunit / interactions. Homodimer. Binds EFCAB6/DJBP and PIAS2. Part of a ternary complex containing PARK7, EFCAB6/DJBP and AR. Interacts (via N-terminus) with OTUD7B. Interacts with BBS1, HIPK1, CLCF1 and MTERF. Forms a complex with PINK1 and PRKN. Interacts (via C-terminus) with NCF1; the interaction is enhanced by LPS and modulates NCF1 phosphorylation and membrane translocation. Interacts with NENF.

Subcellular location. Cell membrane. Cytoplasm. Nucleus. Membrane raft. Mitochondrion. Endoplasmic reticulum.

Tissue specificity. Highly expressed in pancreas, kidney, skeletal muscle, liver, testis and heart. Detected at slightly lower levels in placenta and brain (at protein level). Detected in astrocytes, Sertoli cells, spermatogonia, spermatids and spermatozoa. Expressed by pancreatic islets at higher levels than surrounding exocrine tissues.

Post-translational modifications. Sumoylated on Lys-130 by PIAS2 or PIAS4; which is enhanced after ultraviolet irradiation and essential for cell-growth promoting activity and transforming activity. Cys-106 is easily oxidized to sulfinic acid. Undergoes cleavage of a C-terminal peptide and subsequent activation of protease activity in response to oxidative stress.

Disease relevance. Parkinson disease 7 (PARK7) [MIM:606324] A neurodegenerative disorder characterized by resting tremor, postural tremor, bradykinesia, muscular rigidity, anxiety and psychotic episodes. PARK7 has onset before 40 years, slow progression and initial good response to levodopa. Some patients may show traits reminiscent of amyotrophic lateral sclerosis-parkinsonism/dementia complex (Guam disease). The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Deglycase activity does not require glutathione as a cofactor, however, glycated glutathione constitutes a PARK7 substrate.

Induction. By hydrogen peroxide and UV irradiation. In pancreatic islets, expression increases under hyperglycemic conditions. Expression is also induced by sulforaphane, an isothiocyanate obtained from cruciferous vegetables.

Similarity. Belongs to the peptidase C56 family.

RefSeq proteins (2): NP_001116849, NP_009193* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002818	DJ-1/PfpI	Domain
IPR006287	DJ-1	Family
IPR029062	Class_I_gatase-like	Homologous_superfamily
IPR050325	Prot/Nucl_acid_deglycase	Family

Pfam: PF01965

Enzyme classification (BRENDA):

• EC 3.5.1.124 — protein deglycase (BRENDA: 7 organisms, 46 substrates, 5 inhibitors, 13 Km, 13 kcat entries)
• EC 4.2.1.130 — D-lactate dehydratase (BRENDA: 72 organisms, 28 substrates, 25 inhibitors, 21 Km, 21 kcat entries)

Substrate kinetics (BRENDA)

15 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
METHYLGLYOXAL	0.157–1900	13
PHENYLGLYOXAL	0.0118–13	3
N-ACETYL-L-CYSTEINE	0.14–0.181	2
N-ACETYL-L-LYSINE	6.25–18.18	2
4-NITROPHENYL ACETATE	2.85	1
6,8-DIFLUORO-4-METHYLUMBELLLIFERONE	0.151	1
METHYLGLYOXAL	0.2508	1
N-ACETYL-L-ARGININE	5.88	1
N6-(1-HYDROXY-2-OXOPROPYL)-N2-ACETYL-L-LYSINE	0.35	1
NOMEGA-(1-HYDROXY-2-OXOPROPYL)-NALPHA-ACETYL-L-A	0.44	1
S-(1-HYDROXY-2-OXOPROPYL)-N-ACETYL-L-CYSTEINE	0.32	1
2-OXOPROPANAL	156.9	1
METHYLGLYOXYL GUANOSINE 5’-MONOPHOSPHATE	0.475	1
METHYLGLYOXYL N-ACETYLCYSTEINE	0.432	1
2-OXOETHANAL	—	0

Catalyzed reactions (Rhea), 12 shown:

• N(omega)-(1-hydroxy-2-oxopropyl)-L-arginyl-[protein] + H2O = lactate + L-arginyl-[protein] + H(+) (RHEA:49548)
• N(6)-(1-hydroxy-2-oxopropyl)-L-lysyl-[protein] + H2O = lactate + L-lysyl-[protein] + H(+) (RHEA:49552)
• S-(1-hydroxy-2-oxopropyl)-L-cysteinyl-[protein] + H2O = lactate + L-cysteinyl-[protein] + H(+) (RHEA:49556)
• N(omega)-(1-hydroxy-2-oxoethyl)-L-arginyl-[protein] + H2O = L-arginyl-[protein] + glycolate + H(+) (RHEA:57188)
• N(6)-(1-hydroxy-2-oxoethyl)-L-lysyl-[protein] + H2O = glycolate + L-lysyl-[protein] + H(+) (RHEA:57192)
• S-(1-hydroxy-2-oxoethyl)-L-cysteinyl-[protein] + H2O = glycolate + L-cysteinyl-[protein] + H(+) (RHEA:57196)
• N(2)-(1-hydroxy-2-oxopropyl)-dGTP + H2O = lactate + dGTP + H(+) (RHEA:57244)
• N(2)-(1-hydroxy-2-oxoethyl)-dGTP + H2O = dGTP + glycolate + H(+) (RHEA:57248)
• N(2)-(1-hydroxy-2-oxoethyl)-GTP + H2O = glycolate + GTP + H(+) (RHEA:57252)
• N(2)-(1-hydroxy-2-oxopropyl)-GTP + H2O = lactate + GTP + H(+) (RHEA:57256)
• N(2)-(1-hydroxy-2-oxopropyl)-GDP + H2O = lactate + GDP + H(+) (RHEA:57260)
• N(2)-(1-hydroxy-2-oxoethyl)-GDP + H2O = glycolate + GDP + H(+) (RHEA:57264)

UniProt features (70 total): mutagenesis site 18, sequence variant 12, helix 11, strand 10, modified residue 5, lipid moiety-binding region 3, turn 3, active site 2, initiator methionine 1, chain 1, cross-link 1, propeptide 1, sequence conflict 1, site 1

Structure

Experimental structures (PDB)

88 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9YFR	X-RAY DIFFRACTION	0.92
9YGX	X-RAY DIFFRACTION	0.97
9YH8	X-RAY DIFFRACTION	1
2RK3	X-RAY DIFFRACTION	1.05
9YCU	X-RAY DIFFRACTION	1.05
1P5F	X-RAY DIFFRACTION	1.1
5SY9	X-RAY DIFFRACTION	1.1
5SYA	X-RAY DIFFRACTION	1.1
2RK4	X-RAY DIFFRACTION	1.15
2RK6	X-RAY DIFFRACTION	1.15
3CZ9	X-RAY DIFFRACTION	1.15
3EZG	X-RAY DIFFRACTION	1.15
5SY6	X-RAY DIFFRACTION	1.15
4P36	X-RAY DIFFRACTION	1.18
1SOA	X-RAY DIFFRACTION	1.2
2OR3	X-RAY DIFFRACTION	1.2
3CZA	X-RAY DIFFRACTION	1.2
3F71	X-RAY DIFFRACTION	1.2
7PA2	X-RAY DIFFRACTION	1.21
4ZGG	X-RAY DIFFRACTION	1.23
6AF7	X-RAY DIFFRACTION	1.3
3CY6	X-RAY DIFFRACTION	1.35
4P2G	X-RAY DIFFRACTION	1.35
6E5Z	X-RAY DIFFRACTION	1.35
4BTE	X-RAY DIFFRACTION	1.38
6AF9	X-RAY DIFFRACTION	1.39
7PA3	X-RAY DIFFRACTION	1.42
4S0Z	X-RAY DIFFRACTION	1.45
6AFC	X-RAY DIFFRACTION	1.45
4MTC	X-RAY DIFFRACTION	1.47

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99497-F1	98.43	0.98

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 (3): 106 (nucleophile); 126; 149–150 (cleavage; by casp6)

Post-translational modifications (9): 182, 46, 53, 106, 130, 2, 67, 106, 148

Mutagenesis-validated functional residues (18):

Position	Phenotype
10	abolishes detoxification activity on methylglyocal-adducted coa.
18	strongly decreases enzymatic activity. almost abolishes detoxification activity on methylglyocal-adducted coa.
18	strongly decreases enzymatic activity.
46	reduces protein stability. no effect on oxidation.
46	reduces protein stability. no effect on oxidation. reduced localization in lipid rafts; when associated with a-106.
46	no effect on mitochondrial translocation neither on deglycase activity.
51	disrupts dimer formation and strongly reduces ability to eliminate hydrogen peroxide.
53	strongly reduces chaperone activity and ability to eliminate hydrogen peroxide.
53	no effect on mitochondrial translocation neither on deglycase activity.
106	abolishes enzymatic activity. abolishes oxidation, association with mitochondria and protease activity. no effect on cha
106	abolishes oxidation and association with mitochondria. no effect on chaperone activity.
106	loss of protein and nucleic acid deglycase activity. no effect on mitochondrial translocation. reduced protease activity
126	strongly decreases enzymatic activity.
130	partially compensates for loss of stability; when associated with p-166.
179	no effect on detoxification activity on methylglyocal-adducted coa.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-3899300	SUMOylation of transcription cofactors
R-HSA-9613829	Chaperone Mediated Autophagy
R-HSA-9615710	Late endosomal microautophagy
R-HSA-9646399	Aggrephagy

MSigDB gene sets: 693 (showing top): GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_SINGLE_FERTILIZATION, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_BEHAVIOR, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_NEUROTRANSMITTER_UPTAKE

GO Biological Process (83): positive regulation of acute inflammatory response to antigenic stimulus (GO:0002866), DNA repair (GO:0006281), proteolysis (GO:0006508), autophagy (GO:0006914), inflammatory response (GO:0006954), response to oxidative stress (GO:0006979), mitochondrion organization (GO:0007005), Ras protein signal transduction (GO:0007265), single fertilization (GO:0007338), adult locomotory behavior (GO:0008344), methylglyoxal metabolic process (GO:0009438), detoxification of copper ion (GO:0010273), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), lactate biosynthetic process (GO:0019249), removal of superoxide radicals (GO:0019430), insulin secretion (GO:0030073), protein repair (GO:0030091), androgen receptor signaling pathway (GO:0030521), positive regulation of protein-containing complex assembly (GO:0031334), negative regulation of protein ubiquitination (GO:0031397), negative regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032435), positive regulation of interleukin-8 production (GO:0032757), negative regulation of protein sumoylation (GO:0033234), cellular response to oxidative stress (GO:0034599), cellular response to glyoxal (GO:0036471), glucose homeostasis (GO:0042593), hydrogen peroxide metabolic process (GO:0042743), regulation of neuron apoptotic process (GO:0043523), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of transcription by RNA polymerase II (GO:0045944), glycolate biosynthetic process (GO:0046295), negative regulation of protein export from nucleus (GO:0046826), regulation of inflammatory response (GO:0050727), detoxification of mercury ion (GO:0050787), protein stabilization (GO:0050821), dopamine uptake involved in synaptic transmission (GO:0051583), regulation of mitochondrial membrane potential (GO:0051881), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), membrane depolarization (GO:0051899)

GO Molecular Function (35): transcription coactivator activity (GO:0003713), mRNA binding (GO:0003729), signaling receptor binding (GO:0005102), copper ion binding (GO:0005507), enzyme activator activity (GO:0008047), peptidase activity (GO:0008233), superoxide dismutase copper chaperone activity (GO:0016532), oxidoreductase activity, acting on peroxide as acceptor (GO:0016684), oxygen sensor activity (GO:0019826), enzyme binding (GO:0019899), kinase binding (GO:0019900), cytokine binding (GO:0019955), peptidase inhibitor activity (GO:0030414), signaling receptor activator activity (GO:0030546), tyrosine 3-monooxygenase activator activity (GO:0036470), L-dopa decarboxylase activator activity (GO:0036478), protein deglycase activity (GO:0036524), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), small protein activating enzyme binding (GO:0044388), ubiquitin-like protein conjugating enzyme binding (GO:0044390), cadherin binding (GO:0045296), mercury ion binding (GO:0045340), nuclear androgen receptor binding (GO:0050681), peroxiredoxin activity (GO:0051920), ubiquitin-protein transferase inhibitor activity (GO:0055105), scaffold protein binding (GO:0097110), DNA-binding transcription factor binding (GO:0140297), cupric ion binding (GO:1903135), cuprous ion binding (GO:1903136), ubiquitin-specific protease binding (GO:1990381), glyoxalase (glycolic acid-forming) activity (GO:1990422), RNA binding (GO:0003723), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (22): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial intermembrane space (GO:0005758), mitochondrial matrix (GO:0005759), endoplasmic reticulum (GO:0005783), centriole (GO:0005814), cytosol (GO:0005829), plasma membrane (GO:0005886), adherens junction (GO:0005912), synaptic vesicle (GO:0008021), PML body (GO:0016605), axon (GO:0030424), cell body (GO:0044297), membrane raft (GO:0045121), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), sperm midpiece (GO:0097225), membrane (GO:0016020), neuron projection (GO:0043005)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Autophagy	2
SUMO E3 ligases SUMOylate target proteins	1
Selective autophagy	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
protein binding	4
cytoplasm	4
intracellular membrane-bounded organelle	3
protein metabolic process	2
gene expression	2
regulation of gene expression	2
molecular function activator activity	2
catalytic activity, acting on a protein	2
enzyme binding	2
enzyme activator activity	2
acute inflammatory response to antigenic stimulus	1
positive regulation of acute inflammatory response	1
positive regulation of inflammatory response to antigenic stimulus	1
regulation of acute inflammatory response to antigenic stimulus	1
DNA metabolic process	1
DNA damage response	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
defense response	1
response to stress	1
organelle organization	1
small GTPase-mediated signal transduction	1
fertilization	1
locomotory behavior	1
adult behavior	1
aldehyde metabolic process	1
ketone metabolic process	1
detoxification of inorganic compound	1
stress response to copper ion	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
lactate metabolic process	1
monocarboxylic acid biosynthetic process	1
superoxide metabolic process	1
cellular response to superoxide	1
cellular oxidant detoxification	1
protein secretion	1
peptide hormone secretion	1

Protein interactions and networks

STRING

5034 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PARK7	PINK1	Q9BXM7	999
PARK7	PRKN	O60260	996
PARK7	HSPA9	P30036	988
PARK7	SNCA	P37840	986
PARK7	LRRK2	Q5S007	984
PARK7	ATP13A2	Q9NQ11	957
PARK7	KEAP1	Q14145	914
PARK7	EFCAB6	Q5THR3	909
PARK7	HSPA4	P34932	893
PARK7	VDAC1	P21796	890
PARK7	FBXO7	Q9Y3I1	864
PARK7	NUCLEOLIN	P19338	856
PARK7	OTUD7B	Q6GQQ9	849
PARK7	MAP3K5	Q99683	847
PARK7	NCF1	P14598	835

IntAct

197 interactions, top by confidence:

A	B	Type	Score
FADD	CASP8	psi-mi:“MI:0914”(association)	0.980
HDAC1	MTA2	psi-mi:“MI:0403”(colocalization)	0.950
HDAC1	MTA2	psi-mi:“MI:0915”(physical association)	0.950
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
PPP2R1B	STRN	psi-mi:“MI:0914”(association)	0.730
FADD	TNFRSF10A	psi-mi:“MI:0914”(association)	0.730
PARK7	DAXX	psi-mi:“MI:0915”(physical association)	0.710
PARK7	DAXX	psi-mi:“MI:0403”(colocalization)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PARK7	PARK7	psi-mi:“MI:0915”(physical association)	0.690
BBS1	PARK7	psi-mi:“MI:0915”(physical association)	0.670
PARK7	BBS1	psi-mi:“MI:0915”(physical association)	0.670
PARK7	OTUB1	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (491): GOPC (Two-hybrid), PARK7 (Affinity Capture-Western), PARK2 (Affinity Capture-Western), PARK7 (Affinity Capture-RNA), PARK7 (Affinity Capture-RNA), ANXA7 (Co-fractionation), ENO1 (Co-fractionation), IMPA2 (Co-fractionation), ITPA (Co-fractionation), LYPLA1 (Co-fractionation), MIF (Co-fractionation), PARK7 (Co-fractionation), PARK7 (Co-fractionation), PARK7 (Co-fractionation), PARK7 (Co-fractionation)

ESM2 similar proteins: A1YER2, A1YFX9, A2T7G9, B0BNF8, F6V515, O88767, O95372, P12863, P17764, P21820, P29401, P32929, P40142, P48494, P48758, P50137, P78330, P82197, P93394, Q0II59, Q148G4, Q2KHU0, Q3ZBV9, Q5E946, Q5I0K3, Q5R4C1, Q5RB83, Q5XJ36, Q60HC7, Q60HG7, Q6B855, Q6P1N9, Q6P8M1, Q6UWP2, Q71R50, Q7TQ35, Q7Z6V5, Q7ZV22, Q8QZT1, Q8TDX5

Diamond homologs: A1Z9J4, O16228, O28987, O59413, O88767, P55880, P90994, Q10356, Q46948, Q51732, Q54MG7, Q58377, Q5E946, Q5XJ36, Q7TQ35, Q8UW59, Q8VY09, Q95LI9, Q99497, Q99LX0, Q9FPF0, Q9MAH3, Q9V1F8, Q9VA37, O06006, Q9M8R4, P47275, Q8G9F9, Q5JGM7

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PARK7	“form complex”	“MTA1/DJ1 complex”	binding
PRKN	“down-regulates quantity by destabilization”	PARK7	ubiquitination
MAPKAPK5	“up-regulates activity”	PARK7	phosphorylation
AKT1	“up-regulates activity”	PARK7	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 130 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RAF activation	5	16.5×	3e-03
Negative regulation of MAPK pathway	5	13.0×	3e-03
Toll Like Receptor 10 (TLR10) Cascade	5	10.6×	4e-03
Toll Like Receptor 5 (TLR5) Cascade	5	10.6×	4e-03
MyD88 cascade initiated on plasma membrane	5	10.0×	5e-03
Signaling by NTRK1 (TRKA)	5	9.7×	5e-03
Toll Like Receptor 3 (TLR3) Cascade	5	9.5×	5e-03
TRIF (TICAM1)-mediated TLR4 signaling	5	9.3×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
extrinsic apoptotic signaling pathway via death domain receptors	5	17.4×	3e-03
endocytosis	8	6.6×	6e-03
negative regulation of gene expression	11	6.6×	1e-03
positive regulation of apoptotic process	11	5.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	7
Uncertain significance	56
Likely benign	31
Benign	41

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
1334459	NM_007262.5(PARK7):c.322G>A (p.Gly108Ser)	Pathogenic
1399835	NM_007262.5(PARK7):c.82C>T (p.Arg28Ter)	Pathogenic
2425707	NC_000001.10:g.(?8022846)(8037818_?)del	Pathogenic
447914	NM_007262.5(PARK7):c.191_192del (p.Glu64fs)	Pathogenic
573287	NM_007262.5(PARK7):c.105dup (p.Ala36fs)	Pathogenic
584372	NC_000001.11:g.(?7969325)(7969424_?)del	Pathogenic
7063	nsv513788	Pathogenic
7064	NM_007262.5(PARK7):c.497T>C (p.Leu166Pro)	Pathogenic
7065	NM_007262.5(PARK7):c.78G>A (p.Met26Ile)	Pathogenic
7067	NM_007262.5(PARK7):c.192G>C (p.Glu64Asp)	Pathogenic
7069	NM_007262.5(PARK7):c.115G>T (p.Ala39Ser)	Pathogenic
873319	NM_007262.5(PARK7):c.133C>T (p.Gln45Ter)	Pathogenic
1119998	NM_007262.5(PARK7):c.460A>G (p.Thr154Ala)	Likely pathogenic
1319906	NM_007262.5(PARK7):c.83G>A (p.Arg28Gln)	Likely pathogenic
1331350	NM_007262.5(PARK7):c.302T>C (p.Leu101Pro)	Likely pathogenic
3767169	NM_007262.5(PARK7):c.192+1G>T	Likely pathogenic
623671	NM_007262.5(PARK7):c.189dup (p.Glu64fs)	Likely pathogenic
804432	NM_007262.5(PARK7):c.90+1dup	Likely pathogenic
987356	NM_007262.5(PARK7):c.471_473del (p.Pro158del)	Likely pathogenic

SpliceAI

1052 predictions. Top by Δscore:

Variant	Effect	Δscore
1:7962759:TAA:T	acceptor_loss	1.0000
1:7962760:A:AG	acceptor_gain	1.0000
1:7962760:AAG:A	acceptor_gain	1.0000
1:7962761:A:G	acceptor_gain	1.0000
1:7962761:AG:A	acceptor_gain	1.0000
1:7962762:G:GG	acceptor_gain	1.0000
1:7962762:GG:G	acceptor_gain	1.0000
1:7962762:GGC:G	acceptor_gain	1.0000
1:7962762:GGCTT:G	acceptor_gain	1.0000
1:7962873:GGG:G	donor_gain	1.0000
1:7962873:GGGGT:G	donor_loss	1.0000
1:7962874:GG:G	donor_gain	1.0000
1:7962874:GGG:G	donor_gain	1.0000
1:7962875:GG:G	donor_gain	1.0000
1:7962875:GGTAA:G	donor_loss	1.0000
1:7962876:G:GC	donor_loss	1.0000
1:7962876:G:GG	donor_gain	1.0000
1:7962877:T:TC	donor_loss	1.0000
1:7965421:AAGAG:A	donor_loss	1.0000
1:7965422:AGAG:A	donor_loss	1.0000
1:7965423:GAG:G	donor_gain	1.0000
1:7965424:AGGT:A	donor_loss	1.0000
1:7965425:GGT:G	donor_loss	1.0000
1:7965426:G:A	donor_loss	1.0000
1:7965427:T:G	donor_loss	1.0000
1:7969327:T:G	acceptor_gain	1.0000
1:7970889:A:AG	acceptor_gain	1.0000
1:7970890:C:G	acceptor_gain	1.0000
1:7970890:CTA:C	acceptor_loss	1.0000
1:7970891:TAG:T	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000011062 (1:7969910 G>A,T), RS1000178497 (1:7966980 A>G), RS1000234718 (1:7978367 C>T), RS1000316186 (1:7966745 CTGTT>C), RS1000392238 (1:7962221 A>T), RS1000447896 (1:7972084 T>C), RS1000481904 (1:7967690 A>G), RS1000605417 (1:7970688 T>A,G), RS1000823782 (1:7976542 T>C), RS1000863991 (1:7961784 C>G), RS1001035123 (1:7983019 T>A), RS1001056615 (1:7970702 T>C), RS1001077135 (1:7976608 C>A,T), RS1001274317 (1:7973219 C>G), RS1001464874 (1:7983270 C>T)

Disease associations

OMIM: gene MIM:602533 | disease phenotypes: MIM:606324, MIM:137920, MIM:105500, MIM:168600

GenCC curated gene-disease

Disease	Classification	Inheritance
Parkinson disease	Definitive	Autosomal recessive
autosomal recessive early-onset Parkinson disease 7	Strong	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 (8): autosomal recessive early-onset Parkinson disease 7 (MONDO:0011658), young-onset Parkinson disease (MONDO:0017279), juvenile-onset Parkinson disease (MONDO:0000828), motor neuron disorder (MONDO:0020128), renal cysts and diabetes syndrome (MONDO:0007669), amyotrophic lateral sclerosis-parkinsonism-dementia complex (MONDO:0007104), late-onset Parkinson disease (MONDO:0008199), Parkinson disease (MONDO:0005180)

Orphanet (5): Young-onset Parkinson disease (Orphanet:2828), Motor neuron disease (Orphanet:98503), HNF1B-related autosomal dominant tubulointerstitial kidney disease (Orphanet:93111), Parkinson-dementia complex of Guam (Orphanet:90020), Hereditary late-onset Parkinson disease (Orphanet:411602)

HPO phenotypes

44 total (30 of 44 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000551	Color vision defect
HP:0000643	Blepharospasm
HP:0000651	Diplopia
HP:0000713	Agitation
HP:0000716	Depression
HP:0000725	Psychotic episodes
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:0001332	Dystonia
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001348	Brisk reflexes
HP:0002014	Diarrhea
HP:0002018	Nausea
HP:0002019	Constipation
HP:0002063	Rigidity
HP:0002067	Bradykinesia
HP:0002141	Gait imbalance
HP:0002172	Postural instability
HP:0002174	Postural tremor
HP:0002322	Resting tremor
HP:0002548	Parkinsonism with favorable response to dopaminergic medication
HP:0002578	Gastroparesis
HP:0003394	Muscle spasm

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000612_39	Celiac disease	9.000000e-08
GCST000964_5	Ulcerative colitis	5.000000e-09
GCST002286_3	Ischemic stroke	2.000000e-07
GCST004131_79	Inflammatory bowel disease	1.000000e-12
GCST004132_92	Crohn’s disease	3.000000e-06
GCST004133_62	Ulcerative colitis	4.000000e-09
GCST005537_150	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	9.000000e-14
GCST006585_874	Blood protein levels	1.000000e-06
GCST012073_9	Behcet’s disease	2.000000e-06

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D016472	Motor Neuron Disease	C10.574.562; C10.668.467
D010300	Parkinson Disease	C10.228.140.079.862.500; C10.228.662.600.400; C10.574.928.750
C565238	Parkinson Disease 7, Autosomal Recessive Early-Onset (supp.)
C535520	Renal cysts and diabetes syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5169188 (SINGLE PROTEIN), CHEMBL6066048 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

35 potent at pChembl≥5 of 36 total, top 30 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.72	IC50	19	nM	CHEMBL5559797
7.68	IC50	21	nM	CHEMBL5559582
7.26	IC50	54.6	nM	CHEMBL5202724
7.26	Kd	54.81	nM	CHEMBL5653589
7.26	ED50	54.81	nM	CHEMBL5653589
7.20	IC50	62.6	nM	CHEMBL406190
7.07	IC50	85	nM	CHEMBL5192433
7.00	IC50	100	nM	CHEMBL5559797
6.93	IC50	118	nM	CHEMBL5172713
6.93	IC50	118	nM	CHEMBL5176828
6.92	IC50	120	nM	JYQ88
6.89	IC50	130	nM	JYQ88
6.89	IC50	130	nM	CHEMBL5172713
6.75	IC50	180	nM	CHEMBL5205386
6.62	IC50	240	nM	JYQ88
6.57	IC50	267	nM	CHEMBL395485
6.45	IC50	356	nM	CHEMBL5183846
6.29	IC50	510	nM	CHEMBL5209355
6.17	IC50	676	nM	CHEMBL244322
6.16	IC50	700	nM	CHEMBL5200261
6.15	IC50	701	nM	CHEMBL3128205
6.07	IC50	851	nM	CHEMBL5198554
5.77	IC50	1700	nM	CHEMBL5198428
5.65	IC50	2240	nM	CHEMBL6195036
5.63	IC50	2350	nM	CHEMBL5200625
5.62	IC50	2410	nM	CHEMBL396549
5.53	IC50	2930	nM	CHEMBL5170211
5.44	IC50	3600	nM	CHEMBL6195036
5.01	IC50	9790	nM	CHEMBL5207294
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

26 with measured affinity, of 128 total; 23 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3R)-1-cyano-N-[5-[2-fluoro-5-(triazol-1-yl)benzoyl]-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-2-yl]pyrrolidine-3-carboxamide	2071306: Inhibition of PARK7 (unknown origin) using DiFUMAc as substrate preincubated for 1 hrs followed by substrate addition and measured after 1 hrs by fluorescence plate reader analysis	ic50	0.0190	uM
(3R)-1-cyano-N-[5-(3-morpholin-4-ylsulfonylbenzoyl)-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-2-yl]pyrrolidine-3-carboxamide	2071306: Inhibition of PARK7 (unknown origin) using DiFUMAc as substrate preincubated for 1 hrs followed by substrate addition and measured after 1 hrs by fluorescence plate reader analysis	ic50	0.0210	uM
5-fluoro-7-methoxy-1-(2-phenylethyl)indole-2,3-dione	1881353: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate	ic50	0.0546	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148937: Binding affinity to human PARK7 incubated for 45 mins by Kinobead based pull down assay	kd	0.0548	uM
5,7-dibromo-1-(2-phenylethyl)indole-2,3-dione	1881353: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate	ic50	0.0626	uM
3-chloro-5-fluoro-1-(2-phenylethyl)-3H-indol-2-one	1881353: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate	ic50	0.0850	uM
1-ethyl-5-fluoroindole-2,3-dione	1881353: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate	ic50	0.1180	uM
5-fluoro-1-(2-phenylethyl)indole-2,3-dione	1881353: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate	ic50	0.1180	uM
(3R)-N-[5-(2-azidoacetyl)-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-2-yl]-1-cyanopyrrolidine-3-carboxamide	2071306: Inhibition of PARK7 (unknown origin) using DiFUMAc as substrate preincubated for 1 hrs followed by substrate addition and measured after 1 hrs by fluorescence plate reader analysis	ic50	0.1200	uM
4-(2-phenylethyl)naphthalene-1,2-dione	1881353: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate	ic50	0.1800	uM
5,7-dibromo-1-[(4-methoxyphenyl)methyl]indole-2,3-dione	1881353: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate	ic50	0.2670	uM
5-fluoro-1-[(1-phenylcyclopropyl)methyl]indole-2,3-dione	1881353: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate	ic50	0.3560	uM
N-(2-hydroxy-5-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl)-3-prop-2-ynoxynaphthalene-2-carboxamide	1881353: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate	ic50	0.5100	uM
5,7-dibromo-1-[(4-methylphenyl)methyl]indole-2,3-dione	1881353: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate	ic50	0.6760	uM
3,5-difluoro-1-(2-phenylethyl)-3H-indol-2-one	1881353: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate	ic50	0.7000	uM
1-(2-phenylethyl)indole-2,3-dione	1881353: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate	ic50	0.7010	uM
1-(3,3-dimethylbutyl)-5-fluoroindole-2,3-dione	1881353: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate	ic50	0.8510	uM
3,3-dichloro-5-fluoro-1-(2-phenylethyl)indol-2-one	1881353: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate	ic50	1.7000	uM
2-[2,3-dioxo-1-(2-phenylethyl)indol-6-yl]acetic acid	1881353: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate	ic50	2.3500	uM
5,7-dibromo-1-[[4-(trifluoromethyl)phenyl]methyl]indole-2,3-dione	1881353: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate	ic50	2.4100	uM
5-methoxy-1-(2-phenylethyl)indole-2,3-dione	1881353: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate	ic50	2.9300	uM
2,3-dioxo-1-(2-phenylethyl)indole-5-carboxylic acid	1881353: Inhibition of pET3a-His-tagged DJ1 (unknown origin) expressed in Escherichia coli BL21 assessed as decrease in esterase activity using DiFMUAc as substrate	ic50	9.7900	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178993: Inhibition of DJ-1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Rotenone	increases response to substance, decreases response to substance, affects reaction, increases reaction, affects response to substance (+8 more)	11
Paraquat	increases expression, decreases reaction, increases oxidation, affects binding, increases reaction (+4 more)	9
bisphenol A	increases expression, increases methylation, affects expression, affects binding, increases reaction	5
Acetylcysteine	increases reaction, increases expression, decreases reaction, increases oxidation, affects cotreatment (+1 more)	4
sodium arsenite	decreases expression, increases expression	2
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases reaction, increases oxidation, increases sulfation, decreases response to substance	2
4-phenylbutyric acid	decreases reaction, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Copper	increases abundance, affects binding, affects cotreatment, decreases expression	2
Hydrogen Peroxide	increases expression, decreases response to substance	2
Maneb	decreases reaction, increases oxidation, decreases activity, affects cotreatment	2
Mercury	affects binding, increases expression	2
Smoke	decreases expression	2
Thiram	decreases activity, decreases expression	2
Valproic Acid	affects cotreatment, increases expression, affects expression	2
Oxidopamine	increases expression, decreases response to substance, affects localization, affects binding, increases reaction	2
Cadmium Chloride	increases abundance, increases expression, decreases expression	2
GSK-J4	decreases expression	1
3-(4-(morpholin-4-yl)-7H-pyrrolo(2,3-d)pyrimidin-5-yl)benzonitrile	affects cotreatment, decreases reaction, increases oxidation	1
dicrotophos	decreases expression	1
folpet	decreases activity	1
dienochlor	decreases activity	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, decreases expression, affects cotreatment	1
oxamyl	decreases activity	1
propineb	decreases activity	1
mancozeb	decreases activity, increases oxidation	1
pirimiphos methyl	decreases activity	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1

ChEMBL screening assays

62 unique, capped per target: 62 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5106878	Binding	Binding affinity to PARK7 in human HEK293T cells at 1 uM incubated for 1 hr by fluorescence scanning based analysis	Chemical Toolkit for PARK7: Potent, Selective, and High-Throughput. — J Med Chem

Cellosaurus cell lines

34 cell lines: 16 induced pluripotent stem cell, 13 embryonic stem cell, 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A1WA	FJMUUHi001-A	Induced pluripotent stem cell	Male
CVCL_B0PI	TMOi001-A-3	Induced pluripotent stem cell	Female
CVCL_B3DD	Abcam HEK293T PARK7 KO	Transformed cell line	Female
CVCL_C0J9	LCSBi008-A	Induced pluripotent stem cell	Male
CVCL_C0JA	LCSBi008-A-1	Induced pluripotent stem cell	Male
CVCL_C6TL	CIBi013-A	Induced pluripotent stem cell	Male
CVCL_C7UU	WIBR3_DJ1_X1-5DEL_2073	Embryonic stem cell	Female
CVCL_C7UV	WIBRe001-A-26	Embryonic stem cell	Female
CVCL_C7UW	WIBRe001-A-27	Embryonic stem cell	Female
CVCL_C7UX	WIBRe001-A-28	Embryonic stem cell	Female

Clinical trials (associated diseases)

417 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
NCT00526630	PHASE4	COMPLETED	Methylphenidate for the Treatment of Gait Impairment in Parkinson’s Disease
NCT00561678	PHASE4	COMPLETED	Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve
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
NCT00601978	PHASE4	WITHDRAWN	Carbidopa/Levodopa Versus Carbidopa/Levodopa/Entacapone on Markers of Event Related Potentials (ERPs) in Patients With Idiopathic Parkinson’s Disease (PD) and End-of-dose Wearing Off
NCT00632762	PHASE4	COMPLETED	Long-Term Effects of Amantadine in Parkinsonian (AMANDYSK)
NCT00640159	PHASE4	COMPLETED	Selegiline to Zelapar Switch Study in Parkinson Disease Patients
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