autosomal recessive early-onset Parkinson disease 7

Summary

autosomal recessive early-onset Parkinson disease 7 (MONDO:0011658) is a disease caused by PARK7 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PARK7 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 89

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive early-onset Parkinson disease 7
Mondo ID	MONDO:0011658
MeSH	C565238
OMIM	606324
DOID	DOID:0060370
UMLS	C1853445
MedGen	344049
GARD	0018606
Is cancer (heuristic)	no

Also known as: autosomal recessive early-onset Parkinson disease 7 · autosomal recessive early-onset Parkinson disease type 7 · PARK7 · PARK7 Parkinson disease · Parkinson disease 7, autosomal recessive early-onset · Parkinson disease caused by mutation in PARK7

Data availability: 89 ClinVar variants · 3 GenCC gene-disease records · 28 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › basal ganglia disorder › parkinsonian disorder › Parkinson disease › young-onset Parkinson disease › autosomal recessive early-onset Parkinson disease 7

Related subtypes (8): juvenile-onset Parkinson disease, Parkinson disease 12, autosomal recessive juvenile Parkinson disease 2, Parkinson disease 3, autosomal dominant, autosomal recessive early-onset Parkinson disease 6, Parkinson disease 10, early-onset Parkinson disease 20, autosomal recessive early-onset Parkinson disease 23

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

89 retrieved; paginated sample, class counts are floors:

38 uncertain significance, 25 likely benign, 11 pathogenic, 6 benign, 5 likely pathogenic, 3 benign/likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
446717	NM_007262.4(PARK7):c.[-24+75_-24+92dup;487G>A]		Pathogenic	no assertion criteria provided
1334459	NM_007262.5(PARK7):c.322G>A (p.Gly108Ser)	PARK7	Pathogenic	criteria provided, single submitter
1399835	NM_007262.5(PARK7):c.82C>T (p.Arg28Ter)	PARK7	Pathogenic	criteria provided, single submitter
2425707	NC_000001.10:g.(?8022846)(8037818_?)del	PARK7	Pathogenic	criteria provided, single submitter
447914	NM_007262.5(PARK7):c.191_192del (p.Glu64fs)	PARK7	Pathogenic	criteria provided, multiple submitters, no conflicts
573287	NM_007262.5(PARK7):c.105dup (p.Ala36fs)	PARK7	Pathogenic	criteria provided, multiple submitters, no conflicts
584372	NC_000001.11:g.(?7969325)(7969424_?)del	PARK7	Pathogenic	criteria provided, single submitter
7063	nsv513788	PARK7	Pathogenic	no assertion criteria provided
7064	NM_007262.5(PARK7):c.497T>C (p.Leu166Pro)	PARK7	Pathogenic	no assertion criteria provided
7065	NM_007262.5(PARK7):c.78G>A (p.Met26Ile)	PARK7	Pathogenic	no assertion criteria provided
7067	NM_007262.5(PARK7):c.192G>C (p.Glu64Asp)	PARK7	Pathogenic	no assertion criteria provided
1319906	NM_007262.5(PARK7):c.83G>A (p.Arg28Gln)	PARK7	Likely pathogenic	no assertion criteria provided
1331350	NM_007262.5(PARK7):c.302T>C (p.Leu101Pro)	PARK7	Likely pathogenic	criteria provided, single submitter
3767169	NM_007262.5(PARK7):c.192+1G>T	PARK7	Likely pathogenic	criteria provided, single submitter
804432	NM_007262.5(PARK7):c.90+1dup	PARK7	Likely pathogenic	criteria provided, single submitter
987356	NM_007262.5(PARK7):c.471_473del (p.Pro158del)	PARK7	Likely pathogenic	criteria provided, multiple submitters, no conflicts
707607	NM_007262.5(PARK7):c.501A>G (p.Ala167=)	PARK7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1015099	NM_007262.5(PARK7):c.16G>T (p.Ala6Ser)	PARK7	Uncertain significance	criteria provided, single submitter
1338986	NM_007262.5(PARK7):c.253T>C (p.Ser85Pro)	PARK7	Uncertain significance	criteria provided, single submitter
1365948	NM_007262.5(PARK7):c.233G>A (p.Gly78Asp)	PARK7	Uncertain significance	criteria provided, single submitter
1419175	NM_007262.5(PARK7):c.395A>G (p.Lys132Arg)	PARK7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1425067	NM_007262.5(PARK7):c.437T>G (p.Val146Gly)	PARK7	Uncertain significance	criteria provided, single submitter
1468432	NM_007262.5(PARK7):c.271A>G (p.Ile91Val)	PARK7	Uncertain significance	criteria provided, single submitter
1519810	NM_007262.5(PARK7):c.328A>G (p.Thr110Ala)	PARK7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1931055	NM_007262.5(PARK7):c.444dup (p.Asp149fs)	PARK7	Uncertain significance	criteria provided, single submitter
1943858	NM_007262.5(PARK7):c.482G>C (p.Ser161Thr)	PARK7	Uncertain significance	criteria provided, single submitter
2049252	NM_007262.5(PARK7):c.103G>A (p.Val35Ile)	PARK7	Uncertain significance	criteria provided, multiple submitters, no conflicts
2055014	NM_007262.5(PARK7):c.494C>T (p.Ala165Val)	PARK7	Uncertain significance	criteria provided, single submitter
2202253	NM_007262.5(PARK7):c.142C>T (p.Arg48Cys)	PARK7	Uncertain significance	criteria provided, single submitter
2202695	NM_007262.5(PARK7):c.515T>A (p.Leu172Gln)	PARK7	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

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

Gene	Classification	Inheritance	Disease	Records
PARK7	Definitive	Autosomal recessive	Parkinson disease	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PARK7	Orphanet:2828	Young-onset Parkinson disease
PARK7	Orphanet:90020	Parkinson-dementia complex of Guam

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PARK7	HGNC:16369	ENSG00000116288	Q99497	Parkinson disease protein 7	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PARK7	Parkinson disease protein 7	Multifunctional protein with controversial molecular function which plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

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

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PARK7	Enzyme (other)	yes	3.5.1.124	DJ-1/PfpI, DJ-1, Class_I_gatase-like

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
adult organism	1
deltoid	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PARK7	294	ubiquitous	marker	adult organism, tibia, deltoid

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PARK7	5,722

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PARK7	Q99497	88

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Chaperone Mediated Autophagy	1	496.5×	0.004	PARK7
Late endosomal microautophagy	1	326.3×	0.004	PARK7
Aggrephagy	1	248.3×	0.004	PARK7
SUMOylation of transcription cofactors	1	243.0×	0.004	PARK7

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of acute inflammatory response to antigenic stimulus	1	16852.0×	3e-04	PARK7
cellular response to glyoxal	1	16852.0×	3e-04	PARK7
glycolate biosynthetic process	1	16852.0×	3e-04	PARK7
detoxification of mercury ion	1	16852.0×	3e-04	PARK7
detoxification of hydrogen peroxide	1	16852.0×	3e-04	PARK7
obsolete methylglyoxal catabolic process to lactate	1	16852.0×	3e-04	PARK7
guanine deglycation	1	16852.0×	3e-04	PARK7
obsolete guanine deglycation, methylglyoxal removal	1	16852.0×	3e-04	PARK7
guanine deglycation, glyoxal removal	1	16852.0×	3e-04	PARK7
cellular detoxification of methylglyoxal	1	16852.0×	3e-04	PARK7
regulation of supramolecular fiber organization	1	16852.0×	3e-04	PARK7
negative regulation of death-inducing signaling complex assembly	1	16852.0×	3e-04	PARK7
negative regulation of TRAIL-activated apoptotic signaling pathway	1	16852.0×	3e-04	PARK7
glyoxal metabolic process	1	16852.0×	3e-04	PARK7
obsolete positive regulation of L-dopa biosynthetic process	1	16852.0×	3e-04	PARK7
methylglyoxal metabolic process	1	8426.0×	4e-04	PARK7
detection of oxidative stress	1	8426.0×	4e-04	PARK7
negative regulation of protein K48-linked deubiquitination	1	8426.0×	4e-04	PARK7
positive regulation of dopamine biosynthetic process	1	8426.0×	4e-04	PARK7
negative regulation of nitrosative stress-induced intrinsic apoptotic signaling pathway	1	8426.0×	4e-04	PARK7
lactate biosynthetic process	1	5617.3×	6e-04	PARK7
positive regulation of mitochondrial electron transport, NADH to ubiquinone	1	5617.3×	6e-04	PARK7
negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway	1	5617.3×	6e-04	PARK7
hydrogen peroxide metabolic process	1	4213.0×	7e-04	PARK7
positive regulation of autophagy of mitochondrion	1	4213.0×	7e-04	PARK7
positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	1	3370.4×	8e-04	PARK7
regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	1	3370.4×	8e-04	PARK7
negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide	1	3370.4×	8e-04	PARK7
protein repair	1	2808.7×	9e-04	PARK7
negative regulation of protein export from nucleus	1	2106.5×	0.001	PARK7

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PARK7	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	PARK7

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PARK7	62	Binding:62

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PARK7	3.5.1.124, 4.2.1.130	protein deglycase, D-lactate dehydratase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

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

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	PARK7

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	PARK7
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.