PRKN

Chr 6AR

parkin RBR E3 ubiquitin protein ligase

Also known as: AR-JP, LPRS2, PARK2, PDJ

NCBI Gene: 5071ENSG00000185345UniProt: O60260

The precise function of this gene is unknown; however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. Mutations in this gene are known to cause Parkinson disease and autosomal recessive juvenile Parkinson disease. Alternative splicing of this gene produces multiple transcript variants encoding distinct isoforms. Additional splice variants of this gene have been described but currently lack transcript support. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Adenocarcinoma of lung, somaticMIM #211980
Ovarian cancer, somaticMIM #167000
Parkinson disease, juvenile, type 2MIM #600116
AR
UniProtParkinson disease 2
390
ClinVar variants
103
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— PRKN
🧬
Gene-Disease Validity (ClinGen)
Parkinson disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
103 Pathogenic / Likely Pathogenic· 165 VUS of 390 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.86LOEUF
pLI 0.000
Z-score 2.10
OE 0.55 (0.36–0.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.86Z-score
OE missense 1.15 (1.04–1.26)
310 obs / 270.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.55 (0.36–0.86)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.15 (1.04–1.26)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.15
0≤1.21.6
LoF obs/exp: 14 / 25.4Missense obs/exp: 310 / 270.1Syn Z: -1.23

ClinVar Variant Classifications

390 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic84
Likely Pathogenic19
VUS165
Likely Benign79
Benign38
Conflicting5
84
Pathogenic
19
Likely Pathogenic
165
VUS
79
Likely Benign
38
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
79
0
84
Likely Pathogenic
6
3
10
0
19
VUS
0
98
66
1
165
Likely Benign
0
3
37
39
79
Benign
0
3
33
2
38
Conflicting
—5
Total1110722542390

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PRKN · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Adenocarcinoma of lung, somatic

MIM #211980

Molecular basis of disorder known

Ovarian cancer, somatic

MIM #167000

Molecular basis of disorder known

Parkinson disease, juvenile, type 2

MIM #600116

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — PRKN
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Monogenic Parkinson's Disease: Genotype, Phenotype, Pathophysiology, and Genetic Testing.
Jia F et al.·Genes (Basel)
2022Review
Parkin and PINK1 mitigate STING-induced inflammation.
Sliter DA et al.·Nature
2018
Autophagy in age-related macular degeneration.
Kaarniranta K et al.·Autophagy
2023Review
PRKN-regulated mitophagy and cellular senescence during COPD pathogenesis.
Araya J et al.·Autophagy
2019
Biomarker of Neuroinflammation in Parkinson's Disease.
Liu TW et al.·Int J Mol Sci
2022Review
Autophagy deficiency abolishes liver mitochondrial DNA segregation.
Tostes K et al.·Autophagy
2022
The mutation spectrum of Parkinson-disease-related genes in early-onset Parkinson's disease in ethnic Chinese.
Chen YP et al.·Eur J Neurol
2022
Alternative mitochondrial quality control mediated by extracellular release.
Choong CJ et al.·Autophagy
2021
DJ-1 is an essential downstream mediator in PINK1/parkin-dependent mitophagy.
Imberechts D et al.·Brain
2022
The role of genetics in Parkinson's disease: a large cohort study in Chinese mainland population.
Zhao Y et al.·Brain
2020Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Alternative Translation Initiation in PRKN Delays the Onset of Parkinson's Disease and Offers a Therapeutic Target.
Hach A et al.·Ann Neurol
2026
PRKAB2 as a tumor suppressor in renal cell carcinoma: inhibiting mitophagy via the LRPPRC-PRKN/parkin interaction and cardiolipin biosynthesis.
Chen K et al.·Autophagy
2026
PRKN activation for mitophagy requires an NME3-regulated phosphatidic acid signal that separates mitochondria from endoplasmic reticulum tethering.
Chen CW et al.·Autophagy
2026
Oxidative Stress and PRKN-Mediated Senescence Link RhoA/ROCK Signaling to Epithelial Remodeling in Allergic Rhinitis.
Yuan X et al.·Antioxidants (Basel)
2026🔓 Open AccessFunctional
PRKN-Mediated Ubiquitin-Proteasome Degradation of METTL3 Promotes Cellular Senescence.
Chen L et al.·Aging Cell
2026🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Morbid ObesityBariatric SurgeryTelerehabilitation

Exercise to Fight Obesity

RECRUITING
NCT06934681Phase NAInstituto de Investigacion Sanitaria La FeStarted 2025-05-19
Usual Care GroupControlled exercise with telerehabilitation
Parkinson DiseaseNervous System DisorderNeurodegenerative Diseases

Molecular and Functional Imaging in Monogenic PD.

RECRUITING
NCT05518617University of ExeterStarted 2022-07-01
Positron Emission Tomography (PET) scan using DASB tracer

External Resources

Links to major genomics databases and tools