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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
PRKN
parkin RBR E3 ubiquitin protein ligase
Chromosome 6 Β· 6q26
NCBI Gene: 5071Ensembl: ENSG00000185345.25HGNC: HGNC:8607UniProt: O60260
989PubMed Papers
22Diseases
0Drugs
91Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTranscription Factor
RESEARCH IMPACT
Highly StudiedTrendingVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
SCF ubiquitin ligase complexnegative regulation of glucokinase activitynegative regulation of insulin secretionmitochondrionYoung adult-onset Parkinsonismyoung-onset Parkinson diseaselung cancerovarian cancer
✦AI Summary

PRKN encodes parkin, an E3 ubiquitin ligase that plays a critical role in mitochondrial quality control and cellular homeostasis. The protein functions within the PINK1-PRKN pathway to regulate mitophagy, the selective degradation of damaged or dysfunctional mitochondria 12. Upon mitochondrial damage, PINK1 phosphorylation activates PRKN, which then ubiquitinates mitochondrial proteins including VDAC1, TOMM20, and MFN1/MFN2 to promote mitophagy 31. PRKN catalyzes various types of ubiquitination (K6, K11, K48, K63-linked) depending on cellular context and substrate requirements 4. Beyond mitophagy, PRKN protects cells from inflammatory responses triggered by mitochondrial damage-associated molecular patterns, as demonstrated in PRKN knockout mice showing enhanced inflammation following exhaustive exercise 5. The protein also regulates cellular senescence and oxidative stress responses, with PRKN deficiency leading to accumulation of damaged mitochondria and accelerated aging in disease models 6. Mutations in PRKN cause early-onset Parkinson's disease, highlighting its critical role in neuronal survival 7. Therapeutically, compounds that enhance PRKN-mediated mitophagy show promise for neurodegenerative diseases, while PRKN dysregulation contributes to cancer cell survival under metabolic stress 8.

Sources cited
1
PRKN and PINK1 mitigate inflammatory responses by preventing STING-mediated inflammation following mitochondrial damage
PMID: 30135585
2
PRKN regulates mitophagy and cellular senescence, with deficiency leading to enhanced airway damage in COPD models
PMID: 30290714
3
PHB2 promotes PINK1-PRKN mitophagy through stabilization of PINK1 and recruitment of PRKN to mitochondria
PMID: 31177901
4
PRKN-mediated ubiquitination of VDAC1 triggers mitophagy, with regulation by GPCPD1 under hypoxic conditions
PMID: 36803235
5
USP33 deubiquitinates PRKN and antagonizes its role in mitophagy, particularly affecting K63-linked ubiquitination
PMID: 31432739
6
Spautin-1 promotes PINK1-PRKN-dependent mitophagy by stabilizing PINK1 at the outer mitochondrial membrane
PMID: 39051473
7
PRKN mutations cause early-onset Parkinson's disease and the PINK1/PRKN pathway is central to mitochondrial quality control
PMID: 33323315
8
MANF facilitates breast cancer cell survival through PRKN-mediated mitophagy regulation under glucose starvation conditions
PMID: 39147386
Disease Associationsβ“˜22
Young adult-onset ParkinsonismOpen Targets
0.84Strong
young-onset Parkinson diseaseOpen Targets
0.60Moderate
lung cancerOpen Targets
0.58Moderate
ovarian cancerOpen Targets
0.57Moderate
DystoniaOpen Targets
0.51Moderate
Parkinson diseaseOpen Targets
0.48Moderate
ovarian neoplasmOpen Targets
0.46Moderate
diabetes mellitusOpen Targets
0.42Moderate
Abnormality of the skeletal systemOpen Targets
0.41Moderate
type 2 diabetes mellitusOpen Targets
0.40Moderate
Parkinson disease 12Open Targets
0.37Weak
leprosyOpen Targets
0.35Weak
smoking initiationOpen Targets
0.35Weak
obesityOpen Targets
0.34Weak
lung carcinomaOpen Targets
0.34Weak
Hereditary late-onset Parkinson diseaseOpen Targets
0.34Weak
autism spectrum disorderOpen Targets
0.34Weak
cervical carcinomaOpen Targets
0.34Weak
hypertensionOpen Targets
0.33Weak
Tietze syndromeOpen Targets
0.32Weak
Parkinson diseaseUniProt
Parkinson disease 2UniProt
Pathogenic Variants91
NM_004562.3(PRKN):c.155del (p.Asn52fs)Pathogenic
Autosomal recessive juvenile Parkinson disease 2|not provided|Lung cancer;Ovarian cancer;Autosomal recessive juvenile Parkinson disease 2
β˜…β˜…β˜†β˜†2026β†’ Residue 52
NM_004562.3(PRKN):c.850G>C (p.Gly284Arg)Pathogenic
not provided|Autism spectrum disorder|Autosomal recessive juvenile Parkinson disease 2
β˜…β˜…β˜†β˜†2026β†’ Residue 284
NM_004562.3(PRKN):c.101_102del (p.Gln34fs)Pathogenic
not provided|Young-onset Parkinson disease|Autosomal recessive juvenile Parkinson disease 2
β˜…β˜…β˜†β˜†2025β†’ Residue 34
NM_004562.3(PRKN):c.823C>T (p.Arg275Trp)Pathogenic
Autosomal recessive juvenile Parkinson disease 2|not provided|Young-onset Parkinson disease|Autosomal recessive juvenile Parkinson disease 2;Ovarian neoplasm;Leprosy, susceptibility to, 2;Lung carcinoma|See cases|PRKN-related disorder|Parkinson disease 12|Ovarian cancer|Ovarian cancer;Autosomal recessive juvenile Parkinson disease 2;Lung cancer
β˜…β˜…β˜†β˜†2025β†’ Residue 275
NM_004562.3(PRKN):c.125G>C (p.Arg42Pro)Pathogenic
not provided|Autosomal recessive juvenile Parkinson disease 2
β˜…β˜…β˜†β˜†2025β†’ Residue 42
NM_004562.3(PRKN):c.758G>A (p.Cys253Tyr)Pathogenic
not provided|Autosomal recessive juvenile Parkinson disease 2|Ovarian cancer|Ovarian cancer;Lung cancer;Autosomal recessive juvenile Parkinson disease 2
β˜…β˜…β˜†β˜†2025β†’ Residue 253
NM_004562.3(PRKN):c.167T>A (p.Val56Glu)Pathogenic
Autosomal recessive juvenile Parkinson disease 2|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 56
NM_004562.3(PRKN):c.1083+1delPathogenic
Autosomal recessive juvenile Parkinson disease 2|not provided
β˜…β˜…β˜†β˜†2025
NM_004562.3(PRKN):c.1289G>A (p.Gly430Asp)Pathogenic
Autosomal recessive juvenile Parkinson disease 2|not provided|PRKN-related disorder|Young-onset Parkinson disease|Ovarian cancer|Ovarian cancer;Autosomal recessive juvenile Parkinson disease 2;Lung cancer
β˜…β˜…β˜†β˜†2025β†’ Residue 430
NM_004562.3(PRKN):c.633A>T (p.Lys211Asn)Pathogenic
Autosomal recessive juvenile Parkinson disease 2|not provided|Ovarian cancer;Autosomal recessive juvenile Parkinson disease 2;Lung cancer|Ovarian cancer
β˜…β˜…β˜†β˜†2025β†’ Residue 211
NM_004562.3(PRKN):c.337_376del (p.Pro113fs)Pathogenic
not provided|Autosomal recessive juvenile Parkinson disease 2|Autosomal recessive juvenile Parkinson disease 2;Ovarian cancer;Lung cancer
β˜…β˜…β˜†β˜†2024β†’ Residue 113
NM_004562.3(PRKN):c.1321T>C (p.Cys441Arg)Pathogenic
not provided|Autosomal recessive juvenile Parkinson disease 2|Autosomal recessive juvenile Parkinson disease 2;Ovarian cancer;Lung cancer
β˜…β˜…β˜†β˜†2024β†’ Residue 441
NM_004562.3(PRKN):c.601_602insA (p.Cys201Ter)Pathogenic
not provided|Lung adenocarcinoma
β˜…β˜…β˜†β˜†2024β†’ Residue 201
NM_004562.3(PRKN):c.635G>A (p.Cys212Tyr)Pathogenic
Autosomal recessive juvenile Parkinson disease 2|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 212
NM_004562.3(PRKN):c.98G>A (p.Arg33Gln)Pathogenic
not provided|PRKN-related disorder|Lung cancer;Ovarian cancer;Autosomal recessive juvenile Parkinson disease 2|Autosomal recessive juvenile Parkinson disease 2
β˜…β˜…β˜†β˜†2024β†’ Residue 33
NM_004562.3(PRKN):c.992del (p.Leu331fs)Likely pathogenic
not provided|Ovarian cancer;Lung cancer;Autosomal recessive juvenile Parkinson disease 2
β˜…β˜…β˜†β˜†2024β†’ Residue 331
NM_004562.3(PRKN):c.220_221dup (p.Trp74fs)Pathogenic
not provided|Autosomal recessive juvenile Parkinson disease 2|Ovarian cancer;Lung cancer;Autosomal recessive juvenile Parkinson disease 2
β˜…β˜…β˜†β˜†2024β†’ Residue 74
NM_004562.3(PRKN):c.1A>G (p.Met1Val)Pathogenic
not provided|Young-onset Parkinson disease
β˜…β˜…β˜†β˜†2023β†’ Residue 1
NM_004562.3(PRKN):c.73C>T (p.Gln25Ter)Pathogenic
not provided|Lung cancer;Ovarian neoplasm;Autosomal recessive juvenile Parkinson disease 2
β˜…β˜…β˜†β˜†2022β†’ Residue 25
NM_004562.3(PRKN):c.804T>A (p.Cys268Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2021β†’ Residue 268
View on ClinVar β†—
Related Genes
HSP90AA1Protein interaction100%UBE2NProtein interaction100%UBA52Protein interaction100%SLC6A3Protein interaction100%SNCAIPProtein interaction100%ADRM1Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Brain
18%
Ovary
11%
Liver
5%
Lung
5%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
PRKNHSP90AA1UBE2NUBA52SLC6A3SNCAIPADRM1
PROTEIN STRUCTURE
Preparing viewer…
PDB4I1F Β· 1.58 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.17LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.92 [0.72–1.17]
RankingsWhere PRKN stands among ~20K protein-coding genes
  • #164of 20,598
    Most Researched989 Β· top 1%
  • #834of 5,498
    Most Pathogenic Variants91 Β· top quartile
  • #12,241of 17,882
    Most Constrained (LOEUF)1.17
Genes detectedPRKN
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
Parkin and PINK1 mitigate STING-induced inflammation.
PMID: 30135585
Nature Β· 2018
1.00
2
PRKN-regulated mitophagy and cellular senescence during COPD pathogenesis.
PMID: 30290714
Autophagy Β· 2019
0.90
3
Parkinson's disease variant detection and disclosure: PD GENEration, a North American study.
PMID: 39074992
Brain Β· 2024
0.80
4
PHB2 (prohibitin 2) promotes PINK1-PRKN/Parkin-dependent mitophagy by the PARL-PGAM5-PINK1 axis.
PMID: 31177901
Autophagy Β· 2020
0.80
5
Mitophagy.
PMID: 24070474
Essays Biochem Β· 2013
0.78