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GeneE
25 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.
PINK1
PTEN induced kinase 1
Chromosome 1 Β· 1p36.12
NCBI Gene: 65018Ensembl: ENSG00000158828.9HGNC: HGNC:14581UniProt: Q9BXM7
510PubMed Papers
21Diseases
0Drugs
47Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneKinase
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
hemopoiesismagnesium ion bindingprotease bindingprotein kinase activityYoung adult-onset ParkinsonismParkinson disease 6DystoniaParkinson disease
✦AI Summary

PINK1 (PTEN-induced kinase 1) is a serine/threonine kinase that functions as a mitochondrial damage sensor, orchestrating cellular responses ranging from cytoprotection to elimination of severely compromised mitochondria 1. Under normal conditions, PINK1 transits through the mitochondrial outer membrane via the TOM complex and is cleaved and released into the cytosol 1. Upon mitochondrial depolarization or stress, PINK1 accumulates at the outer mitochondrial membrane where it phosphorylates polyubiquitin chains at Ser-65, recruiting and activating PARKIN (PRKN) to initiate selective autophagy of damaged mitochondria (mitophagy) 2. PINK1 recruits autophagy receptors NDP52 and optineurin to mitochondria, which then recruit upstream autophagy machinery including ULK1 and WIPI1 2. The PINK1-PRKN pathway also promotes mitochondrial fission through phosphorylation of fission proteins like MFN2 and activation of DNM1L, preventing refusion of damaged mitochondria with healthy networks 3. PINK1 mutations cause early-onset Parkinson's disease 1, and impaired PINK1/PRKN-mediated mitophagy contributes to multiple neurodegenerative disorders including Alzheimer's disease and amyotrophic lateral sclerosis 3. Additionally, PINK1-regulated mitophagy dysfunction is implicated in COPD pathogenesis and hepatocellular carcinoma, suggesting therapeutic potential in modulating this pathway 45.

Sources cited
1
PINK1 is a mitochondrial damage sensor; structurally stabilized at TOM-VDAC complexes; translocates through TOM40 and is cleaved in healthy mitochondria
PMID: 40080546
2
PINK1 phosphorylates ubiquitin at Ser-65 to activate PARKIN; recruits NDP52 and optineurin autophagy receptors to mitochondria independent of PARKIN; phospho-ubiquitin serves as autophagy signal
PMID: 26266977
3
PINK1/PARKIN mutations cause familial Parkinson's disease; impaired mitophagy contributes to Alzheimer's, Huntington's, amyotrophic lateral sclerosis and eye diseases; gene augmentation therapeutic potential
PMID: 33168089
4
PINK1-PRKN-mediated mitophagy dysfunction implicated in COPD pathogenesis; PRKN levels rate-limiting in cigarette smoke-induced mitochondrial damage and cellular senescence
PMID: 30290714
5
PINK1-PRKN mitophagy dysfunction involved in hepatocellular carcinoma drug resistance; CDK9 inhibitors block PINK1-PRKN pathway via SIRT1-FOXO3-BNIP3 axis
PMID: 34890308
Disease Associationsβ“˜21
Young adult-onset ParkinsonismOpen Targets
0.84Strong
Parkinson disease 6Open Targets
0.56Moderate
DystoniaOpen Targets
0.51Moderate
Parkinson diseaseOpen Targets
0.42Moderate
young-onset Parkinson diseaseOpen Targets
0.37Weak
genetic disorderOpen Targets
0.19Weak
neuroblastomaOpen Targets
0.14Weak
late-onset Parkinson diseaseOpen Targets
0.14Weak
Hereditary late-onset Parkinson diseaseOpen Targets
0.14Weak
leprosyOpen Targets
0.13Weak
neoplasmOpen Targets
0.10Weak
hepatocellular carcinomaOpen Targets
0.10Weak
acute kidney injuryOpen Targets
0.10Weak
cancerOpen Targets
0.10Suggestive
esophageal squamous cell carcinomaOpen Targets
0.10Suggestive
non-small cell lung carcinomaOpen Targets
0.09Suggestive
Miyoshi myopathyOpen Targets
0.09Suggestive
Alzheimer diseaseOpen Targets
0.09Suggestive
osteosarcomaOpen Targets
0.08Suggestive
ovarian cancerOpen Targets
0.08Suggestive
Parkinson disease 6UniProt
Pathogenic Variants47
NM_032409.3(PINK1):c.1474C>T (p.Arg492Ter)Pathogenic
not provided|Autosomal recessive early-onset Parkinson disease 6|PINK1-related disorder|Thymoma
β˜…β˜…β˜†β˜†2025β†’ Residue 492
NM_032409.3(PINK1):c.1040T>C (p.Leu347Pro)Pathogenic
Autosomal recessive early-onset Parkinson disease 6|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 347
NM_032409.3(PINK1):c.1252-2_1272delLikely pathogenic
Autosomal recessive early-onset Parkinson disease 6
β˜…β˜…β˜†β˜†2025
NM_032409.3(PINK1):c.268_283del (p.Trp90fs)Pathogenic
Autosomal recessive early-onset Parkinson disease 6
β˜…β˜…β˜†β˜†2025β†’ Residue 90
NM_032409.3(PINK1):c.1366C>T (p.Gln456Ter)Pathogenic
Autosomal recessive early-onset Parkinson disease 6|not provided|PINK1-related disorder
β˜…β˜…β˜†β˜†2024β†’ Residue 456
NM_032409.3(PINK1):c.938C>T (p.Thr313Met)Pathogenic
Autosomal recessive early-onset Parkinson disease 6
β˜…β˜…β˜†β˜†2024β†’ Residue 313
NM_032409.3(PINK1):c.960-2A>GLikely pathogenic
PINK1-related disorder|Autosomal recessive early-onset Parkinson disease 6
β˜…β˜…β˜†β˜†2024
NM_032409.3(PINK1):c.1252-1G>APathogenic
Autosomal recessive early-onset Parkinson disease 6
β˜…β˜…β˜†β˜†2023
NM_032409.3(PINK1):c.1501C>T (p.Arg501Ter)Pathogenic
Autosomal recessive early-onset Parkinson disease 6|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 501
NM_032409.3(PINK1):c.774C>A (p.Tyr258Ter)Pathogenic
Autosomal recessive early-onset Parkinson disease 6|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 258
NM_032409.3(PINK1):c.13C>T (p.Gln5Ter)Pathogenic
Autosomal recessive early-onset Parkinson disease 6
β˜…β˜†β˜†β˜†2025β†’ Residue 5
NM_032409.3(PINK1):c.1488+1G>APathogenic
Autosomal recessive early-onset Parkinson disease 6
β˜…β˜†β˜†β˜†2025
NM_032409.3(PINK1):c.85_106del (p.Tyr29fs)Pathogenic
Autosomal recessive early-onset Parkinson disease 6
β˜…β˜†β˜†β˜†2025β†’ Residue 29
NM_032409.3(PINK1):c.131del (p.Glu44fs)Likely pathogenic
Autosomal recessive early-onset Parkinson disease 6
β˜…β˜†β˜†β˜†2025β†’ Residue 44
NM_032409.3(PINK1):c.619C>T (p.Arg207Ter)Pathogenic
Autosomal recessive early-onset Parkinson disease 6
β˜…β˜†β˜†β˜†2025β†’ Residue 207
NM_032409.3(PINK1):c.665G>A (p.Trp222Ter)Pathogenic
Autosomal recessive early-onset Parkinson disease 6
β˜…β˜†β˜†β˜†2025β†’ Residue 222
NM_032409.3(PINK1):c.1124-1G>ALikely pathogenic
Autosomal recessive early-onset Parkinson disease 6
β˜…β˜†β˜†β˜†2025
NM_032409.3(PINK1):c.1080_1081del (p.His360fs)Likely pathogenic
Autosomal recessive early-onset Parkinson disease 6
β˜…β˜†β˜†β˜†2025β†’ Residue 360
NM_032409.3(PINK1):c.1225G>A (p.Gly409Arg)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 409
NM_032409.3(PINK1):c.1396dup (p.Tyr466fs)Pathogenic
Autosomal recessive early-onset Parkinson disease 6
β˜…β˜†β˜†β˜†2024β†’ Residue 466
View on ClinVar β†—
Related Genes
HSP90AA1Protein interaction100%HSP90AB1Protein interaction100%UBA52Protein interaction100%UBBProtein interaction100%UBCProtein interaction100%GBA1Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Heart
93%
Liver
42%
Lung
24%
Ovary
21%
Bone Marrow
9%
Gene Interaction Network
Click a node to explore
PINK1HSP90AA1HSP90AB1UBA52UBBUBCGBA1
PROTEIN STRUCTURE
Preparing viewer…
PDB9EII Β· 2.75 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.31LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.06 [0.85–1.31]
RankingsWhere PINK1 stands among ~20K protein-coding genes
  • #520of 20,598
    Most Researched510 Β· top 5%
  • #1,381of 5,498
    Most Pathogenic Variants47
  • #13,814of 17,882
    Most Constrained (LOEUF)1.31
Genes detectedPINK1
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
PINK1/PARKIN signalling in neurodegeneration and neuroinflammation.
PMID: 33168089
Acta Neuropathol Commun Β· 2020
1.00
2
Structure of human PINK1 at a mitochondrial TOM-VDAC array.
PMID: 40080546
Science Β· 2025
0.90
3
The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy.
PMID: 26266977
Nature Β· 2015
0.80
4
A new pathway for mitochondrial quality control: mitochondrial-derived vesicles.
PMID: 25107473
EMBO J Β· 2014
0.76
5
PRKN-regulated mitophagy and cellular senescence during COPD pathogenesis.
PMID: 30290714
Autophagy Β· 2019
0.70