PINK1

Chr 1AR

PTEN induced kinase 1

Also known as: BRPK, PARK6

NCBI Gene: 65018ENSG00000158828UniProt: Q9BXM7

This gene encodes a serine/threonine protein kinase that localizes to mitochondria. It is thought to protect cells from stress-induced mitochondrial dysfunction. Mutations in this gene cause one form of autosomal recessive early-onset Parkinson disease. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Parkinson disease 6, early onsetMIM #605909
AR
474
ClinVar variants
64
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— PINK1
🧬
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
64 Pathogenic / Likely Pathogenic· 215 VUS of 474 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.
1.14LOEUF
pLI 0.000
Z-score 1.05
OE 0.77 (0.53–1.14)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.13Z-score
OE missense 0.98 (0.89–1.08)
308 obs / 314.4 exp
Tolerant

Mild missense constraint

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.0.77 (0.53–1.14)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.89–1.08)
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.1.19
0≤1.21.6
LoF obs/exp: 18 / 23.5Missense obs/exp: 308 / 314.4Syn Z: -1.76

ClinVar Variant Classifications

474 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic22
VUS215
Likely Benign127
Benign38
Conflicting30
42
Pathogenic
22
Likely Pathogenic
215
VUS
127
Likely Benign
38
Benign
30
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
5
26
0
42
Likely Pathogenic
11
5
6
0
22
VUS
0
167
40
8
215
Likely Benign
0
8
49
70
127
Benign
0
3
32
3
38
Conflicting
—30
Total2218815381474

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

View in ClinVar →

Protein Context — Lollipop Plot

PINK1 · 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

Parkinson disease 6, early onset

MIM #605909

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — PINK1
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
Mitochondria and Parkinson's Disease: Clinical, Molecular, and Translational Aspects.
Borsche M et al.·J Parkinsons Dis
2021Review
PRKN-regulated mitophagy and cellular senescence during COPD pathogenesis.
Araya J et al.·Autophagy
2019
Targeting mitophagy in neurodegenerative diseases.
Antico O et al.·Nat Rev Drug Discov
2025Review
PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1.
Geisler S et al.·Nat Cell Biol
2010
The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy.
Bingol B et al.·Nature
2014
PINK1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis.
Lee SY et al.·Stem Cell Res Ther
2021
DJ-1 is an essential downstream mediator in PINK1/parkin-dependent mitophagy.
Imberechts D et al.·Brain
2022
The genetic landscape of high-risk neuroblastoma.
Pugh TJ et al.·Nat Genet
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
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
Parkinson Disease

Aquaporin-4 Single Nucleotide Polymorphisms in Patients With Idiopathic and Familial Parkinson's Disease

ACTIVE NOT RECRUITING
NCT04553185University of ExeterStarted 2018-11-28
Study procedure

External Resources

Links to major genomics databases and tools