PINK1

Chr 1AR

PTEN induced kinase 1

Also known as: BRPK, PARK6

NCBI Gene: 65018 ENSG00000158828 UniProt: Q9BXM7 OMIM: 608309

The protein is a serine/threonine kinase that acts as a sensor of mitochondrial damage and coordinates mitochondrial quality control mechanisms, including the removal of dysfunctional mitochondria through mitophagy. Mutations cause autosomal recessive early-onset Parkinson disease 6, typically manifesting in childhood or young adulthood. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with its recessive inheritance pattern where single functional copies are sufficient.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

ARLOEUF 1.141 OMIM phenotype

Clinical Summary— PINK1

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Gene-Disease Validity (ClinGen)

Parkinson disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

54 unique Pathogenic / Likely Pathogenic· 210 VUS of 468 total submissions

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Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — PINK1

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.13Z-score

OE missense 0.98 (0.89–1.08)

308 obs / 314.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.77 (0.53–1.14)

0≤0.351.4

Missense OE?0.98 (0.89–1.08)

0≤0.61.4

Synonymous OE?1.19

0≤1.21.6

LoF obs/exp: 18 / 23.5Missense obs/exp: 308 / 314.4Syn Z: -1.76

ClinVar Variant Classifications

468 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32

Likely Pathogenic22

VUS210

Likely Benign127

Benign38

Conflicting30

Pathogenic

Likely Pathogenic

210

VUS

127

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	22	6	4	0	32
Likely Pathogenic	16	5	1	0	22
VUS	0	171	31	8	210
Likely Benign	0	8	49	70	127
Benign	0	3	32	3	38
Conflicting	—				30
Total	38	193	117	81	459

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap PINK1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →