PINK1

PTEN induced kinase 1, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 1:20633457-20651511

Previous symbols: [ "PARK6" ]

Links

ENSG00000158828 ∙ NCBI:65018 ∙ OMIM:608309 ∙ HGNC:14581 ∙ Uniprot:Q9BXM7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive early-onset Parkinson disease 6 (Strong), mode of inheritance: AR
• autosomal recessive early-onset Parkinson disease 6 (Definitive), mode of inheritance: AR
• young-onset Parkinson disease (Supportive), mode of inheritance: AR
• autosomal recessive early-onset Parkinson disease 6 (Strong), mode of inheritance: AR
• Parkinson disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Parkinson disease 6, early onset	AR	Neurologic	Response to levodopa has been documented	Neurologic	15505170; 15349870; 15087508; 15955954; 15970950; 16969854; 17030667; 16769864; 16966503; 16632486; 18685134; 18541801; 21784538; 22581678; 22956510
Heterozygotes may display more subtle signs of disease, and have been described as susceptibility alleles

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PINK1 gene.

• Autosomal recessive early-onset Parkinson disease 6 (291 variants)
• not provided (111 variants)
• Parkinson Disease, Recessive (16 variants)
• Inborn genetic diseases (14 variants)
• not specified (12 variants)
• Congenital disorder of glycosylation (12 variants)
• See cases (2 variants)
• PINK1-related condition (1 variants)
• PINK1-Related Parkinsonism (1 variants)
• Neuroblastoma (1 variants)
• Parkinson disease, autosomal recessive early-onset, digenic, PINK1/DJ1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PINK1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	47	3	57
missense	2	3	122	4	3	134
nonsense	7	2	1			10
start loss						0
frameshift	6	1	1			8
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	3				4
splice region			9	4	2	15
non coding			27	41	28	96
Total	16	9	160	92	34

Highest pathogenic variant AF is 0.0000525

Variants in PINK1

This is a list of pathogenic ClinVar variants found in the PINK1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-20633561-C-T		Autosomal recessive early-onset Parkinson disease 6	Pathogenic (Sep 16, 2022)
1-20633572-C-T		Autosomal recessive early-onset Parkinson disease 6	Likely benign (Feb 10, 2023)
1-20633573-C-G		Autosomal recessive early-onset Parkinson disease 6	Uncertain significance (Dec 02, 2021)
1-20633579-C-A			Uncertain significance (Sep 13, 2016)
1-20633595-C-T		Autosomal recessive early-onset Parkinson disease 6 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 02, 2023)
1-20633611-C-T		Autosomal recessive early-onset Parkinson disease 6	Likely benign (Nov 22, 2023)
1-20633613-C-T		Autosomal recessive early-onset Parkinson disease 6	Uncertain significance (Jan 17, 2022)
1-20633615-G-A		not specified • Autosomal recessive early-onset Parkinson disease 6 • PINK1-related disorder	Conflicting classifications of pathogenicity (Feb 18, 2022)
1-20633617-C-G		Autosomal recessive early-onset Parkinson disease 6	Likely benign (Mar 03, 2023)
1-20633622-CCGGCCGGGCCTACGGCTTGGGG-C		Autosomal recessive early-onset Parkinson disease 6	Pathogenic (Aug 09, 2022)
1-20633624-G-C		Autosomal recessive early-onset Parkinson disease 6	Uncertain significance (Sep 09, 2020)
1-20633633-T-G		Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
1-20633636-G-A		Autosomal recessive early-onset Parkinson disease 6	Likely benign (Sep 19, 2023)
1-20633636-G-C		Autosomal recessive early-onset Parkinson disease 6	Conflicting classifications of pathogenicity (Dec 10, 2023)
1-20633639-T-G		Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
1-20633649-C-G		Autosomal recessive early-onset Parkinson disease 6	Uncertain significance (Aug 09, 2022)
1-20633660-G-A		Inborn genetic diseases	Uncertain significance (Feb 21, 2024)
1-20633661-C-T		Autosomal recessive early-onset Parkinson disease 6	Uncertain significance (Aug 24, 2023)
1-20633664-G-T		Autosomal recessive early-onset Parkinson disease 6	Uncertain significance (Oct 13, 2022)
1-20633672-C-T		Autosomal recessive early-onset Parkinson disease 6	Uncertain significance (Jul 10, 2019)
1-20633677-G-A		Autosomal recessive early-onset Parkinson disease 6	Likely benign (Feb 12, 2022)
1-20633687-G-C		Autosomal recessive early-onset Parkinson disease 6 • See cases • Inborn genetic diseases	Uncertain significance (May 16, 2022)
1-20633689-C-G		Autosomal recessive early-onset Parkinson disease 6	Likely benign (Dec 12, 2023)
1-20633701-A-G		Autosomal recessive early-onset Parkinson disease 6	Likely benign (Aug 03, 2023)
1-20633703-C-T			Uncertain significance (Jul 17, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PINK1	protein_coding	protein_coding	ENST00000321556	8	18057

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.87e-10	0.397	125630	0	118	125748	0.000469

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.129	308	314	0.980	0.0000191	3651
Missense in Polyphen		106	122.22	0.86728		1429
Synonymous	-1.75	166	140	1.19	0.00000926	1296
Loss of Function	1.05	18	23.5	0.766	0.00000137	253

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00117	0.00117
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00103	0.00103
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000353	0.000352
Middle Eastern	0.00103	0.00103
South Asian	0.000394	0.000392
Other	0.000980	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins. Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy) by mediating activation and translocation of PRKN (PubMed:14607334, PubMed:15087508, PubMed:19229105, PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:23620051, PubMed:23754282, PubMed:23933751, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:24896179, PubMed:25527291). Targets PRKN to dysfunctional depolarized mitochondria through the phosphorylation of MFN2 (PubMed:23620051). Activates PRKN in 2 steps: (1) by mediating phosphorylation at 'Ser-65' of PRKN and (2) mediating phosphorylation of ubiquitin, converting PRKN to its fully-active form (PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25527291). Required for ubiquinone reduction by mitochondrial complex I by mediating phosphorylation of complex I subunit NDUFA10 (By similarity). {ECO:0000250|UniProtKB:Q99MQ3, ECO:0000269|PubMed:14607334, ECO:0000269|PubMed:15087508, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:19966284, ECO:0000269|PubMed:20404107, ECO:0000269|PubMed:20798600, ECO:0000269|PubMed:23620051, ECO:0000269|PubMed:23754282, ECO:0000269|PubMed:23933751, ECO:0000269|PubMed:24660806, ECO:0000269|PubMed:24751536, ECO:0000269|PubMed:24784582, ECO:0000269|PubMed:24896179, ECO:0000269|PubMed:25527291}.
• Disease: DISEASE: Parkinson disease 6 (PARK6) [MIM:605909]: An early-onset form of Parkinson disease, a neurodegenerative disorder characterized by parkinsonian signs such as rigidity, resting tremor and bradykinesia. A subset of patients manifest additional symptoms including hyperreflexia, autonomic instability, dementia and psychiatric disturbances. Symptoms show diurnal fluctuation and can improve after sleep. PARK6 pathogenesis involves respiratory complex I deficiency causing mitochondrial depolarization and dysfunction. Inheritance is autosomal recessive. {ECO:0000269|PubMed:15087508, ECO:0000269|PubMed:15349860, ECO:0000269|PubMed:15349870, ECO:0000269|PubMed:15505171, ECO:0000269|PubMed:15596610, ECO:0000269|PubMed:15955953, ECO:0000269|PubMed:15970950, ECO:0000269|PubMed:16009891, ECO:0000269|PubMed:16207217, ECO:0000269|PubMed:16207731, ECO:0000269|PubMed:16257123, ECO:0000269|PubMed:16401616, ECO:0000269|PubMed:16482571, ECO:0000269|PubMed:16632486, ECO:0000269|PubMed:16966503, ECO:0000269|PubMed:17030667, ECO:0000269|PubMed:18286320, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:20798600, ECO:0000269|PubMed:22043288, ECO:0000269|PubMed:22956510, ECO:0000269|PubMed:24652937, ECO:0000269|PubMed:24784582}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Mitophagy - animal - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Parkinsons Disease Pathway;Pink/Parkin Mediated Mitophagy;Mitophagy (Consensus)

Recessive Scores

• pRec: 0.176

Intolerance Scores

• loftool: 0.788
• rvis_EVS: -0.46
• rvis_percentile_EVS: 23.63

Haploinsufficiency Scores

• pHI: 0.143
• hipred: Y
• hipred_score: 0.564
• ghis: 0.507

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.988

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pink1
• Phenotype: taste/olfaction phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: pink1
• Affected structure: dopaminergic neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: autophagy of mitochondrion;positive regulation of protein phosphorylation;regulation of oxidative phosphorylation;response to ischemia;protein phosphorylation;ubiquitin-dependent protein catabolic process;response to oxidative stress;mitochondrion organization;regulation of hydrogen peroxide metabolic process;negative regulation of gene expression;regulation of mitochondrion organization;positive regulation of peptidase activity;macroautophagy;positive regulation of macroautophagy;negative regulation of macroautophagy;protein ubiquitination;peptidyl-serine phosphorylation;respiratory electron transport chain;regulation of protein ubiquitination;positive regulation of protein ubiquitination;activation of protein kinase B activity;positive regulation of synaptic transmission, dopaminergic;positive regulation of peptidyl-serine phosphorylation;positive regulation of dopamine secretion;cellular response to oxidative stress;positive regulation of protein dephosphorylation;intracellular signal transduction;peptidyl-serine autophosphorylation;TORC2 signaling;positive regulation of I-kappaB kinase/NF-kappaB signaling;regulation of protein complex assembly;negative regulation of neuron apoptotic process;positive regulation of translation;negative regulation of JNK cascade;protein stabilization;positive regulation of DNA-binding transcription factor activity;positive regulation of ubiquitin-protein transferase activity;regulation of mitochondrial membrane potential;positive regulation of protein kinase B signaling;regulation of proteasomal protein catabolic process;cellular response to hypoxia;establishment of protein localization to mitochondrion;maintenance of protein location in mitochondrion;positive regulation of mitochondrial fission;positive regulation of release of cytochrome c from mitochondria;negative regulation of mitochondrial fission;cellular response to toxic substance;positive regulation of mitophagy in response to mitochondrial depolarization;mitochondrion to lysosome transport;regulation of cellular response to oxidative stress;positive regulation of histone deacetylase activity;regulation of synaptic vesicle transport;negative regulation of autophagosome assembly;positive regulation of mitochondrial electron transport, NADH to ubiquinone;regulation of autophagy of mitochondrion;negative regulation of autophagy of mitochondrion;negative regulation of oxidative stress-induced cell death;negative regulation of oxidative stress-induced neuron death;regulation of protein targeting to mitochondrion;negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway;negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway;negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide;positive regulation of cristae formation;positive regulation of protein targeting to mitochondrion;positive regulation of free ubiquitin chain polymerization;positive regulation of NMDA glutamate receptor activity;cellular response to hydrogen sulfide;regulation of reactive oxygen species metabolic process;negative regulation of reactive oxygen species metabolic process;positive regulation of ATP biosynthetic process;negative regulation of intrinsic apoptotic signaling pathway
• Cellular component: ubiquitin ligase complex;chromatin;nucleus;cytoplasm;mitochondrion;mitochondrial outer membrane;mitochondrial outer membrane translocase complex;mitochondrial inner membrane;mitochondrial intermembrane space;cytosol;cytoskeleton;membrane;axon;growth cone;integral component of mitochondrial outer membrane;TORC2 complex;cell body;perinuclear region of cytoplasm;Lewy body;astrocyte projection
• Molecular function: magnesium ion binding;protease binding;protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;calcium-dependent protein kinase activity;kinase activity;peptidase activator activity;ubiquitin protein ligase binding;protein kinase B binding;C3HC4-type RING finger domain binding