PARK7
Parkinsonism associated deglycase, the group of Glutamine amidotransferase class 1 domain containing
Basic information
Region (hg38): 1:7954290-7985505
Links
Phenotypes
GenCC
Source:
- autosomal recessive early-onset Parkinson disease 7 (Strong), mode of inheritance: AR
- autosomal recessive early-onset Parkinson disease 7 (Strong), mode of inheritance: AR
- autosomal recessive early-onset Parkinson disease 7 (Moderate), mode of inheritance: AR
- young-onset Parkinson disease (Supportive), mode of inheritance: AR
- Parkinson disease (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Parkinson disease 7, autosomal recessive early-onset | AR | Neurologic | Response to levodopa has been documented | Neurologic | 11462174; 11835383; 12953260; 12446870; 14638971; 16240358; 20837857; 21506293; 22956510 |
ClinVar
This is a list of variants' phenotypes submitted to
- Autosomal recessive early-onset Parkinson disease 7 (4 variants)
- not provided (2 variants)
- Amyotrophic lateral sclerosis-parkinsonism-dementia complex (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PARK7 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 | 10 | |||||
| missense | 36 | 42 | ||||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 5 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| splice region | 1 | 4 | 4 | 9 | ||
| non coding | 15 | 37 | 58 | |||
| Total | 5 | 4 | 45 | 27 | 37 |
Highest pathogenic variant AF is 0.00000657
Variants in PARK7
This is a list of pathogenic ClinVar variants found in the PARK7 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-7961680-G-A | Parkinson Disease, Recessive | Benign/Likely benign (Aug 14, 2018) | ||
| 1-7961690-G-C | Parkinson Disease, Recessive | Uncertain significance (Jun 14, 2016) | ||
| 1-7961718-T-C | Autosomal recessive early-onset Parkinson disease 7 | Benign (Jan 12, 2018) | ||
| 1-7961737-T-A | Autosomal recessive early-onset Parkinson disease 7 | Uncertain significance (Jan 12, 2018) | ||
| 1-7961747-C-T | Autosomal recessive early-onset Parkinson disease 7 | Benign (Aug 17, 2018) | ||
| 1-7961787-G-C | Autosomal recessive early-onset Parkinson disease 7 | Uncertain significance (Jan 13, 2018) | ||
| 1-7961850-GGTGCTGGACGGTGTCCCT-G | Benign (Oct 04, 2019) | |||
| 1-7961850-G-GGTGCTGGACGGTGTCCCT | Benign (Feb 18, 2021) | |||
| 1-7961913-G-T | Benign (Aug 14, 2018) | |||
| 1-7962111-C-T | Benign (Aug 15, 2018) | |||
| 1-7962137-G-T | Benign (Aug 14, 2018) | |||
| 1-7962693-T-G | Benign (Sep 30, 2018) | |||
| 1-7962712-CAG-C | Benign (Aug 14, 2018) | |||
| 1-7962740-CT-C | Benign (Aug 22, 2020) | |||
| 1-7962740-CTT-C | Benign (May 23, 2021) | |||
| 1-7962740-C-CT | Benign (May 16, 2020) | |||
| 1-7962764-C-T | Autosomal recessive early-onset Parkinson disease 7 • not specified | Benign (Jan 30, 2020) | ||
| 1-7962801-G-T | Autosomal recessive early-onset Parkinson disease 7 | Uncertain significance (Aug 15, 2022) | ||
| 1-7962813-C-G | Autosomal recessive early-onset Parkinson disease 7 | Uncertain significance (Nov 29, 2018) | ||
| 1-7962839-G-A | Autosomal recessive early-onset Parkinson disease 7 | Likely benign (Aug 09, 2022) | ||
| 1-7962841-C-T | Autosomal recessive early-onset Parkinson disease 7 | Uncertain significance (Sep 09, 2019) | ||
| 1-7962844-T-C | Autosomal recessive early-onset Parkinson disease 7 | Uncertain significance (Jan 12, 2018) | ||
| 1-7962852-G-A | Uncertain significance (Aug 01, 2018) | |||
| 1-7962858-G-A | Autosomal recessive early-onset Parkinson disease 7 | Uncertain significance (Jan 13, 2018) | ||
| 1-7962863-G-A | Autosomal recessive early-onset Parkinson disease 7 | Pathogenic (Jul 01, 2012) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PARK7 | protein_coding | protein_coding | ENST00000493678 | 6 | 31215 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.753 | 0.245 | 125743 | 0 | 5 | 125748 | 0.0000199 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.165 | 104 | 109 | 0.956 | 0.00000613 | 1216 |
| Missense in Polyphen | 22 | 28.303 | 0.77729 | 333 | ||
| Synonymous | 0.342 | 37 | 39.7 | 0.931 | 0.00000234 | 389 |
| Loss of Function | 2.47 | 1 | 8.97 | 0.112 | 4.64e-7 | 108 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000867 | 0.0000867 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000879 | 0.00000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Protein and nucleotide deglycase that catalyzes the deglycation of the Maillard adducts formed between amino groups of proteins or nucleotides and reactive carbonyl groups of glyoxals (PubMed:25416785, PubMed:28596309). Thus, functions as a protein deglycase that repairs methylglyoxal- and glyoxal-glycated proteins, and releases repaired proteins and lactate or glycolate, respectively. Deglycates cysteine, arginine and lysine residues in proteins, and thus reactivates these proteins by reversing glycation by glyoxals. Acts on early glycation intermediates (hemithioacetals and aminocarbinols), preventing the formation of advanced glycation endproducts (AGE) that cause irreversible damage (PubMed:25416785, PubMed:28013050, PubMed:26995087). Also functions as a nucleotide deglycase able to repair glycated guanine in the free nucleotide pool (GTP, GDP, GMP, dGTP) and in DNA and RNA. Is thus involved in a major nucleotide repair system named guanine glycation repair (GG repair), dedicated to reversing methylglyoxal and glyoxal damage via nucleotide sanitization and direct nucleic acid repair (PubMed:28596309). Also displays an apparent glyoxalase activity that in fact reflects its deglycase activity (PubMed:22523093). Plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease; functions probably related to its primary function (PubMed:17015834, PubMed:20304780, PubMed:18711745, PubMed:12796482, PubMed:19229105, PubMed:25416785, PubMed:26995087). It is involved in neuroprotective mechanisms like the stabilization of NFE2L2 and PINK1 proteins, male fertility as a positive regulator of androgen signaling pathway as well as cell growth and transformation through, for instance, the modulation of NF-kappa-B signaling pathway (PubMed:12612053, PubMed:15502874, PubMed:14749723, PubMed:17015834, PubMed:21097510, PubMed:18711745). Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death (PubMed:16390825). Required for correct mitochondrial morphology and function as well as for autophagy of dysfunctional mitochondria (PubMed:19229105, PubMed:16632486). Plays a role in regulating expression or stability of the mitochondrial uncoupling proteins SLC25A14 and SLC25A27 in dopaminergic neurons of the substantia nigra pars compacta and attenuates the oxidative stress induced by calcium entry into the neurons via L-type channels during pacemaking (PubMed:18711745). Regulates astrocyte inflammatory responses, may modulate lipid rafts-dependent endocytosis in astrocytes and neuronal cells (PubMed:23847046). In pancreatic islets, involved in the maintenance of mitochondrial reactive oxygen species (ROS) levels and glucose homeostasis in an age- and diet dependent manner. Protects pancreatic beta cells from cell death induced by inflammatory and cytotoxic setting (By similarity). Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress (PubMed:18626009). Metal- binding protein able to bind copper as well as toxic mercury ions, enhances the cell protection mechanism against induced metal toxicity (PubMed:23792957). In macrophages, interacts with the NADPH oxidase subunit NCF1 to direct NADPH oxidase-dependent ROS production, and protects against sepsis (By similarity). {ECO:0000250|UniProtKB:Q99LX0, ECO:0000269|PubMed:11477070, ECO:0000269|PubMed:12612053, ECO:0000269|PubMed:12855764, ECO:0000269|PubMed:12939276, ECO:0000269|PubMed:14749723, ECO:0000269|PubMed:15181200, ECO:0000269|PubMed:15502874, ECO:0000269|PubMed:15976810, ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:17015834, ECO:0000269|PubMed:18626009, ECO:0000269|PubMed:18711745, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:20186336, ECO:0000269|PubMed:20304780, ECO:0000269|PubMed:21097510, ECO:0000269|PubMed:22523093, ECO:0000269|PubMed:23792957, ECO:0000269|PubMed:23847046, ECO:0000269|PubMed:25416785, ECO:0000269|PubMed:26995087, ECO:0000269|PubMed:28013050, ECO:0000269|PubMed:28596309, ECO:0000269|PubMed:9070310}.;
- Disease
- DISEASE: Parkinson disease 7 (PARK7) [MIM:606324]: A neurodegenerative disorder characterized by resting tremor, postural tremor, bradykinesia, muscular rigidity, anxiety and psychotic episodes. PARK7 has onset before 40 years, slow progression and initial good response to levodopa. Some patients may show traits reminiscent of amyotrophic lateral sclerosis- parkinsonism/dementia complex (Guam disease). {ECO:0000269|PubMed:12446870, ECO:0000269|PubMed:12851414, ECO:0000269|PubMed:12953260, ECO:0000269|PubMed:14607841, ECO:0000269|PubMed:14713311, ECO:0000269|PubMed:15254937, ECO:0000269|PubMed:15365989, ECO:0000269|PubMed:17846173, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:22523093, ECO:0000269|PubMed:23792957, ECO:0000269|PubMed:23847046}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Parkinson,s disease - Homo sapiens (human);Androgen receptor signaling pathway;Synaptic Vesicle Pathway;Parkinsons Disease Pathway;AndrogenReceptor;Alpha-synuclein signaling
(Consensus)
Recessive Scores
- pRec
- 0.541
Intolerance Scores
- loftool
- 0.129
- rvis_EVS
- 0.08
- rvis_percentile_EVS
- 60.09
Haploinsufficiency Scores
- pHI
- 0.195
- hipred
- Y
- hipred_score
- 0.831
- ghis
- 0.537
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.979
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Park7
- 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- park7
- Affected structure
- post-vent region
- Phenotype tag
- abnormal
- Phenotype quality
- apoptotic
Gene ontology
- Biological process
- negative regulation of protein phosphorylation;positive regulation of acute inflammatory response to antigenic stimulus;DNA repair;negative regulation of protein kinase activity;proteolysis;protein deglycosylation;autophagy;inflammatory response;mitochondrion organization;Ras protein signal transduction;single fertilization;adult locomotory behavior;methylglyoxal metabolic process;detoxification of copper ion;positive regulation of gene expression;negative regulation of gene expression;enzyme active site formation via L-cysteine sulfinic acid;lactate biosynthetic process;insulin secretion;negative regulation of protein ubiquitination;negative regulation of protein binding;activation of protein kinase B activity;negative regulation of proteasomal ubiquitin-dependent protein catabolic process;positive regulation of interleukin-8 production;positive regulation of peptidyl-serine phosphorylation;negative regulation of protein sumoylation;positive regulation of NAD(P)H oxidase activity;cellular response to oxidative stress;cellular response to glyoxal;peptidyl-cysteine deglycation;peptidyl-arginine deglycation;peptidyl-lysine deglycation;protein deglycation, glyoxal removal;protein deglycation, methylglyoxal removal;glutathione deglycation;glucose homeostasis;hydrogen peroxide metabolic process;negative regulation of apoptotic process;regulation of neuron apoptotic process;negative regulation of neuron apoptotic process;regulation of TRAIL receptor biosynthetic process;positive regulation of transcription by RNA polymerase II;glycolate biosynthetic process;negative regulation of protein export from nucleus;regulation of inflammatory response;detoxification of mercury ion;protein stabilization;positive regulation of DNA-binding transcription factor activity;negative regulation of ubiquitin-protein transferase activity;dopamine uptake involved in synaptic transmission;regulation of mitochondrial membrane potential;positive regulation of protein kinase B signaling;membrane depolarization;membrane hyperpolarization;negative regulation of cell death;regulation of androgen receptor signaling pathway;cellular response to hydrogen peroxide;positive regulation of protein homodimerization activity;cellular oxidant detoxification;guanine deglycation;guanine deglycation, methylglyoxal removal;guanine deglycation, glyoxal removal;positive regulation of protein localization to nucleus;negative regulation of neuron death;positive regulation of superoxide dismutase activity;negative regulation of protein acetylation;positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway;negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway;regulation of supramolecular fiber organization;positive regulation of mitochondrial electron transport, NADH to ubiquinone;negative regulation of death-inducing signaling complex assembly;negative regulation of protein K48-linked deubiquitination;negative regulation of TRAIL-activated apoptotic signaling pathway;positive regulation of pyrroline-5-carboxylate reductase activity;positive regulation of tyrosine 3-monooxygenase activity;positive regulation of dopamine biosynthetic process;glyoxal metabolic process;positive regulation of L-dopa biosynthetic process;positive regulation of L-dopa decarboxylase activity;negative regulation of oxidative stress-induced cell death;negative regulation of hydrogen peroxide-induced cell death;negative regulation of hydrogen peroxide-induced neuron death;negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway;negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway;negative regulation of reactive oxygen species biosynthetic process;positive regulation of reactive oxygen species biosynthetic process;positive regulation of autophagy of mitochondrion;negative regulation of nitrosative stress-induced intrinsic apoptotic signaling pathway;negative regulation of ubiquitin-specific protease activity;positive regulation of oxidative phosphorylation uncoupler activity;positive regulation of transcription regulatory region DNA binding;positive regulation of androgen receptor activity;negative regulation of extrinsic apoptotic signaling pathway;negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
- Cellular component
- chromatin;nucleus;nucleoplasm;cytoplasm;mitochondrion;mitochondrial respiratory chain complex I;mitochondrial intermembrane space;mitochondrial matrix;endoplasmic reticulum;cytosol;plasma membrane;cell-cell adherens junction;PML body;axon;cell body;membrane raft;perinuclear region of cytoplasm;extracellular exosome;presynapse
- Molecular function
- core promoter binding;double-stranded DNA binding;single-stranded DNA binding;transcription coactivator activity;mRNA binding;signaling receptor binding;copper ion binding;protein binding;transcription factor binding;peptidase activity;superoxide dismutase copper chaperone activity;oxidoreductase activity, acting on peroxide as acceptor;enzyme binding;kinase binding;cytokine binding;tyrosine 3-monooxygenase activator activity;L-dopa decarboxylase activator activity;protein deglycase activity;identical protein binding;protein homodimerization activity;small protein activating enzyme binding;ubiquitin-like protein conjugating enzyme binding;cadherin binding;mercury ion binding;androgen receptor binding;peroxiredoxin activity;repressing transcription factor binding;scaffold protein binding;cupric ion binding;cuprous ion binding;ubiquitin-specific protease binding