PARG
protein-codingpoly(ADP-ribose) glycohydrolase
Gene summary
Poly(ADP-ribose) glycohydrolase (PARG) is the major enzyme responsible for the catabolism of poly(ADP-ribose), a reversible covalent-modifier of chromosomal proteins. The protein is found in many tissues and may be subject to proteolysis generating smaller, active products. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~151.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PARG variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003631.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 53 | 53 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 55 | 1 | 0 | 56 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003622.2 | 18 | MANE Select | |
| Ensembl | ENSP00000484285.1 | 18 | MANE Select | |
| RefSeq | NP_001290415.1 | 17 | Standard | |
| RefSeq | NP_001290416.1 | 16 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- DNA Repair
- POLB-Dependent Long Patch Base Excision Repair
- Resolution of AP sites via the multiple-nucleotide patch replacement pathway
- Resolution of Abasic Sites (AP sites)
- Base Excision Repair
Biological Process
- carbohydrate metabolic process
- regulation of DNA repair
- nucleotide-sugar metabolic process
- ATP generation from poly-ADP-D-ribose
Molecular Function
- poly(ADP-ribose) glycohydrolase activity
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- mitochondrial matrix
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000402038
- Coding exons
- 14
- Length
- 104391
- Individuals with no LoFs
- 124336
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 124338
- p
- 0.00000804
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.11 | 147 | 239 | 0.616 | 0.0000130 | 3187 |
| Missense (PolyPhen) | 57 | 122.41 | 0.46565 | 1649 | ||
| Synonymous | 0.619 | 78 | 85.3 | 0.915 | 0.00000485 | 899 |
| Loss of Function | 4.02 | 7 | 31.2 | 0.224 | 0.00000200 | 368 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000011 | 0.0000089 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Poly(ADP-ribose) synthesized after DNA damage is only present transiently and is rapidly degraded by poly(ADP-ribose) glycohydrolase (PubMed:23102699). PARG acts both as an endo- and exoglycosidase, releasing PAR of different length as well as ADP- ribose monomers (PubMed:23102699). Required for retinoid acid- dependent gene transactivation, probably by dePARsylating histone demethylase KDM4D, allowing chromatin derepression at RAR- dependent gene promoters (PubMed:23102699). Involved in the synthesis of ATP in the nucleus, together with PARP1, NMNAT1 and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257). {ECO:0000269|PubMed:23102699, ECO:0000269|PubMed:27257257}.;
Recessive Scores
- pRec
- 0.135
Essentials
- Indispensability pred.
- E
- Indispensability score
- 0.658
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |