PARP2
protein-codingpoly(ADP-ribose) polymerase 2, the group of Poly(ADP-ribose) polymerases
Gene summary
This gene encodes poly(ADP-ribosyl)transferase-like 2 protein, which contains a catalytic domain and is capable of catalyzing a poly(ADP-ribosyl)ation reaction. This protein has a catalytic domain which is homologous to that of poly (ADP-ribosyl) transferase, but lacks an N-terminal DNA binding domain which activates the C-terminal catalytic domain of poly (ADP-ribosyl) transferase. The basic residues within the N-terminal region of this protein may bear potential DNA-binding properties, and may be involved in the nuclear and/or nucleolar targeting of the protein. Two alternatively spliced transcript variants encoding distinct isoforms have been found. [provided by RefSeq, Jul 2008]
- ADPRTL2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.3 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 PARP2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001042618.2. 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 | 2 | 3 | |||
| missense | 74 | 3 | 2 | 79 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 78 | 4 | 4 | 86 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001036083.1 | 16 | MANE Select | |
| Ensembl | ENSP00000392972.3 | 16 | MANE Select | |
| RefSeq | NP_005475.2 | 16 | Standard | |
| Ensembl | ENSP00000250416.5 | 16 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Base excision repair - Homo sapiens (human)
- Necroptosis - Homo sapiens (human)
- Apoptosis - Homo sapiens (human)
- NAD+ biosynthetic pathways
- HDR through MMEJ (alt-NHEJ)
Biological Process
- DNA repair
- base-excision repair
- double-strand break repair
- protein ADP-ribosylation
- peptidyl-serine ADP-ribosylation
Molecular Function
- DNA binding
- NAD+ ADP-ribosyltransferase activity
- protein binding
- protein ADP-ribosylase activity
Cellular Component
- nucleus
- nucleoplasm
- nucleolus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000250416
- Coding exons
- 16
- Length
- 14324
- Individuals with no LoFs
- 124554
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 241
- Defined
- 124796
- p
- 0.000970
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.490 | 292 | 317 | 0.923 | 0.0000159 | 3839 |
| Missense (PolyPhen) | 93 | 107.36 | 0.86624 | 1370 | ||
| Synonymous | 1.40 | 94 | 113 | 0.833 | 0.00000538 | 1057 |
| Loss of Function | 1.60 | 25 | 35.3 | 0.709 | 0.00000181 | 424 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0035 | 0.0034 | notable |
| Latino/Admixed American | 0.0017 | 0.0017 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00050 | 0.00050 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00048 | 0.00048 | rare |
| South Asian | 0.0021 | 0.0021 | notable |
| Other | 0.00067 | 0.00066 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism (PubMed:10364231, PubMed:28190768). This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks (PubMed:10364231). Mediates serine ADP-ribosylation of target proteins following interaction with HPF1; HPF1 conferring serine specificity (PubMed:28190768). {ECO:0000269|PubMed:10364231, ECO:0000269|PubMed:28190768}.;
Recessive Scores
- pRec
- 0.120
Intolerance Scores
- LoFtool
- 0.981
- RVIS EVS
- -0.07
- RVIS percentile EVS
- 48.69
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.952
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |