PARP1
protein-codingpoly(ADP-ribose) polymerase 1, the group of Zinc fingers PARP-type|Poly(ADP-ribose) polymerases
Gene summary
This gene encodes a chromatin-associated enzyme, poly(ADP-ribosyl)transferase, which modifies various nuclear proteins by poly(ADP-ribosyl)ation. The modification is dependent on DNA and is involved in the regulation of various important cellular processes such as differentiation, proliferation, and tumor transformation and also in the regulation of the molecular events involved in the recovery of cell from DNA damage. In addition, this enzyme may be the site of mutation in Fanconi anemia, and may participate in the pathophysiology of type I diabetes. [provided by RefSeq, Jul 2008]
- PPOL
- ADPRT
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~47.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0700092
Submitter: G2P
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PARP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001618.4. 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 | 3 | 18 | 5 | 26 | ||
| missense | 97 | 9 | 2 | 108 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 108 | 27 | 7 | 142 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001609.2 | 23 | MANE Select | |
| Ensembl | ENSP00000355759.5 | 23 | MANE Select | |
| Ensembl | ENSP00000504745.1 | 9 | Standard | |
| Ensembl | ENSP00000503396.1 | 22 | 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)
- NF-kappa B signaling pathway - Homo sapiens (human)
- Corticotropin-releasing hormone signaling pathway
Biological Process
- negative regulation of transcription by RNA polymerase II
- nucleotide-excision repair, DNA damage recognition
- telomere maintenance
- double-strand break repair via homologous recombination
- DNA repair
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA binding
- RNA binding
- NAD+ ADP-ribosyltransferase activity
Cellular Component
- nuclear chromosome, telomeric region
- nucleus
- nuclear envelope
- nucleoplasm
- transcription factor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000366794
- Coding exons
- 23
- Length
- 47389
- Individuals with no LoFs
- 125703
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 45
- Defined
- 125748
- p
- 0.000179
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.818 | 494 | 548 | 0.902 | 0.0000330 | 6704 |
| Missense (PolyPhen) | 97 | 161.67 | 0.59998 | 1911 | ||
| Synonymous | -2.11 | 263 | 223 | 1.18 | 0.0000153 | 1894 |
| Loss of Function | 4.52 | 16 | 50.7 | 0.316 | 0.00000261 | 664 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00020 | 0.00020 | rare |
| Ashkenazi Jewish | 0.00040 | 0.00040 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00019 | 0.00019 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00033 | 0.00033 | 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. 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:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272). Mediates the poly(ADP-ribosyl)ation of APLF and CHFR (PubMed:17396150). Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production (PubMed:17177976). Required for PARP9 and DTX3L recruitment to DNA damage sites (PubMed:23230272). PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272). Mediates serine ADP-ribosylation of target proteins following interaction with HPF1; HPF1 conferring serine specificity (PubMed:28190768). Mediates the poly(ADP-ribosyl)ation of histones in a HPF1-dependent manner (PubMed:27067600). Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy- consuming (PubMed:27257257). {ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:17396150, ECO:0000269|PubMed:18172500, ECO:0000269|PubMed:19344625, ECO:0000269|PubMed:19661379, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:27257257, ECO:0000269|PubMed:28190768}.;
Recessive Scores
- pRec
- 0.665
Intolerance Scores
- LoFtool
- 0.721
- RVIS EVS
- -0.97
- RVIS percentile EVS
- 8.98
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.621
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |