PARP1
poly(ADP-ribose) polymerase 1, the group of Zinc fingers PARP-type|Poly(ADP-ribose) polymerases
Basic information
Region (hg38): 1:226360210-226408154
Previous symbols: [ "PPOL", "ADPRT" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PARP1 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 | 12 | |||||
| missense | 31 | 41 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | 2 | |||
| non coding | 1 | |||||
| Total | 0 | 0 | 31 | 15 | 8 |
Variants in PARP1
This is a list of pathogenic ClinVar variants found in the PARP1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-226361987-G-C | not specified | Uncertain significance (May 23, 2024) | ||
| 1-226362016-C-T | PARP1-related disorder | Likely benign (Feb 19, 2019) | ||
| 1-226362035-C-T | not specified | Uncertain significance (Dec 16, 2023) | ||
| 1-226363128-T-C | PARP1-related disorder | Benign (Nov 16, 2019) | ||
| 1-226363988-T-C | not specified | Uncertain significance (Mar 05, 2024) | ||
| 1-226365061-T-G | not specified | Uncertain significance (Apr 08, 2022) | ||
| 1-226365067-T-G | PARP1-related disorder | Likely benign (Sep 22, 2019) | ||
| 1-226366015-C-T | not specified | Uncertain significance (May 08, 2024) | ||
| 1-226367544-C-T | not specified | Uncertain significance (Apr 25, 2022) | ||
| 1-226367601-A-G | Benign (Oct 08, 2019) | |||
| 1-226368226-C-T | Likely benign (Jul 04, 2018) | |||
| 1-226368272-C-T | not specified | Uncertain significance (Jul 05, 2023) | ||
| 1-226368300-C-T | not specified | Uncertain significance (Mar 21, 2023) | ||
| 1-226368315-A-G | not specified | Uncertain significance (Sep 26, 2023) | ||
| 1-226370490-T-G | not specified | Uncertain significance (May 10, 2024) | ||
| 1-226377135-G-A | PARP1-related disorder | Benign (Jul 21, 2018) | ||
| 1-226377207-G-T | not specified | Uncertain significance (Apr 14, 2022) | ||
| 1-226377209-A-G | not specified | Uncertain significance (Apr 14, 2022) | ||
| 1-226377256-C-T | not specified | Uncertain significance (May 20, 2024) | ||
| 1-226377257-T-C | not specified | Uncertain significance (Jan 16, 2024) | ||
| 1-226377302-A-G | not specified | Uncertain significance (Sep 25, 2023) | ||
| 1-226379178-T-C | not specified | Uncertain significance (Oct 25, 2022) | ||
| 1-226379258-C-T | PARP1-related disorder | Benign (Nov 25, 2019) | ||
| 1-226380023-C-A | not specified | Uncertain significance (Dec 21, 2023) | ||
| 1-226380075-C-A | not specified | Uncertain significance (Apr 06, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PARP1 | protein_coding | protein_coding | ENST00000366794 | 23 | 47389 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000334 | 1.00 | 125703 | 0 | 45 | 125748 | 0.000179 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.818 | 494 | 548 | 0.902 | 0.0000330 | 6704 |
| Missense in 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 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000202 | 0.000202 |
| Ashkenazi Jewish | 0.000397 | 0.000397 |
| East Asian | 0.000109 | 0.000109 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.000194 | 0.000193 |
| Middle Eastern | 0.000109 | 0.000109 |
| South Asian | 0.000196 | 0.000196 |
| Other | 0.000326 | 0.000326 |
dbNSFP
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}.;
- Pathway
- 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;Nanoparticle triggered regulated necrosis;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;NAD metabolism, sirtuins and aging;NAD+ metabolism;NAD+ biosynthetic pathways;Protein alkylation leading to liver fibrosis;HDR through MMEJ (alt-NHEJ);DNA Repair;Signal Transduction;Gene expression (Transcription);DNA Double-Strand Break Repair;caspase cascade in apoptosis;induction of apoptosis through dr3 and dr4/5 death receptors;hiv-1 nef: negative effector of fas and tnf;opposing roles of aif in apoptosis and cell survival;Generic Transcription Pathway;SUMOylation of DNA damage response and repair proteins;Homology Directed Repair;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;RNA Polymerase II Transcription;Downregulation of SMAD2/3:SMAD4 transcriptional activity;AndrogenReceptor;POLB-Dependent Long Patch Base Excision Repair;SUMOylation;Resolution of AP sites via the multiple-nucleotide patch replacement pathway;Resolution of Abasic Sites (AP sites);Base Excision Repair;Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer;Integrin-linked kinase signaling;DNA Damage Recognition in GG-NER;Signaling by TGF-beta Receptor Complex;Formation of Incision Complex in GG-NER;Dual Incision in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Signaling by TGF-beta family members;Caspase Cascade in Apoptosis;Notch-mediated HES/HEY network;Nucleotide Excision Repair
(Consensus)
Recessive Scores
- pRec
- 0.665
Intolerance Scores
- loftool
- 0.721
- rvis_EVS
- -0.97
- rvis_percentile_EVS
- 8.98
Haploinsufficiency Scores
- pHI
- 0.908
- hipred
- Y
- hipred_score
- 0.706
- ghis
- 0.634
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.621
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Parp1
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); hearing/vestibular/ear 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); vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; 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); reproductive system phenotype;
Gene ontology
- 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;nucleotide-excision repair, preincision complex stabilization;nucleotide-excision repair, preincision complex assembly;nucleotide-excision repair, DNA incision, 5'-to lesion;double-strand break repair;transcription by RNA polymerase II;protein ADP-ribosylation;apoptotic process;cellular response to DNA damage stimulus;mitochondrion organization;transforming growth factor beta receptor signaling pathway;response to gamma radiation;positive regulation of cardiac muscle hypertrophy;regulation of SMAD protein complex assembly;protein autoprocessing;peptidyl-serine ADP-ribosylation;signal transduction involved in regulation of gene expression;macrophage differentiation;mitochondrial DNA metabolic process;cellular response to insulin stimulus;positive regulation of intracellular estrogen receptor signaling pathway;nucleotide-excision repair, DNA incision;cellular response to oxidative stress;cellular response to UV;protein modification process;DNA damage response, detection of DNA damage;mitochondrial DNA repair;regulation of DNA methylation;positive regulation of transcription by RNA polymerase II;regulation of catalytic activity;positive regulation of mitochondrial depolarization;positive regulation of SMAD protein signal transduction;protein poly-ADP-ribosylation;global genome nucleotide-excision repair;cellular response to zinc ion;positive regulation of protein localization to nucleus;positive regulation of neuron death;regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway;positive regulation of single strand break repair;regulation of cellular protein localization;response to aldosterone;negative regulation of telomere maintenance via telomere lengthening;cellular response to amyloid-beta;positive regulation of myofibroblast differentiation;ATP generation from poly-ADP-D-ribose;positive regulation of transcription regulatory region DNA binding;negative regulation of ATP biosynthetic process
- Cellular component
- nuclear chromosome, telomeric region;nucleus;nuclear envelope;nucleoplasm;transcription factor complex;nucleolus;mitochondrion;membrane;protein-containing complex;protein-DNA complex;site of DNA damage
- 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;protein binding;transcription factor binding;zinc ion binding;enzyme binding;protein kinase binding;estrogen receptor binding;identical protein binding;histone deacetylase binding;protein N-terminus binding;NAD binding;R-SMAD binding;protein ADP-ribosylase activity