PARP1

poly(ADP-ribose) polymerase 1, the group of Zinc fingers PARP-type|Poly(ADP-ribose) polymerases

Basic information

Region (hg38): 1:226360209-226408154

Previous symbols: [ "PPOL", "ADPRT" ]

Links

ENSG00000143799 ∙ NCBI:142 ∙ OMIM:173870 ∙ HGNC:270 ∙ Uniprot:P09874 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PARP1 gene.

• Inborn genetic diseases (25 variants)
• not provided (13 variants)

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				3	4	7
missense			24	2	3	29
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding					1	1
Total	0	0	24	5	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
1-226362016-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)
1-226367544-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)
1-226377135-G-A		PARP1-related disorder	Benign (Mar 18, 2019)
1-226377207-G-T		not specified	Uncertain significance (Apr 14, 2022)
1-226377209-A-G		not specified	Uncertain significance (Apr 14, 2022)
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)
1-226380091-G-A			Likely benign (Nov 01, 2022)
1-226380094-G-A		PARP1-related disorder	Likely benign (Feb 18, 2019)
1-226380111-G-T		not specified	Likely benign (Mar 04, 2024)
1-226381123-G-A		PARP1-related disorder	Benign (Apr 04, 2019)

GnomAD

Source: gnomAD

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: dbNSFP

• 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