PARP1 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the PARP1 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | PARP1 |
|---|---|
| Full Name | poly(ADP-ribose) polymerase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q42.12 |
| NCBI Gene ID | 142 ncbi.nlm.nih.gov/gene/142 |
| Ensembl ID | ENSG00000143799 |
| UniProt ID | P09874 |
| OMIM ID | 173870 |
| HGNC ID | 270 |
| Aliases | ADPRT, ADPRT1, PARP, PPOL, pADPRT-1 |
Description
The PARP1 gene encodes poly(ADP-ribose) polymerase 1, a nuclear enzyme that catalyzes the transfer of ADP-ribose units from NAD+ to target proteins, playing a critical role in DNA damage detection and repair, chromatin remodeling, and regulation of apoptosis. PARP1 is involved in base excision repair (BER) and is a key target for cancer therapy, particularly in BRCA-mutated tumors.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (breast, ovarian, pancreatic, etc.) | PARP1 overexpression or altered activity contributes to genomic instability and tumor progression; PARP inhibitors exploit synthetic lethality in BRCA-deficient tumors. | ClinVar, COSMIC |
| Neurodegenerative disorders (e.g., Alzheimer's, Parkinson's) | Excessive PARP1 activation depletes NAD+ and ATP, leading to cell death and neuroinflammation. | OMIM, PubMed |
| Inflammatory diseases | PARP1 regulates pro-inflammatory gene expression via NF-κB and AP-1 pathways. | OMIM, PubMed |
| Stroke and ischemia-reperfusion injury | PARP1 overactivation exacerbates oxidative stress-induced cell death. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 10.2 | Medium |
| Heart | 8.5 | Medium |
| Liver | 12.4 | High |
| Kidney | 9.8 | Medium |
| Lung | 7.6 | Medium |
| Testis | 15.3 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 18.5 | High expression; commonly used for PARP1 studies |
| MCF7 (breast cancer) | 12.3 | Moderate expression; responsive to PARP inhibitors |
| A549 (lung cancer) | 9.8 | Moderate expression |
| HepG2 (liver cancer) | 14.2 | High expression |
| K562 (leukemia) | 8.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.260A>G (p.Tyr87Cys) | Missense | 0.01% | Reduced catalytic activity; associated with increased cancer risk |
| c.2285C>T (p.Pro762Leu) | Missense | 0.02% | Altered DNA binding; potential impact on PARP inhibitor sensitivity |
| c.3076G>A (p.Val1026Met) | Missense | 0.005% | Unknown functional effect; reported in COSMIC |
| c.1234delA (p.Arg412fs) | Frameshift | Rare | Loss of function; may lead to genomic instability |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish PARP1 catalytic activity or DNA binding, leading to impaired DNA repair and increased genomic instability.
Gain of Function (GOF)
Rare mutations that enhance PARP1 activity, potentially causing excessive PARylation and NAD+ depletion, contributing to cell death.
Dominant Negative (DN)
Mutations that produce a truncated or altered PARP1 protein that interferes with wild-type function, often by competing for DNA binding sites.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • NAD+ ADP-ribosyltransferase activity |
| • protein ADP-ribosylase activity | • zinc ion binding |
| • chromatin binding | • damaged DNA binding |
| • protein homodimerization activity | • nucleus |
| • chromatin | • DNA repair |
| • base-excision repair | • apoptotic process |
| • response to oxidative stress | • regulation of transcription by RNA polymerase II |
Pathways
• Base excision repair (BER)
• Double-strand break repair (homologous recombination and non-homologous end joining)
• Apoptosis signaling
• NF-κB signaling
• p53 pathway
• Cellular response to DNA damage stimulus
Protein Summary
PARP1 is a 113 kDa nuclear protein composed of three main domains: an N-terminal DNA-binding domain containing zinc fingers, a central auto-modification domain, and a C-terminal catalytic domain. It binds to DNA single- and double-strand breaks and synthesizes poly(ADP-ribose) chains on itself and other acceptor proteins, facilitating DNA repair complex assembly. PARP1 also interacts with histones and chromatin remodelers to modulate chromatin structure. Its activity is essential for genomic stability, and its inhibition is a therapeutic strategy in cancers with defective homologous recombination repair.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PARP14 Knockout HEK293 Cell Line | EDJ-KQ3727 | Human | 54625 | Details Get a Quote |
| PARP10 Knockout HEK293 Cell Line | EDJ-KQ9460 | Human | 84875 | Details Get a Quote |
| PARP16 Knockout HEK293 Cell Line | EDJ-KQ13904 | Human | 54956 | Details Get a Quote |
| PARP11 Knockout HEK293 Cell Line | EDJ-KQ14684 | Human | 57097 | Details Get a Quote |
| PARP12 Knockout HEK293 Cell Line | EDJ-KQ14685 | Human | 64761 | Details Get a Quote |
| PARP15 Knockout HEK293 Cell Line | EDJ-KQ14686 | Human | 165631 | Details Get a Quote |
| PARP1 Knockout HEK293 Cell Line | EDJ-KQ17835 | Human | 142 | Details Get a Quote |
| PARP1 Knockout A-549 Cell Line | EDJ-KQ18138 | Human | 142 | Details Get a Quote |
| PARP1 Knockout HCT 116 Cell Line | EDJ-KQ18139 | Human | 142 | Details Get a Quote |
| PARP1 Knockout HeLa Cell Line | EDJ-KQ20195 | Human | 142 | Details Get a Quote |
| PARP14 Knockout A-549 Cell Line | EDJ-KQ25772 | Human | 54625 | Details Get a Quote |
| PARP14 Knockout HCT 116 Cell Line | EDJ-KQ25773 | Human | 54625 | Details Get a Quote |
| PARP14 Knockout HeLa Cell Line | EDJ-KQ25774 | Human | 54625 | Details Get a Quote |
| PARP10 Knockout HeLa Cell Line | EDJ-KQ37401 | Human | 84875 | Details Get a Quote |
| PARP11 Knockout A-549 Cell Line | EDJ-KQ44982 | Human | 57097 | Details Get a Quote |
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