PARP1 Gene Complete Identifier and Functional Mapping Reference

Executive summary

PARP1 (Poly[ADP-ribose] polymerase 1; HGNC:270) is a ubiquitously expressed nuclear enzyme and the founding member of the PARP family, encoded on chromosome 1 and best known for its central role in DNA damage response and repair, including base excision repair, double-strand break repair, and genomic stability maintenance. It is one of the most clinically actionable targets in oncology: four PARP inhibitors (olaparib, niraparib, talazoparib, rucaparib) have reached Phase 4 approval for cancers including ovarian, breast, pancreatic, and prostate, with response strongly predicted by BRCA1/BRCA2 mutation status through synthetic lethality. The protein is exceptionally well-characterized structurally, with 103 experimental PDB entries, and its AlphaFold model achieves a mean pLDDT of 83.23, with 51% of residues at very high confidence. GWAS data link PARP1 to leukocyte telomere length (p = 2.0×10⁻¹⁸) and melanoma susceptibility, consistent with its genome-stability function. Despite ~115 ClinVar variants, none are classified Pathogenic or Likely Pathogenic, though AlphaMissense flags over 100 missense variants as likely pathogenic, particularly clustering around residues 990–1009.

Gene identifiers

Gene symbol: PARP1

Transcript identifiers

Ensembl Transcripts

Total Ensembl transcripts: 37

RefSeq mRNA Transcripts

Total RefSeq mRNA: 6

CCDS IDs

Canonical Transcript (ENST00000366794) - Exons

Total exons: 23

Protein identifiers

UniProt accessions

RefSeq protein (NP_) accessions

Protein domains and families

InterPro (14 entries)

Pfam (7 entries)

SMART (4 entries)

CDD/NCBI Conserved Domain Database (3 entries)

PANTHER (2 entries)

Antibody availability

No entries found in the biobtree antibody database for PARP1. However, external antibody resources include:

• Human Protein Atlas (HPA) — antibodies available for PARP1 via HPA database
• Commercial sources — widely available from major antibody vendors (Abcam, Santa Cruz, Cell Signaling, etc.)

Structure

Experimental Structures

Total: 103 PDB entries

X-ray Crystallography (98 structures)

1. 1UK0 — 3.0 Å
2. 1UK1 — 3.0 Å
3. 1WOK — 3.0 Å
4. 2RCW — 2.8 Å
5. 2RD6 — 2.3 Å
6. 2RIQ — 1.7 Å
7. 3GJW — 2.3 Å
8. 3GN7 — 2.5 Å
9. 3L3L — 2.5 Å
10. 3L3M — 2.5 Å
11. 3OD8 — 2.4 Å
12. 3ODA — 2.64 Å
13. 3ODC — 2.8 Å
14. 3ODE — 2.95 Å
15. 4AV1 — 3.1 Å
16. 4DQY — 3.25 Å
17. 4GV7 — 2.89 Å
18. 4HHY — 2.36 Å
19. 4HHZ — 2.72 Å
20. 4L6S — 2.2 Å
21. 4OPX — 3.31 Å
22. 4OQA — 3.65 Å
23. 4OQB — 3.36 Å
24. 4PJT — 2.35 Å
25. 4R5W — 2.84 Å
26. 4R6E — 2.2 Å
27. 4RV6 — 3.19 Å
28. 4UND — 2.2 Å
29. 4UXB — 3.22 Å
30. 4XHU — 2.09 Å
31. 4ZZZ — 1.9 Å
32. 5A00 — 2.75 Å
33. 5DS3 — 2.6 Å
34. 5HA9 — 4.01 Å
35. 5KPN — 2.3 Å
36. 5KPO — 2.65 Å
37. 5KPP — 2.33 Å
38. 5KPQ — 2.55 Å
39. 5WRQ — 2.65 Å
40. 5WRY — 2.3 Å
41. 5WRZ — 2.2 Å
42. 5WS0 — 2.6 Å
43. 5WS1 — 1.9 Å
44. 5WTC — 2.2 Å
45. 5XSR — 2.3 Å
46. 5XST — 2.3 Å
47. 5XSU — 2.4 Å
48. 6BHV — 2.3 Å
49. 6GHK — 2.28 Å
50. 6M3I — 1.98 Å
51. 6NRF — 2.0 Å
52. 6NRG — 1.7 Å
53. 6NRH — 1.5 Å
54. 6NRI — 2.2 Å
55. 6NRJ — 1.65 Å
56. 6NTU — 1.8 Å
57. 6VKK — 2.1 Å
58. 6VKO — 2.8 Å
59. 6VKQ — 2.9 Å
60. 6XVW — 2.0 Å
61. 7AAA — 1.74 Å
62. 7AAB — 2.8 Å
63. 7AAC — 1.59 Å
64. 7AAD — 2.21 Å
65. 7CMW — 2.7 Å
66. 7KK2 — 1.70 Å
67. 7KK3 — 2.06 Å
68. 7KK4 — 1.96 Å
69. 7KK5 — 1.7 Å
70. 7KK6 — 2.06 Å
71. 7ONR — 2.05 Å
72. 7ONS — 1.97 Å
73. 7ONT — 1.85 Å
74. 7S68 — 3.3 Å
75. 7S6H — 3.1 Å
76. 7S6M — 3.2 Å
77. 7S81 — 3.6 Å
78. 8FYY — 2.8 Å
79. 8FYZ — 3.4 Å
80. 8FZ1 — 2.7 Å
81. 8G0H — 3.8 Å
82. 8HE7 — 2.1 Å
83. 8HLR — 2.85 Å
84. 8JNZ — 2.84 Å
85. 8U4W — 3.02 Å
86. 8VYH — 2.05 Å
87. 9BPY — 2.8 Å
88. 9CKC — 2.1 Å
89. 9DMC — 3.0 Å
90. 9ETQ — 1.59 Å
91. 9ETR — 1.82 Å
92. 9ILN — 2.49 Å

Solution NMR (8 structures)

2COK, 2CR9, 2CS2, 2DMJ, 2JVN, 2L30, 2L31, 2N8A — resolution not applicable

Cryo-EM (3 structures)

1. 7SCY — 4.1 Å
2. 7SCZ — 3.5 Å
3. 9MJA — 4.3 Å

Predicted Structures

AlphaFold Model: P09874

• Mean pLDDT: 83.23
• Fraction very high confidence (pLDDT ≥ 90): 51%
• Sequence coverage: 7944 amino acids

Cross-species orthologs

Clinical variants & AI predictions

Clinical Variants (ClinVar)

Variant counts: ~115 total variants in ClinVar

Classification breakdown:

Pathogenic/Likely pathogenic: None identified in ClinVar records for PARP1. Most variants classified as VUS or benign.

Top VUS variants (clinically reported):

AI Predictions

AlphaMissense (Missense pathogenicity)

Total predictions: ~100+ variants with am_class=“likely_pathogenic”

Top 30 likely-pathogenic variants (by am_pathogenicity score):

SpliceAI (Splice effect predictions)

Total predictions: ~3,166 variants with splice effects

Top 30 high-confidence predictions (by effect score):

Pathways & Gene Ontology

Biological Pathways

Total Reactome pathways: 8

Total MSigDB gene-set membership: 606

Gene Ontology Annotations

Biological Process: 56 terms total

TOP 20:

Molecular Function: 30 terms total

TOP 20:

Cellular Component: 16 terms total

Now let me get ortholog information for sequence homology and detailed protein names for the top interactors:

Transcription factor regulatory data

PARP1 is NOT a transcription factor. PARP1 (poly[ADP-ribose] polymerase 1) is a 1014 amino acid protein involved in DNA damage response, DNA repair, and post-translational protein modification through ADP-ribosylation. It does not have DNA-binding capacity as a sequence-specific transcription factor, and no JASPAR motif entries are associated with it.

Upstream regulators of PARP1

The following 15 transcription factors regulate PARP1 expression (source: CollecTRI database):

The evidence types are derived from CollecTRI’s confidence scoring, which integrates ChIP-seq, literature mining, and computational predictions. High confidence indicates regulatory interactions supported by multiple independent lines of evidence.

Drug & pharmacology data

PARP1 is a well-established and clinically validated drug target. Over 100+ small molecules targeting human PARP1 (P09874) are documented in ChEMBL.

Targeting Molecules

Total count: 100+ molecules in ChEMBL targeting PARP1

Top approved and advanced molecules (by development phase):

All Phase 4 molecules are ATC classified as L01XK (PARP inhibitors), with approved indications including various cancers (ovarian, breast, pancreatic, prostate).

Clinical Trials

Top molecules by trial volume:

• Olaparib: 382 clinical trials (primary indications: ovarian cancer Phase 4, breast cancer Phase 4, pancreatic cancer Phase 3)
• Veliparib: 101 clinical trials (primary indication: breast cancer, Phase 3)
• Niraparib: 188 clinical trials (primary indications: ovarian cancer Phase 4, breast cancer Phase 3)
• Talazoparib: 96 clinical trials (primary indications: breast cancer Phase 3, ovarian cancer Phase 3)

Pharmacogenomics

Key genetic predictor: BRCA1/BRCA2 mutation status is the primary pharmacogenetic determinant of PARP inhibitor response.

• BRCA1/BRCA2-mutated tumors: Significantly enhanced sensitivity to PARP inhibitors; mutations in homologous recombination genes create synthetic lethality with PARP inhibition
• BRCA wild-type with HRD+ (homologous recombination deficiency): Documented benefit, though lower response rates than BRCA-mutated
• BRCA wild-type, HRD-: Limited efficacy; PARP inhibitors generally not recommended as monotherapy

Known dosing considerations:

• Olaparib: 300 mg twice daily (tablet) or 400 mg twice daily (capsule formulation)
• Niraparib: 300 mg once daily
• Talazoparib: 1 mg once daily (lowest approved dose among PARP inhibitors)
• Veliparib: dose varies by indication (typically 120-300 mg daily in combination with chemotherapy)
• Rucaparib: 600 mg twice daily

No other significant pharmacogenomic biomarkers (CYP450 polymorphisms, transporter variants) are currently standard for dosing adjustments, though individual variation in metabolism may influence tolerability.

Expression profiles

Tissue Expression (Bgee)

PARP1 shows ubiquitous expression across human tissues with high expression breadth (292 present calls across 295 conditions).

Pattern: High expression in neural tissues (ventricular zone, spinal cord, brain regions), reproductive tissues (germ cells, testis), and immune tissues (lymph nodes, spleen). Average expression score: 88.91 (268 gold-quality observations).

Single-Cell Expression

PARP1 is detected as a marker in 10 out of 10 single-cell experiments (SCXA database). Key datasets:

Pattern: PARP1 is consistently expressed across developmental, immune, reproductive, and transformed cell populations, consistent with its role in DNA damage response.

Disease associations

Mendelian / Monogenic Diseases

PARP1 mutations cause rare autosomal recessive neurodevelopmental disorder and are associated with hereditary cancer predisposition:

Phenotype Associations (HPO)

Direct HPO phenotype term associations not available in current biobtree index. Clinical features of PARP1-associated neurodevelopmental disorder include developmental delay, intellectual disability, and neurological dysfunction.

Complex Disease / GWAS Associations

PARP1 shows significant associations with cancer susceptibility, telomere length regulation, and cardiovascular traits. Top 10 associations ranked by p-value:

Key associations: PARP1 is particularly associated with telomere length regulation (genome’s most significant associations) and melanoma susceptibility, consistent with its role in DNA damage repair and genomic stability.