RPA1: Replication Protein A1, the Major Single-Stranded DNA Binding Subunit
Essential for DNA replication, repair, and recombination; implicated in cancer and genetic instability
Gene Information Card
| Symbol | RPA1 |
|---|---|
| Full Name | Replication Protein A1 |
| Gene Type | Protein coding |
| Chromosomal Location | 17p13.3 |
| NCBI Gene ID | 6117 ncbi.nlm.nih.gov/gene/6117 |
| Ensembl ID | ENSG00000132383 |
| UniProt ID | P27694 |
| OMIM ID | 179835 |
| HGNC ID | 10289 |
| Aliases | RPA70, REPA1, RF-A, RP-A, MST075 |
Description
RPA1 encodes the largest subunit (70 kDa) of replication protein A (RPA), a heterotrimeric single-stranded DNA-binding protein essential for DNA replication, repair, recombination, and the DNA damage response. RPA binds and stabilizes single-stranded DNA intermediates, coordinating the recruitment of downstream factors. Loss or mutation of RPA1 leads to genomic instability and has been associated with various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | RPA1 overexpression or mutation disrupts DNA repair fidelity, promoting genomic instability | COSMIC; ClinVar |
| Ovarian cancer | Altered RPA1 expression correlates with defective homologous recombination | COSMIC; NCBI |
| Lung cancer | Somatic mutations in RPA1 impair replication stress response | COSMIC; ClinVar |
| Colorectal cancer | RPA1 variants linked to microsatellite instability | COSMIC; NCBI |
| Fanconi anemia-like syndrome | Biallelic RPA1 mutations cause bone marrow failure and developmental defects | OMIM #179835; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 52.3 | High |
| Bone marrow | 38.1 | High |
| Lymph node | 35.7 | High |
| Brain | 12.4 | Medium |
| Liver | 9.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 45.2 | Cervical carcinoma; high proliferation |
| HEK293 | 40.1 | Embryonic kidney; robust expression |
| K562 | 38.5 | Leukemia; active DNA replication |
| MCF7 | 42.0 | Breast cancer; elevated in cycling cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2101C>T (p.Arg701Trp) | Missense | 0.02% (gnomAD) | Reduced DNA-binding affinity; associated with cancer predisposition |
| c.1873G>A (p.Val625Met) | Missense | 0.01% (gnomAD) | Impaired RPA complex stability |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss of protein expression; severe genomic instability |
| c.1234_1235insA | Frameshift | Somatic (COSMIC) | Truncation; loss of function in tumors |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or abolish DNA-binding activity lead to loss of RPA function, causing replication stress and genomic instability.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported; overexpression in tumors may confer a proliferative advantage.
Dominant Negative (DN)
Certain missense mutations (e.g., p.Arg701Trp) can disrupt RPA heterotrimer assembly, interfering with wild-type function in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• DNA replication (Reactome: R-HSA-69306)
• Homology Directed Repair (Reactome: R-HSA-5693532)
• Nucleotide Excision Repair (Reactome: R-HSA-5696398)
• Mismatch Repair (Reactome: R-HSA-5358501)
• Telomere Maintenance (Reactome: R-HSA-157579)
Protein Summary
RPA1 (70 kDa) is the largest subunit of the heterotrimeric replication protein A complex. It contains four oligonucleotide/oligosaccharide-binding (OB) folds that mediate high-affinity single-stranded DNA binding. RPA1 is essential for the initiation and elongation phases of DNA replication, as well as for DNA repair pathways including nucleotide excision repair, homologous recombination, and mismatch repair. The protein also participates in the DNA damage checkpoint response by recruiting ATR-ATRIP to sites of damage. Post-translational modifications such as phosphorylation regulate its activity and interactions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRPA1 Overexpression HEK293 Stable Cell Line | EDJ-GQ74 | Human | 8989 | Details Get a Quote |
| TRPA1 Knockout HEK293 Cell Line | EDJ-KQ1284 | Human | 8989 | Details Get a Quote |
| TRPA1 Knockout A-549 Cell Line | EDJ-KQ21981 | Human | 8989 | Details Get a Quote |
| TRPA1 Knockout HeLa Cell Line | EDJ-KQ21983 | Human | 8989 | Details Get a Quote |
| TRPA1 Knockout HCT 116 Cell Line | EDJ-KQ72001 | Human | 8989 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
