RPA3: Replication Protein A3, a Key Component of the RPA Complex
Essential for DNA replication, repair, and recombination; implicated in cancer and genetic disorders.
Gene Information Card
| Symbol | RPA3 |
|---|---|
| Full Name | Replication Protein A3 |
| Gene Type | Protein coding |
| Chromosomal Location | 7p21.3 |
| NCBI Gene ID | 6119 ncbi.nlm.nih.gov/gene/6119 |
| Ensembl ID | ENSG00000106399 |
| UniProt ID | P35244 |
| OMIM ID | 179837 |
| HGNC ID | 10291 |
| Aliases | RPA14, REPA3, RP-A p14 |
Description
RPA3 encodes the 14 kDa subunit of the heterotrimeric Replication Protein A (RPA) complex, which is essential for DNA replication, repair, and recombination. RPA binds single-stranded DNA (ssDNA) with high affinity, protecting it from degradation and preventing secondary structure formation. The RPA3 subunit, together with RPA2, forms a structural core that stabilizes the complex and facilitates DNA binding. RPA3 is critical for maintaining genomic stability and is involved in the DNA damage response.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | RPA3 overexpression may promote genomic instability and tumor progression; altered RPA complex dynamics affect DNA repair efficiency. | COSMIC; PMID: 25691885 |
| Ovarian Cancer | RPA3 mutations and copy number alterations are observed; loss of RPA function impairs homologous recombination repair. | COSMIC; PMID: 27197191 |
| Fanconi Anemia | RPA3 deficiency disrupts DNA interstrand crosslink repair, contributing to bone marrow failure and cancer predisposition. | OMIM; PMID: 19615732 |
| Lung Cancer | RPA3 upregulation correlates with poor prognosis; RPA complex hyperactivation may drive replication stress tolerance. | COSMIC; PMID: 29367608 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Bone Marrow | 12.8 | Medium |
| Lymph Node | 10.5 | Medium |
| Spleen | 9.1 | Low |
| Brain | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.4 | Cervical cancer cell line; high expression |
| HEK293 | 14.7 | Embryonic kidney; moderate expression |
| MCF7 | 12.1 | Breast cancer; moderate expression |
| A549 | 11.3 | Lung cancer; moderate expression |
| K562 | 9.8 | Leukemia; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.194C>T (p.Pro65Leu) | Missense | <0.01% | May reduce ssDNA binding affinity; reported in COSMIC |
| c.287G>A (p.Arg96His) | Missense | <0.01% | Located in OB-fold domain; potential loss of function |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Likely leads to truncated protein; loss of function |
| c.340_341insA (p.Gln114fs) | Frameshift | <0.01% | Predicted to cause nonsense-mediated decay; loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations in the OB-fold domain or start codon are predicted to impair ssDNA binding or protein stability, reducing RPA complex activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported for RPA3 in curated databases.
Dominant Negative (DN)
No dominant-negative mutations have been characterized; however, mutations affecting subunit interaction may exert dominant effects in heterozygous state.
View complete mutation data：
Gene Ontology (GO)
| • DNA replication | • DNA repair |
| • DNA recombination | • single-stranded DNA binding |
| • nucleotide-excision repair | • double-strand break repair via homologous recombination |
| • telomere maintenance | • cellular response to DNA damage stimulus |
Pathways
• DNA replication (Reactome: R-HSA-69306)
• Homologous recombination (Reactome: R-HSA-5693565)
• Nucleotide excision repair (Reactome: R-HSA-5696398)
• Fanconi anemia pathway (Reactome: R-HSA-6783310)
• Telomere maintenance (Reactome: R-HSA-157579)
Protein Summary
RPA3 (14 kDa) is the smallest subunit of the heterotrimeric Replication Protein A complex. It forms a stable dimer with RPA2, which together with RPA1 constitutes the high-affinity ssDNA-binding module. The protein contains an OB-fold domain that contributes to DNA binding and complex assembly. RPA3 is essential for the structural integrity of RPA and its functions in DNA replication, repair, and recombination. Post-translational modifications such as phosphorylation regulate its activity during the cell cycle and DNA damage response.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RPA3 Knockout HEK293 Cell Line | EDJ-KQ50572 | Human | 6119 | Details Get a Quote |
| RPA3 Knockout HeLa Cell Line | EDJ-KQ54338 | Human | 6119 | Details Get a Quote |
| RPA3 Knockout A-549 Cell Line | EDJ-KQ62833 | Human | 6119 | Details Get a Quote |
| RPA3 Knockout HCT 116 Cell Line | EDJ-KQ71300 | Human | 6119 | Details Get a Quote |
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