RPA1

Chr 17p13.3

replication protein A1

Aliases:: REPA1, RPA70, HSSB, RF-A, RP-A
MANE:: ENST00000254719.10

OMIM: 179835 ↗NCBI: 6117 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

RPA1 · P27694

v62025-08-01

Predicted Aligned Error matrix for RPA1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

83.8/ 100

Confident

616 residues

Confidence breakdown

Very high(≥ 90)62%
Confident(70–90)24%
Low(50–70)3%
Very low(< 50)12%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Cytopenia - NOT Fanconi anaemia
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary fibrosis familial
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

pulmonary fibrosis and/or bone marrow failure, telomere-related, 6
0.57
non-small cell lung adenocarcinoma
0.30
cancer
0.30
basal cell carcinoma
0.29
prostate carcinoma
0.28
melanocytic nevus
0.27
lung cancer
0.26
melanoma
0.26
skin cancer
0.26
bronchus cancer
0.26

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Replication protein A 70 kDa DNA-binding subunit

As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism (PubMed:17596542, PubMed:27723717, PubMed:27723720). Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage (PubMed:9430682). In the cellular response to DNA damage, the RPA complex controls DNA repair and DNA damage checkpoint activation. Through recruitment of ATRIP activates the ATR kinase a master regulator of the DNA damage response (PubMed:24332808). It is required for the recruitment of the DNA double-strand break repair factors RAD51 and RAD52 to chromatin in response to DNA damage (PubMed:17765923). Also recruits to sites of DNA damage proteins like XPA and XPG that are involved in nucleotide excision repair and is required for this mechanism of DNA repair (PubMed:7697716). Also plays a role in base excision repair (BER) probably through interaction with UNG (PubMed:9765279). Also recruits SMARCAL1/HARP, which is involved in replication fork restart, to sites of DNA damage. Plays a role in telomere maintenance (PubMed:17959650, PubMed:34767620). As part of the alternative replication protein A complex, aRPA, binds single-stranded DNA and probably plays a role in DNA repair. Compared to the RPA2-containing, canonical RPA complex, may not support chromosomal DNA replication and cell cycle progression through S-phase. The aRPA may not promote efficient priming by DNA polymerase alpha but could support DNA synthesis by polymerase delta in presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange (PubMed:19996105). RPA stimulates 5'-3' helicase activity of the BRIP1/FANCJ (PubMed:17596542)