replication protein A3, the group of Nucleotide excision repair

Basic information

Region (hg38): 7:7636517-7718607





Source: genCC

No genCC data.


This is a list of variants' phenotypes submitted to ClinVar and linked to the RPA3 gene.

  • Inborn genetic diseases (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RPA3 gene is commonly pathogenic or not.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous 0
missense 3 3
nonsense 0
start loss 0
frameshift 0
inframe indel 0
splice variant 0
non coding 0
Total 0 0 3 0 0

Variants in RPA3

This is a list of pathogenic ClinVar variants found in the RPA3 region.

Position Type Phenotype Significance ClinVar
7-7637020-C-G Inborn genetic diseases Uncertain significance (Nov 03, 2022)link
7-7637051-A-C Inborn genetic diseases Uncertain significance (May 16, 2023)link
7-7637065-C-T Inborn genetic diseases Uncertain significance (Jun 09, 2022)link
7-7639107-C-A Inborn genetic diseases Uncertain significance (Jun 30, 2023)link
7-7640366-G-A Inborn genetic diseases Uncertain significance (May 31, 2023)link
7-7640390-G-A Inborn genetic diseases Uncertain significance (Aug 02, 2021)link


Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RPA3protein_codingprotein_codingENST00000223129 482090
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense in Polyphen1921.3320.89068265
Loss of Function-1.55105.921.693.41e-770

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0002110.000210
Ashkenazi Jewish0.000.00
East Asian0.0001090.000109
European (Non-Finnish)0.0001320.000132
Middle Eastern0.0001090.000109
South Asian0.0002970.000294


Source: dbNSFP

FUNCTION: 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. 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. 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). Plays also 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. May also play a role in telomere maintenance. RPA3 has its own single- stranded DNA-binding activity and may be responsible for polarity of the binding of the complex to DNA (PubMed:19010961). 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). {ECO:0000269|PubMed:19010961, ECO:0000269|PubMed:19116208, ECO:0000269|PubMed:19996105, ECO:0000269|PubMed:7697716, ECO:0000269|PubMed:9430682, ECO:0000269|PubMed:9765279, ECO:0000303|PubMed:24332808}.;
Fanconi anemia pathway - Homo sapiens (human);Nucleotide excision repair - Homo sapiens (human);Mismatch repair - Homo sapiens (human);DNA replication - Homo sapiens (human);Homologous recombination - Homo sapiens (human);Retinoblastoma (RB) in Cancer;G1 to S cell cycle control;DNA Replication;Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta);Mismatch Repair;HDR through Single Strand Annealing (SSA);HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);Fanconi Anemia Pathway;DNA Repair;Gene expression (Transcription);DNA Double-Strand Break Repair;HSF1 activation;Generic Transcription Pathway;Regulation of HSF1-mediated heat shock response;Homology Directed Repair;Cellular responses to stress;RNA Polymerase II Transcription;G2/M DNA damage checkpoint;Activation of ATR in response to replication stress;G2/M Checkpoints;Cell Cycle Checkpoints;Activation of the pre-replicative complex;Mitotic G1-G1/S phases;DNA Replication;Removal of the Flap Intermediate;Processive synthesis on the lagging strand;Lagging Strand Synthesis;DNA strand elongation;Synthesis of DNA;S Phase;PCNA-Dependent Long Patch Base Excision Repair;Resolution of AP sites via the multiple-nucleotide patch replacement pathway;Resolution of Abasic Sites (AP sites);Base Excision Repair;Cellular responses to external stimuli;Removal of the Flap Intermediate from the C-strand;Processive synthesis on the C-strand of the telomere;Telomere C-strand (Lagging Strand) Synthesis;Extension of Telomeres;Telomere Maintenance;Chromosome Maintenance;Cellular response to heat stress;G1/S Transition;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Recognition of DNA damage by PCNA-containing replication complex;Translesion synthesis by REV1;Translesion Synthesis by POLH;Translesion synthesis by POLK;DNA Replication Pre-Initiation;M/G1 Transition;Translesion synthesis by POLI;Termination of translesion DNA synthesis;Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template;DNA Damage Bypass;Cell Cycle;Formation of Incision Complex in GG-NER;Dual Incision in GG-NER;Gap-filling DNA repair synthesis and ligation in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Cell Cycle, Mitotic;Processing of DNA double-strand break ends;Dual incision in TC-NER;Presynaptic phase of homologous DNA pairing and strand exchange;Homologous DNA Pairing and Strand Exchange;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair;Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha);HDR through Homologous Recombination (HRR) (Consensus)

Recessive Scores


Intolerance Scores


Haploinsufficiency Scores




Gene Damage Prediction

Primary ImmunodeficiencyLowLowLow

Mouse Genome Informatics

Gene name

Gene ontology

Biological process
G1/S transition of mitotic cell cycle;telomere maintenance;double-strand break repair via homologous recombination;DNA replication;transcription-coupled nucleotide-excision repair;base-excision repair;nucleotide-excision repair;nucleotide-excision repair, preincision complex stabilization;nucleotide-excision repair, preincision complex assembly;nucleotide-excision repair, DNA incision, 5'-to lesion;nucleotide-excision repair, DNA gap filling;mismatch repair;regulation of mitotic cell cycle;translesion synthesis;telomere maintenance via semi-conservative replication;nucleotide-excision repair, DNA incision;interstrand cross-link repair;regulation of cell population proliferation;error-prone translesion synthesis;DNA damage response, detection of DNA damage;error-free translesion synthesis;regulation of cellular response to heat
Cellular component
nucleoplasm;DNA replication factor A complex;site of double-strand break
Molecular function
damaged DNA binding;single-stranded DNA binding;protein binding