RPA3
replication protein A3, the group of Nucleotide excision repair
Basic information
Region (hg38): 7:7636518-7718607
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
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.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 8 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 8 | 0 | 0 |
Variants in RPA3
This is a list of pathogenic ClinVar variants found in the RPA3 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 7-7637020-C-G | not specified | Uncertain significance (Nov 03, 2022) | ||
| 7-7637051-A-C | not specified | Uncertain significance (May 16, 2023) | ||
| 7-7637065-C-T | not specified | Uncertain significance (Jun 09, 2022) | ||
| 7-7637875-C-T | not specified | Likely benign (Mar 19, 2024) | ||
| 7-7639074-T-C | not specified | Uncertain significance (Apr 26, 2024) | ||
| 7-7639107-C-A | not specified | Uncertain significance (Jun 30, 2023) | ||
| 7-7640355-C-G | not specified | Uncertain significance (Jan 31, 2024) | ||
| 7-7640366-G-A | not specified | Uncertain significance (May 31, 2023) | ||
| 7-7640390-G-A | not specified | Uncertain significance (Aug 02, 2021) | ||
| 7-7640405-A-G | not specified | Uncertain significance (Oct 03, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RPA3 | protein_coding | protein_coding | ENST00000223129 | 4 | 82090 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 8.55e-9 | 0.0242 | 125712 | 0 | 35 | 125747 | 0.000139 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.644 | 81 | 66.2 | 1.22 | 0.00000305 | 795 |
| Missense in Polyphen | 19 | 21.332 | 0.89068 | 265 | ||
| Synonymous | -0.248 | 26 | 24.4 | 1.06 | 0.00000130 | 220 |
| Loss of Function | -1.55 | 10 | 5.92 | 1.69 | 3.41e-7 | 70 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000211 | 0.000210 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000109 | 0.000109 |
| Finnish | 0.000139 | 0.000139 |
| European (Non-Finnish) | 0.000132 | 0.000132 |
| Middle Eastern | 0.000109 | 0.000109 |
| South Asian | 0.000297 | 0.000294 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- 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}.;
- Pathway
- 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
- pRec
- 0.224
Intolerance Scores
- loftool
- rvis_EVS
- 0.04
- rvis_percentile_EVS
- 56.25
Haploinsufficiency Scores
- pHI
- 0.922
- hipred
- Y
- hipred_score
- 0.578
- ghis
- 0.704
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.789
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Low | Low | Low |
| Cancer | Low | Low | Low |
Mouse Genome Informatics
- Gene name
- Rpa3
- Phenotype
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