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GeneBe

RPA1

replication protein A1, the group of Nucleotide excision repair

Basic information

Region (hg38): 17:1829701-1900082

Links

ENSG00000132383NCBI:6117OMIM:179835HGNC:10289Uniprot:P27694AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • pulmonary fibrosis and/or bone marrow failure, telomere-related, 6 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6ADAllergy/Immunology/Infectious; Hematologic; PulmonaryThe condition can involve immunologic manifestations, and awareness may allow early diagnosis and medical management (eg, with IVIG); Surveillance and prompt treatment of bone marrow failure may reduce morbidity; For treatment related to pulmonary fibrosis, early recognition may allow prompt medical management; HSCT has been describedAllergy/Immunology/Infectious; Dermatologic; Hematologic; Pulmonary34767620

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RPA1 gene.

  • Inborn genetic diseases (23 variants)
  • not specified (7 variants)
  • not provided (2 variants)
  • Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6 (1 variants)
  • RPA1-related short telomere syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RPA1 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
4
clinvar
4
missense
23
clinvar
1
clinvar
24
nonsense
0
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
1
1
non coding
4
clinvar
4
Total 0 0 23 1 8

Variants in RPA1

This is a list of pathogenic ClinVar variants found in the RPA1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
17-1830105-A-G not specified Benign (Jan 24, 2024)2688031
17-1842798-C-A Benign (Jun 05, 2018)718295
17-1843952-G-A Benign (Jun 05, 2018)718296
17-1843990-C-G Inborn genetic diseases Uncertain significance (Aug 04, 2021)2357884
17-1844682-G-A Inborn genetic diseases Uncertain significance (Dec 07, 2021)2386694
17-1844734-A-G not specified Benign (Jan 24, 2024)2687931
17-1853057-A-G not specified Benign (Jan 24, 2024)2687984
17-1853102-A-G Inborn genetic diseases Uncertain significance (Feb 03, 2022)2275589
17-1853142-C-G Inborn genetic diseases Uncertain significance (Mar 11, 2022)2398600
17-1853164-T-G Inborn genetic diseases Uncertain significance (Nov 15, 2021)2261283
17-1872510-T-G Inborn genetic diseases Uncertain significance (Jan 26, 2023)2479558
17-1875675-A-G Inborn genetic diseases Uncertain significance (Oct 06, 2021)2253772
17-1875678-G-A Inborn genetic diseases Uncertain significance (Nov 21, 2022)2328996
17-1875679-C-T Inborn genetic diseases Uncertain significance (Nov 21, 2022)2328997
17-1877286-T-A Inborn genetic diseases Uncertain significance (Oct 12, 2021)2254992
17-1877304-T-C Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6 Pathogenic (May 10, 2023)1342932
17-1879020-G-A Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6 Pathogenic (May 10, 2023)1342931
17-1879263-A-G RPA1-related short telomere syndrome • Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6 Uncertain significance (Sep 10, 2018)1327121
17-1879296-A-G Inborn genetic diseases Uncertain significance (Apr 05, 2023)2533403
17-1879297-A-G Inborn genetic diseases Uncertain significance (Aug 08, 2022)2305948
17-1879330-A-G Inborn genetic diseases Likely benign (Oct 04, 2022)2209311
17-1879366-G-A Inborn genetic diseases Uncertain significance (Nov 30, 2022)2404150
17-1879663-C-T not specified Benign (Jan 24, 2024)2688119
17-1879676-A-T Inborn genetic diseases Uncertain significance (Aug 02, 2023)2599521
17-1880518-T-C not specified Benign (Jan 24, 2024)2688148

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RPA1protein_codingprotein_codingENST00000254719 1770381
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.08780.9121257240231257470.0000915
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.222923570.8190.00002054043
Missense in Polyphen83118.60.699841339
Synonymous-0.1171411391.010.000009081149
Loss of Function4.341039.40.2540.00000235415

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001770.000177
Ashkenazi Jewish0.000.00
East Asian0.00005450.0000544
Finnish0.00004630.0000462
European (Non-Finnish)0.0001150.000114
Middle Eastern0.00005450.0000544
South Asian0.00009860.0000980
Other0.000.00

dbNSFP

Source: dbNSFP

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 (PubMed:27723720, PubMed:27723717). 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). 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 (PubMed:17959650). 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:12791985, ECO:0000269|PubMed:17765923, ECO:0000269|PubMed:17959650, ECO:0000269|PubMed:19116208, ECO:0000269|PubMed:19996105, ECO:0000269|PubMed:24332808, ECO:0000269|PubMed:27723717, ECO:0000269|PubMed:27723720, ECO:0000269|PubMed:7697716, ECO:0000269|PubMed:7700386, ECO:0000269|PubMed:9430682, ECO:0000269|PubMed:9765279}.;
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);Homologous recombination;Retinoblastoma (RB) in Cancer;ATR Signaling;G1 to S cell cycle control;DNA Replication;Mismatch repair;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;hypoxia and p53 in the cardiovascular system;Generic Transcription Pathway;Regulation of HSF1-mediated heat shock response;SUMOylation of DNA damage response and repair proteins;Homology Directed Repair;Cellular responses to stress;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;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;SUMOylation;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;atm signaling pathway;Fanconi anemia pathway;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;ATR signaling pathway;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
0.160

Intolerance Scores

loftool
0.638
rvis_EVS
-1.11
rvis_percentile_EVS
6.78

Haploinsufficiency Scores

pHI
0.998
hipred
Y
hipred_score
0.793
ghis
0.686

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
E
essential_gene_gene_trap
E
gene_indispensability_pred
E
gene_indispensability_score
0.985

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Rpa1
Phenotype
cellular phenotype; immune system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm;

Zebrafish Information Network

Gene name
rpa1
Affected structure
head
Phenotype tag
abnormal
Phenotype quality
flat

Gene ontology

Biological process
G1/S transition of mitotic cell cycle;telomere maintenance;double-strand break repair via homologous recombination;DNA replication;DNA-dependent DNA replication;DNA unwinding involved in DNA replication;DNA repair;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;DNA recombination;cellular response to DNA damage stimulus;telomere maintenance via telomerase;translesion synthesis;telomere maintenance via semi-conservative replication;nucleotide-excision repair, DNA incision;protein localization to chromosome;interstrand cross-link repair;error-prone translesion synthesis;DNA damage response, detection of DNA damage;meiotic cell cycle;error-free translesion synthesis;regulation of cellular response to heat
Cellular component
nuclear chromosome, telomeric region;nucleus;nucleoplasm;DNA replication factor A complex;PML body;site of DNA damage
Molecular function
damaged DNA binding;single-stranded DNA binding;protein binding;single-stranded telomeric DNA binding;sequence-specific DNA binding;metal ion binding;G-rich strand telomeric DNA binding