RPA4

replication protein A4, the group of Nucleotide excision repair

Basic information

Region (hg38): X:96883907-96885467

Links

ENSG00000204086 ∙ NCBI:29935 ∙ OMIM:300767 ∙ HGNC:30305 ∙ Uniprot:Q13156 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RPA4 gene.

• Inborn genetic diseases (14 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RPA4 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				1		1
missense			13	2		15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	13	3	0

Variants in RPA4

This is a list of pathogenic ClinVar variants found in the RPA4 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-96884323-G-A			Likely benign (Mar 01, 2023)
X-96884336-A-G		not specified	Uncertain significance (Dec 27, 2022)
X-96884354-C-A		not specified	Uncertain significance (Jun 27, 2023)
X-96884398-G-C		not specified	Uncertain significance (Sep 16, 2021)
X-96884410-A-G		not specified	Likely benign (Mar 12, 2024)
X-96884512-G-A		not specified	Uncertain significance (Jul 05, 2022)
X-96884635-G-C		not specified	Uncertain significance (Aug 09, 2021)
X-96884682-T-C			Likely benign (Oct 01, 2022)
X-96884701-C-G		not specified	Uncertain significance (Jul 12, 2023)
X-96884828-G-A		not specified	Uncertain significance (Mar 29, 2022)
X-96884851-C-A		not specified	Uncertain significance (Jan 09, 2024)
X-96884878-G-T		not specified	Conflicting classifications of pathogenicity (Feb 01, 2024)
X-96884902-C-T		not specified	Uncertain significance (Dec 17, 2023)
X-96884903-G-A		not specified	Uncertain significance (Feb 03, 2022)
X-96884903-G-T		not specified	Likely benign (Aug 22, 2023)
X-96884959-G-A		not specified	Uncertain significance (Jun 28, 2022)
X-96884984-C-A		not specified	Uncertain significance (Mar 22, 2023)
X-96885017-A-G		not specified	Uncertain significance (Aug 10, 2023)
X-96885029-A-G		not specified	Uncertain significance (Feb 05, 2024)
X-96885091-G-A		not specified	Uncertain significance (Oct 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RPA4	protein_coding	protein_coding	ENST00000373040	1	1540

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	0.251	107	115	0.934	0.00000952	1730
Missense in Polyphen		24	22.638	1.0601		417
Synonymous	1.51	34	47.2	0.720	0.00000432	520
Loss of Function

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish
East Asian
Finnish
European (Non-Finnish)
Middle Eastern
South Asian
Other

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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 polymerase delta synthesis in the presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange. {ECO:0000269|PubMed:19116208, ECO:0000269|PubMed:19942684, ECO:0000269|PubMed:19996105, ECO:0000269|PubMed:20545304}.
• 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);DNA Replication;Activation of the pre-replicative complex;Mitotic G1-G1/S phases;DNA Replication;G1/S Transition;DNA Replication Pre-Initiation;M/G1 Transition;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Intolerance Scores

• loftool: 0.539
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.19

Haploinsufficiency Scores

• pHI: 0.172
• hipred: N
• hipred_score: 0.329
• ghis: 0.394

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.914

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: DNA damage checkpoint;G1/S transition of mitotic cell cycle;telomere maintenance via recombination;double-strand break repair via homologous recombination;DNA replication;DNA topological change;DNA unwinding involved in DNA replication;DNA replication initiation;base-excision repair;nucleotide-excision repair;mismatch repair;mitotic recombination;telomere maintenance via telomerase;reciprocal meiotic recombination;heteroduplex formation;nuclear DNA replication;positive regulation of helicase activity;regulation of DNA damage checkpoint
• Cellular component: chromosome, telomeric region;chromatin;condensed nuclear chromosome;nucleus;nucleoplasm;DNA replication factor A complex;site of double-strand break
• Molecular function: damaged DNA binding;double-stranded DNA binding;single-stranded DNA binding;protein binding;sequence-specific DNA binding;G-rich strand telomeric DNA binding