RPA1

Chr 17AD

replication protein A1

Also known as: HSSB, MST075, PFBMFT6, REPA1, RF-A, RP-A, RPA70

This gene encodes the largest subunit of the heterotrimeric Replication Protein A (RPA) complex, which binds to single-stranded DNA (ssDNA), forming a nucleoprotein complex that plays an important role in DNA metabolism, being involved in DNA replication, repair, recombination, telomere maintenance, and co-ordinating the cellular response to DNA damage through activation of the ataxia telangiectasia and Rad3-related protein (ATR) kinase. The nucleoprotein complex protects the single-stranded DNA from nucleases, prevents formation of secondary structures that would interfere with repair, and co-ordinates the recruitment and departure of different genome maintenance factors. This subunit contains four oligonucleotide/oligosaccharide-binding (OB) domains, though the majority of ssDNA binding occurs in two of these domains. The heterotrimeric complex has two different modes of ssDNA binding, a low-affinity and high-affinity mode, determined by which ssDNA binding domains are utilized. The different binding modes differ in the length of DNA bound and in the proteins with which it interacts, thereby playing a role in regulating different genomic maintenance pathways. [provided by RefSeq, Sep 2017]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 6MIM #619767
AD

Clinical highlights

Gene-disease validity (ClinGen)
dyskeratosis congenita and related telomere biology disorder · ADLimitednot for standalone diagnostic reporting
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
2
Active trials
33
Pubs (1 yr)
P/LP submissions
P/LP missense
0.43
LOEUF
Multiple*
Mechanism· predicted
📖
GeneReview available — RPA1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.43LOEUF
pLI 0.088
Z-score 4.34
OE 0.25 (0.160.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.22Z-score
OE missense 0.82 (0.740.90)
292 obs / 356.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.25 (0.160.43)
00.351.4
Missense OE?0.82 (0.740.90)
00.61.4
Synonymous OE?1.01
01.21.6
LoF obs/exp: 10 / 39.4Missense obs/exp: 292 / 356.7Syn Z: -0.12

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RPA1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.