RPA3

Chr 7

replication protein A3

Also known as: REPA3, RP-A p14

NCBI Gene: 6119 ENSG00000106399 UniProt: P35244 OMIM: 179837

The RPA3 protein is part of the replication protein A complex that binds and stabilizes single-stranded DNA during replication and DNA repair processes. Mutations cause autosomal recessive hypomyelinating leukodystrophy-18 with eventual neurodegeneration, typically presenting in infancy with progressive motor regression and seizures. The gene shows minimal constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Enables damaged DNA binding activity and single-stranded DNA binding activity. Involved in DNA metabolic process. Part of DNA replication factor A complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 1.95

Clinical Summary— RPA3

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

16 VUS of 24 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.95LOEUF

pLI 0.000

Z-score -1.55

OE 1.69 (0.96–1.95)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.64Z-score

OE missense 1.22 (1.02–1.47)

81 obs / 66.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.69 (0.96–1.95)

0≤0.351.4

Missense OE?1.22 (1.02–1.47)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 10 / 5.9Missense obs/exp: 81 / 66.2Syn Z: -0.25

ClinVar Variant Classifications

24 submitted variants in ClinVar

ClinVar

Classification Summary

VUS16

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	16	16
Likely Benign	1	1
Benign	0	0
Total	17	17

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

28 pathogenic / likely-pathogenic (of 40) ClinVar copy-number / structural variants overlap RPA3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →