RFC3

Chr 13

replication factor C subunit 3

Also known as: RFC38

NCBI Gene: 5983ENSG00000133119UniProt: P40938OMIM: 600405

RFC3 encodes the 38 kDa subunit of replication factor C (RFC), which loads proliferating cell nuclear antigen (PCNA) onto primed DNA during DNA replication by polymerases delta and epsilon. Biallelic RFC3 mutations cause autosomal recessive immunodeficiency with severe combined immunodeficiency (SCID) phenotype, reflecting the critical role of DNA replication in rapidly dividing immune cells. The gene shows minimal constraint against loss-of-function variants in the general population (pLI near 0), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.94
Clinical Summary— RFC3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
43 unique Pathogenic / Likely Pathogenic· 47 VUS of 101 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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
0.94LOEUF
pLI 0.000
Z-score 1.75
OE 0.57 (0.36–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.13Z-score
OE missense 1.03 (0.91–1.16)
196 obs / 191.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.57 (0.36–0.94)
0≤0.351.4
Missense OE1.03 (0.91–1.16)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 11 / 19.3Missense obs/exp: 196 / 191.0Syn Z: -0.14
DN
0.79top 25%
GOF
0.4579th %ile
LOF
0.2969th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

101 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
VUS47
Likely Benign1
43
Pathogenic
47
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
43
0
43
Likely Pathogenic
0
0
0
0
0
VUS
0
41
6
0
47
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total04150091

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

View in ClinVar →

Protein Context — Lollipop Plot

RFC3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 3 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients