RFC2

Chr 7

replication factor C subunit 2

Also known as: RFC40

NCBI Gene: 5982ENSG00000049541UniProt: P35250

This gene encodes a member of the activator 1 small subunits family. The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins, proliferating cell nuclear antigen (PCNA) and replication factor C (RFC). Replication factor C, also called activator 1, is a protein complex consisting of five distinct subunits. This gene encodes the 40 kD subunit, which has been shown to be responsible for binding ATP and may help promote cell survival. Disruption of this gene is associated with Williams syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been described. A pseudogene of this gene has been defined on chromosome 2. [provided by RefSeq, Jul 2013]

1
Active trials
84
Pathogenic / LP
130
ClinVar variants
9
Pubs (1 yr)
1.2
Missense Z
0.98
LOEUF
Clinical Summary— RFC2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
84 Pathogenic / Likely Pathogenic· 42 VUS of 130 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.000
Z-score 1.64
OE 0.60 (0.39–0.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.15Z-score
OE missense 0.77 (0.68–0.88)
160 obs / 206.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.60 (0.39–0.98)
0≤0.351.4
Missense OE0.77 (0.68–0.88)
0≤0.61.4
Synonymous OE1.06
0≤1.21.6
LoF obs/exp: 12 / 19.9Missense obs/exp: 160 / 206.7Syn Z: -0.46
DN
DN
0.79top 25%
GOF
0.5170th %ile
LOF
0.2774th %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

130 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic83
Likely Pathogenic1
VUS42
Likely Benign3
Benign1
83
Pathogenic
1
Likely Pathogenic
42
VUS
3
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
83
0
83
Likely Pathogenic
0
0
1
0
1
VUS
0
37
5
0
42
Likely Benign
0
1
0
2
3
Benign
0
0
1
0
1
Total038902130

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

View in ClinVar →

RFC2 · protein map & ClinVar variants

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

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 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