RFC1

Chr 4AR

replication factor C subunit 1

Also known as: A1, CANVAS, MHCBFB, PO-GA, RECC1, RFC, RFC140

NCBI Gene: 5981ENSG00000035928UniProt: P35251OMIM: 102579

This gene encodes the large subunit of replication factor C, a five subunit DNA polymerase accessory protein, which is a DNA-dependent ATPase required for eukaryotic DNA replication and repair. The large subunit acts as an activator of DNA polymerases, binds to the 3' end of primers, and promotes coordinated synthesis of both strands. It may also have a role in telomere stability. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Mar 2011]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cerebellar ataxia, neuropathy, and vestibular areflexia syndromeMIM #614575
AR

Clinical highlights

Gene-disease validity (ClinGen)
cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome · ARDefinitivesufficient evidence for diagnostic panels
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.
5
Active trials
96
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.30
LOEUF· LoF intol.
LOF
Mechanism· predicted
📖
GeneReview available — RFC1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.30LOEUF
pLI 0.973
Z-score 5.84
OE 0.18 (0.12–0.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
1.38Z-score
OE missense 0.84 (0.78–0.91)
502 obs / 597.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.18 (0.12–0.30)
0≤0.351.4
Missense OE?0.84 (0.78–0.91)
0≤0.61.4
Synonymous OE?1.01
0≤1.21.6
LoF obs/exp: 11 / 59.6Missense obs/exp: 502 / 597.0Syn Z: -0.12

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

RFC1 · protein map & ClinVar variants

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

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