RFC1
Chr 4ARreplication factor C subunit 1
Also known as: A1, CANVAS, MHCBFB, PO-GA, RECC1, RFC, RFC140
The RFC1 protein is the large subunit of replication factor C, a DNA polymerase accessory complex that loads PCNA onto DNA and is essential for DNA replication and repair. Biallelic RFC1 mutations cause cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), which involves the cerebellum, peripheral nerves, and vestibular system. RFC1 follows autosomal recessive inheritance and is highly constrained against loss-of-function variants.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in 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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
KPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II
RECRUITINGLong Term Outcomes After Vestibular Implantation
RECRUITINGTAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer
RECRUITINGPathogenic Insights and Search for Biomarkers in RFC1-ataxia/CANVAS
RECRUITINGExternal Resources
Links to major genomics databases and tools