RFC1 Gene - Replication Factor C Subunit 1
Genetic and Functional Insights into RFC1 and Its Role in Neurological Disorders
Gene Information Card
| Symbol | RFC1 |
|---|---|
| Full Name | Replication Factor C Subunit 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 4p14 |
| NCBI Gene ID | 5981 ncbi.nlm.nih.gov/gene/5981 |
| Ensembl ID | ENSG00000035928 |
| UniProt ID | P35251 |
| OMIM ID | 102579 |
| HGNC ID | 9969 |
| Aliases | A1, RFC140, PO-GA, MGC5178, RFC1_HUMAN |
Description
The RFC1 gene encodes the large subunit of replication factor C (RFC), a five-subunit DNA polymerase accessory protein essential for DNA replication and repair. RFC loads the proliferating cell nuclear antigen (PCNA) clamp onto DNA, enabling processive DNA synthesis. Biallelic intronic AAGGG repeat expansions in RFC1 cause cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), a late-onset neurodegenerative disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) | Biallelic intronic AAGGG repeat expansions in RFC1 lead to reduced RFC1 expression and impaired DNA replication/repair, causing neuronal dysfunction. | OMIM #614575, ClinVar |
| RFC1-related ataxia | Same mechanism as CANVAS; phenotypic variability includes isolated ataxia or neuropathy. | ClinVar, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Cerebellum | 15.1 | Medium |
| Spinal cord | 10.8 | Medium |
| Testis | 18.5 | High |
| Lymph node | 9.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.7 | nTPM from GTEx |
| HeLa | 11.2 | nTPM from GTEx |
| K562 | 8.9 | nTPM from GTEx |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| AAGGG repeat expansion (intronic) | Repeat expansion | ~0.7% in European populations | Loss of function; reduced RFC1 mRNA and protein levels |
| c.1A>G (p.Met1Val) | Missense | Rare | Likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Biallelic AAGGG repeat expansions reduce RFC1 expression, impairing PCNA loading and DNA replication/repair, leading to neurodegeneration.
Gain of Function (GOF)
No evidence of gain-of-function mutations in RFC1.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • DNA replication | • DNA repair |
| • PCNA loading | • nucleotide-excision repair |
| • DNA clamp loader activity | • ATP binding |
| • nucleus |
Pathways
• DNA replication (KEGG hsa03030)
• Mismatch repair (KEGG hsa03430)
• Nucleotide excision repair (KEGG hsa03420)
Protein Summary
RFC1 is the 140 kDa large subunit of the replication factor C complex, which acts as a clamp loader for PCNA. It is essential for DNA replication and repair. The protein contains an ATP-binding domain and interacts with other RFC subunits to load PCNA onto primed DNA templates. Loss of RFC1 function due to repeat expansions causes CANVAS.
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