RFC1

RFC1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2EBU, 2K6G, 2K7F
Identifiers
Aliases	RFC1, RFC, replication factor C subunit 1, A1, PO-GA, RECC1, MHCBFB, RFC140, CANVAS
External IDs	OMIM: 102579; MGI: 97891; HomoloGene: 2187; GeneCards: RFC1; OMA:RFC1 - orthologs
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4p14 Start 39,287,456 bp[1] End 39,366,375 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5 C3.1|5 33.61 cM Start 65,419,193 bp[2] End 65,493,013 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon ventricular zone sural nerve body of pancreas epithelium of colon testicle ganglionic eminence bone marrow cells right adrenal cortex tonsil Top expressed in genital tubercle tail of embryo otic placode primitive streak otic vesicle saccule zygote epiblast cumulus cell morula More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding protein binding enzyme activator activity ATP binding DNA clamp loader activity DNA binding sequence-specific DNA binding double-stranded DNA binding protein domain specific binding DNA clamp unloader activity Cellular component nucleoplasm extracellular exosome DNA replication factor C complex nucleus nucleolus cytoplasm Elg1 RFC-like complex protein-containing complex Biological process DNA-dependent DNA replication nucleotide-excision repair, DNA gap filling regulation of transcription, DNA-templated telomere maintenance via telomerase error-free translesion synthesis transcription, DNA-templated error-prone translesion synthesis DNA replication translesion synthesis transcription-coupled nucleotide-excision repair nucleotide-excision repair, DNA incision DNA repair nucleotide-excision repair, DNA incision, 5'-to lesion positive regulation of catalytic activity negative regulation of transcription by RNA polymerase II negative regulation of transcription, DNA-templated positive regulation of transcription, DNA-templated telomere maintenance via semi-conservative replication DNA clamp unloading Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5981 19687 Ensembl ENSG00000035928 ENSMUSG00000029191 UniProt P35251 P35601 RefSeq (mRNA) NM_001204747 NM_002913 NM_001363495 NM_001363496 NM_011258 NM_001347357 NM_001347358 RefSeq (protein) NP_001191676 NP_002904 NP_001350424 NP_001350425 NP_001334286 NP_001334287 NP_035388 Location (UCSC) Chr 4: 39.29 – 39.37 Mb Chr 5: 65.42 – 65.49 Mb PubMed search [3] [4]
Wikidata
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Replication factor C subunit 1 is a protein that in humans is encoded by the RFC1 gene.^[5][6]

The protein encoded by this gene is the large subunit of replication factor C, which is a five subunit DNA polymerase accessory protein. Replication factor C is a DNA-dependent ATPase that is required for eukaryotic DNA replication and repair. The protein acts as an activator of DNA polymerases, binds to the 3' end of primers, and promotes coordinated synthesis of both strands. It also may have a role in telomere stability.^[6]

RFC1 has been shown to interact with:

• BRD4,^[7]
• HDAC1,^[8]
• PCNA,^{[7][9][10][11][12]}
• RELA^[13] and
• RFC3.^[14][15][16]

Biallelic intronic repeat expansions (a series of repeating nucleotide sequences) in the replication factor C subunit 1 (RFC1) gene causes cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS).^[17] Within the poly(A) tail of an AluSx3 element in RFC1, there are eleven repeats of the pentanucleotide "AAAAG". Repeat expansion and polymorphic configuration are observed in part of the population, with increased number of repeats associated to alternative "AAAGG", "AAGGG" and "ACAGG" pentanucleotides.^[18] In particular, biallelic "AAGGG" and "ACAGG" repeat expansion have disproportionately been observed in patients with CANVAS. Biallelic "AAGGG" repeat expansion is also reported in a high number of sporadic cases of late-onset ataxia,^[17] isolate sensory neuropathy^[19][20] and, less frequently, isolate cerebellar ataxia.^[21] Due to a diagnostic overlap with CANVAS, researchers have also investigated the presence of RFC1 expansions in pathologically confirmed multiple system atrophy (MSA) but found a similar alteration frequency (0.7%) to a healthy population, suggesting RFC1 does not have a role in this disease.^[22]

Mutant biallelic intronic repeat expansions do not affect RFC1 expression in patient peripheral and brain tissue, suggesting no overt loss of function of this gene.^[17]

In patients with the pathogenic RFC1 expansion, sensory neuropathy appears to be a predominant feature and patients may also present with symptoms such as cerebellar dysfunction, vestibular involvement and a dry spasmodic cough therefore, genetic testing is recommended in those with these symptoms.^[23]