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 stabili... See more...

Aliases for RFC1 Gene

Aliases for RFC1 Gene

  • Replication Factor C Subunit 1 2 3 4 5
  • Replication Factor C (Activator 1) 1, 145kDa 2 3
  • Replication Factor C 140 KDa Subunit 3 4
  • Replication Factor C Large Subunit 3 4
  • Activator 1 140 KDa Subunit 3 4
  • Activator 1 Large Subunit 3 4
  • DNA-Binding Protein PO-GA 3 4
  • Activator 1 Subunit 1 3 4
  • RF-C 140 KDa Subunit 3 4
  • A1 140 KDa Subunit 3 4
  • RFC140 3 4
  • Replication Factor C (Activator 1) 1 (145kD) 2
  • MHC Binding Factor, Beta 3
  • Replication Factor C1 3
  • CANVAS 3
  • MHCBFB 3
  • PO-GA 3
  • RECC1 3
  • RFC 3
  • A1 3

External Ids for RFC1 Gene

Previous GeneCards Identifiers for RFC1 Gene

  • GC04M039463
  • GC04M039123
  • GC04M039186
  • GC04M039111
  • GC04M038965
  • GC04M038615

Summaries for RFC1 Gene

Entrez Gene Summary for RFC1 Gene

  • 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]

GeneCards Summary for RFC1 Gene

RFC1 (Replication Factor C Subunit 1) is a Protein Coding gene. Diseases associated with RFC1 include Cerebellar Ataxia, Neuropathy, And Vestibular Areflexia Syndrome and Cerebellar Ataxia With Neuropathy And Bilateral Vestibular Areflexia Syndrome. Among its related pathways are DNA Damage Response and Transcription-Coupled Nucleotide Excision Repair (TC-NER). Gene Ontology (GO) annotations related to this gene include sequence-specific DNA binding and double-stranded DNA binding.

UniProtKB/Swiss-Prot Summary for RFC1 Gene

  • The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins PCNA and activator 1. This subunit binds to the primer-template junction. Binds the PO-B transcription element as well as other GA rich DNA sequences. Could play a role in DNA transcription regulation as well as DNA replication and/or repair. Can bind single- or double-stranded DNA.
  • Interacts with C-terminus of PCNA. 5' phosphate residue is required for binding of the N-terminal DNA-binding domain to duplex DNA, suggesting a role in recognition of non-primer template DNA structures during replication and/or repair.

Gene Wiki entry for RFC1 Gene

Additional gene information for RFC1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RFC1 Gene

Genomics for RFC1 Gene

GeneHancer (GH) Regulatory Elements for RFC1 Gene

Promoters and enhancers for RFC1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04J039364 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 762.3 +0.4 416 2.7 E2F8 SP1 ZBTB40 MLX RBPJ POLR2A ATF1 CREB1 HCFC1 RUNX1 RFC1 ENSG00000250568 WDR19 KLF3 ZBTB12BP PDS5A FAM114A1 RNU6-887P KLB RHOH
GH04J039390 Promoter/Enhancer 0.7 EPDnew FANTOM5 Ensembl 750.3 -24.4 -24420 0.4 RFC1 RF00026-775 lnc-KLB-2
GH04J040295 Enhancer 0.9 Ensembl dbSUPER 46.9 -928.7 -928720 1 ZBTB6 LCORL TRIM22 ZFP41 SOX6 IKZF1 MLLT1 ZNF680 ZNF560 YBX1 PDS5A RFC1 N4BP2 ZBTB12BP UGDH-AS1 ENSG00000250568 APBB2 ENSG00000250906 HSALNG0034001 LINC02265
GH04J040288 Enhancer 1.5 FANTOM5 Ensembl ENCODE dbSUPER 24.6 -924.1 -924120 6.2 ZBTB40 SIX5 SMARCE1 RUNX1 CC2D1A L3MBTL2 MAX DACH1 TEAD4 ZNF148 PDS5A RFC1 RHOH N4BP2 CHRNA9 ENSG00000250906 RBM47 HSALNG0034001 LINC02265
GH04J040189 Promoter/Enhancer 2.1 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 16.3 -833.6 -833597 22.4 SIN3A ZNF24 SP1 ZBTB40 SMARCE1 RBPJ NR2F6 CREB1 HCFC1 MIXL1 RHOH N4BP2 PDS5A ZBTB12BP ENSG00000250906 RFC1 ENSG00000250568 RBM47 LOC344967 CHRNA9
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RFC1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the RFC1 gene promoter:
  • aMEF-2
  • C/EBPalpha
  • FOXO4
  • GATA-1
  • POU2F1
  • POU2F1a
  • Sp1

Genomic Locations for RFC1 Gene

Genomic Locations for RFC1 Gene
chr4:39,287,449-39,366,381
(GRCh38/hg38)
Size:
78,933 bases
Orientation:
Minus strand
chr4:39,289,069-39,368,001
(GRCh37/hg19)
Size:
78,933 bases
Orientation:
Minus strand

Genomic View for RFC1 Gene

Genes around RFC1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RFC1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RFC1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RFC1 Gene

Proteins for RFC1 Gene

  • Protein details for RFC1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P35251-RFC1_HUMAN
    Recommended name:
    Replication factor C subunit 1
    Protein Accession:
    P35251
    Secondary Accessions:
    • A8K6E7
    • Q5XKF5
    • Q6PKU0
    • Q86V41
    • Q86V46

    Protein attributes for RFC1 Gene

    Size:
    1148 amino acids
    Molecular mass:
    128255 Da
    Quaternary structure:
    • Heterotetramer of subunits RFC2, RFC3, RFC4 and RFC5 that can form a complex either with RFC1 or with RAD17. The former interacts with PCNA in the presence of ATP, while the latter has ATPase activity but is not stimulated by PCNA.

    Three dimensional structures from OCA and Proteopedia for RFC1 Gene

    Alternative splice isoforms for RFC1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RFC1 Gene

Post-translational modifications for RFC1 Gene

  • Ubiquitination at Lys243, Lys468, Lys551, Lys556, Lys645, and Lys700
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for RFC1 Gene

Domains & Families for RFC1 Gene

Gene Families for RFC1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for RFC1 Gene

GenScript: Design optimal peptide antigens:
  • Replication factor C large subunit (RFC1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P35251

UniProtKB/Swiss-Prot:

RFC1_HUMAN :
  • Belongs to the activator 1 large subunit family.
Family:
  • Belongs to the activator 1 large subunit family.
genes like me logo Genes that share domains with RFC1: view

Function for RFC1 Gene

Molecular function for RFC1 Gene

UniProtKB/Swiss-Prot Function:
The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins PCNA and activator 1. This subunit binds to the primer-template junction. Binds the PO-B transcription element as well as other GA rich DNA sequences. Could play a role in DNA transcription regulation as well as DNA replication and/or repair. Can bind single- or double-stranded DNA.
UniProtKB/Swiss-Prot Function:
Interacts with C-terminus of PCNA. 5' phosphate residue is required for binding of the N-terminal DNA-binding domain to duplex DNA, suggesting a role in recognition of non-primer template DNA structures during replication and/or repair.
GENATLAS Biochemistry:
replication factor C1,component of complex A-1,DNA polymerase accessory protein "clamp loader",ATP dependent,required to assemble PCNA and polymerase delta on the DNA template

Phenotypes From GWAS Catalog for RFC1 Gene

Gene Ontology (GO) - Molecular Function for RFC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0003677 DNA binding IBA 21873635
GO:0003689 DNA clamp loader activity IEA --
GO:0003690 double-stranded DNA binding IEA --
GO:0005515 protein binding IPI 9488738
genes like me logo Genes that share ontologies with RFC1: view
genes like me logo Genes that share phenotypes with RFC1: view

Human Phenotype Ontology for RFC1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for RFC1 Gene

MGI Knock Outs for RFC1:
  • Rfc1 Rfc1<tm1b(KOMP)Mbp>

Animal Model Products

  • Taconic Biosciences Mouse Models for RFC1

CRISPR Products

miRNA for RFC1 Gene

miRTarBase miRNAs that target RFC1

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RFC1

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for RFC1 Gene

Localization for RFC1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RFC1 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RFC1 gene
Compartment Confidence
nucleus 5
cytosol 2
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for RFC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA --
GO:0005654 nucleoplasm TAS --
GO:0005663 DNA replication factor C complex IEA,IDA 9488738
GO:0005730 nucleolus IEA --
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with RFC1: view

Pathways & Interactions for RFC1 Gene

PathCards logo

SuperPathways for RFC1 Gene

SuperPathway Contained pathways
1 Telomere C-strand (Lagging Strand) Synthesis
2 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template
3 Transcription-Coupled Nucleotide Excision Repair (TC-NER)
4 DNA Double-Strand Break Repair
5 Mismatch repair
.54
genes like me logo Genes that share pathways with RFC1: view

Pathways by source for RFC1 Gene

1 GeneGo (Thomson Reuters) pathway for RFC1 Gene
2 Qiagen pathways for RFC1 Gene
  • Mismatch Repair in Eukaryotes
  • Nucleotide Excision Repair Pathway

Gene Ontology (GO) - Biological Process for RFC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IEA --
GO:0006260 DNA replication IEA --
GO:0006261 DNA-dependent DNA replication TAS 8248204
GO:0006281 DNA repair IEA --
GO:0006283 transcription-coupled nucleotide-excision repair TAS --
genes like me logo Genes that share ontologies with RFC1: view

No data available for SIGNOR curated interactions for RFC1 Gene

Drugs & Compounds for RFC1 Gene

(4) Drugs for RFC1 Gene - From: DGIdb and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Pralatrexate Approved, Investigational Pharma inhibitor Antifolate,a folate analog, RFC-1 targeted DHFR inhibitor 0

(3) Additional Compounds for RFC1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with RFC1: view

Transcripts for RFC1 Gene

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RFC1

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for RFC1 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8a · 8b · 8c ^ 9 ^ 10 ^ 11a · 11b ^ 12a · 12b ^ 13a · 13b ^ 14a · 14b ^ 15a · 15b · 15c ^ 16 ^
SP1: - -
SP2: -
SP3: - -
SP4:
SP5: -
SP6: -
SP7:
SP8: -
SP9:
SP10:
SP11:
SP12:
SP13:

ExUns: 17a · 17b ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^ 24 ^ 25 ^ 26 ^ 27a · 27b ^ 28a · 28b
SP1:
SP2:
SP3:
SP4: -
SP5:
SP6:
SP7:
SP8:
SP9:
SP10: -
SP11:
SP12:
SP13:

Relevant External Links for RFC1 Gene

GeneLoc Exon Structure for
RFC1
ECgene alternative splicing isoforms for
RFC1

Expression for RFC1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for RFC1 Gene

Protein differential expression in normal tissues from HIPED for RFC1 Gene

This gene is overexpressed in Lung (29.9), Peripheral blood mononuclear cells (9.5), and Pancreatic juice (6.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for RFC1 Gene



Protein tissue co-expression partners for RFC1 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of RFC1 Gene:

RFC1

SOURCE GeneReport for Unigene cluster for RFC1 Gene:

Hs.507475

mRNA Expression by UniProt/SwissProt for RFC1 Gene:

P35251-RFC1_HUMAN
Tissue specificity: Wide tissue distribution. Undetectable in placental tissue.

Evidence on tissue expression from TISSUES for RFC1 Gene

  • Liver(4.3)
  • Skin(4.2)
  • Nervous system(3.6)
genes like me logo Genes that share expression patterns with RFC1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for RFC1 Gene

Orthologs for RFC1 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for RFC1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RFC1 33 32
  • 99.51 (n)
OneToOne
dog
(Canis familiaris)
Mammalia RFC1 33 32
  • 90.48 (n)
OneToOne
cow
(Bos Taurus)
Mammalia RFC1 33 32
  • 88.93 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Rfc1 17 33 32
  • 83.81 (n)
rat
(Rattus norvegicus)
Mammalia Rfc1 32
  • 83.5 (n)
oppossum
(Monodelphis domestica)
Mammalia RFC1 33
  • 77 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia RFC1 33
  • 72 (a)
OneToOne
chicken
(Gallus gallus)
Aves RFC1 33 32
  • 72.15 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia RFC1 33
  • 64 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia rfc1 32
  • 66.39 (n)
zebrafish
(Danio rerio)
Actinopterygii rfc1 33 32
  • 62.15 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Gnf1 33 34 32
  • 51.03 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP001290 32
  • 49.89 (n)
worm
(Caenorhabditis elegans)
Secernentea rfc-1 33 34
  • 36 (a)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes RFC1 35 33 32
  • 48.9 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0D06897g 32
  • 48.01 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ACR102W 32
  • 46.88 (n)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes rfc1 32
  • 49.04 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 33
  • 49 (a)
OneToOne
bread mold
(Neurospora crassa)
Ascomycetes NCU06767 32
  • 47.85 (n)
Species where no ortholog for RFC1 was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for RFC1 Gene

ENSEMBL:
Gene Tree for RFC1 (if available)
TreeFam:
Gene Tree for RFC1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for RFC1: view image

Paralogs for RFC1 Gene

(1) SIMAP similar genes for RFC1 Gene using alignment to 5 proteins:

  • RFC1_HUMAN
  • D6RAD2_HUMAN
  • E0CX09_HUMAN
  • H0Y8U4_HUMAN
  • H0Y9P8_HUMAN
genes like me logo Genes that share paralogs with RFC1: view

No data available for Paralogs for RFC1 Gene

Variants for RFC1 Gene

Sequence variations from dbSNP and Humsavar for RFC1 Gene

SNP ID Clin Chr 04 pos Variation AA Info Type
rs1000028373 -- 39,317,701(-) T/C intron_variant
rs1000055739 -- 39,331,188(-) T/A/C intron_variant
rs1000066643 -- 39,320,206(-) A/G intron_variant
rs1000089352 -- 39,362,966(-) G/A intron_variant
rs1000195076 -- 39,324,537(-) T/C intron_variant

Structural Variations from Database of Genomic Variants (DGV) for RFC1 Gene

Variant ID Type Subtype PubMed ID
dgv1474e212 CNV loss 25503493
esv3600276 CNV gain 21293372
nsv1131790 CNV deletion 24896259

Variation tolerance for RFC1 Gene

Residual Variation Intolerance Score: 12.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.19; 52.07% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RFC1 Gene

Human Gene Mutation Database (HGMD)
RFC1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
RFC1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RFC1 Gene

Disorders for RFC1 Gene

MalaCards: The human disease database

(3) MalaCards diseases for RFC1 Gene - From: HGMD, OMIM, ClinVar, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search RFC1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for RFC1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with RFC1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for RFC1 Gene

Publications for RFC1 Gene

  1. Replication factor C interacts with the C-terminal side of proliferating cell nuclear antigen. (PMID: 8999859) Mossi R … Hübscher U (The Journal of biological chemistry 1997) 3 4 23 56
  2. cDNAs encoding the large subunit of human replication factor C. (PMID: 8248204) Bunz F … Stillman B (Proceedings of the National Academy of Sciences of the United States of America 1993) 3 4 23 56
  3. Genetic variation in genes interacting with BRCA1/2 and risk of breast cancer in the Cypriot population. (PMID: 19714462) Loizidou MA … Kyriacou K (Breast cancer research and treatment 2010) 3 43 56
  4. Pharmacogenomic variations in treatment protocols for childhood acute lymphoblastic leukemia. (PMID: 19774638) Yang YL … Hu CY (Pediatric blood & cancer 2010) 3 43 56
  5. Association between genetic variants in the base excision repair pathway and outcomes after hematopoietic cell transplantations. (PMID: 20226869) Thyagarajan B … Arora M (Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 2010) 3 43 56

Products for RFC1 Gene

Sources for RFC1 Gene