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26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RFC2
replication factor C subunit 2
Chromosome 7 · 7q11.23
NCBI Gene: 5982Ensembl: ENSG00000049541.11HGNC: HGNC:9970UniProt: A0A087WVY3
186PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
DNA RepairHub Gene
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
DNA clamp loader activitysingle-stranded DNA helicase activityprotein bindingDNA-templated DNA replicationneurodegenerative diseaseovarian dysfunctionhypotensionsystemic lupus erythematosus
✦AI Summary

RFC2 (replication factor C subunit 2) is a critical component of the replication factor C complex that plays essential roles in DNA replication and repair processes. As part of the RFC complex, RFC2 functions in ATP-dependent loading of proliferating cell nuclear antigen (PCNA) onto primed DNA templates, facilitating DNA polymerase delta and epsilon activity during DNA synthesis 1. The protein contributes to leading strand-specific PCNA loading through the CHTF18-RFC2/5 complex, which is crucial for maintaining genome stability and DNA replication processivity 1. RFC2 has significant clinical relevance across multiple cancer types. It is upregulated in colorectal cancer, where it promotes tumor progression through activation of aerobic glycolysis and the MET/PI3K/AKT/mTOR pathway 2. In glioblastoma, RFC2 expression correlates with poor patient survival, and its downregulation enhances chemotherapy sensitivity 3. The gene also shows oncogenic properties in cervical cancer, promoting cell proliferation, migration, and invasion 4. Additionally, RFC2 may contribute to Williams syndrome pathogenicity, as knockout zebrafish models demonstrate developmental abnormalities including small head and brain, jaw defects, and vascular problems 5. RFC2 expression is regulated by various microRNAs including miR-744 and miR-4749-5p, suggesting potential therapeutic targeting opportunities 63.

Sources cited
1
RFC2 is part of the CHTF18-RFC2/5 complex involved in leading strand-specific PCNA loading and DNA replication processivity
PMID: 41339636
2
RFC2 is upregulated in colorectal cancer and promotes tumor progression through aerobic glycolysis and MET/PI3K/AKT/mTOR pathway activation
PMID: 37821801
3
RFC2 expression correlates with poor survival in glioblastoma patients and its downregulation enhances temozolomide chemotherapy sensitivity
PMID: 32422304
4
RFC2 promotes cervical cancer cell proliferation, migration, and invasion
PMID: 40037867
5
RFC2 knockout zebrafish exhibit Williams syndrome-like phenotypes including developmental abnormalities
PMID: 39368701
6
RFC2 is regulated by miR-744 and promotes colorectal cancer cell proliferation through cell cycle modulation
PMID: 32239691
7
RFC2 is targeted by miR-4749-5p in glioblastoma
PMID: 32422304
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.51Moderate
ovarian dysfunctionOpen Targets
0.28Weak
hypotensionOpen Targets
0.24Weak
systemic lupus erythematosusOpen Targets
0.11Weak
gliomaOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
glioblastoma multiformeOpen Targets
0.08Suggestive
cancerOpen Targets
0.08Suggestive
Werner syndromeOpen Targets
0.05Suggestive
liver cancerOpen Targets
0.05Suggestive
posterior cortical atrophyOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.04Suggestive
rheumatoid arthritisOpen Targets
0.04Suggestive
systemic sclerodermaOpen Targets
0.04Suggestive
myositisOpen Targets
0.03Suggestive
Pallister-Hall syndromeOpen Targets
0.03Suggestive
cervical cancerOpen Targets
0.03Suggestive
cervicitisOpen Targets
0.03Suggestive
sarcomaOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PCNAProtein interaction100%RAD17Protein interaction100%ATAD5Protein interaction100%RAD9AProtein interaction100%HUS1Protein interaction99%BRCA1Protein interaction94%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
85%
Liver
77%
Lung
60%
Ovary
49%
Heart
41%
Gene Interaction Network
Click a node to explore
RFC2PCNARAD17ATAD5RAD9AHUS1BRCA1
PROTEIN STRUCTURE
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PDB8UMV · 2.75 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.39LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.82 [0.51–1.39]
RankingsWhere RFC2 stands among ~20K protein-coding genes
  • #2,313of 20,598
    Most Researched186 · top quartile
  • #14,447of 17,882
    Most Constrained (LOEUF)1.39
Genes detectedRFC2
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
RFC2 may contribute to the pathogenicity of Williams syndrome revealed in a zebrafish model.
PMID: 39368701
J Genet Genomics · 2024
1.00
2
RFC2 promotes aerobic glycolysis and progression of colorectal cancer.
PMID: 37821801
BMC Gastroenterol · 2023
0.90
3
The Absence of Intra-Tumoral Tertiary Lymphoid Structures is Associated with a Worse Prognosis and mTOR Signaling Activation in Hepatocellular Carcinoma with Liver Transplantation: A Multicenter Retrospective Study.
PMID: 38498682
Adv Sci (Weinh) · 2024
0.84
4
RFC2: a prognosis biomarker correlated with the immune signature in diffuse lower-grade gliomas.
PMID: 35210438
Sci Rep · 2022
0.80
5
Expanding the genetic and phenotypic landscape of replication factor C complex-related disorders: RFC4 deficiency is linked to a multisystemic disorder.
PMID: 39106866
Am J Hum Genet · 2024
0.72