RFC4 Gene - Replication Factor C Subunit 4
Essential component of the DNA replication and repair machinery
Gene Information Card
| Symbol | RFC4 |
|---|---|
| Full Name | Replication Factor C Subunit 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q27.3 |
| NCBI Gene ID | 5984 ncbi.nlm.nih.gov/gene/5984 |
| Ensembl ID | ENSG00000163947 |
| UniProt ID | P35249 |
| OMIM ID | 600404 |
| HGNC ID | 9970 |
| Aliases | RFC37, A1, MGC27291 |
Description
RFC4 encodes the 37 kDa subunit of replication factor C (RFC), a five-subunit clamp loader complex essential for DNA replication and repair. RFC loads proliferating cell nuclear antigen (PCNA) onto DNA, enabling processive DNA synthesis by DNA polymerase delta and epsilon. The protein also participates in the DNA damage checkpoint response and is involved in nucleotide excision repair.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | Altered expression and mutations in RFC4 may disrupt DNA replication fidelity, contributing to genomic instability and tumorigenesis. | COSMIC; PMID: 23535731 |
| Breast Cancer | Overexpression of RFC4 has been observed in breast cancer tissues, potentially promoting cell proliferation and resistance to DNA damage. | COSMIC; PMID: 25691885 |
| Lung Cancer | Somatic mutations and copy number alterations in RFC4 are reported in lung adenocarcinoma, affecting DNA repair pathways. | COSMIC; PMID: 22980975 |
| Hepatocellular Carcinoma | Upregulation of RFC4 correlates with poor prognosis and may enhance tumor growth via PCNA loading. | PMID: 31065110 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Bone Marrow | 18.2 | Medium |
| Lymph Node | 15.7 | Medium |
| Brain | 6.3 | Low |
| Liver | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 22.4 | Cervical cancer cell line |
| A549 | 19.8 | Lung carcinoma cell line |
| MCF7 | 17.3 | Breast cancer cell line |
| HEK293 | 14.6 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | <0.1% | Unknown functional impact; reported in COSMIC |
| c.487G>A (p.Gly163Ser) | Missense | <0.1% | Reported in colorectal cancer; potential loss of function |
| c.724C>T (p.Arg242Trp) | Missense | <0.1% | Reported in lung cancer; uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Missense mutations in the ATP-binding domain may impair clamp loading activity, reducing DNA replication efficiency.
Gain of Function (GOF)
Not well characterized; overexpression in tumors suggests possible gain-of-function in proliferation.
Dominant Negative (DN)
Mutations that disrupt RFC complex assembly could act as dominant negatives, inhibiting wild-type function.
View complete mutation data：
Gene Ontology (GO)
| • DNA replication | • DNA repair |
| • DNA clamp loader activity | • ATP binding |
| • nucleotide-excision repair | • cell cycle checkpoint |
Pathways
• DNA replication (KEGG: hsa03030)
• Nucleotide excision repair (KEGG: hsa03420)
• Mismatch repair (KEGG: hsa03430)
• Cell cycle (KEGG: hsa04110)
Protein Summary
RFC4 is a 37 kDa subunit of the replication factor C complex. It contains an ATP-binding domain and is essential for loading PCNA onto primed DNA templates. The protein interacts with other RFC subunits (RFC1, RFC2, RFC3, RFC5) and with PCNA. RFC4 is ubiquitously expressed with highest levels in testis and bone marrow. Its role in DNA replication and repair makes it a potential target in cancer therapy.
Related Services
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|---|---|---|---|---|
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