RAD17
RAD17 Checkpoint Clamp Loader Component
Gene Information Card
| Symbol | RAD17 |
|---|---|
| Full Name | RAD17 checkpoint clamp loader component |
| Gene Type | protein-coding |
| Chromosomal Location | 5q13.2 |
| NCBI Gene ID | 5884 ncbi.nlm.nih.gov/gene/5884 |
| Ensembl ID | ENSG00000152942 |
| UniProt ID | O75943 |
| OMIM ID | 603139 |
| HGNC ID | 9807 |
| Aliases | RAD24, hRAD17, CCYC, R24L |
Description
RAD17 is a protein-coding gene that encodes a component of the checkpoint clamp loader complex, which is essential for the activation of cell cycle checkpoints in response to DNA damage. The protein forms a complex with RFC2-5 and loads the RAD9-HUS1-RAD1 (9-1-1) clamp onto DNA, facilitating the activation of the CHK1 kinase and subsequent cell cycle arrest. RAD17 is involved in the DNA damage response pathway and is critical for maintaining genomic stability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | Altered RAD17 expression and mutations may impair DNA damage checkpoint signaling, contributing to genomic instability and tumorigenesis. | PMID: 15601843; COSMIC |
| Lung Cancer | Somatic mutations and reduced expression of RAD17 have been reported, potentially compromising DNA repair and promoting carcinogenesis. | PMID: 17699752; COSMIC |
| Colorectal Cancer | RAD17 mutations and loss of heterozygosity are observed, associated with defective checkpoint activation and tumor progression. | PMID: 18245496; COSMIC |
| Fanconi Anemia | RAD17 interacts with the Fanconi anemia pathway; defects may contribute to chromosomal instability. | PMID: 12893777 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Bone Marrow | 12.8 | Medium |
| Lymph Node | 10.5 | Medium |
| Brain | 6.3 | Low |
| Liver | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.5 | Cervical cancer cell line |
| A549 | 12.1 | Lung cancer cell line |
| MCF7 | 11.3 | Breast cancer cell line |
| HEK293 | 9.8 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1100C>T (p.Thr367Met) | Missense | <1% | May affect protein stability and checkpoint function |
| c.1522G>A (p.Glu508Lys) | Missense | <1% | Reported in colorectal cancer; potential loss of function |
| c.1843_1844del (p.Leu615fs) | Frameshift | <1% | Truncating mutation; likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or disrupt the clamp loader complex impair DNA damage checkpoint activation, leading to genomic instability.
Gain of Function (GOF)
No gain-of-function mutations are currently documented for RAD17.
Dominant Negative (DN)
Some missense mutations may produce a dominant-negative effect by forming non-functional complexes with wild-type RFC subunits, interfering with normal checkpoint signaling.
View complete mutation data：
Gene Ontology (GO)
| • DNA damage checkpoint | • cell cycle checkpoint |
| • DNA repair | • protein binding |
| • ATP binding | • nucleotide-excision repair |
| • chromatin binding |
Pathways
• ATM signaling pathway
• ATR signaling pathway
• Cell cycle checkpoints
• DNA damage response
• Fanconi anemia pathway
Protein Summary
The RAD17 protein (UniProt O75943) is a 670-amino acid checkpoint clamp loader component. It contains an ATP-binding domain and shares homology with replication factor C (RFC) subunits. RAD17 forms a heteropentameric complex with RFC2, RFC3, RFC4, and RFC5, which loads the RAD9-RAD1-HUS1 (9-1-1) clamp onto DNA at sites of damage. This loading is essential for the activation of the ATR-CHK1 signaling cascade, leading to cell cycle arrest and DNA repair. The protein is predominantly nuclear and is expressed in multiple tissues, with highest levels in testis and bone marrow.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RAD17 Knockout HEK293 Cell Line | EDJ-KQ50558 | Human | 5884 | Details Get a Quote |
| RAD17 Knockout HeLa Cell Line | EDJ-KQ54288 | Human | 5884 | Details Get a Quote |
| RAD17 Knockout A-549 Cell Line | EDJ-KQ62784 | Human | 5884 | Details Get a Quote |
| RAD17 Knockout HCT 116 Cell Line | EDJ-KQ71249 | Human | 5884 | Details Get a Quote |
