RAD18
E3 ubiquitin-protein ligase involved in DNA damage tolerance and post-replication repair
Gene Information Card
| Symbol | RAD18 |
|---|---|
| Full Name | RAD18 E3 ubiquitin protein ligase |
| Gene Type | Protein coding |
| Chromosomal Location | 3p25.3 |
| NCBI Gene ID | 56852 ncbi.nlm.nih.gov/gene/56852 |
| Ensembl ID | ENSG00000170962 |
| UniProt ID | Q9NS91 |
| OMIM ID | 605256 |
| HGNC ID | 9819 |
| Aliases | RNF73, hRAD18 |
Description
RAD18 encodes an E3 ubiquitin-protein ligase that plays a central role in DNA damage tolerance by mediating monoubiquitination of PCNA at Lys164. This modification recruits translesion synthesis (TLS) polymerases to bypass replication-blocking lesions. RAD18 also participates in post-replication repair and homologous recombination. The protein contains a RING finger domain and a SAP domain, and it interacts with RAD6 (UBE2A/UBE2B) to form a ubiquitin-conjugating complex.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Dysregulation of RAD18 promotes genomic instability and tumorigenesis through aberrant TLS and impaired DNA repair | COSMIC, ClinVar |
| Fanconi anemia-like phenotype | Loss-of-function mutations in RAD18 impair DNA interstrand crosslink repair | OMIM, ClinVar |
| Immunodeficiency | Defective RAD18-mediated DNA repair may contribute to immune system dysfunction | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Bone marrow | 8.2 | Medium |
| Lymph node | 6.1 | Low |
| Brain | 3.4 | Low |
| Liver | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.3 | Moderate expression |
| HeLa | 8.7 | Moderate expression |
| K562 | 6.5 | Low expression |
| A549 | 5.9 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.205C>T (p.Arg69Cys) | Missense | <0.01% | Reduced ubiquitin ligase activity; associated with genomic instability |
| c.497_498del (p.Lys166Argfs*12) | Frameshift | <0.01% | Loss of function; predicted to truncate protein |
| c.1024G>A (p.Glu342Lys) | Missense | <0.01% | Unknown functional effect; reported in COSMIC |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that disrupt the RING finger domain or SAP domain lead to loss of E3 ligase activity and impaired PCNA monoubiquitination.
Gain of Function (GOF)
Not well characterized; some missense variants may increase TLS activity, potentially promoting mutagenesis.
Dominant Negative (DN)
Mutations that retain RING domain but disrupt PCNA interaction may act as dominant-negative by sequestering RAD6.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Translesion synthesis (TLS) pathway
• Post-replication repair pathway
• Fanconi anemia pathway
• Ubiquitin-mediated proteolysis
Protein Summary
RAD18 is a 487-amino acid E3 ubiquitin-protein ligase (UniProt Q9NS91) containing an N-terminal RING finger domain (residues 28-67) required for ubiquitin transfer, and a C-terminal SAP domain (residues 370-400) involved in DNA binding. The protein forms a heterodimer with RAD6 (UBE2A or UBE2B) to monoubiquitinate PCNA at Lys164, a key step in recruiting TLS polymerases. RAD18 also interacts with other DNA repair factors such as REV1 and POLH. Its expression is cell cycle-regulated and peaks in S phase.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RAD18 Knockout HEK293 Cell Line | EDJ-KQ14984 | Human | 56852 | Details Get a Quote |
| RAD18 Knockout A-549 Cell Line | EDJ-KQ45483 | Human | 56852 | Details Get a Quote |
| RAD18 Knockout HCT 116 Cell Line | EDJ-KQ45484 | Human | 56852 | Details Get a Quote |
| RAD18 Knockout HeLa Cell Line | EDJ-KQ45485 | Human | 56852 | Details Get a Quote |
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