ERCC5 Gene: Structure, Function, and Clinical Significance
A comprehensive guide to the ERCC5 gene, its role in DNA repair, associated diseases, and clinical implications.
Gene Information Card
| Symbol | ERCC5 |
|---|---|
| Full Name | ERCC excision repair 5, endonuclease |
| Gene Type | Protein coding |
| Chromosomal Location | 13q33.1 |
| NCBI Gene ID | 2073 ncbi.nlm.nih.gov/gene/2073 |
| Ensembl ID | ENSG00000134899 |
| UniProt ID | P28715 |
| OMIM ID | 133530 |
| HGNC ID | 3437 |
| Aliases | XPG, COFS3, UVDR, XPGC |
Description
The ERCC5 gene encodes a single-stranded DNA endonuclease that is a critical component of the nucleotide excision repair (NER) pathway. This enzyme makes an incision 3' to the DNA damage site during NER, facilitating the removal of bulky DNA adducts caused by UV radiation and environmental mutagens. Mutations in ERCC5 lead to a range of disorders, including xeroderma pigmentosum (XP), Cockayne syndrome, and cerebro-oculo-facio-skeletal syndrome, and increase cancer susceptibility.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Xeroderma Pigmentosum Group G (XPG) | Loss-of-function mutations impair NER, leading to defective repair of UV-induced DNA damage, causing photosensitivity and skin cancers. | ClinVar; OMIM #133530 |
| Cockayne Syndrome (CS) | Some ERCC5 mutations cause a combined XP/CS phenotype, with features of both diseases, due to impaired transcription-coupled repair and oxidative DNA damage repair. | OMIM #133540; PubMed |
| Cerebro-Oculo-Facio-Skeletal Syndrome (COFS) | Severe mutations leading to profound NER deficiency, resulting in developmental defects and neurodegeneration. | OMIM #610758; ClinVar |
| Cancer Susceptibility | Polymorphisms and reduced ERCC5 expression are associated with increased risk of various cancers, including lung, breast, and skin cancers. | COSMIC; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Thyroid | 15.2 | Medium |
| Adrenal Gland | 12.3 | Medium |
| Testis | 11.8 | Medium |
| Kidney | 10.5 | Medium |
| Liver | 9.7 | Low |
| Brain | 8.4 | Low |
| Heart | 7.9 | Low |
| Lung | 7.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 12.5 | Cervical cancer cell line; moderate expression |
| A549 | 10.2 | Lung carcinoma; moderate expression |
| MCF7 | 9.8 | Breast cancer; moderate expression |
| HepG2 | 8.7 | Liver cancer; low expression |
| K562 | 7.5 | Leukemia; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3730C>T (p.Arg1244Ter) | Nonsense | Rare | Loss of function; truncation of protein, causing XP-G |
| c.2201A>G (p.Asp734Gly) | Missense | Rare | Loss of function; affects catalytic activity, causing XP-G |
| c.3862C>T (p.Arg1288Cys) | Missense | Rare | Loss of function; associated with XP/CS complex |
| c.IVS10+2T>G | Splice site | Rare | Loss of function; aberrant splicing, causing XP-G |
Mutation functional classification
Loss of Function (LOF)
Most ERCC5 mutations are loss-of-function, leading to defective NER and increased UV sensitivity. These mutations are typically associated with XP-G and related disorders.
Gain of Function (GOF)
No gain-of-function mutations have been reported for ERCC5.
Dominant Negative (DN)
Some missense mutations may exert a dominant-negative effect by interfering with the NER complex, but this is not well established.
View complete mutation data：
Gene Ontology (GO)
| • DNA endonuclease activity | • single-stranded DNA endodeoxyribonuclease activity |
| • protein binding | • nucleotide-excision repair |
| • DNA repair | • response to UV |
| • nucleus | • DNA incision |
| • 3'-to lesion |
Pathways
• Nucleotide Excision Repair
• Global Genome Nucleotide Excision Repair
• Transcription-Coupled Nucleotide Excision Repair
Protein Summary
The ERCC5 protein (also known as XPG) is a 1186-amino acid endonuclease that is essential for nucleotide excision repair. It cleaves the damaged DNA strand 3' to the lesion, creating a nick that allows for the removal of the damaged oligonucleotide. The protein also participates in transcription-coupled repair and has a role in the removal of oxidative DNA damage. Structurally, it contains an N-terminal catalytic domain and a C-terminal domain, both of which are required for its endonuclease activity. Mutations that disrupt these domains lead to disease phenotypes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ERCC5 Knockout HEK293 Cell Line | EDJ-KQ4552 | Human | 2073 | Details Get a Quote |
| ERCC5 Knockout HCT 116 Cell Line | EDJ-KQ25929 | Human | 2073 | Details Get a Quote |
| ERCC5 Knockout A-549 Cell Line | EDJ-KQ27188 | Human | 2073 | Details Get a Quote |
| ERCC5 Knockout HeLa Cell Line | EDJ-KQ27190 | Human | 2073 | Details Get a Quote |
| BIVM-ERCC5 Knockout HEK293 Cell Line | EDJ-KQ52506 | Human | 100533467 | Details Get a Quote |
| BIVM-ERCC5 Knockout HeLa Cell Line | EDJ-KQ60971 | Human | 100533467 | Details Get a Quote |
| BIVM-ERCC5 Knockout A-549 Cell Line | EDJ-KQ69446 | Human | 100533467 | Details Get a Quote |
| BIVM-ERCC5 Knockout HCT 116 Cell Line | EDJ-KQ77797 | Human | 100533467 | Details Get a Quote |
| ERCC5 (p.A513T) Point Mutation in HAP1 Cell Line | EDC03468 | Human | 2073 | Details Get a Quote |
| ERCC5 (p.G1080R) Point Mutation in HAP1 Cell Line | EDC03469 | Human | 2073 | Details Get a Quote |
| ERCC5 (c.672+660G>A )Point Mutation in HAP1 Cell Line | EDC03467 | Human | 2073 | Details Get a Quote |
