ERCC1 Gene: Structure, Function, and Clinical Significance in DNA Repair
Comprehensive guide to ERCC1 (Excision Repair Cross-Complementation Group 1): genomic location, protein function, associated diseases, expression profiles, and mutation landscape.
Gene Information Card
| Symbol | ERCC1 |
|---|---|
| Full Name | ERCC1 excision repair 1, endonuclease non-catalytic subunit |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.32 (GRCh38: chr19:45,407,334-45,451,805) |
| NCBI Gene ID | 2067 ncbi.nlm.nih.gov/gene/2067 |
| Ensembl ID | ENSG00000012061 |
| UniProt ID | P07992 |
| OMIM ID | 126380 |
| HGNC ID | 3433 |
| Aliases | COFS4, RAD10 |
Description
The ERCC1 gene encodes a DNA repair endonuclease that forms a heterodimer with ERCC4 (XPF) to catalyze the 5' incision during nucleotide excision repair (NER). It is essential for removing bulky DNA adducts, including UV-induced photoproducts and cisplatin-induced crosslinks. ERCC1 also participates in interstrand crosslink repair and homologous recombination. Defects in ERCC1 cause cerebro-oculo-facio-skeletal syndrome (COFS) and are associated with increased cancer risk and chemotherapy sensitivity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cerebro-oculo-facio-skeletal syndrome (COFS) | Loss-of-function mutations in ERCC1 impair NER, leading to developmental defects and neurodegeneration. | OMIM: 126380; ClinVar |
| Xeroderma pigmentosum (complementation group G-like phenotype) | ERCC1 mutations can cause severe NER deficiency, resulting in UV sensitivity and skin cancers. | OMIM; PubMed |
| Cockayne syndrome (severe form) | ERCC1 defects disrupt transcription-coupled repair, causing growth failure and neurological abnormalities. | OMIM; PubMed |
| Lung cancer (non-small cell lung cancer) | Low ERCC1 expression is associated with improved response to platinum-based chemotherapy but may increase genomic instability. | COSMIC; PubMed |
| Ovarian cancer | ERCC1 expression levels correlate with resistance to cisplatin; high expression predicts poor survival. | COSMIC; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | High |
| Thyroid | 10.2 | High |
| Adrenal gland | 9.8 | High |
| Liver | 8.5 | Medium |
| Lung | 7.9 | Medium |
| Kidney | 7.2 | Medium |
| Brain | 5.1 | Low |
| Skeletal muscle | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung carcinoma) | 8.9 | High expression; used in cisplatin resistance studies. |
| MCF7 (Breast carcinoma) | 7.5 | Moderate expression; ERCC1 levels affect DNA repair capacity. |
| HeLa (Cervical carcinoma) | 6.8 | Moderate expression; commonly used in NER assays. |
| HepG2 (Liver carcinoma) | 7.1 | Moderate expression; relevant for hepatotoxicity studies. |
| K562 (Leukemia) | 5.4 | Low expression; may influence drug sensitivity. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2251C>T (p.Arg751Ter) | Nonsense | Rare | Truncated protein; loss of function leading to COFS. |
| c.470T>C (p.Leu157Pro) | Missense | Rare | Disrupts ERCC1-XPF interaction; impairs NER. |
| c.548A>G (p.Asn183Ser) | Missense | Rare | Reduced endonuclease activity; associated with UV sensitivity. |
| c.682C>T (p.Arg228Trp) | Missense | Rare | Affects DNA binding; causes mild NER deficiency. |
| c.IVS7+1G>A | Splice site | Rare | Splicing defect; leads to exon skipping and loss of function. |
Mutation functional classification
Loss of Function (LOF)
Most ERCC1 mutations are loss-of-function, impairing NER and crosslink repair, leading to developmental disorders and cancer predisposition.
Gain of Function (GOF)
No gain-of-function mutations have been reported; ERCC1 acts as a tumor suppressor in the context of DNA repair.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by forming inactive heterodimers with XPF, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • DNA repair | • nucleotide-excision repair |
| • endonuclease activity | • protein heterodimerization |
| • damaged DNA binding | • response to UV |
| • cell cycle checkpoint | • apoptotic process |
Pathways
• Nucleotide Excision Repair (NER) - Global Genome Repair (GGR)
• Nucleotide Excision Repair (NER) - Transcription-Coupled Repair (TCR)
• Interstrand Crosslink Repair (ICL)
• Double-Strand Break Repair via Homologous Recombination (HR)
Protein Summary
The ERCC1 protein (297 amino acids, ~32.5 kDa) forms a heterodimer with ERCC4 (XPF) to create a structure-specific endonuclease that cleaves the 5' side of DNA lesions during NER. It contains a helix-hairpin-helix (HhH) domain for DNA binding and an ERCC4-like nuclease domain (though catalytically inactive). ERCC1 is essential for repairing bulky adducts and crosslinks, and its expression levels are used as a biomarker for chemotherapy response.
Related Services
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| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PERCC1 Knockout HEK293 Cell Line | EDJ-KQ14729 | Human | 105371045 | Details Get a Quote |
| ERCC1 (p.N118=) Point Mutation in HAP1 Cell Line | EDC03287 | Human | 2067 | Details Get a Quote |
| ERCC1 (c.*590T>C) Point Mutation in HAP1 Cell Line | EDC03282 | Human | 2067 | Details Get a Quote |
| ERCC1 (c.*527C>T) Point Mutation in HAP1 Cell Line | EDC03283 | Human | 2067 | Details Get a Quote |
| ERCC1 (c.*427-429 TTCdel) Point Mutation in HAP1 Cell Line | EDC03284 | Human | 2067 | Details Get a Quote |
| ERCC1 (c.603-631T>C )Point Mutation in HAP1 Cell Line | EDC03285 | Human | 2067 | Details Get a Quote |
| ERCC1 (c.525+33C>A )Point Mutation in HAP1 Cell Line | EDC03286 | Human | 2067 | Details Get a Quote |
| ERCC1 (c.-8+10033G>C )Point Mutation in HAP1 Cell Line | EDC03288 | Human | 2067 | Details Get a Quote |
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