ERCC5
Chr 13ARERCC excision repair 5, endonuclease
Also known as: COFS3, ERCC5-201, ERCM2, UVDR, XPG, XPGC
This gene encodes a single-strand DNA endonuclease that makes the 3' incision during nucleotide excision repair following UV-induced DNA damage and is involved in transcription-coupled DNA repair. Biallelic mutations cause xeroderma pigmentosum group G, characterized by extreme UV sensitivity and increased skin cancer risk, with some patients also developing Cockayne syndrome featuring severe growth defects and intellectual disability, or the more severe cerebrooculofacioskeletal syndrome with early-onset neurodegeneration. The gene follows autosomal recessive inheritance and is highly constrained against loss-of-function variants.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
500 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 22 | 0 | 56 | 0 | 78 |
Likely Pathogenic | 30 | 6 | 3 | 0 | 39 |
VUS | 4 | 145 | 21 | 6 | 176 |
Likely Benign | 0 | 6 | 39 | 100 | 145 |
Benign | 0 | 2 | 38 | 1 | 41 |
Conflicting | — | 20 | |||
| Total | 56 | 159 | 157 | 107 | 499 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ERCC5 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
The Myelin Disorders Biorepository Project
RECRUITINGRare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
RECRUITINGExternal Resources
Links to major genomics databases and tools