ERCC5

Chr 13AR

ERCC excision repair 5, endonuclease

Also known as: COFS3, ERCC5-201, ERCM2, UVDR, XPG, XPGC

NCBI Gene: 2073ENSG00000134899UniProt: P28715

This gene encodes a single-strand specific DNA endonuclease that makes the 3' incision in DNA excision repair following UV-induced damage. The protein may also function in other cellular processes, including RNA polymerase II transcription, and transcription-coupled DNA repair. Mutations in this gene cause xeroderma pigmentosum complementation group G (XP-G), which is also referred to as xeroderma pigmentosum VII (XP7), a skin disorder characterized by hypersensitivity to UV light and increased susceptibility for skin cancer development following UV exposure. Some patients also develop Cockayne syndrome, which is characterized by severe growth defects, cognitive disability, and cachexia. Read-through transcription exists between this gene and the neighboring upstream BIVM (basic, immunoglobulin-like variable motif containing) gene. [provided by RefSeq, Feb 2011]

Primary Disease Associations & Inheritance

Cerebrooculofacioskeletal syndrome 3MIM #616570
AR
Xeroderma pigmentosum, group GMIM #278780
AR
Xeroderma pigmentosum, group G/Cockayne syndromeMIM #278780
AR
UniProtCerebro-oculo-facio-skeletal syndrome 3
649
ClinVar variants
176
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— ERCC5
🧬
Gene-Disease Validity (ClinGen)
xeroderma pigmentosum group G · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
176 Pathogenic / Likely Pathogenic· 205 VUS of 649 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.81LOEUF
pLI 0.000
Z-score 2.64
OE 0.59 (0.43–0.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.12Z-score
OE missense 0.99 (0.92–1.05)
628 obs / 636.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.59 (0.43–0.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.92–1.05)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 28 / 47.7Missense obs/exp: 628 / 636.4Syn Z: -0.15

ClinVar Variant Classifications

649 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic133
Likely Pathogenic43
VUS205
Likely Benign159
Benign60
Conflicting49
133
Pathogenic
43
Likely Pathogenic
205
VUS
159
Likely Benign
60
Benign
49
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
18
4
111
0
133
Likely Pathogenic
26
6
11
0
43
VUS
4
164
30
7
205
Likely Benign
0
15
41
103
159
Benign
0
8
47
5
60
Conflicting
—49
Total48197240115649

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.

Gene2Phenotype Curations

ERCC5-related xeroderma pigmentosum, group G

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkinCancer
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cerebrooculofacioskeletal syndrome 3

MIM #616570

Molecular basis of disorder known

Autosomal recessive

Xeroderma pigmentosum, group G

MIM #278780

Molecular basis of disorder known

Autosomal recessive

Xeroderma pigmentosum, group G/Cockayne syndrome

MIM #278780

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ERCC5
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Efficacy of Exome-Targeted Capture Sequencing to Detect Mutations in Known Cerebellar Ataxia Genes.
Coutelier M et al.·JAMA Neurol
2018
Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings.
Bonache S et al.·J Cancer Res Clin Oncol
2018
ATR inhibition augments the efficacy of lurbinectedin in small-cell lung cancer.
Schultz CW et al.·EMBO Mol Med
2023
Association between the ERCC5 Asp1104His polymorphism and cancer risk: a meta-analysis.
Zhu ML et al.·PLoS One
2012Meta-analysis
Heterogeneity and overlaps in nucleotide excision repair disorders.
Ferri D et al.·Clin Genet
2020Review
Polymorphisms of XPG/ERCC5 and risk of squamous cell carcinoma of the head and neck.
Ma H et al.·Pharmacogenet Genomics
2012
To develop a prognostic model for neoadjuvant immunochemotherapy efficacy in esophageal squamous cell carcinoma by analyzing the immune microenvironment.
Yehan Z et al.·Front Immunol
2024Functional
Variants of ERCC5 and the outcome of platinum-based regimens in non-small cell lung cancer: a prospective cohort study.
Abdalkhalek ES et al.·Med Oncol
2022Cohort
ERCC polymorphisms and prognosis of patients with osteosarcoma.
Li J et al.·Tumour Biol
2014Meta-analysis
ERCC5/XPG, ERCC1, and BRCA1 gene status and clinical benefit of trabectedin in patients with soft tissue sarcoma.
Italiano A et al.·Cancer
2011Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Exploring Erythrocyte Glycophorin a Somatic Mutations and ERCC5 Genotypes in Atomic Bomb Survivors: An Association Analysis.
Hayashi T et al.·Radiat Res
2026
Altered expression of nucleotide excision repair genes ERCC2 and ERCC5 in prostate cancer tissues.
Abdulla A et al.·Cancer Genet
2026
The clinical spectrum associated with ERCC5 mutations: Is there a relationship between phenotype and genotype?
Zhang J et al.·Pediatr Discov
2024🔓 Open Access
Relationship between XPA, XPB/ERCC3, XPF/ERCC4, and XPG/ERCC5 Polymorphisms and the Susceptibility to Head and Neck Carcinoma: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis.
Imani MM et al.·Medicina (Kaunas)
2024🔓 Open AccessReview
Polymorphisms in ERCC1, ERCC4 and ERCC5 genes as biomarkers of susceptibility for pesticide-induced DNA damage in North-West Indian agricultural workers.
Kaur K et al.·Biomarkers
2023
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Rare DisordersUndiagnosed DisordersDisorders of Unknown Prevalence

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

RECRUITING
NCT01793168Sanford HealthStarted 2010-07
LeukodystrophyWhite Matter DiseaseLeukoencephalopathies

The Myelin Disorders Biorepository Project

RECRUITING
NCT03047369Children's Hospital of PhiladelphiaStarted 2016-12-08

External Resources

Links to major genomics databases and tools