ERCC1

Chr 19AR

ERCC excision repair 1, endonuclease non-catalytic subunit

Also known as: COFS4, RAD10, UV20

NCBI Gene: 2067ENSG00000012061UniProt: P07992

The product of this gene functions in the nucleotide excision repair pathway, and is required for the repair of DNA lesions such as those induced by UV light or formed by electrophilic compounds including cisplatin. The encoded protein forms a heterodimer with the XPF endonuclease (also known as ERCC4), and the heterodimeric endonuclease catalyzes the 5' incision in the process of excising the DNA lesion. The heterodimeric endonuclease is also involved in recombinational DNA repair and in the repair of inter-strand crosslinks. Mutations in this gene result in cerebrooculofacioskeletal syndrome, and polymorphisms that alter expression of this gene may play a role in carcinogenesis. Multiple transcript variants encoding different isoforms have been found for this gene. The last exon of this gene overlaps with the CD3e molecule, epsilon associated protein gene on the opposite strand. [provided by RefSeq, Oct 2009]

Primary Disease Associations & Inheritance

Cerebrooculofacioskeletal syndrome 4MIM #610758
AR
UniProtCerebro-oculo-facio-skeletal syndrome 4
303
ClinVar variants
23
Pathogenic / LP
0.00
pLI score
4
Active trials
Clinical Summary— ERCC1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 115 VUS of 303 total submissions
💊
Clinical Trials
4 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.
1.30LOEUF
pLI 0.000
Z-score 0.72
OE 0.80 (0.51–1.30)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.66Z-score
OE missense 0.86 (0.76–0.98)
165 obs / 190.8 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.0.80 (0.51–1.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.76–0.98)
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.1.04
0≤1.21.6
LoF obs/exp: 12 / 15.0Missense obs/exp: 165 / 190.8Syn Z: -0.32

ClinVar Variant Classifications

303 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic10
VUS115
Likely Benign92
Benign36
Conflicting3
13
Pathogenic
10
Likely Pathogenic
115
VUS
92
Likely Benign
36
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
10
0
13
Likely Pathogenic
5
0
5
0
10
VUS
1
109
5
0
115
Likely Benign
0
8
43
41
92
Benign
0
4
30
2
36
Conflicting
—3
Total81229343269

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ERCC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ERCC1-related cerebrooculofacioskeletal syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cerebrooculofacioskeletal syndrome 4

MIM #610758

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Pharmacogenomics and gemcitabine.
Rosell R et al.·Ann Oncol
2006Review
Problems of variable biomarker evaluation in stratified medicine research--A case study of ERCC1 in non-small-cell lung cancer.
Malottki K et al.·Lung Cancer
2016
DNA repair gene ERCC1 polymorphisms may contribute to the risk of glioma.
Yuan G et al.·Tumour Biol
2014Meta-analysis
Persistent TFIIH binding to non-excised DNA damage causes cell and developmental failure.
Muniesa-Vargas A et al.·Nat Commun
2024
XPF-ERCC1 protects liver, kidney and blood homeostasis outside the canonical excision repair pathways.
Mulderrig L et al.·PLoS Genet
2020
Perspectives of ERCC1 in early-stage and advanced cervical cancer: From experiments to clinical applications.
Du P et al.·Front Immunol
2023Review
Clinical Perspectives of ERCC1 in Bladder Cancer.
Koutsoukos K et al.·Int J Mol Sci
2020Review
ERCC1 as a risk stratifier in platinum-based chemotherapy for nonsmall-cell lung cancer.
Olaussen KA et al.·Curr Opin Pulm Med
2007Review
Heterogeneity and overlaps in nucleotide excision repair disorders.
Ferri D et al.·Clin Genet
2020Review
Functional and physical interactions between ERCC1 and MSH2 complexes for resistance to cis-diamminedichloroplatinum(II) in mammalian cells.
Lan L et al.·DNA Repair (Amst)
2004Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
FB23-2 and Cisplatin Synergize to Inhibit Head and Neck Squamous Cell Carcinoma by Targeting the XPF/ERCC1 Complex.
Jiang Y et al.·Cancer Sci
2026
Liposomal Delivery of Pyronaridine as a Repurposed Inhibitor of ERCC1/XPF for the Sensitization of Colorectal Cancer Cells to Platinum Chemotherapeutics.
Mehinrad P et al.·Mol Pharm
2026🔓 Open Access
Molecular basis of XPF-ERCC1 targeting to SLX4-dependent DNA repair pathways.
Feng J et al.·Nat Commun
2025🔓 Open Access
RETRACTION: UBE2C Induces Cisplatin Resistance via ZEB1/2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cells.
Oncology JO.·J Oncol
2025🔓 Open Access
A Unique Chimeric RNA: ERCC1-iASPP Drives Benzo[a]pyrene-Induced Lung Carcinogenesis via Dual Coding and Non-Coding Mechanisms.
Shan M et al.·Adv Sci (Weinh)
2026🔓 Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Non-small-cell Lung Cancer Patients

Randomized Trial Comparing Standard of Care Versus Immune- Based Combination in Relapsed Stage III Non-small-cell Lung Cancer (NSCLC) Pretreated With Chemoradiotherapy and Durvalumab

RECRUITING
NCT05568212Phase PHASE2Fondazione Ricerca TraslazionaleStarted 2022-05-02
DurvalumabOlaparib tabletSingle-agent chemotherapy
Head and Neck Carcinoma of Unknown PrimaryHead and Neck Squamous Cell CarcinomaStage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7

Testing the Addition of M6620 (VX-970, Berzosertib) to Usual Chemotherapy and Radiation for Head and Neck Cancer

ACTIVE NOT RECRUITING
NCT02567422Phase PHASE1National Cancer Institute (NCI)Started 2017-04-17
BerzosertibCisplatinComputed Tomography
Pancreas Cancer

Prospective Cohort Study of Pancreatic Cancer Patients Treated With Proton Beam Therapy

ENROLLING BY INVITATION
NCT04466189National Cancer Center, KoreaStarted 2018-09-21
Breast Cancer

First-line Gemcitabine Plus Cisplatin in Locally Advanced (IIIC Stage) Breast Cancer Patients

ACTIVE NOT RECRUITING
NCT06531447Phase PHASE2The National Center of Oncology, AzerbaijanStarted 2014-05
CisplatinGemcitabineDoxorubicin

External Resources

Links to major genomics databases and tools