ERCC1

Chr 19AR

ERCC excision repair 1, endonuclease non-catalytic subunit

Also known as: COFS4, RAD10, UV20

The protein functions as a non-catalytic component of a structure-specific DNA repair endonuclease that performs 5'-incisions during nucleotide excision repair and is responsible for repairing DNA lesions including UV-induced damage, interstrand crosslinks, and double-strand breaks. Biallelic mutations cause cerebrooculofacioskeletal syndrome 4, a severe autosomal recessive disorder affecting multiple organ systems including the brain, eyes, face, and skeleton. The gene is highly constrained against loss-of-function variants, reflecting its essential role in DNA repair.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.301 OMIM phenotype
Clinical SummaryERCC1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 114 VUS of 300 total submissions
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — ERCC1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.30LOEUF
pLI 0.000
Z-score 0.72
OE 0.80 (0.511.30)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.66Z-score
OE missense 0.86 (0.760.98)
165 obs / 190.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.80 (0.511.30)
00.351.4
Missense OE0.86 (0.760.98)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 12 / 15.0Missense obs/exp: 165 / 190.8Syn Z: -0.32
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveERCC1-related cerebrooculofacioskeletal syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6841th %ile
GOF
0.3590th %ile
LOF
0.3550th %ile

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

300 submitted variants in ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic10
VUS114
Likely Benign93
Benign37
Conflicting4
11
Pathogenic
10
Likely Pathogenic
114
VUS
93
Likely Benign
37
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
6
0
11
Likely Pathogenic
8
0
2
0
10
VUS
1
109
4
0
114
Likely Benign
1
8
42
42
93
Benign
0
4
30
3
37
Conflicting
4
Total151218445269

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.

3D Protein StructureAlphaFold
Clinical Literature
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