ERCC8

Chr 5AR

ERCC excision repair 8, CSA ubiquitin ligase complex subunit

Also known as: CKN1, CSA, UVSS2

The ERCC8 protein serves as the substrate-recognition component of the CSA complex, an E3 ubiquitin ligase that facilitates transcription-coupled nucleotide excision repair by mediating ubiquitination of RNA polymerase II when it stalls at DNA lesions. Mutations cause Cockayne syndrome, an autosomal recessive disorder characterized by growth failure, premature aging, neurodegeneration, and extreme sensitivity to ultraviolet radiation. The gene is not loss-of-function intolerant (pLI near zero), consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismARLOEUF 1.352 OMIM phenotypes
Clinical SummaryERCC8
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Gene-Disease Validity (ClinGen)
Cockayne syndrome type 1 · 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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.35LOEUF
pLI 0.000
Z-score 0.20
OE 0.96 (0.691.35)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.40Z-score
OE missense 1.08 (0.971.21)
221 obs / 204.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.96 (0.691.35)
00.351.4
Missense OE1.08 (0.971.21)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 23 / 24.0Missense obs/exp: 221 / 204.8Syn Z: -0.09
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveERCC8-related Cockayne syndromeLOFAR

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

DN
0.6259th %ile
GOF
0.4973th %ile
LOF
0.4430th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ERCC8 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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