ERCC8

Chr 5q12.1

ERCC excision repair 8, CSA ubiquitin ligase complex subunit

Aliases:: CSA
MANE:: ENST00000676185.1

OMIM: 609412 ↗NCBI: 1161 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

AlphaFold predicted structure

ERCC8 · Q13216

v62025-08-01

Predicted Aligned Error matrix for ERCC8 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

91.6/ 100

Very high

396 residues

Confidence breakdown

Very high(≥ 90)86%
Confident(70–90)6%
Low(50–70)2%
Very low(< 50)6%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Arthrogryposis
BIALLELIC, autosomal or pseudoautosomal
Bilateral congenital or childhood onset cataracts
BIALLELIC, autosomal or pseudoautosomal
DDG2P
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy
BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder
BIALLELIC, autosomal or pseudoautosomal
Inherited white matter disorders
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal

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Disease associations (Open Targets)

Cockayne syndrome type 1
0.83
Cockayne syndrome
0.80
UV-sensitive syndrome 2
0.72
UV-sensitive syndrome
0.62
hereditary disease
0.47
Cockayne syndrome type 2
0.37
Cockayne syndrome type 3
0.37
Parkinson disease
0.29
Abnormality of the nervous system
0.27
intelligence
0.23

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

DNA excision repair protein ERCC-8

Substrate-recognition component of the CSA complex, a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, involved in transcription-coupled nucleotide excision repair (TC-NER), a process during which RNA polymerase II-blocking lesions are rapidly removed from the transcribed strand of active genes (PubMed:12732143, PubMed:16751180, PubMed:16964240, PubMed:32142649, PubMed:34526721, PubMed:38316879, PubMed:38600235, PubMed:38600236). Following recruitment to lesion-stalled RNA polymerase II (Pol II), the CSA complex mediates ubiquitination of Pol II subunit POLR2A/RPB1 at 'Lys-1268', a critical TC-NER checkpoint, governing RNA Pol II stability and initiating DNA damage excision by TFIIH recruitment (PubMed:12732143, PubMed:16751180, PubMed:16964240, PubMed:32142649, PubMed:32355176, PubMed:34526721, PubMed:38316879, PubMed:38600235, PubMed:38600236). The CSA complex also promotes the ubiquitination and subsequent proteasomal degradation of ERCC6/CSB in a UV-dependent manner; ERCC6 degradation is essential for the recovery of RNA synthesis after transcription-coupled repair (PubMed:16751180). Also plays a role in DNA double-strand breaks (DSSBs) repair by non-homologous end joining (NHEJ) (PubMed:29545921)