ERCC6

Chr 10

ERCC excision repair 6, chromatin remodeling factor

Also known as: ARMD5, CKN2, COFS, COFS1, CSB, CSB-PGBD3, POF11, RAD26

NCBI Gene: 2074 ENSG00000225830 UniProt: Q03468

This gene encodes a DNA-binding protein essential for transcription-coupled nucleotide excision repair and chromatin remodeling, with DNA-dependent ATPase activity that removes DNA lesions and regulates double-strand break repair. Mutations cause autosomal recessive Cockayne syndrome type B and cerebrooculofacioskeletal syndrome 1, both early-onset multisystem disorders with neurodegeneration, growth failure, and photosensitivity. The protein is critical for neuronal differentiation and has very low tolerance for loss-of-function mutations (LOEUF 0.802).

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a DNA-binding protein that is important in transcription-coupled excision repair. The encoded protein has ATP-stimulated ATPase activity, interacts with several transcription and excision repair proteins, and may promote complex formation at DNA repair sites. Mutations in this gene are associated with Cockayne syndrome type B and cerebrooculofacioskeletal syndrome 1. Alternative splicing occurs between a splice site from exon 5 of this gene to the 3' splice site upstream of the open reading frame (ORF) of the adjacent gene, piggyback-derived-3 (GeneID:267004), which activates the alternative polyadenylation site downstream of the piggyback-derived-3 ORF. The resulting transcripts encode a fusion protein that shares sequence with the product of each individual gene. [provided by RefSeq, Mar 2016]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCockayne syndrome B

UniProtCerebro-oculo-facio-skeletal syndrome 1

UniProtDe Sanctis-Cacchione syndrome

UniProtMacular degeneration, age-related, 5

Clinical highlights

Gene-disease validity (ClinGen)

Cockayne spectrum with or without cerebrooculofacioskeletal syndrome · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.80

LOEUF

LOF

Mechanism· G2P

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GeneReview available — ERCC6