ERCC2

Chr 19AR

ERCC excision repair 2, TFIIH core complex helicase subunit

Also known as: COFS2, CXPD, EM9, TFIIH, TTD, TTD1, XPD

NCBI Gene: 2068 ENSG00000104884 UniProt: P18074 OMIM: 126340

The ERCC2 protein functions as an ATP-dependent DNA helicase that is essential for transcription-coupled nucleotide excision repair and serves as a core component of the TFIIH transcription factor complex. Autosomal recessive mutations cause xeroderma pigmentosum group D (a cancer-prone syndrome with extreme sun sensitivity), trichothiodystrophy (characterized by brittle hair and developmental abnormalities), and cerebrooculofacioskeletal syndrome. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with its recessive inheritance pattern where heterozygous carriers are typically unaffected.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The nucleotide excision repair pathway is a mechanism to repair damage to DNA. The protein encoded by this gene is involved in transcription-coupled nucleotide excision repair and is an integral member of the basal transcription factor BTF2/TFIIH complex. The gene product has ATP-dependent DNA helicase activity and belongs to the RAD3/XPD subfamily of helicases. Defects in this gene can result in three different disorders, the cancer-prone syndrome xeroderma pigmentosum complementation group D, trichothiodystrophy, and Cockayne syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Cerebrooculofacioskeletal syndrome 2MIM #610756

Trichothiodystrophy 1, photosensitiveMIM #601675

Xeroderma pigmentosum, group DMIM #278730

UniProtCerebro-oculo-facio-skeletal syndrome 2

Clinical highlights

Gene-disease validity (ClinGen)

xeroderma pigmentosum group D · 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

1.09

LOEUF

LOF

Mechanism· G2P

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GeneReview available — ERCC2