ERCC4

Chr 16AR

ERCC excision repair 4, endonuclease catalytic subunit

Also known as: ERCC11, FANCQ, RAD1, XFEPS, XPF

NCBI Gene: 2072 ENSG00000175595 UniProt: Q92889 OMIM: 133520

The protein functions as a catalytic component of a structure-specific DNA repair endonuclease that makes 5-prime incisions essential for nucleotide excision repair and interstrand cross-link repair. Mutations cause autosomal recessive conditions including xeroderma pigmentosum group F, Fanconi anemia complementation group Q, Cockayne syndrome overlap disorders, and XFE progeroid syndrome, affecting DNA repair mechanisms that protect against UV damage and other genotoxic stresses. The gene shows very low constraint against loss-of-function variants, which is consistent with recessive inheritance where heterozygous carriers are typically unaffected.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene forms a complex with ERCC1 and is involved in the 5' incision made during nucleotide excision repair. This complex is a structure specific DNA repair endonuclease that interacts with EME1. Defects in this gene are a cause of xeroderma pigmentosum complementation group F (XP-F), or xeroderma pigmentosum VI (XP6).[provided by RefSeq, Mar 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Fanconi anemia, complementation group QMIM #615272

Xeroderma pigmentosum, group FMIM #278760

Xeroderma pigmentosum, type F/Cockayne syndromeMIM #278760

XFE progeroid syndromeMIM #610965

UniProtFanconi anemia complementation group Q

Clinical highlights

Gene-disease validity (ClinGen)

xeroderma pigmentosum group F · 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

0.90

LOEUF

LOF

Mechanism· G2P

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GeneReview available — ERCC4