Alt. symbols: XPF | RAD1 | FANCQ

Approved name: ERCC excision repair 4, endonuclease catalytic subunit
Alt. names: excision repair cross-complementing rodent repair deficiency, complementation group 4, excision repair cross-complementation group 4 | xeroderma pigmentosum, complementation group F

Location: 16p13.12: 13920138 - 13952348 (+)
Gene type: protein_coding, 16 transcripts.

Scores: LoFtool: 0.878000 | pLI: 0.00000000 | LOEUF: 0.896

HGNC: 3436

NCBI: 2072, RefSeq: NG_011442.1

Ensembl: ENSG00000175595.16

LRG_463 | Status: public

OMIM: 133520

Expression | ProteinAtlas

ERCC4 encodes XPF, the DNA endonuclease/catalytic component that partners with ERCC1 to form the ERCC1-XPF enzyme complex, which is essential for DNA nucleotide excision repair (NER). The ERCC1-XPF nuclease complex functions in pathways to repair double-strand breaks in DNA, and also contributes to the homologous recombination aspect of inter-strand cross-link repair.

Bi-allelic frameshift, nonsense, missense and splice site mutations in ERCC4 have been linked to 4 autosomal recessive conditions: Fanconi anemia, complementation group Q [MIM:615272], XFE progeroid syndrome [MIM:610965], Xeroderma pigmentosum (XP), type F [MIM:278760], as well as an XP/Cockayne syndrome overlap phenotype. Complete ERCC4 loss-of-function (LOF) in humans has not been observed thus far. Cells with disabling mutations in ERCC4 are more sensitive than normal to particular DNA damagi ng agents, including ultraviolet radiation and chemicals that cause crosslinking between DNA strands. Complete deletion of ERCC4 is incompatible with life in mice, and mice expressing low levels of ERCC4 show defects in DNA repair, accompanied by metabolic stress-induced changes in physiology that result in premature ageing (PMID:21612988). A complete (homozygous) deletion of ERCC4 in humans has not been observed thus far. At least a dozen of pathogenic mutations in ERCC4 have been reported in humans, including frameshift (i.e. p.Thr173fs, p.Ile357fs, p.Thr495fs, p.Glu628fs, p.Ile800fs), missense (i.e. p.Arg153Pro, p.Cys236Arg, p.Arg689Ser, p.Leu230Pro), nonsense (i.e. p.Tyr577*), and splice-site (i.e. c.793-2A>G) mutations. Immunodeficiency or autoimmunity have not been specifically described for ERCC4-associated conditions. [Load More]