Gene XPA
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Also known as
Xeroderma pigmentosum complementation group A, XP1, XPACOverview
XPA (Xeroderma Pigmentosum Group A) encodes a zinc finger protein that plays a central role in nucleotide excision repair (NER), the primary pathway for removing bulky DNA lesions caused by ultraviolet radiation and certain chemical carcinogens. XPA acts as a scaffold protein, coordinating the assembly of the NER complex at sites of DNA damage and verifying damage recognition before repair synthesis begins. This gene is essential for both global genome NER and transcription-coupled NER.Pathogenic mutations in XPA cause xeroderma pigmentosum complementation group A (XP-A), the most common and often most severe form of xeroderma pigmentosum. This autosomal recessive disorder is characterized by extreme sensitivity to sunlight, with a dramatically increased risk of skin cancers (over 1000-fold increased risk) that often appear in childhood. Many XP-A patients also develop progressive neurological degeneration, including cognitive decline, hearing loss, and progressive motor impairment.
Beyond rare disease mutations, common genetic variants in XPA may influence DNA repair capacity and cancer susceptibility in the general population. These polymorphisms have been associated with differences in skin cancer risk, particularly in individuals with high sun exposure. Understanding XPA genetics can inform personalized UV protection strategies, cancer screening recommendations, and assessment of chemotherapy response, as NER is also involved in repairing platinum-based chemotherapy-induced DNA damage.