XPA

Chr 9AR

XPA, DNA damage recognition and repair factor

Also known as: XP1, XPAC

NCBI Gene: 7507 ENSG00000136936 UniProt: P23025 OMIM: 611153

This gene encodes a zinc finger protein that initiates DNA nucleotide excision repair by binding to damaged sites and serving as a scaffold to assemble the repair complex, particularly for UV-induced DNA damage. Mutations cause xeroderma pigmentosum group A, an autosomal recessive disorder characterized by extreme UV hypersensitivity and markedly increased skin cancer risk. The gene is highly constrained against loss-of-function variants (pLI near 0, LOEUF 0.97), reflecting its essential role in DNA repair.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a zinc finger protein plays a central role in nucleotide excision repair (NER), a specialized type of DNA repair. NER is responsible for repair of UV radiation-induced photoproducts and DNA adducts induced by chemical carcinogens and chemotherapeutic drugs. The encoded protein interacts with DNA and several NER proteins, acting as a scaffold to assemble the NER incision complex at sites of DNA damage. Mutations in this gene cause Xeroderma pigmentosum complementation group A (XP-A), an autosomal recessive skin disorder featuring hypersensitivity to sunlight and increased risk for skin cancer. [provided by RefSeq, Aug 2017]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Xeroderma pigmentosum, group AMIM #278700

Clinical highlights

Gene-disease validity (ClinGen)

xeroderma pigmentosum group A · 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

0.97

LOEUF

LOF

Mechanism· G2P

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GeneReview available — XPA