XRCC3

Overview

XRCC3 (X-Ray Repair Cross Complementing 3) encodes a member of the RecA/Rad51 family of proteins involved in homologous recombination repair of DNA double-strand breaks. It forms a complex with RAD51C and is essential for maintaining genomic stability. Germline pathogenic variants in XRCC3 have been identified in familial cancer syndromes and may confer susceptibility to lung cancer.

Alterations observed in the corpus

  • Recurrent germline pathogenic/likely-pathogenic variant identified in an Indian familial non-small-cell lung cancer cohort enriched for young lung cancer; also observed alongside ATM, CHEK2, BAP1, FANCA, FANCI, FANCM, and LZTR1 in 17% (13/78) of familial NSCLC cases PMID:27346245

Cancer types (linked)

  • NSCLC — germline P/LP variant observed in Indian familial NSCLC cohort enriched for young patients (<40 years) PMID:27346245

Co-occurrence and mutual exclusivity

  • Co-occurs with other DNA-repair and Fanconi anemia pathway germline variants (ATM, CHEK2, BAP1, FANCA, FANCI, FANCM, LZTR1) in familial NSCLC cases PMID:27346245

Therapeutic relevance

  • As a homologous recombination repair gene, germline XRCC3 deficiency may predict sensitivity to platinum-based chemotherapy or PARP inhibitors, though clinical validation in NSCLC is lacking.

Open questions

  • Whether germline XRCC3 variants confer a quantified lung cancer risk comparable to BRCA1/2 remains to be established in larger, population-based cohorts.

Sources

This page was processed by crosslinker on 2026-05-14.