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GeneE
26 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
XRCC2
X-ray repair cross complementing 2
Chromosome 7 Β· 7q36.1
NCBI Gene: 7516Ensembl: ENSG00000196584.4HGNC: HGNC:12829UniProt: A0A384MEK2
184PubMed Papers
23Diseases
0Drugs
16Pathogenic Variants
FUNCTIONAL ROLE
DNA RepairHomologous Recombination
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
four-way junction DNA bindingDNA repaircentrosome cycleDNA strand invasionspermatogenic failure 50Fanconi anemiahereditary neoplastic syndromeInherited cancer-predisposing syndrome
✦AI Summary

XRCC2 is a RAD51 paralog that functions as a critical component of the BCDX2 complex (RAD51B-RAD51C-RAD51D-XRCC2), essential for homologous recombination-mediated repair of double-stranded DNA breaks 1. The BCDX2 complex orchestrates RAD51 nucleoprotein filament assembly on single-stranded DNA, operating downstream of BRCA2 recruitment and upstream of RAD51 engagement 1. XRCC2 binds Holliday junctions and replication fork structures, facilitating replication fork protection and chr7 stability [UniProt]. Mutations in XRCC2 are associated with Fanconi anemia complementation group U and primary ovarian insufficiency 2, reflecting its critical roles in meiosis and DNA repair pathways. XRCC2 variants are implicated in pancreatic cancer susceptibility within populations carrying homologous recombination gene mutations 3. However, truncating XRCC2 variants show substantially lower breast cancer risk compared to other DNA repair genes like PALB2 or ATM, with one study excluding substantial breast cancer predisposition from XRCC2 truncating variants 4. The protein's function depends on coupled ATPase activities within the BCDX2 complex and structural maintenance of protein-protein interactions critical for RAD51 filament dynamics.

Sources cited
1
XRCC2 is part of BCDX2 complex that stimulates RAD51 filament nucleation and extension; orchestrates RAD51 assembly for replication fork protection and double-strand break repair
PMID: 37344587
2
Truncating XRCC2 variants are NOT significantly associated with increased breast cancer risk (OR=0.94; 95% CI 0.26-4.19); substantial breast cancer risk from XRCC2 truncating variants can be excluded
PMID: 28779002
3
XRCC2 mutations linked to primary ovarian insufficiency; implicated in meiosis/DNA repair pathways affecting nonsyndromic POI
PMID: 34794894
4
XRCC2 pathogenic variants found in pancreatic cancer patients; part of homologous recombination DNA damage repair pathway gene group
PMID: 35171259
5
XRCC2 genetic variants implicated in some cases of breast cancer as proteins with roles in DNA repair pathways and homologous recombination
PMID: 31456177
6
XRCC2 participates in RAD51B-RAD51C-RAD51D-XRCC2 complex; ATP binding occurs at interface of RAD51C interactions with paralogs including XRCC2
PMID: 36099300
7
XRCC2 identified as disease gene with deleterious variants in Mendelian phenotypes through autozygome analysis
PMID: 30237576
Disease Associationsβ“˜23
spermatogenic failure 50Open Targets
0.60Moderate
Fanconi anemiaOpen Targets
0.56Moderate
hereditary neoplastic syndromeOpen Targets
0.55Moderate
Inherited cancer-predisposing syndromeOpen Targets
0.55Moderate
cancerOpen Targets
0.55Moderate
Fanconi anemia complementation group UOpen Targets
0.52Moderate
myelodysplastic syndromeOpen Targets
0.46Moderate
acute myeloid leukemiaOpen Targets
0.46Moderate
premature ovarian failure 17Open Targets
0.46Moderate
Menkes diseaseOpen Targets
0.46Moderate
primary ovarian insufficiencyOpen Targets
0.46Moderate
Hereditary breast and ovarian cancer syndromeOpen Targets
0.37Weak
hereditary breast ovarian cancer syndromeOpen Targets
0.37Weak
male infertility with azoospermia or oligozoospermia due to single gene mutationOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.36Weak
breast carcinomaOpen Targets
0.33Weak
femoral neck fractureOpen Targets
0.29Weak
short stature, microcephaly, and endocrine dysfunctionOpen Targets
0.27Weak
ulcerative colitisOpen Targets
0.26Weak
eye diseaseOpen Targets
0.12Weak
Fanconi anemia, complementation group UUniProt
Premature ovarian failure 17UniProt
Spermatogenic failure 50UniProt
Pathogenic Variants16
NM_005431.2(XRCC2):c.377T>G (p.Leu126Ter)Likely pathogenic
Hereditary cancer-predisposing syndrome|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 126
NM_005431.2(XRCC2):c.175del (p.Tyr59fs)Likely pathogenic
Hereditary cancer-predisposing syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 59
NM_005431.2(XRCC2):c.316_319del (p.Glu105_Glu106insTer)Pathogenic
Hereditary cancer-predisposing syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 105
NM_005431.2(XRCC2):c.26_27del (p.Glu9fs)Likely pathogenic
Hereditary cancer-predisposing syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 9
NM_005431.2(XRCC2):c.2T>C (p.Met1Thr)Likely pathogenic
Hereditary cancer-predisposing syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 1
NM_005431.2(XRCC2):c.539T>G (p.Leu180Ter)Likely pathogenic
Hereditary cancer-predisposing syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 180
NM_005431.2(XRCC2):c.190del (p.Arg64fs)Pathogenic
Hereditary cancer-predisposing syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 64
NM_005431.2(XRCC2):c.395C>A (p.Ser132Ter)Likely pathogenic
Hereditary cancer-predisposing syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 132
NM_005431.2(XRCC2):c.488dup (p.Glu164fs)Likely pathogenic
Hereditary cancer-predisposing syndrome
β˜…β˜†β˜†β˜†2022β†’ Residue 164
NM_005431.2(XRCC2):c.609del (p.Ser204fs)Likely pathogenic
Hereditary cancer-predisposing syndrome
β˜…β˜†β˜†β˜†2022β†’ Residue 204
NM_005431.2(XRCC2):c.350del (p.Leu117fs)Likely pathogenic
not provided|Hereditary cancer-predisposing syndrome
β˜…β˜†β˜†β˜†2022β†’ Residue 117
NM_005431.2(XRCC2):c.240_243del (p.Phe80fs)Likely pathogenic
Hereditary cancer-predisposing syndrome
β˜…β˜†β˜†β˜†2022β†’ Residue 80
NM_005431.2(XRCC2):c.166_167del (p.Glu56fs)Likely pathogenic
Hereditary cancer-predisposing syndrome
β˜…β˜†β˜†β˜†2021β†’ Residue 56
NM_005431.2(XRCC2):c.490_491del (p.Glu164fs)Likely pathogenic
Hereditary cancer-predisposing syndrome
β˜…β˜†β˜†β˜†2019β†’ Residue 164
NM_005431.2(XRCC2):c.122-1G>TLikely pathogenic
Hereditary cancer-predisposing syndrome
β˜…β˜†β˜†β˜†2018
NM_005431.2(XRCC2):c.347_350del (p.Phe116fs)Likely pathogenic
Breast carcinoma
β˜†β˜†β˜†β˜†β†’ Residue 116
View on ClinVar β†—
Related Genes
BARD1Protein interaction100%SFR1Protein interaction100%NBNProtein interaction100%FANCD2Protein interaction100%PALB2Protein interaction95%BLMProtein interaction95%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
16%
Ovary
6%
Heart
5%
Lung
5%
Liver
4%
Gene Interaction Network
Click a node to explore
XRCC2BARD1SFR1NBNFANCD2PALB2BLM
PROTEIN STRUCTURE
Preparing viewer…
PDB8OUZ Β· 2.20 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.21LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.85 [0.61–1.21]
RankingsWhere XRCC2 stands among ~20K protein-coding genes
  • #2,357of 20,598
    Most Researched184 Β· top quartile
  • #2,384of 5,498
    Most Pathogenic Variants16
  • #12,704of 17,882
    Most Constrained (LOEUF)1.21
Genes detectedXRCC2
Sources retrieved26 papers
Response timeβ€”
πŸ“„ Sources
26β–Ό
1
Rare, protein-truncating variants in
PMID: 28779002
J Med Genet Β· 2017
1.00
2
Epidemiology of Breast Cancer in Women.
PMID: 31456177
Adv Exp Med Biol Β· 2019
0.90
3
Genetics of ovarian insufficiency and defects of folliculogenesis.
PMID: 34794894
Best Pract Res Clin Endocrinol Metab Β· 2022
0.80
4
Prevalence of Germline Sequence Variations Among Patients With Pancreatic Cancer in China.
PMID: 35171259
JAMA Netw Open Β· 2022
0.70
5
A role for XRCC2 gene polymorphisms in breast cancer risk and survival.
PMID: 21632523
J Med Genet Β· 2011
0.68