XRCC2

Chr 7AR

X-ray repair cross complementing 2

Also known as: FANCU, POF17, SPGF50

NCBI Gene: 7516ENSG00000196584UniProt: O43543

This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. This gene is involved in the repair of DNA double-strand breaks by homologous recombination and it functionally complements Chinese hamster irs1, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Fanconi anemia, complementation group UMIM #617247
AR
?Premature ovarian failure 17MIM #619146
AR
Spermatogenic failure 50MIM #619145
AR
594
ClinVar variants
41
Pathogenic / LP
0.00
pLI score
3
Active trials
Clinical Summary— XRCC2
🧬
Gene-Disease Validity (ClinGen)
Fanconi anemia complementation group U · ARLimited

Limited evidence — not for standalone diagnostic reporting

3 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
41 Pathogenic / Likely Pathogenic· 375 VUS of 594 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.37LOEUF
pLI 0.000
Z-score 0.58
OE 0.83 (0.52–1.37)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.13Z-score
OE missense 1.03 (0.90–1.18)
152 obs / 147.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.83 (0.52–1.37)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.90–1.18)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.81
0≤1.21.6
LoF obs/exp: 11 / 13.3Missense obs/exp: 152 / 147.7Syn Z: 1.09

ClinVar Variant Classifications

594 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic12
VUS375
Likely Benign136
Benign12
Conflicting30
29
Pathogenic
12
Likely Pathogenic
375
VUS
136
Likely Benign
12
Benign
30
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
29
0
29
Likely Pathogenic
8
1
3
0
12
VUS
19
296
58
2
375
Likely Benign
0
7
26
103
136
Benign
0
1
11
0
12
Conflicting
—30
Total27305127105594

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

XRCC2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Fanconi anemia, complementation group U

MIM #617247

Molecular basis of disorder known

Autosomal recessive

?Premature ovarian failure 17

MIM #619146

Molecular basis of disorder known

Autosomal recessive

Spermatogenic failure 50

MIM #619145

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — XRCC2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks.
Decker B et al.·J Med Genet
2017
Prevalence of Germline Sequence Variations Among Patients With Pancreatic Cancer in China.
Yin L et al.·JAMA Netw Open
2022Cohort
Functional and Clinical Characterization of Variants of Uncertain Significance Identifies a Hotspot for Inactivating Missense Variants in RAD51C.
Hu C et al.·Cancer Res
2023Functional
Autozygome and high throughput confirmation of disease genes candidacy.
Maddirevula S et al.·Genet Med
2019
Homologous recombination-deficient mutation cluster in tumor suppressor RAD51C identified by comprehensive analysis of cancer variants.
Prakash R et al.·Proc Natl Acad Sci U S A
2022
Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings.
Bonache S et al.·J Cancer Res Clin Oncol
2018
Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer Genes in Patients Lacking Known BRCA Mutations.
Caminsky NG et al.·Hum Mutat
2016Cohort
Overexpressed XRCC2 as an independent risk factor for poor prognosis in glioma patients.
Liu Z et al.·Mol Med
2021Meta-analysis
Structural insights into BCDX2 complex function in homologous recombination.
Rawal Y et al.·Nature
2023
Germline Sequencing Analysis to Inform Clinical Gene Panel Testing for Aggressive Prostate Cancer.
Darst BF et al.·JAMA Oncol
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Cryo-electron microscopic visualization of RAD51 filament assembly and end-capping by XRCC3-RAD51C-RAD51D-XRCC2.
Greenhough LA et al.·Science
2026🔓 Open Access
Integrated case-control and in silico analysis of DNA double-strand break repair gene variants (RAD51, XRCC2, XRCC3, XRCC4, and LIG4) for ovarian cancer susceptibility.
Sistla HC et al.·Gene
2026
The association between XRCC2 and BCORL1 expression with sperm DNA fragmentation index in infertile men candidates undergoing intracytoplasmic sperm injection (ICSI).
Paknejad R et al.·Tissue Cell
2025
Discovery of novel xanthohumol C derivatives regulating XRCC2 transcription and expression for the treatment of colorectal cancer.
Zhu Q et al.·Bioorg Med Chem
2025
FIGL1 attenuates meiotic interhomolog repair and is counteracted by the RAD51 paralog XRCC2 and the chromosome axis protein ASY1 during meiosis.
Emmenecker C et al.·New Phytol
2024🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING
NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21
NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies
Malignant Neoplasm of BreastBreast Cancer

Comprehensive Analysis of Predictors of the Treatment With Pembrolizumab and Olaparib in Patients With Unresectable or Metastatic HER2 Negative Breast Cancer and a Deleterious Germline Mutation or a Homologous Recombination Deficiency (COMPRENDO

ACTIVE NOT RECRUITING
NCT05033756Phase PHASE2Institut fuer FrauengesundheitStarted 2022-07-30
Pembrolizumab Injection [Keytruda]Olaparib Oral Tablet [Lynparza]
Prostate Cancer

PROMISE Registry: A Prostate Cancer Registry of Outcomes and Germline Mutations for Improved Survival and Treatment Effectiveness

RECRUITING
NCT04995198Prostate Cancer Clinical Trials ConsortiumStarted 2021-05-03

External Resources

Links to major genomics databases and tools