XRCC2

Chr 7AR

X-ray repair cross complementing 2

The protein repairs DNA double-strand breaks through homologous recombination as part of the RAD51 paralog complex, maintaining chromosome stability. Biallelic mutations cause Fanconi anemia complementation group U, characterized by progressive bone marrow failure, developmental abnormalities, and increased cancer predisposition with autosomal recessive inheritance. The gene shows extreme constraint against loss-of-function variants in the general population.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
DNmechanismARLOEUF 1.373 OMIM phenotypes
Clinical SummaryXRCC2
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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.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — XRCC2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.37LOEUF
pLI 0.000
Z-score 0.58
OE 0.83 (0.521.37)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.13Z-score
OE missense 1.03 (0.901.18)
152 obs / 147.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.83 (0.521.37)
00.351.4
Missense OE1.03 (0.901.18)
00.61.4
Synonymous OE0.81
01.21.6
LoF obs/exp: 11 / 13.3Missense obs/exp: 152 / 147.7Syn Z: 1.09
DN
0.6649th %ile
GOF
0.3986th %ile
LOF
0.3452th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold
Clinical Literature
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