XRCC1

Chr 19AR

X-ray repair cross complementing 1

Also known as: RCC, SCAR26

NCBI Gene: 7515ENSG00000073050UniProt: P18887

The protein encoded by this gene is involved in the efficient repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. This protein interacts with DNA ligase III, polymerase beta and poly (ADP-ribose) polymerase to participate in the base excision repair pathway. It may play a role in DNA processing during meiogenesis and recombination in germ cells. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Spinocerebellar ataxia, autosomal recessive 26MIM #617633
AR
167
ClinVar variants
9
Pathogenic / LP
0.00
pLI score
3
Active trials
Clinical Summary— XRCC1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 89 VUS of 167 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.
0.74LOEUF
pLI 0.000
Z-score 2.85
OE 0.51 (0.36–0.74)
Tolerant

Typical tolerance to LoF variation

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.
0.72Z-score
OE missense 0.90 (0.82–0.98)
348 obs / 387.6 exp
Tolerant

Mild missense constraint

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.0.51 (0.36–0.74)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.82–0.98)
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.0.91
0≤1.21.6
LoF obs/exp: 20 / 39.3Missense obs/exp: 348 / 387.6Syn Z: 0.89

ClinVar Variant Classifications

167 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic3
VUS89
Likely Benign23
Benign14
Conflicting1
6
Pathogenic
3
Likely Pathogenic
89
VUS
23
Likely Benign
14
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
1
2
0
3
VUS
1
75
13
0
89
Likely Benign
0
9
3
11
23
Benign
0
4
5
5
14
Conflicting
—1
Total1892916136

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

View in ClinVar →

Protein Context — Lollipop Plot

XRCC1 · 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

?Spinocerebellar ataxia, autosomal recessive 26

MIM #617633

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Proteogenomic Markers of Chemotherapy Resistance and Response in Triple-Negative Breast Cancer.
Anurag M et al.·Cancer Discov
2022
Hereditary ataxias and paraparesias: clinical and genetic update.
Parodi L et al.·Curr Opin Neurol
2018Review
XRCC1 and XPD genetic polymorphisms and susceptibility to age-related cataract: a meta-analysis.
Chi XX et al.·Mol Vis
2015Meta-analysis
Clinical and Genetic Characterization of Brazilian Patients with Ataxia and Oculomotor Apraxia.
da Costa SCG et al.·Mov Disord
2022Cohort
XRCC1 polymorphism and lung cancer risk.
Schneider J et al.·Expert Rev Mol Diagn
2008Review
XRCC1 and XPD polymorphisms: clinical outcomes and risk of prostate cancer in Bangladeshi population.
Ahmed N et al.·Mol Biol Rep
2024
Association between XRCC1 Arg280His polymorphism and risk of hepatocellular carcinoma: a systematic review and meta-analysis.
Xu W et al.·Genet Mol Res
2015Meta-analysis
DNA repair and cyclin D1 polymorphisms and styrene-induced genotoxicity and immunotoxicity.
Kuricova M et al.·Toxicol Appl Pharmacol
2005Review
Association between polymorphisms in XRCC1 gene and clinical outcomes of patients with lung cancer: a meta-analysis.
Cui Z et al.·BMC Cancer
2012Review
XRCC1 and XPD genetic polymorphisms and clinical outcomes of gastric cancer patients treated with oxaliplatin-based chemotherapy: a meta-analysis.
Zhang X et al.·Tumour Biol
2014Meta-analysis
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Regulation of Activity of DNA Polymerases β and λ by XRCC1, PARP1, and PARP2 Proteins.
Lebedeva NA et al.·Biochemistry (Mosc)
2026
XRCC1 Arg399Gln Genetic Variant Increases Colorectal Cancer Susceptibility: A Comprehensive Meta-Analysis.
Kampalli PK et al.·Asian Pac J Cancer Prev
2025🔓 Open Access
Associations between XRCC1-Arg399Gln polymorphism and the risk of prostate cancer: an updated meta-analysis.
Deng J et al.·Amino Acids
2025🔓 Open Access
Potential risk genotypes associated with symptoms of pesticide poisoning based on polymorphisms in the XRCC1 (rs25487 and rs1799782), SOD2 (rs4880), PON1 (rs662) and GSTP1 (rs1695) genes, in farmers in the Cienega region.
Flores Gutiérrez CA et al.·J Investig Med
2025
The Role of Single Nucleotide Polymorphisms at the Arg399Gln Locus of the XRCC1 Gene in Patients with Non-Small Cell Lung Cancer (NSCLC).
Smolarz B et al.·Int J Mol Sci
2025🔓 Open AccessCohort
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Mesothelioma, Malignant Pleural

Genetic Susceptibility in MAlignant Pleural Mesothelioma: Clinical Implication of GermliNE VariaTionS

RECRUITING
NCT06886672Fondazione IRCCS Policlinico San Matteo di PaviaStarted 2023-06-15
Colorectal Cancer

Diet Modulation of Bacterial Sulfur and Bile Acid Metabolism and Colon Cancer Risk

ENROLLING BY INVITATION
NCT03550885Phase NAUniversity of Illinois at ChicagoStarted 2018-08-01
High taurine and saturated fat dietLow in taurine and saturated fat diet
Head and Neck Carcinoma of Unknown PrimaryHead and Neck Squamous Cell CarcinomaStage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7

Testing the Addition of M6620 (VX-970, Berzosertib) to Usual Chemotherapy and Radiation for Head and Neck Cancer

ACTIVE NOT RECRUITING
NCT02567422Phase PHASE1National Cancer Institute (NCI)Started 2017-04-17
BerzosertibCisplatinComputed Tomography

External Resources

Links to major genomics databases and tools