XRCC1

Chr 19AR

X-ray repair cross complementing 1

Also known as: RCC, SCAR26

XRCC1 encodes a scaffold protein that mediates DNA single-strand break repair by assembling repair protein complexes and regulating PARP1 activity during base excision repair. Mutations cause autosomal recessive spinocerebellar ataxia 26, affecting the cerebellum and causing progressive coordination problems. The gene is highly constrained against loss-of-function variants (pLI near 0, LOEUF 0.74), indicating that complete loss of function is likely incompatible with normal development.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.741 OMIM phenotype
Clinical SummaryXRCC1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 89 VUS of 163 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — XRCC1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.74LOEUF
pLI 0.000
Z-score 2.85
OE 0.51 (0.360.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.72Z-score
OE missense 0.90 (0.820.98)
348 obs / 387.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.51 (0.360.74)
00.351.4
Missense OE0.90 (0.820.98)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 20 / 39.3Missense obs/exp: 348 / 387.6Syn Z: 0.89

ClinVar Variant Classifications

163 submitted variants in ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic3
VUS89
Likely Benign24
Benign14
Conflicting1
6
Pathogenic
3
Likely Pathogenic
89
VUS
24
Likely Benign
14
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
5
0
6
Likely Pathogenic
1
1
1
0
3
VUS
2
76
11
0
89
Likely Benign
0
9
3
12
24
Benign
0
4
5
5
14
Conflicting
1
Total4902517137

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗