XRCC1

Chr 19AR

X-ray repair cross complementing 1

Also known as: RCC, SCAR26

NCBI Gene: 7515 ENSG00000073050 UniProt: P18887 OMIM: 194360

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

ARLOEUF 0.741 OMIM phenotype

Clinical Summary— XRCC1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 80 VUS of 148 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

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.000

Z-score 2.85

OE 0.51 (0.36–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.72Z-score

OE missense 0.90 (0.82–0.98)

348 obs / 387.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.36–0.74)

0≤0.351.4

Missense OE?0.90 (0.82–0.98)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 20 / 39.3Missense obs/exp: 348 / 387.6Syn Z: 0.89

ClinVar Variant Classifications

148 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic3

VUS80

Likely Benign23

Benign14

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	2	1	0	0	3
VUS	2	76	2	0	80
Likely Benign	0	9	2	12	23
Benign	0	4	5	5	14
Conflicting	—				1
Total	5	90	9	17	122

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap XRCC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →