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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RAD1
RAD1 checkpoint DNA exonuclease
Chromosome 5 · 5p13.2
NCBI Gene: 5810Ensembl: ENSG00000113456.21HGNC: HGNC:9806UniProt: O60671
89PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
DNA Repair
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
checkpoint clamp complexchromosomeDNA damage checkpoint signalingnucleoplasmneurodegenerative diseaseAdult-onset autosomal recessive sideroblastic anemiahemolytic anemia due to glutathione reductase deficiencydehydrated hereditary stomatocytosis
✦AI Summary

RAD1 is a checkpoint DNA exonuclease and core component of the 9-1-1 cell-cycle checkpoint response complex, essential for DNA damage recognition and repair 12. The 9-1-1 complex is recruited to DNA lesions by the RAD17-RFC clamp loader and functions as a sliding clamp platform facilitating long-patch base excision repair (LP-BER) 34. RAD1 stabilizes DNA polymerase beta, endonuclease FEN1, and DNA ligase I activity at LP-BER sites, enhancing their catalytic efficiency 564. The 9-1-1 complex also recruits RHINO to double-strand breaks during S phase 7 and directs microhomology-mediated end-joining (MMEJ) repair in mitosis 8. Structurally, RAD1's interdomain connecting loop binds FEN1 peptides with high affinity, providing molecular specificity for damage repair versus replication functions 9. RAD1 is evolutionarily conserved across eukaryotes, with the human locus localized to chromosome 5.2, a region frequently altered in lung and bladder cancers 1011. These findings establish RAD1 as a critical hub coordinating multiple DNA repair pathways and cell cycle checkpoints.

Sources cited
1
RAD1 is a component of the 9-1-1 checkpoint response complex with major DNA repair role
PMID: 10846170
2
RAD1 component of 9-1-1 complex in DNA repair
PMID: 10884395
3
9-1-1 complex recruitment to DNA lesions by RAD17-RFC clamp loader
PMID: 12578958
4
RAD1 functions as sliding clamp platform for long-patch base excision repair proteins
PMID: 15871698
5
9-1-1 complex stimulates POLB, FEN1, and LIG1 activity in LP-BER
PMID: 15314187
6
9-1-1 complex stabilizes FEN1 cleavage and LIG1 on LP-BER substrates
PMID: 15556996
7
9-1-1 complex necessary for RHINO recruitment to DSBs during S phase
PMID: 21659603
8
RAD1-containing 9-1-1 complex directs MMEJ repair in mitosis through RHINO interaction
PMID: 37440612
9
RAD1 interdomain connecting loop binds FEN1 PIP box peptides, providing damage repair specificity
PMID: 19535328
10
Human RAD1 localized to chromosome 5p13, a region altered in lung and bladder cancers
PMID: 9828137
11
Human RAD1 homolog shows evolutionary conservation and maps to chromosome 5p13.2
PMID: 9828139
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.33Weak
Adult-onset autosomal recessive sideroblastic anemiaOpen Targets
0.05Suggestive
hemolytic anemia due to glutathione reductase deficiencyOpen Targets
0.05Suggestive
dehydrated hereditary stomatocytosisOpen Targets
0.05Suggestive
Rh deficiency syndromeOpen Targets
0.04Suggestive
Hemolytic anemia due to red cell pyruvate kinase deficiencyOpen Targets
0.04Suggestive
hemolytic anemia due to erythrocyte adenosine deaminase overproductionOpen Targets
0.04Suggestive
primary familial polycythemia due to EPO receptor mutationOpen Targets
0.04Suggestive
gluthathione peroxidase deficiencyOpen Targets
0.04Suggestive
response to xenobiotic stimulusOpen Targets
0.04Suggestive
microcytic anemia with liver iron overloadOpen Targets
0.04Suggestive
asthmaOpen Targets
0.04Suggestive
FTH1-related iron overloadOpen Targets
0.04Suggestive
hemochromatosis type 5Open Targets
0.04Suggestive
infectionOpen Targets
0.04Suggestive
poisoningOpen Targets
0.04Suggestive
galactokinase deficiencyOpen Targets
0.04Suggestive
hereditary hyperferritinemia with congenital cataractsOpen Targets
0.04Suggestive
sideroblastic anemia 3Open Targets
0.04Suggestive
hemolytic anemia due to diphosphoglycerate mutase deficiencyOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RFC5Protein interaction100%RFC4Protein interaction100%RFC3Protein interaction100%BRCA1Protein interaction94%FEN1Protein interaction94%ATRProtein interaction94%
Tissue Expression6 tissues
Brain
100%
Heart
68%
Bone Marrow
40%
Lung
38%
Ovary
30%
Liver
29%
Gene Interaction Network
Click a node to explore
RAD1RFC5RFC4RFC3BRCA1FEN1ATR
PROTEIN STRUCTURE
Preparing viewer…
PDB8GNN · 2.12 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.08LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.71 [0.48–1.08]
RankingsWhere RAD1 stands among ~20K protein-coding genes
  • #5,377of 20,598
    Most Researched89
  • #10,912of 17,882
    Most Constrained (LOEUF)1.08
Genes detectedRAD1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
R-loop-derived cytoplasmic RNA-DNA hybrids activate an immune response.
PMID: 36544021
Nature · 2023
1.00
2
RHINO directs MMEJ to repair DNA breaks in mitosis.
PMID: 37440612
Science · 2023
0.90
3
Dual Processing of R-Loops and Topoisomerase I Induces Transcription-Dependent DNA Double-Strand Breaks.
PMID: 31533039
Cell Rep · 2019
0.80
4
A human and mouse homolog of the Schizosaccharomyces pombe rad1+ cell cycle checkpoint control gene.
PMID: 9828137
Genomics · 1998
0.70
5
RAD1, a human structural homolog of the Schizosaccharomyces pombe RAD1 cell cycle checkpoint gene.
PMID: 9828139
Genomics · 1998
0.60