RAD1

Summary

RAD1 (RAD1 checkpoint DNA exonuclease, HGNC:9806) is a protein-coding gene on chromosome 5p13.2, encoding Cell cycle checkpoint protein RAD1 (O60671). Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair. It is a selective cancer dependency (DepMap: 49.5% of cell lines).

This gene encodes a component of a heterotrimeric cell cycle checkpoint complex, known as the 9-1-1 complex, that is activated to stop cell cycle progression in response to DNA damage or incomplete DNA replication. The 9-1-1 complex is recruited by RAD17 to affected sites where it may attract specialized DNA polymerases and other DNA repair effectors. Alternatively spliced transcript variants of this gene have been described.

Source: NCBI Gene 5810 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 61 total — 1 likely-pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 49.5% of screened cell lines
• MANE Select transcript: NM_002853

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9806
Approved symbol	RAD1
Name	RAD1 checkpoint DNA exonuclease
Location	5p13.2
Locus type	gene with protein product
Status	Approved
Aliases	HRAD1, REC1
Ensembl gene	ENSG00000113456
Ensembl biotype	protein_coding
OMIM	603153
Entrez	5810

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000325577, ENST00000341754, ENST00000382038, ENST00000506311, ENST00000511456, ENST00000512192, ENST00000513914, ENST00000886887, ENST00000886888, ENST00000938495, ENST00000938496, ENST00000938497, ENST00000956463, ENST00000956464

RefSeq mRNA: 1 — MANE Select: NM_002853 NM_002853

CCDS: CCDS3905

Canonical transcript exons

ENST00000382038 — 6 exons

Exon	Start	End
ENSE00001490735	34905260	34908948
ENSE00001783631	34914695	34914961
ENSE00002050809	34915416	34915504
ENSE00003563046	34913470	34913578
ENSE00003576836	34911554	34911812
ENSE00003661041	34909258	34909356

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 97.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.1327 / max 144.7490, expressed in 1811 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61247	12.6010	1795
61249	3.0978	1443
61248	2.4338	1331

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.09	gold quality
oocyte	CL:0000023	96.41	gold quality
nipple	UBERON:0002030	94.73	gold quality
urethra	UBERON:0000057	93.34	gold quality
visceral pleura	UBERON:0002401	92.45	gold quality
renal medulla	UBERON:0000362	92.39	gold quality
superior surface of tongue	UBERON:0007371	92.12	gold quality
ventral tegmental area	UBERON:0002691	92.02	gold quality
pylorus	UBERON:0001166	91.92	gold quality
cardia of stomach	UBERON:0001162	91.24	gold quality
adrenal tissue	UBERON:0018303	91.20	gold quality
calcaneal tendon	UBERON:0003701	91.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.04	gold quality
buccal mucosa cell	CL:0002336	90.95	gold quality
trabecular bone tissue	UBERON:0002483	90.81	gold quality
pericardium	UBERON:0002407	90.73	gold quality
superior vestibular nucleus	UBERON:0007227	90.69	gold quality
trigeminal ganglion	UBERON:0001675	90.48	gold quality
mammalian vulva	UBERON:0000997	90.46	gold quality
ganglionic eminence	UBERON:0004023	90.41	gold quality
sperm	CL:0000019	90.27	silver quality
mucosa of paranasal sinus	UBERON:0005030	90.27	gold quality
pons	UBERON:0000988	90.21	gold quality
inferior vagus X ganglion	UBERON:0005363	90.20	gold quality
penis	UBERON:0000989	90.13	gold quality
cranial nerve II	UBERON:0000941	90.12	gold quality
pleura	UBERON:0000977	90.06	gold quality
superficial temporal artery	UBERON:0001614	89.97	gold quality
blood vessel layer	UBERON:0004797	89.87	gold quality
lateral globus pallidus	UBERON:0002476	89.75	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	8.51
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

123 targeting RAD1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 49.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 21)

• Rad9, Hus1, and Rad1 heterotrimeric complex chromatin binding is a proximal event in the checkpoint signaling cascade (PMID:12228248)
• RAD1 is a potential intrinsic chaperone in the stabilization of HUS1 for the heterotrimeric (RAD9-RAD1-HUS1) checkpoint complex formation. (PMID:15122316)
• The human Rad9/Rad1/Hus1 complex interacts with and stimulates DNA polymerase beta activity. (PMID:15314187)
• complex with rad9 and hus1 is a damage-specific activator of flap endonuclease 1 (PMID:15556996)
• The long-patch base excision machinery is an important target of the Rad9-Rad1-Hus1 complex, thus enhancing the quality control of DNA. (PMID:15871698)
• PCNA and the Rad9/Rad1/Hus1 complex can independently bind and activate Fen1; acetylation of Fen1 by p300-HAT abolished the stimulatory effect of the complex but not that of PCNA, suggesting a possible mechanism of regulation of this repair pathway (PMID:16216273)
• human DNA ligase I is stimulated by the Rad9-rad1-Hus1 checkpoint complex (PMID:16731526)
• These data provide in vivo evidence that the human 9-1-1 complex participates in DNA repair in addition to its previously described role in DNA damage sensing. (PMID:16814252)
• Human NEIL1 DNA glycosylase activity is significantly stimulated by hRad1 and by the Rad9/Rad1/Hus1 heterotrimer. (PMID:17395641)
• we report successful tri-cistronic cloning, overexpression and purification of a three-protein complex of Rad9, Rad1 and Hus1 using a single hexa-histidine tag. (PMID:17493829)
• Jab1 physically associates with the 9-1-1 complex; this association is mediated through direct interaction between Jab1 and Rad1, one of the subunits of the 9-1-1 complex (PMID:17583730)
• Human thymine DNA glycosylase activity is significantly stimulated by hHus1, hRad1, hRad9 separately, and by the 9-1-1 complex. (PMID:17855402)
• The DNA binding domain (DBD) within the hLigI catalytic fragment interacts with both PCNA and the heterotrimeric cell-cycle checkpoint clamp, hRad9-hRad1-hHus1 (9-1-1). (PMID:19523882)
• The interdomain connecting loops (IDC loop) of hRad9, hHus1, and hRad1 are largely divergent and unique structural features of the 9-1-1 complex that are proposed to contribute to DNA damage recognition. (PMID:19535328)
• Rad9-Rad1-Hus1 complex enhances in vitro activity of 8-oxoguanine DNA glycosylase. (PMID:19615952)
• 9-1-1 complex is a component of the mismatch repair involved in MNNG-induced damage response. (PMID:20188637)
• CK2 plays a crucial role in the ATR-dependent checkpoint pathway through its ability to phosphorylate Ser-341 and Ser-387 of the Rad9 subunit of the Rad9-Hus1-Rad1 complex (PMID:20545769)
• The RAD1 is loaded to damaged sites where it serves as a platform for the selective recruitment of checkpoint and repair proteins. (PMID:21978893)
• Data show models for the ternary PCNA/FEN1/DNA and Rad9-Rad1-Hus1 (9-1-1 complex)/FEN1/DNA assemblies. (PMID:22586102)
• Intramolecular binding of the rad9 C-terminus in the checkpoint clamp Rad9-Hus1-Rad1 is closely linked with its DNA binding. (PMID:26088138)
• Dominant alleles of RAD51, TP53 and XRCC1 combined genotypes indicated a strong protective role against hereditary breast cancer. (PMID:26954070)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rad1	ENSDARG00000040559
mus_musculus	Rad1	ENSMUSG00000022248
rattus_norvegicus	Rad1	ENSRNOG00000018063
drosophila_melanogaster	Rad1	FBGN0026778
caenorhabditis_elegans		WBGENE00003417

Protein

Protein identifiers

Cell cycle checkpoint protein RAD1 — O60671 (reviewed: O60671)

Alternative names: Rad1-like DNA damage checkpoint protein

All UniProt accessions (2): D6R9A1, O60671

UniProt curated annotations — full annotation on UniProt →

Function. Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair. The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex. Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3’-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates. The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase.

Subunit / interactions. Component of the toroidal 9-1-1 (RAD9-RAD1-HUS1) complex, composed of RAD9A, RAD1 and HUS1. The 9-1-1 complex associates with LIG1, POLB, FEN1, RAD17, HDAC1, RPA1 and RPA2. The 9-1-1 complex associates with the RAD17-RFC complex. RAD1 interacts with POLB, FEN1, HUS1, HUS1B, RAD9A and RAD9B. Interacts with DNAJC7. Interacts with RHNO1; interaction is direct.

Subcellular location. Nucleus.

Tissue specificity. Expressed in testis, uterus, bladder, spleen, ovaries, lung, brain and muscle (at protein level).

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the rad1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
O60671-1	1, Hrad1A	yes
O60671-2	2, Hrad1B
O60671-3	3

RefSeq proteins (1): NP_002844* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003011	Cell_cycle_checkpoint_Rad1	Family
IPR003021	Rad1_Rec1_Rad17	Family
IPR046938	DNA_clamp_sf	Homologous_superfamily

Pfam: PF02144

UniProt features (50 total): strand 23, helix 8, mutagenesis site 7, sequence variant 5, splice variant 3, turn 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
8GNN	X-RAY DIFFRACTION	2.12
6J8Y	X-RAY DIFFRACTION	2.4
3A1J	X-RAY DIFFRACTION	2.5
8WU8	X-RAY DIFFRACTION	2.81
3G65	X-RAY DIFFRACTION	2.9
3GGR	X-RAY DIFFRACTION	3.2
7Z6H	ELECTRON MICROSCOPY	3.59

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60671-F1	89.56	0.75

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (7):

Position	Phenotype
155	reduced binding to rhno1; when associated with a-244 and a-254.
226–233	abolishes association of the 9-1-1 complex with rad17.
244	reduced binding to rhno1; when associated with a-155 and a-254.
254	reduced binding to rhno1; when associated with a-155 and a-244.
256	reduced binding to rhno1; when associated with a-64 and a-266.
266	reduced binding to rhno1; when associated with a-64 and a-256.
64	reduced binding to rhno1; when associated with a-256 and a-266.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-176187	Activation of ATR in response to replication stress
R-HSA-5685938	HDR through Single Strand Annealing (SSA)
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-5693616	Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-69473	G2/M DNA damage checkpoint
R-HSA-9709570	Impaired BRCA2 binding to RAD51

MSigDB gene sets: 259 (showing top): PID_FANCONI_PATHWAY, GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_RESPONSE_TO_IONIZING_RADIATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, PID_TELOMERASE_PATHWAY, GOBP_REGULATION_OF_NUCLEAR_DIVISION, KAAB_FAILED_HEART_ATRIUM_DN, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GOBP_REGULATION_OF_MEIOTIC_NUCLEAR_DIVISION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, GEORGES_CELL_CYCLE_MIR192_TARGETS, REACTOME_ACTIVATION_OF_ATR_IN_RESPONSE_TO_REPLICATION_STRESS

GO Biological Process (6): DNA damage checkpoint signaling (GO:0000077), DNA repair (GO:0006281), DNA damage response (GO:0006974), substantia nigra development (GO:0021762), meiotic recombination checkpoint signaling (GO:0051598), cellular response to ionizing radiation (GO:0071479)

GO Molecular Function (3): damaged DNA binding (GO:0003684), protein binding (GO:0005515), double-stranded DNA 3’-5’ DNA exonuclease activity (GO:0008311)

GO Cellular Component (4): nucleoplasm (GO:0005654), chromosome (GO:0005694), checkpoint clamp complex (GO:0030896), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
G2/M Checkpoints	2
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	2
Homologous DNA Pairing and Strand Exchange	1
Regulation of TP53 Activity	1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA integrity checkpoint signaling	1
signal transduction in response to DNA damage	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
midbrain development	1
neural nucleus development	1
meiotic cell cycle checkpoint signaling	1
negative regulation of meiotic nuclear division	1
response to ionizing radiation	1
cellular response to radiation	1
DNA binding	1
binding	1
3’-5’-DNA exonuclease activity	1
double-stranded DNA exodeoxyribonuclease activity	1
nuclear lumen	1
cellular anatomical structure	1
intracellular membraneless organelle	1
condensed nuclear chromosome	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

840 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAD1	RAD51B	O15315	958
RAD1	HUS1	O60921	954
RAD1	RAD9A	Q99638	922
RAD1	SLC20A1	Q8WUM9	826
RAD1	SLC7A1	P30825	712
RAD1	ATP12A	P54707	635
RAD1	TOPBP1	Q92547	590
RAD1	RAD17	O75943	574
RAD1	SLC7A6	Q92536	549
RAD1	RAD51	Q06609	507
RAD1	ATR	Q13535	499
RAD1	ATM	Q13315	467
RAD1	NUCB1	Q02818	447
RAD1	CPNE2	Q96FN4	445
RAD1	CHEK1	O14757	445

IntAct

33 interactions, top by confidence:

A	B	Type	Score
HUS1	RAD1	psi-mi:“MI:0915”(physical association)	0.840
RAD1	HUS1	psi-mi:“MI:0915”(physical association)	0.840
HUS1	RAD1	psi-mi:“MI:0914”(association)	0.840
RAD1	RAD9A	psi-mi:“MI:0915”(physical association)	0.670
RAD9A	RAD1	psi-mi:“MI:0914”(association)	0.670
PRKN	RAD1	psi-mi:“MI:0915”(physical association)	0.560
HUS1	ZBTB14	psi-mi:“MI:0914”(association)	0.530
HUS1B	ZBTB14	psi-mi:“MI:0914”(association)	0.530
HUS1B	RAD1	psi-mi:“MI:0914”(association)	0.530
RAD1	PRMT5	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
RAD1	ZBTB14	psi-mi:“MI:0914”(association)	0.350
RFC4	RAD1	psi-mi:“MI:0914”(association)	0.350
RHNO1	RAD1	psi-mi:“MI:0914”(association)	0.350
SLC27A6	NBAS	psi-mi:“MI:0914”(association)	0.350
TP53BP1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270
BRCA1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (139): RAD1 (Affinity Capture-MS), RAD1 (Affinity Capture-MS), ZBTB14 (Affinity Capture-MS), RAD9A (Affinity Capture-MS), RAD1 (Affinity Capture-MS), ZBTB14 (Affinity Capture-MS), RAD1 (Affinity Capture-MS), RAD9A (Affinity Capture-MS), RAD1 (Affinity Capture-MS), RAD1 (Affinity Capture-Western), RAD1 (Reconstituted Complex), RAD1 (Affinity Capture-Western), RAD1 (Proximity Label-MS), RAD1 (Proximity Label-MS), RAD9A (Affinity Capture-Western)

ESM2 similar proteins: A0A0G2JTR4, A1L1L6, A4IF63, A4II46, A6QNS3, A6QQZ7, D2GXS7, D3ZQG6, F7H9X2, O43929, O54956, O60671, O60921, O82134, O82797, P17070, P22177, P24314, Q00268, Q0VFT9, Q12979, Q2HJF8, Q43124, Q43266, Q5R6Z7, Q5R7X9, Q5SSL4, Q5T2T1, Q5U2Y3, Q6DFV5, Q6NVC5, Q8AVG0, Q8BG51, Q8BQY8, Q8BVD5, Q8IWZ6, Q8IXI2, Q8K2G4, Q8R5L3, Q91W86

Diamond homologs: O60671, Q5R7X9, Q9QWZ1, Q9VQD4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RAD1	up-regulates	TOPBP1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 16 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Impaired BRCA2 binding to RAD51	5	128.6×	1e-08
HDR through Single Strand Annealing (SSA)	5	122.0×	1e-08
Presynaptic phase of homologous DNA pairing and strand exchange	5	113.3×	1e-08
G2/M DNA damage checkpoint	6	60.1×	1e-08
Processing of DNA double-strand break ends	6	57.1×	1e-08
Regulation of TP53 Activity through Phosphorylation	5	49.0×	9e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

61 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	40
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4796452	GRCh38/hg38 5p13.3-11(chr5:30831208-46273389)x3	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1862 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:34908883:C:G	R244P	1.000
5:34908816:A:C	F266L	0.999
5:34908816:A:T	F266L	0.999
5:34908818:A:G	F266L	0.999
5:34908860:A:G	S252P	0.999
5:34908862:A:G	L251P	0.999
5:34908890:A:G	S242P	0.999
5:34908901:G:A	S238F	0.999
5:34908947:A:C	Y223D	0.999
5:34911752:A:G	L123P	0.999
5:34911758:A:G	L121P	0.999
5:34914705:G:T	A63D	0.999
5:34914706:C:G	A63P	0.999
5:34914712:C:G	A61P	0.999
5:34914750:C:T	G48D	0.999
5:34914751:C:G	G48R	0.999
5:34908862:A:C	L251R	0.998
5:34908901:G:T	S238Y	0.998
5:34908913:G:T	A234E	0.998
5:34909352:A:G	S191P	0.998
5:34909354:A:G	L190S	0.998
5:34911590:A:G	L177P	0.998
5:34911647:A:G	L158P	0.998
5:34911724:G:C	C132W	0.998
5:34911726:A:G	C132R	0.998
5:34911797:A:G	L108P	0.998
5:34913501:A:C	C92W	0.998
5:34913503:A:G	C92R	0.998
5:34913511:A:G	L89P	0.998
5:34914701:A:C	F64L	0.998

dbSNP variants (sampled 300 via entrez): RS1000154959 (5:34916318 G>A,C), RS1000450483 (5:34916667 A>C,T), RS1000792447 (5:34905978 G>A), RS1001577269 (5:34916337 G>A), RS1001629751 (5:34916128 G>A), RS1001808508 (5:34914542 C>A,T), RS1001960375 (5:34905396 T>G), RS1002156015 (5:34905826 T>A,C), RS1002256354 (5:34907779 A>T), RS1002514813 (5:34906338 A>G), RS1002583428 (5:34915257 C>A,T), RS1002589734 (5:34906108 C>A,G), RS1002635613 (5:34915057 A>C,T), RS1003075071 (5:34912856 C>T), RS1003431751 (5:34917470 A>G)

Disease associations

OMIM: gene MIM:603153 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003518_4	Daytime sleep phenotypes	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3309116 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

4 potent at pChembl≥5 of 6 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.00	EC50	1000	nM	CHEMBL1162148
5.70	Kd	2000	nM	CHEMBL1162148
5.30	EC50	5000	nM	CHEMBL1271993
5.25	Kd	5600	nM	CHEMBL1567670

PubChem BioAssay actives

4 with measured affinity, of 6 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-isothiocyanato-2-[(E)-2-(4-isothiocyanato-2-sulfophenyl)ethenyl]benzenesulfonic acid	1178404: Inhibition of RAD1 (unknown origin) binding to ssDNA	ec50	1.0000	uM
3-chloro-1-(3,4-dichlorophenyl)-4-morpholin-4-ylpyrrole-2,5-dione	1178404: Inhibition of RAD1 (unknown origin) binding to ssDNA	ec50	5.0000	uM
3-benzyl-2-[(E)-2-pyridin-3-ylethenyl]quinazolin-4-one	1178405: Binding affinity to RAD1 (unknown origin) by surface plasmon resonance method	kd	5.6000	uM

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Doxorubicin	affects reaction, affects expression, affects response to substance, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, decreases expression	2
Cadmium Chloride	decreases expression	2
lasiocarpine	decreases expression, increases metabolic processing	1
triphenyl phosphate	affects expression	1
kojic acid	increases expression	1
riddelliine	decreases expression, increases metabolic processing	1
butyraldehyde	decreases expression	1
quinoline yellow	increases expression	1
ochratoxin A	decreases acetylation, decreases expression	1
M-VAC protocol	increases response to substance	1
cylindrospermopsin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	increases expression, decreases reaction	1
Acetylcysteine	decreases reaction, increases expression	1
Arecoline	decreases expression	1
Cadmium	decreases expression	1
Coumestrol	increases expression	1
Hydrogen Peroxide	decreases expression	1
Piroxicam	decreases expression	1
Plant Extracts	increases expression, affects cotreatment	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Monocrotaline	decreases expression, increases metabolic processing	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3377958	Binding	Inhibition of RAD1 (unknown origin) binding to ssDNA	Targeting the homologous recombination pathway by small molecule modulators. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2D8	Abcam HeLa RAD1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.