RAD17

Summary

RAD17 (RAD17 checkpoint clamp loader component, HGNC:9807) is a protein-coding gene on chromosome 5q13.2, encoding Cell cycle checkpoint protein RAD17 (O75943). Essential for sustained cell growth, maintenance of chromosomal stability, and ATR-dependent checkpoint activation upon DNA damage. It is a common-essential gene (DepMap: required in 93.6% of cancer cell lines).

The protein encoded by this gene is highly similar to the gene product of Schizosaccharomyces pombe rad17, a cell cycle checkpoint gene required for cell cycle arrest and DNA damage repair in response to DNA damage. This protein shares strong similarity with DNA replication factor C (RFC), and can form a complex with RFCs. This protein binds to chromatin prior to DNA damage and is phosphorylated by the checkpoint kinase ATR following damage. This protein recruits the RAD1-RAD9-HUS1 checkpoint protein complex onto chromatin after DNA damage, which may be required for its phosphorylation. The phosphorylation of this protein is required for the DNA-damage-induced cell cycle G2 arrest, and is thought to be a critical early event during checkpoint signaling in DNA-damaged cells. Multiple alternatively spliced transcript variants of this gene, which encode four distinct protein isoforms, have been reported. Two pseudogenes, located on chromosomes 7 and 13, have been identified.

Source: NCBI Gene 5884 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 122 total
• Cancer dependency (DepMap): dependent in 93.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_133338

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9807
Approved symbol	RAD17
Name	RAD17 checkpoint clamp loader component
Location	5q13.2
Locus type	gene with protein product
Status	Approved
Aliases	Rad24, RAD17Sp, CCYC
Ensembl gene	ENSG00000152942
Ensembl biotype	protein_coding
OMIM	603139
Entrez	5884

Gene structure

Transcript identifiers

Ensembl transcripts: 57 — 52 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000282891, ENST00000305138, ENST00000345306, ENST00000354312, ENST00000354868, ENST00000358030, ENST00000361732, ENST00000380774, ENST00000504177, ENST00000506564, ENST00000507927, ENST00000508320, ENST00000509734, ENST00000511349, ENST00000512785, ENST00000513214, ENST00000514066, ENST00000514626, ENST00000521422, ENST00000616683, ENST00000910356, ENST00000910357, ENST00000910358, ENST00000910359, ENST00000910360, ENST00000910361, ENST00000910362, ENST00000910363, ENST00000910364, ENST00000910365, ENST00000910366, ENST00000910367, ENST00000910368, ENST00000910369, ENST00000910370, ENST00000910371, ENST00000910372, ENST00000910373, ENST00000910374, ENST00000910375, ENST00000910376, ENST00000910377, ENST00000910378, ENST00000910379, ENST00000910380, ENST00000926128, ENST00000926129, ENST00000926130, ENST00000926131, ENST00000926132, ENST00000926133, ENST00000957890, ENST00000957891, ENST00000957892, ENST00000957893, ENST00000957894, ENST00000957895

RefSeq mRNA: 9 — MANE Select: NM_133338 NM_001278622, NM_002873, NM_133338, NM_133339, NM_133340, NM_133341, NM_133342, NM_133343, NM_133344

CCDS: CCDS4003, CCDS4004, CCDS4005, CCDS47226

Canonical transcript exons

ENST00000354868 — 19 exons

Exon	Start	End
ENSE00001135115	69410493	69410550
ENSE00001135132	69396397	69396546
ENSE00001135161	69391831	69392013
ENSE00001202242	69369818	69369933
ENSE00001326494	69400049	69400169
ENSE00001341196	69414031	69414801
ENSE00001486218	69372034	69372217
ENSE00001632558	69371035	69371171
ENSE00003471849	69393155	69393240
ENSE00003476173	69386043	69386095
ENSE00003492959	69386396	69386465
ENSE00003528811	69374628	69374711
ENSE00003547671	69386180	69386305
ENSE00003567092	69389034	69389145
ENSE00003569984	69373830	69374087
ENSE00003662952	69393354	69393500
ENSE00003694323	69371454	69371557
ENSE00003789389	69381901	69382057
ENSE00003790977	69384797	69384933

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 94.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.4088 / max 292.7918, expressed in 1808 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56848	19.1035	1808
56849	0.3053	123

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.53	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.47	gold quality
testis	UBERON:0000473	93.84	gold quality
left testis	UBERON:0004533	93.77	gold quality
right testis	UBERON:0004534	93.77	gold quality
islet of Langerhans	UBERON:0000006	91.08	gold quality
colonic epithelium	UBERON:0000397	90.39	gold quality
endometrium	UBERON:0001295	89.39	gold quality
pancreas	UBERON:0001264	88.89	gold quality
tonsil	UBERON:0002372	88.71	gold quality
calcaneal tendon	UBERON:0003701	88.68	gold quality
ganglionic eminence	UBERON:0004023	88.65	gold quality
lymph node	UBERON:0000029	88.54	gold quality
bone marrow cell	CL:0002092	88.50	gold quality
ventricular zone	UBERON:0003053	88.21	gold quality
corpus callosum	UBERON:0002336	88.03	gold quality
body of pancreas	UBERON:0001150	87.88	gold quality
adrenal tissue	UBERON:0018303	87.49	gold quality
rectum	UBERON:0001052	87.09	gold quality
cortical plate	UBERON:0005343	87.01	gold quality
bone marrow	UBERON:0002371	86.79	gold quality
bone element	UBERON:0001474	86.78	gold quality
smooth muscle tissue	UBERON:0001135	86.73	gold quality
pituitary gland	UBERON:0000007	86.15	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.09	gold quality
skeletal muscle tissue	UBERON:0001134	86.07	gold quality
adenohypophysis	UBERON:0002196	86.03	gold quality
granulocyte	CL:0000094	86.00	gold quality
cortex of kidney	UBERON:0001225	85.87	gold quality
vermiform appendix	UBERON:0001154	85.77	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.29
E-MTAB-4850	no	1060.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting RAD17, 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-5688	99.96	73.23	4504
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-4796-3P	99.08	68.38	1681
HSA-MIR-181A-2-3P	98.91	67.60	1168

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 93.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 32)

• The four alternatively spliced forms differentially expressed in different tissues, in different phases of the cell cycle, and differentially responded to X-irradiation. (PMID:11602352)
• upon replication block a Rad17/RF-C complex is recruited to sites of DNA lesions in late S phase, binds the Rad9/Hus1/Rad1 complex and enables it to interact with PCNA. An interaction of Rad17/RF-C with PCNA is mediated by the small RF-C p37 subunit (PMID:12400013)
• Rad17 localizes to DNA replication sites and interacts with DNA polymerase epsilon. (PMID:14500819)
• replication protein A (RPA) stimulates the binding of the Rad17-Rfc2-5 complex to single-stranded DNA (PMID:14605214)
• we show a requirement for Rad17 and Hus1 to induce G(2) arrest as well as Vpr-induced phosphorylation of histone 2A variant X (H2AX) and formation of nuclear foci containing H2AX and breast cancer susceptibility protein 1 (PMID:15485898)
• interacts with newly identified hMCM7 protein, a core component of the DNA replication apparatus (PMID:15538388)
• Findings reveal a phosphorylation-dependent function of Rad17 in an ATR-Rad17-Claspin-Chk1-signaling cascade that responds to specific replication stress. (PMID:16885023)
• Using siRNA to knock down Rad17 demonstrates that it is not essntial for the DNA replication checkpoint in Hela cells. (PMID:16951182)
• Loss of hRAD17 expression occurs frequently in HNSCC, is often due to genomic deletion, and may facilitate genomic instability in HNSCC (PMID:17657792)
• hRAD17 delayed growth of NIH3T3 fibroblasts transformed by the H-ras oncogene in nude mice. (PMID:18378394)
• Proteolysis of Rad17 by Cdh1/APC regulates checkpoint termination and recovery from genotoxic stress (PMID:20424596)
• Rad9, Rad17, TopBP1 and claspin play essential roles in heat-induced activation of ATR kinase and heat tolerance. (PMID:23383325)
• Data indicate that regulation of Rad17 turnover is through the Cdh1/anaphase-promoting complex pathway in breast cancer cells. (PMID:23637229)
• Knockdown of Rad17 with two independent siRNAs significantly reduced Chk1 phosphorylation and substantial RPA32 Ser33 phosphorylation. (PMID:23684611)
• Our data suggest RAD17 as a novel target protein for gemcitabine combination therapy supplementing or complementing inhibition of CHK1. (PMID:23687379)
• Rad17 is phosphorylated by ATM at Thr622 resulting in a direct interaction of Rad17 with NBS1, facilitating recruitment of MRE11, RAD50 and ATM to the DNA double-strand breaks. (PMID:24534091)
• USP20 and Rad17 interact, and that this interaction is enhanced by UV exposure. We show that USP20 regulation of Rad17 is at the protein level in a proteasome-dependent manner. USP20 depletion results in poor activation of Chk1 protein by phosphorylation (PMID:24923443)
• These data suggest that v-Src attenuates ATR-Chk1 signaling through the inhibition of Rad17-Rad9 interaction. (PMID:24971543)
• Authors show that BRCA1 and RAD17 genes, whose derived proteins play a pivotal role in DNA damage repair, are transcriptional targets of gain-of-function mutant p53 proteins. (PMID:25650659)
• These data indicate that the interaction with the 9-1-1 complex is not required for Rad17 protein to be an efficient substrate for the UV-induced phosphorylation. Our data also raise the possibility that the 9-1-1 complex plays a negative regulatory role in the Rad17 phosphorylation. We also show that the nucleotide-binding activity of Rad17 is required for its nuclear localization. (PMID:27387238)
• In a Japanese population, the variant allele of hRAD17 is significantly associated with a decreased risk of Colorectal Cancer among light smokers and rectal cancer patients and with an increased risk of Colorectal Cancer among heavy smokers. (PMID:28238011)
• The Rad17 C-terminal tail is a molecular switch that regulates the 9-1-1 interaction and the ATR pathway. (PMID:28666868)
• Rad17-S667 in the C-terminal tail is constitutively phosphorylated in vivo in a casein kinase 2-dependent manner, and the phosphorylation is important for 9-1-1 interaction (PMID:29902452)
• DDX11 orchestrates jointly with 9-1-1 and its loader, RAD17, DNA damage tolerance at sites of bulky lesions, and endogenous abasic sites. These functions may explain the essential roles of DDX11 and its similarity with 9-1-1 during development. (PMID:30061412)
• The potential G-quadruplex sequence (PQS) of the RAD17 gene promoter was analyzed in different sequence contexts. With two extra nucleotides of the native sequence on either side of the G4, the structure was found to fold into a hybrid-like G4, similar to the hybrid-1 fold that the human telomere sequence can adopt. (PMID:30063821)
• Human Rad17 is constitutively phosphorylated in vivo on a C-terminal threonine, T670. Rad17-T670 is phosphorylated by casein kinase 1delta/epsilon. (PMID:31353086)
• The noncoding function of NELFA mRNA promotes the development of oesophageal squamous cell carcinoma by regulating the Rad17-RFC2-5 complex. (PMID:31845510)
• IQGAP3 interacts with Rad17 to recruit the Mre11-Rad50-Nbs1 complex and contributes to radioresistance in lung cancer. (PMID:32896617)
• Nuclear translocation promotes proteasomal degradation of human Rad17 protein through the N-terminal destruction boxes. (PMID:34174284)
• The Cell Cycle Checkpoint Gene, RAD17 rs1045051, Is Associated with Prostate Cancer Risk. (PMID:34511607)
• The C-terminal tail of Rad17, iVERGE, binds the 9-1-1 complex independently of AAA+ ATPase domains to provide another clamp-loader interface. (PMID:37713925)
• Identification of RAD17 as a candidate cancer predisposition gene in families with histories of pancreatic and breast cancers. (PMID:38872153)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rad17	ENSDARG00000018918
mus_musculus	Rad17	ENSMUSG00000021635
rattus_norvegicus	Rad17	ENSRNOG00000018353
drosophila_melanogaster	Rad17	FBGN0025808
caenorhabditis_elegans		WBGENE00001998

Protein

Protein identifiers

Cell cycle checkpoint protein RAD17 — O75943 (reviewed: O75943)

Alternative names: RF-C/activator 1 homolog

All UniProt accessions (6): O75943, D6RA84, D6RAW6, D6RHU1, H0Y9J8, H0Y9T7

UniProt curated annotations — full annotation on UniProt →

Function. Essential for sustained cell growth, maintenance of chromosomal stability, and ATR-dependent checkpoint activation upon DNA damage. Has a weak ATPase activity required for binding to chromatin. Participates in the recruitment of the 9-1-1 (RAD1-RAD9-HUS1) complex and RHNO1 onto chromatin, and in CHEK1 activation. Involved in homologous recombination by mediating recruitment of the MRN complex to DNA damage sites. May also serve as a sensor of DNA replication progression.

Subunit / interactions. Part of a DNA-binding complex containing RFC2, RFC3, RFC4 and RFC5. Interacts with RAD1 and RAD9 within the 9-1-1 (RAD1-RAD9-HUS1) complex. Interacts with RAD9B, POLE, SNU13 and MCM7. DNA damage promotes interaction with ATR or ATM and disrupts interaction with the 9-1-1 (RAD1-RAD9-HUS1) complex. Interacts (when phosphorylated) with NBN; promoting recruitment of the MRN complex to DNA damage sites.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Overexpressed in various cancer cell lines and in colon carcinoma (at protein level). Isoform 2 and isoform 3 are the most abundant isoforms in non irradiated cells (at protein level). Ubiquitous at low levels. Highly expressed in testis, where it is expressed within the germinal epithelium of the seminiferous tubuli. Weakly expressed in seminomas (testicular tumors).

Post-translational modifications. Phosphorylation on Ser-646 and Ser-656 is cell cycle-regulated, enhanced by genotoxic stress, and required for activation of checkpoint signaling. Phosphorylation is mediated by ATR upon UV or replication arrest, whereas it may be mediated both by ATR and ATM upon ionizing radiation. Phosphorylation on both sites is required for interaction with RAD1 but dispensable for interaction with RFC3 or RFC4. Phosphorylation at Thr-633 by ATM in response to DNA damage promotes interaction with NBN and recruitment of the MRN complex to DNA damage sites.

Induction. Induced by X-ray irradiation. Induced by X-ray irradiation. Induced by X-ray irradiation.

Similarity. Belongs to the rad17/RAD24 family.

Isoforms (4)

UniProt ID	Names	Canonical?
O75943-1	1, Rad17Sp, FM2	yes
O75943-2	2, Rad17Sp2, FM1
O75943-3	3, FM3
O75943-4	4, FM4

RefSeq proteins (9): NP_001265551, NP_002864, NP_579916, NP_579917, NP_579918, NP_579919, NP_579920, NP_579921, NP_579922 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004582	Checkpoint_prot_Rad17_Rad24	Family
IPR018324	Rad17/Rad24_fun/met	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF03215

Enzyme classification (BRENDA):

• EC 3.6.4.B8 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (41 total): mutagenesis site 9, sequence conflict 8, modified residue 7, region of interest 4, splice variant 4, sequence variant 4, compositionally biased region 2, chain 1, short sequence motif 1, binding site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8GNN	X-RAY DIFFRACTION	2.12
7Z6H	ELECTRON MICROSCOPY	3.59

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75943-F1	69.51	0.37

Functional residue map

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

Ligand- & substrate-binding residues (1): 137–144

Post-translational modifications (7): 71, 86, 359, 633, 646, 656, 55

Mutagenesis-validated functional residues (9):

Position	Phenotype
18–23	strongly reduced interaction with rad1.
143	impairs phosphorylation on s-656. abolishes interaction with the rad1-rad9-hus1 complex; does not affect interaction wit
143	impairs phosphorylation. impairs interaction with dna and the rad1-rad9-hus1 complex; does not affect interaction with r
191	no effect on phosphorylation by atr.
633	impaired phosphorylation by atm and interaction with nbn.
646	reduces by 50% phosphorylation by atr, and abolishes interaction with rad1. abolishes phosphorylation by atr and checkpo
646	abolishes interaction with rad1; when associated with d-656.
656	reduces by 50% phosphorylation by atr, and abolishes interaction with rad1. abolishes phosphorylation by atr and checkpo
656	abolishes interaction with rad1; when associated with d-646.

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: 242 (showing top): PID_FANCONI_PATHWAY, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, CGGAARNGGCNG_UNKNOWN, GOBP_CELL_CYCLE_PHASE_TRANSITION, REACTOME_ACTIVATION_OF_ATR_IN_RESPONSE_TO_REPLICATION_STRESS, KAUFFMANN_DNA_REPAIR_GENES, GOBP_MITOTIC_G2_M_TRANSITION_CHECKPOINT, GOBP_MITOTIC_INTRA_S_DNA_DAMAGE_CHECKPOINT_SIGNALING, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GTGCCTT_MIR506, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, JIANG_TIP30_TARGETS_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_PROTEIN_LOCALIZATION_TO_CHROMOSOME

GO Biological Process (10): DNA replication checkpoint signaling (GO:0000076), DNA damage checkpoint signaling (GO:0000077), DNA repair (GO:0006281), DNA damage response (GO:0006974), negative regulation of DNA replication (GO:0008156), mitotic intra-S DNA damage checkpoint signaling (GO:0031573), mitotic DNA replication checkpoint signaling (GO:0033314), regulation of phosphorylation (GO:0042325), protein localization to site of double-strand break (GO:1990166), chromatin organization (GO:0006325)

GO Molecular Function (6): chromatin binding (GO:0003682), DNA clamp loader activity (GO:0003689), ATP binding (GO:0005524), chromatin-protein adaptor activity (GO:0140463), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), Rad17 RFC-like complex (GO:0031389), site of double-strand break (GO:0035861), chromosome, telomeric region (GO:0000781), chromosome (GO:0005694)

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	2
binding	2
nuclear lumen	2
intracellular membraneless organelle	2
signal transduction in response to DNA damage	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
DNA replication	1
regulation of DNA replication	1
negative regulation of DNA metabolic process	1
mitotic S phase	1
mitotic DNA damage checkpoint signaling	1
DNA replication checkpoint signaling	1
mitotic cell cycle	1
mitotic DNA integrity checkpoint signaling	1
mitotic G2/M transition checkpoint	1
phosphorylation	1
regulation of metabolic process	1
protein localization to chromosome	1
cellular component organization	1
DNA binding	1
ATP-dependent activity, acting on DNA	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
chromatin binding	1
chromatin organization	1
protein-macromolecule adaptor activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
chromosome	1
protein-containing complex	1
site of DNA damage	1
chromosomal region	1

Protein interactions and networks

STRING

2412 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAD17	RFC2	P32846	998
RAD17	RAD9A	Q99638	997
RAD17	HUS1	O60921	993
RAD17	RFC5	P40937	961
RAD17	CHEK1	O14757	955
RAD17	ATRIP	Q8WXE1	950
RAD17	TOPBP1	Q92547	939
RAD17	CLSPN	Q9HAW4	929
RAD17	CHTF18	Q8WVB6	924
RAD17	ATR	Q13535	918
RAD17	ATAD5	Q96QE3	914
RAD17	ATM	Q13315	912
RAD17	SMC5	Q8IY18	858
RAD17	RAD9B	Q6WBX8	834
RAD17	HUS1B	Q8NHY5	817

IntAct

76 interactions, top by confidence:

A	B	Type	Score
HUS1	RAD1	psi-mi:“MI:0914”(association)	0.840
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
RAD17	RFC4	psi-mi:“MI:0914”(association)	0.730
RFC5	RAD17	psi-mi:“MI:0914”(association)	0.730
RFC4	RAD17	psi-mi:“MI:0914”(association)	0.730
RAD9A	RAD1	psi-mi:“MI:0914”(association)	0.670
NBN	RAD17	psi-mi:“MI:0915”(physical association)	0.630
RAD17	NBN	psi-mi:“MI:0914”(association)	0.630
RAD17	NBN	psi-mi:“MI:0915”(physical association)	0.630
NBN	RAD17	psi-mi:“MI:0407”(direct interaction)	0.630
RAD9A	RAD17	psi-mi:“MI:0915”(physical association)	0.560
CBX6	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
HUS1	ZBTB14	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
ASB6	POLR2D	psi-mi:“MI:0914”(association)	0.530
RAD17	MRE11	psi-mi:“MI:0915”(physical association)	0.500
RAD50	RAD17	psi-mi:“MI:0915”(physical association)	0.500
RAD17	RAD17	psi-mi:“MI:0915”(physical association)	0.400
FZR1	RAD17	psi-mi:“MI:0915”(physical association)	0.400
RAD17	FZR1	psi-mi:“MI:0915”(physical association)	0.400
PRMT6	RAD17	psi-mi:“MI:0915”(physical association)	0.370
USP20		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (173): RAD17 (Affinity Capture-MS), RAD17 (Affinity Capture-MS), RFC4 (Affinity Capture-MS), RAD17 (Affinity Capture-MS), RAD17 (Affinity Capture-MS), RFC3 (Affinity Capture-MS), RFC2 (Affinity Capture-MS), RAD17 (Synthetic Lethality), RAD17 (Synthetic Lethality), RAD17 (Synthetic Lethality), RAD17 (Synthetic Lethality), RAD17 (Synthetic Lethality), RAD17 (Protein-peptide), RAD17 (Protein-peptide), RAD17 (Protein-peptide)

ESM2 similar proteins: A4PCD4, A5PKL6, A6QPR9, E1BVR9, F1ND48, O02789, O75943, O94952, P04053, P06526, P09838, P36195, P42118, Q0P4D6, Q0VCL9, Q15061, Q32PJ3, Q3TTL0, Q3U3W5, Q498D5, Q4KM51, Q4R180, Q4R3W5, Q4R6Y8, Q4R7Q1, Q502W6, Q5DJU3, Q5JPI3, Q5R5S1, Q5R652, Q5RL51, Q5SSK3, Q5T8I9, Q66H33, Q6AYF5, Q6DC53, Q6RI63, Q6ZQL4, Q7L8L6, Q8BSE0

Diamond homologs: A0B6D7, A1RSA2, A1RSA3, A1RV38, A1RWU6, A1RWU7, A2BL93, A2SQR6, A2SQT3, A3DNV8, A3DNV9, A3MS27, A4FZL6, A4WGV3, A4WLY0, A4X5X3, A5UMF4, A6TSZ1, A6URV8, A6UWR5, A6VIW1, A7I781, A8AC24, A9A6N2, B0R601, B1YC69, B9LPV1, C3MQ13, C3MVD2, C3N5N1, C3NE95, C3NHF4, C4KHA7, C5A6P8, O22993, O26342, O26343, O29072, O57852, O57853

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ATR	“up-regulates activity”	RAD17	phosphorylation
ATM	unknown	RAD17	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 88 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	8	50.4×	7e-10
HDR through Single Strand Annealing (SSA)	8	47.8×	7e-10
Presynaptic phase of homologous DNA pairing and strand exchange	8	44.4×	8e-10
Activation of ATR in response to replication stress	5	30.7×	3e-05
G2/M DNA damage checkpoint	8	19.6×	5e-07
HDR through Homologous Recombination (HRR)	5	19.4×	2e-04
Regulation of TP53 Activity through Phosphorylation	8	19.2×	5e-07
Processing of DNA double-strand break ends	8	18.6×	6e-07

GO biological processes:

GO term	Partners	Fold	FDR
telomere maintenance	5	17.1×	8e-04
double-strand break repair via homologous recombination	6	12.0×	8e-04
DNA repair	9	7.4×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	92
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2635 predictions. Top by Δscore:

Variant	Effect	Δscore
5:69369934:G:GG	donor_gain	1.0000
5:69370133:GAT:G	donor_gain	1.0000
5:69371063:T:TA	acceptor_gain	1.0000
5:69371064:G:A	acceptor_gain	1.0000
5:69373987:G:GT	donor_gain	1.0000
5:69373988:A:T	donor_gain	1.0000
5:69374626:A:AG	acceptor_gain	1.0000
5:69374627:G:GG	acceptor_gain	1.0000
5:69374627:GC:G	acceptor_gain	1.0000
5:69374627:GCAT:G	acceptor_gain	1.0000
5:69374707:AACAG:A	donor_loss	1.0000
5:69374708:ACAG:A	donor_loss	1.0000
5:69374709:CAG:C	donor_loss	1.0000
5:69374710:AGGTA:A	donor_loss	1.0000
5:69374711:GGTA:G	donor_loss	1.0000
5:69374712:G:A	donor_loss	1.0000
5:69374713:T:G	donor_loss	1.0000
5:69384934:G:GG	donor_gain	1.0000
5:69386038:AATAG:A	acceptor_gain	1.0000
5:69386179:GGAA:G	acceptor_gain	1.0000
5:69386306:G:GA	donor_loss	1.0000
5:69386306:G:GG	donor_gain	1.0000
5:69386307:T:A	donor_loss	1.0000
5:69386386:T:G	acceptor_gain	1.0000
5:69386387:A:AG	acceptor_gain	1.0000
5:69386388:A:G	acceptor_gain	1.0000
5:69386394:A:AG	acceptor_gain	1.0000
5:69386395:G:GG	acceptor_gain	1.0000
5:69386395:GTTTC:G	acceptor_gain	1.0000
5:69386462:CAAGG:C	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000015360 (5:69383227 T>C), RS1000149149 (5:69409518 A>T), RS1000188011 (5:69393503 A>G), RS1000264601 (5:69401218 A>C,G), RS1000302053 (5:69402681 G>A), RS1000392917 (5:69381436 A>G), RS1000446583 (5:69381280 A>G), RS1000536126 (5:69400537 T>A), RS1000599110 (5:69389017 T>A), RS1000665468 (5:69387512 A>G), RS1000737086 (5:69375642 A>C), RS1000793205 (5:69395032 A>G), RS1000831641 (5:69370747 G>T), RS1000842332 (5:69415030 T>C), RS1000946350 (5:69408538 G>A,T)

Disease associations

OMIM: gene MIM:603139 | 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
GCST008062_36	Blood urea nitrogen levels	5.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, affects cotreatment, decreases expression, increases abundance	3
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	2
Acrolein	decreases expression, increases oxidation, increases abundance, affects cotreatment	2
Ozone	increases oxidation, increases abundance, affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tretinoin	increases expression, decreases expression, affects cotreatment	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
bisphenol F	affects cotreatment, decreases methylation	1
pradimicin-IRD	affects expression, affects response to substance	1
dicrotophos	decreases expression	1
lasiocarpine	decreases expression, increases metabolic processing	1
oxybenzone	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
lead acetate	affects cotreatment, decreases expression	1
Nonidet P-40	increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
potassium chromate(VI)	decreases expression	1
chromium hexavalent ion	affects reaction, increases phosphorylation, increases reaction	1
K 7174	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
bisphenol S	increases methylation	1
riccardin D	increases expression	1
BO-1051	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Decitabine	decreases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression, affects cotreatment	1
Arsenic Trioxide	increases expression	1

Clinical trials (associated diseases)

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