RAD9A

Summary

RAD9A (RAD9 checkpoint clamp component A, HGNC:9827) is a protein-coding gene on chromosome 11q13.2, encoding Cell cycle checkpoint control protein RAD9A (Q99638). 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: 86.0% of cell lines).

This gene product is highly similar to Schizosaccharomyces pombe rad9, a cell cycle checkpoint protein required for cell cycle arrest and DNA damage repair. This protein possesses 3’ to 5’ exonuclease activity, which may contribute to its role in sensing and repairing DNA damage. It forms a checkpoint protein complex with RAD1 and HUS1. This complex is recruited by checkpoint protein RAD17 to the sites of DNA damage, which is thought to be important for triggering the checkpoint-signaling cascade. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5883 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 66 total
• Cancer dependency (DepMap): dependent in 86.0% of screened cell lines
• MANE Select transcript: NM_004584

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9827
Approved symbol	RAD9A
Name	RAD9 checkpoint clamp component A
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000172613
Ensembl biotype	protein_coding
OMIM	603761
Entrez	5883

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 5 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000307980, ENST00000529100, ENST00000530934, ENST00000535644, ENST00000538013, ENST00000541132, ENST00000542139, ENST00000543808, ENST00000544620, ENST00000621995, ENST00000622583, ENST00000896645, ENST00000896646

RefSeq mRNA: 2 — MANE Select: NM_004584 NM_001243224, NM_004584

CCDS: CCDS8159

Canonical transcript exons

ENST00000307980 — 11 exons

Exon	Start	End
ENSE00001213590	67391986	67392078
ENSE00001337384	67397464	67398410
ENSE00003465447	67395716	67395825
ENSE00003483129	67395912	67396021
ENSE00003525058	67392654	67392782
ENSE00003558686	67393691	67393790
ENSE00003574680	67392161	67392231
ENSE00003612834	67393496	67393610
ENSE00003663264	67397179	67397386
ENSE00003685093	67396263	67396400
ENSE00003689755	67396111	67396175

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 96.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.2356 / max 382.5812, expressed in 1776 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115444	6.9039	1603
115438	4.7750	1485
115439	0.5187	269
115443	0.0380	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	96.55	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.74	gold quality
granulocyte	CL:0000094	93.67	gold quality
mucosa of transverse colon	UBERON:0004991	92.04	gold quality
right lobe of thyroid gland	UBERON:0001119	91.41	gold quality
adenohypophysis	UBERON:0002196	91.28	gold quality
left lobe of thyroid gland	UBERON:0001120	90.91	gold quality
minor salivary gland	UBERON:0001830	90.77	gold quality
skin of leg	UBERON:0001511	90.75	gold quality
metanephros cortex	UBERON:0010533	90.66	gold quality
endocervix	UBERON:0000458	90.43	gold quality
skin of abdomen	UBERON:0001416	90.20	gold quality
pituitary gland	UBERON:0000007	90.11	gold quality
transverse colon	UBERON:0001157	89.98	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.73	gold quality
lower esophagus mucosa	UBERON:0035834	89.59	gold quality
right testis	UBERON:0004534	89.29	gold quality
left testis	UBERON:0004533	89.28	gold quality
thyroid gland	UBERON:0002046	89.22	gold quality
body of pancreas	UBERON:0001150	89.01	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.00	gold quality
spleen	UBERON:0002106	88.87	gold quality
body of uterus	UBERON:0009853	88.86	gold quality
right lobe of liver	UBERON:0001114	88.69	gold quality
esophagus mucosa	UBERON:0002469	88.62	gold quality
right ovary	UBERON:0002118	88.54	gold quality
apex of heart	UBERON:0002098	88.43	gold quality
body of stomach	UBERON:0001161	88.40	gold quality
ectocervix	UBERON:0012249	88.36	gold quality
left ovary	UBERON:0002119	88.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, YBX1

miRNA regulators (miRDB)

60 targeting RAD9A, 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-6133	100.00	66.48	2064
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-4505	99.27	67.81	2678

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 86.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• These findings indicate that Rad9 is regulated by a c-Abl-dependent mechanism in the apoptotic response to genotoxic stress. (c-abl protein) (PMID:11971963)
• role of C-terminal region in nuclear transport of the hRad9 checkpoint complex (PMID:11994305)
• Rad9, Hus1, and Rad1 heterotrimeric complex chromatin binding is a proximal event in the checkpoint signaling cascade (PMID:12228248)
• Protein kinase C-delta is responsible for constitutive and DNA damage-induced phosphorylation of this protein. (PMID:12628935)
• the Rad9 phospho-tail is a key participant in the transduction of downstream checkpoint signals (PMID:12709442)
• Characterization of nonphosphorylatable mutants has revealed that Rad9 phosphorylation plays a critical role in checkpoint signaling. (PMID:12734188)
• hRad9/hHus1/hRad1 complex acts as a checkpoint sensor during S phase by rapidly localizing to sites of DNA damage and transducing checkpoint responses by facilitating proper localization of downstream checkpoint proteins, including TopBP1. (PMID:12941802)
• HRAD9 and Mrad9 are part of a gene family and reveal a new genetic element encoding a product that interacts with multiple, known cell cycle checkpoint control proteins. (PMID:14500360)
• Data report the identification of Rad9, a key member of the checkpoint Rad protein family, as a coregulator to suppress androgen-androgen receptor transactivation in prostate cancer cells. (PMID:14966297)
• results suggest that the predominant role of Rad9 in embryonic stem cells is to promote survival after replicative stress and topoisomerase-mediated DNA damage (PMID:14988409)
• The human Rad9/Rad1/Hus1 complex interacts with and stimulates DNA polymerase beta activity. (PMID:15314187)
• Rad9 stimulates the carbamoyl phosphate synthetase activity of the multifunctional protein CAD. (PMID:15326225)
• complex with rad1 and hus1 is a damage-specific activator of flap endonuclease 1 (PMID:15556996)
• Rad9 expression may play an important role in cell cycle control in NSCLC cells and may influence NSCLC cell phenotype (PMID:15558813)
• Rad9 plays critical role in the activation of S-phase checkpoint and the maintenance of chromosome stability. (PMID:15773892)
• 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)
• The encoded mammalian proteins participate in promoting resistance to DNA damage, cell cycle checkpoint control, DNA repair, and apoptosis. (PMID:16365875)
• role for Rad9 in telomere stability and homologous recombinational repair as a mechanism for promoting cell survival after ionizing radiation exposure (PMID:16479004)
• 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 hRad9 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)
• Rad9 modulates the P21WAF1 pathway by direct association with p53. (PMID:17511890)
• Rad9 expression correlated closely to significance only with the apoptotic and mitotic indices in epithelial ovarian tumors (PMID:18156970)
• elements found in the aquaporin-5 and the Rad9 (radiation-sensitive 9) genes showed selective AR versus GR binding in band-shift assays and a strong activity and selectivity in functional assays, both as isolated elements and in their original contexts (PMID:18215141)
• Rad9 levels are high in prostate cancer cells due at least in part to aberrant methylation or gene amplification (PMID:18316588)
• up-regulated in breast cancer; mRNA up-regulation correlates with tumor size and local recurrenc;hyperphosphorylated forms of the protein inthe nucleus of the cancer cells (PMID:18616832)
• Disruption of the Rad9-MLH1 interaction by a single-point mutation in Rad9 leads to significantly reduced DNA mismatch repair activity. (PMID:18842633)
• Data show that the basic cleft of the RPA70 N-terminal OB-fold domain binds multiple checkpoint proteins, including RAD9, to promote ATR signaling. (PMID:18936170)
• Rad9 foci were predominately formed in G1 and S phase after UV light, while treatment of cells with ionizing radiation (IR) resulted in accumulation of Rad9 into foci in S and G2. (PMID:19411845)
• 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)
• Rad9A-mediated Claspin localization is a vital step during checkpoint activation. (PMID:20081369)
• 9-1-1 complex is a component of the mismatch repair involved in MNNG-induced damage response. (PMID:20188637)
• results emphasize the importance of Rad9A in preserving genomic integrity in the presence of catenated chromosomes and all types of DNA aberrations (PMID:20305300)
• When over-expressed in HeLa cells, a mutant Rad9 harboring phospho-deficient substitutions at both Ser-341 and Ser-387 residues causes hypersensitivity to UV and methyl methane sulfonate. (PMID:20545769)
• Data indicate that association of RAD18 with DSBs through ubiquitylated H2A and other ubiquitylated chromatin components allows recruitment of RAD9. (PMID:21858012)
• The RAD9 is loaded to damaged sites where it serves as a platform for the selective recruitment of checkpoint and repair proteins. (PMID:21978893)
• Modulation of RAD9A and other cell cycle arrest and DNA repair proteins contribute to the risk of developing a second malignancy in childhood cancer patients. (PMID:21991345)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rad9a	ENSDARG00000056984
mus_musculus	Rad9a	ENSMUSG00000024824
rattus_norvegicus	Rad9a	ENSRNOG00000018729
drosophila_melanogaster	Rad9	FBGN0025807
caenorhabditis_elegans		WBGENE00001997

Paralogs (1): RAD9B (ENSG00000151164)

Protein

Protein identifiers

Cell cycle checkpoint control protein RAD9A — Q99638 (reviewed: Q99638)

Alternative names: DNA repair exonuclease rad9 homolog A

All UniProt accessions (5): Q99638, A0A0G2JMD0, F5H492, F5H4F1, F5H8A2

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. RAD9A possesses 3’->5’ double stranded DNA exonuclease activity.

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. RAD9A interacts with BCL2L1, FEN1, RAD9B, ABL1, RPA1, ATAD5 and RPA2. Interacts with DNAJC7. Interacts (when phosphorylated) with TOPBP1.

Subcellular location. Nucleus.

Post-translational modifications. Constitutively phosphorylated on serine and threonine amino acids in absence of DNA damage. Hyperphosphorylated by PRKCD and ABL1 upon DNA damage. Its phosphorylation by PRKCD may be required for the formation of the 9-1-1 complex. Phosphorylated at Ser-341 and Ser-387 by CK2, promoting interaction with TOPBP1.

Similarity. Belongs to the rad9 family.

RefSeq proteins (2): NP_001230153, NP_004575* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007268	Rad9/Ddc1	Family
IPR026584	Rad9	Family
IPR046938	DNA_clamp_sf	Homologous_superfamily

Pfam: PF04139

UniProt features (67 total): strand 25, mutagenesis site 10, helix 10, modified residue 8, sequence variant 5, region of interest 4, sequence conflict 2, chain 1, compositionally biased region 1, turn 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
8JZY	X-RAY DIFFRACTION	1.5
8GNN	X-RAY DIFFRACTION	2.12
6HM5	X-RAY DIFFRACTION	2.33
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-Q99638-F1	76.52	0.60

Functional residue map

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

Post-translational modifications (8): 341, 375, 380, 387, 28, 272, 277, 328

Mutagenesis-validated functional residues (10):

Position	Phenotype
28	abolishes phosphorylation by abl1.
272	complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with a-277; a-328; a
277	complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with a-272; a-328; a
328	complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with a-272; a-277; a
341	complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with a-272; a-277; a
341	mimics phosphorylation, leading to weak but significant interaction with topbp1; when associated with e-387.
375	complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with a-272; a-277; a
380	complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with a-272; a-277; a
387	complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with a-272; a-277; a
387	mimics phosphorylation, leading to weak but significant interaction with topbp1; when associated with e-341.

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: 225 (showing top): PID_FANCONI_PATHWAY, GOBP_RESPONSE_TO_IONIZING_RADIATION, PID_TELOMERASE_PATHWAY, GOMF_NUCLEASE_ACTIVITY, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, REACTOME_ACTIVATION_OF_ATR_IN_RESPONSE_TO_REPLICATION_STRESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, KAUFFMANN_DNA_REPAIR_GENES, chr11q13, MODULE_70, EFC_Q6, GOBP_MITOTIC_INTRA_S_DNA_DAMAGE_CHECKPOINT_SIGNALING

GO Biological Process (8): DNA replication checkpoint signaling (GO:0000076), DNA damage checkpoint signaling (GO:0000077), DNA repair (GO:0006281), DNA damage response (GO:0006974), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), mitotic intra-S DNA damage checkpoint signaling (GO:0031573), cellular response to ionizing radiation (GO:0071479), positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage (GO:1902231)

GO Molecular Function (11): 3’-5’-DNA exonuclease activity (GO:0008296), double-stranded DNA 3’-5’ DNA exonuclease activity (GO:0008311), SH3 domain binding (GO:0017124), enzyme binding (GO:0019899), protein kinase binding (GO:0019901), histone deacetylase binding (GO:0042826), nuclease activity (GO:0004518), exonuclease activity (GO:0004527), protein binding (GO:0005515), 3’-5’ exonuclease activity (GO:0008408), hydrolase activity (GO:0016787)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), checkpoint clamp complex (GO:0030896)

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
DNA damage response	2
cellular anatomical structure	2
signal transduction in response to DNA damage	1
DNA metabolic process	1
cellular response to stress	1
intrinsic apoptotic signaling pathway	1
mitotic S phase	1
mitotic DNA damage checkpoint signaling	1
response to ionizing radiation	1
cellular response to radiation	1
intrinsic apoptotic signaling pathway in response to DNA damage	1
regulation of intrinsic apoptotic signaling pathway in response to DNA damage	1
positive regulation of intrinsic apoptotic signaling pathway	1
3’-5’ exonuclease activity	1
DNA exonuclease activity, producing 5’-phosphomonoesters	1
3’-5’-DNA exonuclease activity	1
double-stranded DNA exodeoxyribonuclease activity	1
protein domain specific binding	1
protein binding	1
kinase binding	1
enzyme binding	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
hydrolase activity, acting on ester bonds	1
binding	1
exonuclease activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
condensed nuclear chromosome	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

1384 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAD9A	HUS1	O60921	999
RAD9A	RAD17	O75943	997
RAD9A	TOPBP1	Q92547	996
RAD9A	ATRIP	Q8WXE1	986
RAD9A	CHEK2	O96017	974
RAD9A	CLSPN	Q9HAW4	957
RAD9A	HUS1B	Q8NHY5	931
RAD9A	CHEK1	O14757	930
RAD9A	RAD1	O60671	922
RAD9A	ATR	Q13535	922
RAD9A	RPA1	P27694	899
RAD9A	MDC1	Q14676	898
RAD9A	MUTYH	Q9UIF7	891
RAD9A	RAD51	Q06609	889
RAD9A	H3-3A	P06351	870
RAD9A	H3C1	P02295	870

IntAct

36 interactions, top by confidence:

A	B	Type	Score
HUS1	RAD9A	psi-mi:“MI:0915”(physical association)	0.930
RAD9A	HUS1	psi-mi:“MI:0915”(physical association)	0.930
HUS1	RAD1	psi-mi:“MI:0915”(physical association)	0.840
HUS1	RAD1	psi-mi:“MI:0914”(association)	0.840
RFC5	RAD17	psi-mi:“MI:0914”(association)	0.730
RAD1	RAD9A	psi-mi:“MI:0915”(physical association)	0.670
RAD9A	RAD1	psi-mi:“MI:0914”(association)	0.670
RAD9A	RAD17	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
TOPBP1	RAD9A	psi-mi:“MI:0915”(physical association)	0.400
RAD9A	RAD17	psi-mi:“MI:0915”(physical association)	0.400
CLSPN	RAD9A	psi-mi:“MI:0915”(physical association)	0.400
SF3B3	RAD9A	psi-mi:“MI:0915”(physical association)	0.370
RAD1	ZBTB14	psi-mi:“MI:0914”(association)	0.350
KLK2	VWA8	psi-mi:“MI:0914”(association)	0.350
TP53BP1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (205): RAD9A (Affinity Capture-Western), RAD9A (Affinity Capture-MS), RAD9A (Affinity Capture-MS), RAD9A (Affinity Capture-MS), RAD9A (Affinity Capture-Western), RAD9A (Affinity Capture-MS), RAD9A (Affinity Capture-MS), RAD9A (Affinity Capture-MS), RAD9A (Affinity Capture-MS), RAD9A (Affinity Capture-MS), RAD9A (Affinity Capture-MS), RAD9A (Affinity Capture-MS), RAD9A (Affinity Capture-RNA), AR (Two-hybrid), RAD9A (Reconstituted Complex)

ESM2 similar proteins: A0A140LI67, A0A8I6ASZ5, A4QNA8, A7E316, A9JTG5, D2H8V8, D2HHP1, E1BTE1, E6ZIJ1, O54714, O57473, O70260, O89033, P39428, P47817, Q13077, Q14B46, Q3B7D9, Q499V3, Q4R5X9, Q4V832, Q5E9X8, Q5RHI5, Q5VV41, Q5XGX5, Q5XIZ9, Q66JT0, Q68DX3, Q6DFE0, Q6NXW6, Q6P5E6, Q6P9P8, Q6PFE3, Q6WBX7, Q6WBX8, Q8BGE5, Q8BJW7, Q8BMI4, Q8K572, Q99638

Diamond homologs: O96533, Q4R5X9, Q99638, Q9Z0F6, Q499V3, Q5E9X8, Q6WBX7, Q6WBX8

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
CDK1	“up-regulates activity”	RAD9A	phosphorylation
ATM	“up-regulates activity”	RAD9A	phosphorylation
RAD9A	up-regulates	TOPBP1	binding
TLK1	up-regulates	RAD9A	phosphorylation
CDK2	unknown	RAD9A	phosphorylation
TLK1	unknown	RAD9A	phosphorylation
CyclinA2/CDK2	unknown	RAD9A	phosphorylation
ABL1	“up-regulates activity”	RAD9A	phosphorylation
CHEK1	“up-regulates activity”	RAD9A	phosphorylation
ABL1	up-regulates	RAD9A	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 15 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	6	168.3×	3e-11
HDR through Single Strand Annealing (SSA)	6	159.7×	3e-11
Presynaptic phase of homologous DNA pairing and strand exchange	6	148.3×	3e-11
Activation of ATR in response to replication stress	5	136.6×	3e-09
Processing of DNA double-strand break ends	8	83.0×	7e-13
G2/M DNA damage checkpoint	7	76.5×	3e-11
Regulation of TP53 Activity through Phosphorylation	6	64.2×	3e-09

GO biological processes:

GO term	Partners	Fold	FDR
DNA damage checkpoint signaling	6	168.0×	3e-11
double-strand break repair via homologous recombination	6	66.9×	7e-09
DNA repair	7	31.9×	2e-08
DNA damage response	6	22.9×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3565 predictions. Top by Δscore:

Variant	Effect	Δscore
11:67352890:T:A	donor_gain	1.0000
11:67353306:G:C	donor_gain	1.0000
11:67353348:C:A	donor_gain	1.0000
11:67367458:A:AC	donor_gain	1.0000
11:67367459:C:CC	donor_gain	1.0000
11:67392077:GG:G	donor_gain	1.0000
11:67392078:GG:G	donor_gain	1.0000
11:67392078:GGT:G	donor_loss	1.0000
11:67392079:G:GG	donor_gain	1.0000
11:67392080:TGAG:T	donor_loss	1.0000
11:67392081:GAGT:G	donor_loss	1.0000
11:67392226:G:GT	donor_gain	1.0000
11:67392229:GGG:G	donor_gain	1.0000
11:67392230:GGG:G	donor_gain	1.0000
11:67392646:T:TA	acceptor_gain	1.0000
11:67393491:TGCA:T	acceptor_loss	1.0000
11:67393493:CAG:C	acceptor_loss	1.0000
11:67393494:A:AC	acceptor_loss	1.0000
11:67393494:A:AG	acceptor_gain	1.0000
11:67393495:G:GT	acceptor_gain	1.0000
11:67393495:GT:G	acceptor_gain	1.0000
11:67393495:GTC:G	acceptor_gain	1.0000
11:67393495:GTCT:G	acceptor_gain	1.0000
11:67393495:GTCTT:G	acceptor_gain	1.0000
11:67393514:C:CA	acceptor_gain	1.0000
11:67393519:A:AG	acceptor_gain	1.0000
11:67393519:ACT:A	acceptor_gain	1.0000
11:67393521:T:TA	acceptor_gain	1.0000
11:67393522:G:A	acceptor_gain	1.0000
11:67393524:C:CA	acceptor_gain	1.0000

AlphaMissense

2544 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:67392176:T:A	V17D	0.995
11:67396310:T:A	V261D	0.995
11:67392196:G:T	G24W	0.994
11:67392197:G:A	G24E	0.994
11:67392197:G:T	G24V	0.994
11:67392688:C:A	A47D	0.994
11:67393550:T:C	C97R	0.994
11:67392167:G:A	G14D	0.993
11:67392661:T:C	L38P	0.993
11:67392694:C:A	A49D	0.993
11:67393590:T:A	V110D	0.993
11:67392191:G:C	R22P	0.992
11:67392196:G:A	G24R	0.992
11:67392196:G:C	G24R	0.992
11:67392674:C:A	N42K	0.992
11:67392674:C:G	N42K	0.992
11:67392684:T:C	S46P	0.992
11:67392687:G:C	A47P	0.992
11:67392693:G:C	A49P	0.992
11:67396002:T:C	F217S	0.992
11:67392185:T:C	L20P	0.991
11:67392190:C:A	R22S	0.991
11:67392206:T:C	L27P	0.991
11:67396268:C:A	A247D	0.991
11:67392172:G:C	A16P	0.990
11:67392173:C:A	A16D	0.990
11:67392664:G:C	R39P	0.990
11:67393596:T:C	L112P	0.990
11:67396020:G:C	R223P	0.990
11:67396111:G:A	G224R	0.988

dbSNP variants (sampled 300 via entrez): RS1000263849 (11:67392430 C>A,G,T), RS1000361449 (11:67391405 G>GT), RS1000420135 (11:67397913 G>A), RS1001059730 (11:67396963 C>A), RS1001347598 (11:67397088 G>A,C,T), RS1001419422 (11:67393003 C>G,T), RS1001787141 (11:67393341 T>C,G), RS1002419186 (11:67391472 A>G), RS1002420792 (11:67391918 C>T), RS1002880428 (11:67391745 C>G), RS1003053865 (11:67394788 G>A,T), RS1003495860 (11:67394487 C>T), RS1004464965 (11:67392287 G>A), RS1004492032 (11:67392095 C>G,T), RS1004986069 (11:67393592 C>T)

Disease associations

OMIM: gene MIM:603761 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST007293_14	Body fat distribution (arm fat ratio)	9.000000e-08
GCST007294_129	Body fat distribution (trunk fat ratio)	8.000000e-28
GCST007294_95	Body fat distribution (trunk fat ratio)	1.000000e-35
GCST007295_43	Body fat distribution (leg fat ratio)	1.000000e-25
GCST007295_76	Body fat distribution (leg fat ratio)	1.000000e-21

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects binding, affects folding, increases reaction, decreases reaction, decreases methylation	3
bisphenol AF	affects binding, affects folding, increases reaction, decreases reaction	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
myristicin	decreases expression	1
triphenyl phosphate	affects expression	1
methylselenic acid	increases expression	1
VX-agent	increases expression	1
Nonidet P-40	increases expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
bromoacetate	increases expression	1
benzo(e)pyrene	decreases methylation	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
deguelin	decreases expression	1
2-palmitoylglycerol	increases expression	1
7,3’-dihydroxy-4’-methoxyisoflavone	decreases expression	1
CPG-oligonucleotide	increases expression	1
bisphenol S	affects binding, decreases reaction	1
jinfukang	increases expression	1
bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV)	increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	decreases expression, decreases reaction	1
Acetylcysteine	decreases expression, decreases reaction	1
Carmustine	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Methapyrilene	decreases methylation	1

Clinical trials (associated diseases)

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