RAD9B

Summary

RAD9B (RAD9 checkpoint clamp component B, HGNC:21700) is a protein-coding gene on chromosome 12q24.11, encoding Cell cycle checkpoint control protein RAD9B (Q6WBX8).

Predicted to be involved in DNA integrity checkpoint signaling; DNA repair; and cellular response to ionizing radiation. Located in nucleus.

Source: NCBI Gene 144715 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 64 total — 2 pathogenic, 6 likely-pathogenic
• MANE Select transcript: NM_001286535

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21700
Approved symbol	RAD9B
Name	RAD9 checkpoint clamp component B
Location	12q24.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ40346
Ensembl gene	ENSG00000151164
Ensembl biotype	protein_coding
OMIM	608368
Entrez	144715

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000358071, ENST00000392672, ENST00000409246, ENST00000409300, ENST00000409425, ENST00000409461, ENST00000409778, ENST00000433301, ENST00000447044

RefSeq mRNA: 13 — MANE Select: NM_001286535 NM_001286531, NM_001286532, NM_001286533, NM_001286534, NM_001286535, NM_001286536, NM_001368051, NM_001368052, NM_001368053, NM_001368054, NM_001368055, NM_001368056, NM_152442

CCDS: CCDS66469, CCDS73526, CCDS73527, CCDS9148

Canonical transcript exons

ENST00000409300 — 11 exons

Exon	Start	End
ENSE00001583168	110502331	110502383
ENSE00003477261	110518676	110518782
ENSE00003529985	110512779	110512878
ENSE00003541680	110515050	110515156
ENSE00003564612	110506579	110506693
ENSE00003571664	110519794	110519916
ENSE00003601982	110505617	110505772
ENSE00003607337	110522177	110522411
ENSE00003627604	110503806	110503876
ENSE00003655297	110518874	110518938
ENSE00003900563	110530525	110533556

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 84.91.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3014 / max 38.3422, expressed in 121 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127998	0.2709	116
127997	0.0305	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.30	gold quality
right testis	UBERON:0004534	83.46	gold quality
left testis	UBERON:0004533	81.89	gold quality
testis	UBERON:0000473	81.14	gold quality
secondary oocyte	CL:0000655	72.44	gold quality
monocyte	CL:0000576	70.00	gold quality
calcaneal tendon	UBERON:0003701	69.46	gold quality
leukocyte	CL:0000738	69.40	gold quality
muscle of leg	UBERON:0001383	65.52	gold quality
gastrocnemius	UBERON:0001388	65.45	gold quality
ventricular zone	UBERON:0003053	64.38	gold quality
right coronary artery	UBERON:0001625	63.94	gold quality
hindlimb stylopod muscle	UBERON:0004252	63.06	gold quality
stromal cell of endometrium	CL:0002255	62.41	gold quality
smooth muscle tissue	UBERON:0001135	62.29	gold quality
lower esophagus muscularis layer	UBERON:0035833	60.88	gold quality
lower esophagus	UBERON:0013473	60.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	59.30	gold quality
tibial nerve	UBERON:0001323	59.06	gold quality
right atrium auricular region	UBERON:0006631	59.03	gold quality
granulocyte	CL:0000094	58.94	gold quality
cardiac atrium	UBERON:0002081	58.55	gold quality
tendon	UBERON:0000043	58.42	gold quality
ganglionic eminence	UBERON:0004023	58.31	gold quality
bone marrow cell	CL:0002092	58.14	silver quality
vermiform appendix	UBERON:0001154	58.14	gold quality
heart left ventricle	UBERON:0002084	58.00	gold quality
tibial artery	UBERON:0007610	57.92	gold quality
popliteal artery	UBERON:0002250	57.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting RAD9B, 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-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-6870-5P	99.99	68.55	2115
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-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-154-5P	98.92	66.65	733
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-6894-5P	98.70	63.78	809
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-4691-3P	98.11	66.83	1204
HSA-MIR-943	97.81	64.42	694
HSA-MIR-6895-5P	97.05	64.96	522
HSA-MIR-7847-3P	96.63	64.58	952
HSA-MIR-4680-5P	96.43	67.15	893
HSA-MIR-4296	96.35	63.55	1233

Literature-anchored findings (GeneRIF, showing 4)

• The encoded mammalian proteins participate in promoting resistance to DNA damage, cell cycle checkpoint control, DNA repair, and apoptosis. (PMID:16365875)
• Rad9B responds to nucleolar stress after the activation of JNK-dependent stress signalling and ATR-dependent DNA damage response pathways, and actively accumulates within nucleoli, where it does not cause a transcription block. (PMID:22399810)
• Loss of RAD9B impairs early neural development and contributes to the risk for human spina bifida. (PMID:31898828)
• Expression of RAD9B in the mesostriatal system of rats and humans: Overexpression in a 6-OHDA rat model of Parkinson’s disease. (PMID:37460044)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rad9b	ENSDARG00000075632
mus_musculus	Rad9b	ENSMUSG00000038569
rattus_norvegicus	Rad9b	ENSRNOG00000021480
drosophila_melanogaster	Rad9	FBGN0025807
caenorhabditis_elegans		WBGENE00001997

Paralogs (1): RAD9A (ENSG00000172613)

Protein

Protein identifiers

Cell cycle checkpoint control protein RAD9B — Q6WBX8 (reviewed: Q6WBX8)

Alternative names: DNA repair exonuclease rad9 homolog B

All UniProt accessions (5): Q6WBX8, B4DX60, B4DYM6, H7BY23, J3KPN7

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with HUS1, HUS1B, RAD1, RAD9A and RAD17.

Tissue specificity. Expressed in testis and skeletal muscle.

Similarity. Belongs to the rad9 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q6WBX8-5	5	yes
Q6WBX8-1	1
Q6WBX8-2	2
Q6WBX8-3	3
Q6WBX8-4	4

RefSeq proteins (13): NP_001273460, NP_001273461, NP_001273462, NP_001273463, NP_001273464, NP_001273465, NP_001354980, NP_001354981, NP_001354982, NP_001354983, NP_001354984, NP_001354985, NP_689655 (=MANE)

Domains & families (InterPro)

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

Pfam: PF04139

UniProt features (7 total): splice variant 3, sequence conflict 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6WBX8-F1	70.12	0.49

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 (1): 359

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: 125 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_IONIZING_RADIATION, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GOBP_CELL_CYCLE_PHASE_TRANSITION, REACTOME_ACTIVATION_OF_ATR_IN_RESPONSE_TO_REPLICATION_STRESS, KAUFFMANN_DNA_REPAIR_GENES, GOBP_MITOTIC_INTRA_S_DNA_DAMAGE_CHECKPOINT_SIGNALING, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GATA3_01, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_NEGATIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_DNA_DAMAGE_RESPONSE

GO Biological Process (5): DNA replication checkpoint signaling (GO:0000076), DNA repair (GO:0006281), mitotic intra-S DNA damage checkpoint signaling (GO:0031573), cellular response to ionizing radiation (GO:0071479), DNA damage checkpoint signaling (GO:0000077)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), 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 metabolic process	1
DNA damage response	1
mitotic S phase	1
mitotic DNA damage checkpoint signaling	1
response to ionizing radiation	1
cellular response to radiation	1
signal transduction in response to DNA damage	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
condensed nuclear chromosome	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

972 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAD9B	HUS1B	Q8NHY5	985
RAD9B	HUS1	O60921	876
RAD9B	RAD17	O75943	834
RAD9B	TOPBP1	Q92547	696
RAD9B	CHEK1	O14757	435
RAD9B	HORMAD1	Q86X24	425
RAD9B	DMC1	Q14565	414
RAD9B	ATM	Q13315	393
RAD9B	FAM216A	Q8WUB2	390
RAD9B	MEI1	Q5TIA1	389
RAD9B	BPHL	Q86WA6	383
RAD9B	FAM153B	P0C7A2	380
RAD9B	CLSPN	Q9HAW4	376
RAD9B	RFC4	P35249	371
RAD9B	VXN	Q8TAG6	370

IntAct

2 interactions, top by confidence:

A	B	Type	Score
RAD9B	PMS1	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): HUS1 (Affinity Capture-Western), RAD17 (Affinity Capture-Western), RAD1 (Affinity Capture-Western), HUS1B (Affinity Capture-Western), RAD9B (Synthetic Lethality), RAD9B (Affinity Capture-RNA), ITPA (Affinity Capture-MS), PPP2R5D (Affinity Capture-MS), CPSF3L (Affinity Capture-MS), PMS1 (Affinity Capture-MS), RAD9B (Affinity Capture-MS), RAD9B (Proximity Label-MS)

ESM2 similar proteins: A6NDL7, A6QP81, F6HH45, G3HKI1, O35368, O43148, O82312, O95568, Q08DA3, Q13426, Q149N8, Q2HJ93, Q2KIJ2, Q2KIY6, Q4KM84, Q4R3W5, Q4R7K1, Q4R7Q1, Q58CU3, Q58DC7, Q5E9X8, Q5R6Z9, Q5RAK3, Q5T8I9, Q5U2U7, Q5VN06, Q5VZV1, Q5XIX3, Q5ZHP8, Q6WBX8, Q7TPQ3, Q86T96, Q8BK58, Q8BLU2, Q8C0V1, Q8L870, Q8NE18, Q8W032, Q924T3, Q96EW2

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	6
Uncertain significance	41
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
694400	NM_001286535.2(RAD9B):c.960del (p.Ala321fs)	Pathogenic
694421	NM_001286535.2(RAD9B):c.1199dup (p.Arg401fs)	Pathogenic
694312	NM_001286535.2(RAD9B):c.661G>A (p.Gly221Arg)	Likely pathogenic
694313	NC_000012.11:g.110950633C>G	Likely pathogenic
694314	NM_001286535.2(RAD9B):c.336A>G (p.Ile112Met)	Likely pathogenic
694315	NM_001286535.2(RAD9B):c.1060A>G (p.Ser354Gly)	Likely pathogenic
694398	NM_001286535.2(RAD9B):c.28A>G (p.Ser10Gly)	Likely pathogenic
694399	NM_001286535.2(RAD9B):c.645T>A (p.Phe215Leu)	Likely pathogenic

SpliceAI

2425 predictions. Top by Δscore:

Variant	Effect	Δscore
12:110502051:T:TA	donor_gain	1.0000
12:110515048:A:AG	acceptor_gain	1.0000
12:110515049:G:GG	acceptor_gain	1.0000
12:110515093:G:GT	donor_gain	1.0000
12:110515147:G:GT	donor_gain	1.0000
12:110518662:A:AG	acceptor_gain	1.0000
12:110518663:T:G	acceptor_gain	1.0000
12:110518664:A:AG	acceptor_gain	1.0000
12:110518665:A:G	acceptor_gain	1.0000
12:110518666:T:G	acceptor_gain	1.0000
12:110518667:A:AG	acceptor_gain	1.0000
12:110518668:T:G	acceptor_gain	1.0000
12:110518671:A:G	acceptor_gain	1.0000
12:110518674:A:AG	acceptor_gain	1.0000
12:110518674:AG:A	acceptor_loss	1.0000
12:110518675:G:GA	acceptor_gain	1.0000
12:110518675:GAT:G	acceptor_gain	1.0000
12:110518675:GATT:G	acceptor_gain	1.0000
12:110518675:GATTT:G	acceptor_gain	1.0000
12:110518778:TGAAG:T	donor_loss	1.0000
12:110518779:GAAGG:G	donor_loss	1.0000
12:110518780:AAGG:A	donor_loss	1.0000
12:110518782:GGTAA:G	donor_loss	1.0000
12:110518936:G:T	donor_gain	1.0000
12:110518939:G:GG	donor_gain	1.0000
12:110530634:G:GT	donor_gain	1.0000
12:110502047:ACCAT:A	donor_gain	0.9900
12:110502048:CCATC:C	donor_gain	0.9900
12:110502077:C:CT	donor_gain	0.9900
12:110502080:C:CT	donor_gain	0.9900

AlphaMissense

2782 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000063470 (12:110510885 T>C), RS1000117110 (12:110527711 T>A), RS1000168545 (12:110520548 T>C), RS1000405385 (12:110528018 T>C), RS1000434100 (12:110506649 G>C,T), RS1000493168 (12:110532482 G>C), RS1000493857 (12:110519212 T>C), RS1000679062 (12:110512160 T>A,C), RS1000748139 (12:110514118 T>C), RS1000770665 (12:110504960 G>C), RS1000812733 (12:110502758 C>G), RS1000869208 (12:110508940 G>A), RS1000878489 (12:110504100 C>T), RS1000924989 (12:110508538 G>A), RS1000991646 (12:110532151 A>T)

Disease associations

OMIM: gene MIM:608368 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): neural tube defect (MONDO:0018075)

Orphanet (2): Neural tube defect (Orphanet:3388), Spina bifida and other spinal dysraphisms (Orphanet:823)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009436	Neural Tube Defects	C10.500.680; C16.131.666.680

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
perfluorooctane sulfonic acid	increases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
licochalcone B	increases expression	1
Resveratrol	decreases expression	1
Sunitinib	decreases expression	1
Catechin	affects cotreatment, decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	increases methylation	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02230072	PHASE1	COMPLETED	Fetoscopic Meningomyelocele Repair Study
NCT00060606	Not specified	COMPLETED	Management of Myelomeningocele Study (MOMS)
NCT00966927	Not specified	ACTIVE_NOT_RECRUITING	Assessment of Functional Independence and Quality of Life in Adolescents With Spina Bifid
NCT00975338	Not specified	COMPLETED	The LETS Study: A Longitudinal Evaluation of Transition Services
NCT02592291	Not specified	RECRUITING	Mobile Health Self-Management and Support System for Chronic and Complex Health Conditions
NCT03044821	Not specified	TERMINATED	Open Myelomeningocele Repair With High Maternal BMI
NCT03090633	Not specified	ACTIVE_NOT_RECRUITING	Fetoscopic Repair of Isolated Fetal Spina Bifida
NCT03544970	Not specified	COMPLETED	An Audit of the Posterior Fossa Characterization in Open Spina Bifida Based on Tertiary Center Experience
NCT04763382	Not specified	UNKNOWN	The Effect of Nursing Interventions for Clean Intermittent Catheterization Caregivers and Child
NCT05718440	Not specified	RECRUITING	Uronephrological Complications Risk Factors in Spinal Dysraphism
NCT05962086	Not specified	UNKNOWN	Determining Developmental and Clinical Markers Affecting Urinary Function of Children With Spinal Dysraphism
NCT06907732	Not specified	NOT_YET_RECRUITING	Fetoscopic Robotic Open Spina Bifida Treatment