RAD23B

Summary

RAD23B (RAD23 nucleotide excision repair protein B, HGNC:9813) is a protein-coding gene on chromosome 9q31.2, encoding Lysine-specific demethylase RAD23B (P54727). Multifunctional protein that participates in histone H4K20 demethylation, DNA repair, ubiquitin-dependent protein degradation and transcriptional regulation. In precision oncology, RAD23B EXPRESSION confers sensitivity to Vorinostat in Sarcoma (CIViC Level D).

The protein encoded by this gene is one of two human homologs of Saccharomyces cerevisiae Rad23, a protein involved in the nucleotide excision repair (NER). This protein was found to be a component of the protein complex that specifically complements the NER defect of xeroderma pigmentosum group C (XP-c) cell extracts in vitro. This protein was also shown to interact with, and elevate the nucleotide excision activity of 3-methyladenine-DNA glycosylase (MPG), which suggested a role in DNA damage recognition in base excision repair. This protein contains an N-terminal ubiquitin-like domain, which was reported to interact with 26S proteasome, and thus this protein may be involved in the ubiquitin mediated proteolytic pathway in cells. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 5887 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 49 total
• Druggable target: yes
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_002874

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9813
Approved symbol	RAD23B
Name	RAD23 nucleotide excision repair protein B
Location	9q31.2
Locus type	gene with protein product
Status	Approved
Aliases	HHR23B, P58, HR23B
Ensembl gene	ENSG00000119318
Ensembl biotype	protein_coding
OMIM	600062
Entrez	5887

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000358015, ENST00000416373, ENST00000419616, ENST00000442587, ENST00000457811, ENST00000866018, ENST00000866019

RefSeq mRNA: 3 — MANE Select: NM_002874 NM_001244713, NM_001244724, NM_002874

CCDS: CCDS59138, CCDS6769

Canonical transcript exons

ENST00000358015 — 10 exons

Exon	Start	End
ENSE00000718037	107324834	107325004
ENSE00000926767	107306379	107306647
ENSE00000926768	107311682	107311737
ENSE00000926769	107318752	107318879
ENSE00000926770	107321983	107322118
ENSE00000926771	107323890	107324017
ENSE00001401087	107329543	107332189
ENSE00001861528	107283279	107283695
ENSE00003577891	107300141	107300222
ENSE00003603239	107302035	107302114

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 197.3432 / max 985.7325, expressed in 1828 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97888	158.3837	1828
97890	29.0779	1804
97887	3.2736	1529
97889	2.7489	1306
97898	1.6460	1000
97892	0.9673	452
97891	0.5958	356
97897	0.4573	238
97893	0.1007	59
97894	0.0921	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	98.75	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.71	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.57	gold quality
penis	UBERON:0000989	98.51	gold quality
biceps brachii	UBERON:0001507	98.39	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.33	gold quality
triceps brachii	UBERON:0001509	98.20	gold quality
gluteal muscle	UBERON:0002000	98.18	gold quality
jejunum	UBERON:0002115	98.01	gold quality
pharyngeal mucosa	UBERON:0000355	97.99	gold quality
skeletal muscle tissue	UBERON:0001134	97.96	gold quality
body of tongue	UBERON:0011876	97.92	gold quality
embryo	UBERON:0000922	97.90	gold quality
colonic mucosa	UBERON:0000317	97.87	gold quality
jejunal mucosa	UBERON:0000399	97.87	gold quality
tongue	UBERON:0001723	97.78	gold quality
pericardium	UBERON:0002407	97.78	gold quality
deltoid	UBERON:0001476	97.77	gold quality
ventricular zone	UBERON:0003053	97.74	gold quality
superior surface of tongue	UBERON:0007371	97.70	gold quality
heart right ventricle	UBERON:0002080	97.64	gold quality
islet of Langerhans	UBERON:0000006	97.62	gold quality
calcaneal tendon	UBERON:0003701	97.58	gold quality
muscle organ	UBERON:0001630	97.56	gold quality
caput epididymis	UBERON:0004358	97.56	gold quality
gastrocnemius	UBERON:0001388	97.54	gold quality
muscle of leg	UBERON:0001383	97.52	gold quality
cauda epididymis	UBERON:0004360	97.51	gold quality
oviduct epithelium	UBERON:0004804	97.51	gold quality
diaphragm	UBERON:0001103	97.43	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.41
E-GEOD-124858	no	144.64
E-CURD-112	no	2.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

184 targeting RAD23B, 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-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-23A-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 39)

• Gene expression of RAD23B was down-regulated during early apoptosis in human hepatoma cells exposed to Paeoniae Radix extract in vitro. (PMID:12215374)
• analysis of mHR23A/B double-mutant cells showed that HR23 proteins function in nucleotide excision repair by governing xeroderma pigmentosum group C protein stability via partial protection against proteasomal degradation (PMID:12815074)
• structure of the ubiquitin-interacting motif of the proteasome subunit S5a bound to the ubiquitin-like domain of HR23B (PMID:14585839)
• hHR23 binds to polyubiquitylated p53 via its carboxyl-terminal ubiquitin-associated (Uba) domain shielding p53 from deubiquitylation (PMID:14645509)
• Highly expressed in the human testis and in ejaculated spermatozoa. This novel alternative splicing form of RAD23B is correlated with human spermatogenesis. (PMID:15064313)
• the human nucleotide excision repair gene, hHR23B, is epigenetically silenced in interleukin-6-responsive multiple myeloma KAS-6/1 cells (PMID:15550378)
• Results describe the solution structure of a protein fragment containing amino acids 275-342 of hHR23B and compare it with the previously reported solution structures of the corresponding domain of hHR23A. (PMID:15885096)
• intracellular distribution hHR23B is cell cycle dependent (PMID:16253613)
• determined that hHR23A and hHR23B could be co-purified with unique proteolytic and stress-responsive factors from human breast cancer tissues, indicating that they have unique functions in vivo (PMID:16712842)
• Fluorescence correlation spectroscopy of the binding of nucleotide excision repair protein XPC-HHR23B with DNA substrates is reported. (PMID:18574675)
• 26S proteasomes and p97/VCP complexes bind to the ubiquitin-like domain of HHR23B. (PMID:19182904)
• Genetic polymorphisms in RAD23B is associated with Laryngeal cancer risk associated with smoking and alcohol consumption. (PMID:19444904)
• XPC subunit interaction with DNA is stimulated by endogenous HR23B. (PMID:19538122)
• BRG1 stimulates the recruitment of XPG and PCNA to successfully culminate the nucleotide excision repair. (PMID:19740755)
• Single nucleotide polymorphisms of CCND2, RAD23B, GRP78, CEP164, MDM2, and ALDH2 genes were significantly associated with development and recurrence of hepatocellular carcinoma in Japanese patients with hepatitis C virus. (PMID:22004425)
• PNGase-PUB serves not only as p97-binding module but also as a possible activator of HR23 in endoplasmic reticulum-associated degradation mechanisms. (PMID:22575648)
• HR23B expression was associated with disease stabilization for patients with unresectable hepatocellular carcinoma treated with epigenetic therapy using belinostat, a histone deacetylase inhibitor. (PMID:22915658)
• Results define a regulatory mechanism that involves the interplay between HR23B and HDAC6 that influences the biological outcome of HDAC inhibitor treatment. (PMID:23703321)
• Polymorphism in RAD23B gene is associated with breast cancer. (PMID:23776089)
• It is unlikely that the RAD23B 249Val/Val polymorphism may contribute to the individual susceptibility to cancer risk. (PMID:24643114)
• RAD23B has a potential role in breast cancer progression and a tumor suppressor role of nuclear RAD23B in breast cancer. (PMID:24897598)
• Data indicate that phosphorylation provides a mechanism to regulate Rad23/proteasome interaction. (PMID:25311859)
• Data show that nucleotide excision repair factor XPC-RAD23B is a target of poly(ADP-ribosyl)ation catalyzed by poly(ADP-ribose) polymerase 1 (PARP1). (PMID:26170451)
• XPC dissociation from the damage site could become a rate-limiting step in nucleotide excision repair (NER) of certain types of DNA adducts, leading to repression of NER. (PMID:27327897)
• HR23B role in DNA reapair, in protein degradation and stability, tumorigenesis and neurodegenerative disorders [review] (PMID:27771451)
• Several mutations in the two parts of the central “crest” of the arrestin molecule, middle-loop and C-loop, enhanced or reduced arrestin-3 interactions with several GPCRs in receptor subtype and functional state-specific manner. (PMID:28473198)
• polyQ-expanded Htt-N552 and Atx-3 sequester endogenous Ub adaptors, human RAD23 homolog B (hHR23B) and ubiquilin (UBQLN)-2, into inclusions. This sequestration effect is dependent on the UBA domains of Ub adaptors and the conjugated Ub of the aggregated proteins. (PMID:29401586)
• miR-196b improved radiosensitivity of SNU-638 cells by targeting RAD23B. (PMID:29864624)
• Study reports RAD23B copy number variation in 10% (12/119, P </= 0.01) of Sezary syndrome (SS) patients, associated with reduced mRNA expression. RAD23B knockdown in a cutaneous T-cell lymphoma cell line led to a reduction in FK228-induced apoptosis. Findings suggest that RAD23B gene perturbations could reduce sensitivity to histone deacetylase inhibitors in SS patients. (PMID:30910759)
• TYMS was absent in 100% of circulating tumor cells (CTCs) from locally advanced rectal cancer patients with pathologic complete response yet was expressed in 83% of non-responders prior to surgery (S2). RAD23B was expressed in CTCs from 75% of non-responders prior to neoadjuvant chemoradiation (S1) and in 100% of non-responders at S2. 100% of non-responders expressed TYMS mRNA at both timepoints. (PMID:31247977)
• Three types of one-dimensional motion of XPC-RAD23B along damaged DNA were observed: diffusive, immobile and constrained. (PMID:31372632)
• Upregulation of GRIM-19 augments the sensitivity of prostate cancer cells to docetaxel by targeting Rad23b. (PMID:31531888)
• Histone H4K20 Demethylation by Two hHR23 Proteins. (PMID:32209475)
• Inhibition of Excision of Oxidatively Generated Hydantoin DNA Lesions by NEIL1 by the Competitive Binding of the Nucleotide Excision Repair Factor XPC-RAD23B. (PMID:32302101)
• Functional impacts of the ubiquitin-proteasome system on DNA damage recognition in global genome nucleotide excision repair. (PMID:33184426)
• Knockdown of circRAD23B Exerts Antitumor Response in Colorectal Cancer via the Regulation of miR-1205/TRIM44 axis. (PMID:33634427)
• Cytoplasmic RAD23B interacts with CORO1C to synergistically promote colorectal cancer progression and metastasis. (PMID:34062216)
• Deubiquitinase PSMD7 promotes the proliferation, invasion, and cisplatin resistance of gastric cancer cells by stabilizing RAD23B. (PMID:34512150)
• HDAC6 Inhibition Releases HR23B to Activate Proteasomes, Expand the Tumor Immunopeptidome and Amplify T-cell Antimyeloma Activity. (PMID:38747592)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rad23b	ENSDARG00000021550
mus_musculus	Rad23b	ENSMUSG00000028426
rattus_norvegicus	Rad23b	ENSRNOG00000016137
drosophila_melanogaster	CG10694	FBGN0039147
caenorhabditis_elegans		WBGENE00013924

Paralogs (1): RAD23A (ENSG00000179262)

Protein

Protein identifiers

Lysine-specific demethylase RAD23B — P54727 (reviewed: P54727)

Alternative names: UV excision repair protein RAD23 homolog B, XP-C repair-complementing complex 58 kDa protein

All UniProt accessions (4): P54727, H0Y579, Q5W0S4, Q5W0S5

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional protein that participates in histone H4K20 demethylation, DNA repair, ubiquitin-dependent protein degradation and transcriptional regulation. Specifically demethylates mono-, di- and trimethylated ‘Lys-20’ of histone H4 (H4K20me1, H4K20me2, H4K20me3, respectively) into unmethylated forms. Activates the transcription of coding genes by demethylating H4K20me1 and the transcription of repetitive elements by demethylating H4K20me3. Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Binds to polyubiquitin chains. Proposed to be capable to bind simultaneously to the 26S proteasome and to polyubiquitinated substrates and to deliver ubiquitinated proteins to the proteasome. May play a role in endoplasmic reticulum-associated degradation (ERAD) of misfolded glycoproteins by association with PNGase and delivering deglycosylated proteins to the proteasome. Involved in global genome nucleotide excision repair (GG-NER) by acting as component of the XPC complex, a nucleotide-excision repair complex that is involved in damage sensing during global genome nucleotide excision repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA. Recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix including single-stranded loops, mismatched bubbles or single-stranded overhangs. Cooperatively with CETN2 appears to stabilize XPC.

Subunit / interactions. Component of the XPC complex composed of XPC, RAD23B and CETN2. Interacts with NGLY1 and PSMC1. Interacts with ATXN3. Interacts with PSMD4 and PSMC5. Interacts with AMFR.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Highly expressed in the testis and in ejaculated spermatozoa.

Domain organisation. The ubiquitin-like domain mediates interaction with ATXN3.

Similarity. Belongs to the RAD23 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P54727-1	1	yes
P54727-2	2

RefSeq proteins (3): NP_001231642, NP_001231653, NP_002865* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR004806	Rad23	Family
IPR006636	STI1_HS-bd	Domain
IPR009060	UBA-like_sf	Homologous_superfamily
IPR015360	XPC-bd	Domain
IPR015940	UBA	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR036353	XPC-bd_sf	Homologous_superfamily
IPR041811	RAD23A/B_UBA1	Domain

Pfam: PF00240, PF00627, PF09280

Catalyzed reactions (Rhea), 3 shown:

• N(6)-methyl-L-lysyl(20)-[histone H4] + 2-oxoglutarate + O2 = L-lysyl(20)-[histone H4] + formaldehyde + succinate + CO2 (RHEA:67804)
• N(6),N(6)-dimethyl-L-lysyl(20)-[histone H4] + 2-oxoglutarate + O2 = N(6)-methyl-L-lysyl(20)-[histone H4] + formaldehyde + succinate + CO2 (RHEA:85907)
• N(6),N(6),N(6)-trimethyl-L-lysyl(20)-[histone H4] + 2-oxoglutarate + O2 = N(6),N(6)-dimethyl-L-lysyl(20)-[histone H4] + formaldehyde + succinate + CO2 (RHEA:85911)

UniProt features (37 total): helix 10, modified residue 7, domain 4, compositionally biased region 4, strand 4, turn 2, region of interest 2, chain 1, splice variant 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
28JS	ELECTRON MICROSCOPY	3.32
28JV	ELECTRON MICROSCOPY	3.91
8EBS	ELECTRON MICROSCOPY	4
9PCP	ELECTRON MICROSCOPY	4.3
8EBW	ELECTRON MICROSCOPY	5.6
8EBV	ELECTRON MICROSCOPY	7.1
1P1A	SOLUTION NMR
1PVE	SOLUTION NMR
1UEL	SOLUTION NMR
9VFE	SOLUTION NMR
9VFF	SOLUTION NMR
9VFG	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54727-F1	69.52	0.12

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 (7): 155, 160, 164, 174, 186, 199, 202

Mutagenesis-validated functional residues (1):

Position	Phenotype
6	impairs interaction with eef1a1.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-532668	N-glycan trimming in the ER and Calnexin/Calreticulin cycle
R-HSA-5689877	Josephin domain DUBs
R-HSA-5696394	DNA Damage Recognition in GG-NER
R-HSA-5696395	Formation of Incision Complex in GG-NER

MSigDB gene sets: 331 (showing top): REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, MORF_MTA1, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, MORF_MBD4, MORF_RAB5A, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_RESPONSE_TO_PEPTIDE, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MORF_RAD21, TACAATC_MIR508, GOBP_MALE_GAMETE_GENERATION

GO Biological Process (9): nucleotide-excision repair (GO:0006289), spermatogenesis (GO:0007283), regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032434), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), embryonic organ development (GO:0048568), UV-damage excision repair (GO:0070914), cellular response to interleukin-7 (GO:0098761), DNA repair (GO:0006281), DNA damage response (GO:0006974)

GO Molecular Function (11): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), damaged DNA binding (GO:0003684), single-stranded DNA binding (GO:0003697), polyubiquitin modification-dependent protein binding (GO:0031593), histone H4K20 demethylase activity (GO:0035575), ubiquitin binding (GO:0043130), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), proteasome binding (GO:0070628), DNA damage sensor activity (GO:0140612), transcription cis-regulatory region binding (GO:0000976), protein binding (GO:0005515)

GO Cellular Component (6): proteasome complex (GO:0000502), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), XPC complex (GO:0071942), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Global Genome Nucleotide Excision Repair (GG-NER)	2
Asparagine N-linked glycosylation	1
Deubiquitination	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA repair	2
DNA binding	2
developmental process involved in reproduction	1
male gamete generation	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
regulation of proteasomal protein catabolic process	1
regulation of ubiquitin-dependent protein catabolic process	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
embryo development	1
animal organ development	1
cellular response to UV	1
cellular response to cytokine stimulus	1
response to interleukin-7	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
modification-dependent protein binding	1
2-oxoglutarate-dependent dioxygenase activity	1
histone H4 demethylase activity	1
ubiquitin-like protein binding	1
DNA-binding transcription factor binding	1
protein-containing complex binding	1
damaged DNA binding	1
molecular sensor activity	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
binding	1
intracellular protein-containing complex	1
endopeptidase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
nucleotide-excision repair complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

4650 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAD23B	XPC	Q01831	999
RAD23B	CETN2	P41208	996
RAD23B	XPA	P23025	995
RAD23B	ERCC1	P07992	984
RAD23B	ATXN3	P54252	971
RAD23B	ATXN3L	Q9H3M9	965
RAD23B	PSMD4	P55036	955
RAD23B	ERCC2	P18074	953
RAD23B	ERCC3	P19447	905
RAD23B	ERCC4	Q92889	903
RAD23B	DDB1	Q16531	875
RAD23B	DDB2	Q92466	857
RAD23B	GTF2H5	Q6ZYL4	853
RAD23B	ERCC6	Q03468	824
RAD23B	ERCC5	P28715	814

IntAct

237 interactions, top by confidence:

A	B	Type	Score
RAD23B	NGLY1	psi-mi:“MI:0915”(physical association)	0.940
NGLY1	RAD23B	psi-mi:“MI:0915”(physical association)	0.940
NGLY1	RAD23B	psi-mi:“MI:0914”(association)	0.940
XPC	RAD23B	psi-mi:“MI:0915”(physical association)	0.900
RAD23B	PSMD4	psi-mi:“MI:0407”(direct interaction)	0.860
RAD23B	PSMD4	psi-mi:“MI:0915”(physical association)	0.860
PSMD4	RAD23B	psi-mi:“MI:0915”(physical association)	0.860
PSMD4	RAD23B	psi-mi:“MI:0407”(direct interaction)	0.860
RAD23B	USP25	psi-mi:“MI:0915”(physical association)	0.850
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
CETN2	SFI1	psi-mi:“MI:0914”(association)	0.740
XPC	PARP1	psi-mi:“MI:0914”(association)	0.730
XPC	CETN3	psi-mi:“MI:0914”(association)	0.730
RAD23B	PNMA5	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (400): RAD23B (Co-fractionation), RAD23B (Affinity Capture-Western), PUF60 (Two-hybrid), NGLY1 (Two-hybrid), PNMA5 (Two-hybrid), RAD23B (Co-crystal Structure), RAD23B (Affinity Capture-MS), UBC (Reconstituted Complex), UBC (Affinity Capture-Western), UBC (Reconstituted Complex), COMMD4 (Co-fractionation), CORO1B (Co-fractionation), CORO1C (Co-fractionation), DNAAF5 (Co-fractionation), G6PD (Co-fractionation)

ESM2 similar proteins: A1CDT9, A1DCU5, A3KMV2, I7HUG0, O00233, O17453, O35226, O35987, O61742, O74803, P0CS14, P0CS15, P40087, P54725, P54726, P54727, P54728, P55034, P55035, Q0CJ13, Q0U3Y6, Q10169, Q10256, Q1DNB9, Q1EBV4, Q29RK4, Q2H085, Q2USD7, Q3SZ19, Q40742, Q4I5I4, Q4KMA2, Q4WGS4, Q54JB0, Q54LV1, Q5AY89, Q6BK42, Q6CFI3, Q6CNS3, Q6FQE9

Diamond homologs: A3KMV2, O65381, O74803, P0C030, P0C031, P0C073, P16709, P32628, P48510, P54725, P54726, P54727, P54728, P62975, P68197, Q05120, Q29RK4, Q40742, Q4KMA2, Q54LV1, Q84L30, Q84L31, Q84L32, Q84L33, Q865C5, Q8RUC6, Q93725, Q9SHE7, A3KPW9, A4IH17, A5D9M6, A7X5R6, C4YP88, D5LXJ0, G1SK22, P05759, P0C016, P0C032, P0C273, P0C275

SIGNOR signaling

17 interactions.

A	Effect	B	Mechanism
NGLY1	“up-regulates activity”	RAD23B	binding
RAD23B	up-regulates	Protein_degradation
RAD23B	“down-regulates activity”	PAX3	binding
UBE3A	“down-regulates quantity by destabilization”	RAD23B	polyubiquitination
DNA_damage	up-regulates	RAD23B
DDB1	up-regulates	RAD23B
ERCC8	“up-regulates activity”	RAD23B
ERCC6	“up-regulates activity”	RAD23B
XAB2	“up-regulates activity”	RAD23B
RAD23B	“up-regulates activity”	TFIIH	binding
RAD23B	“up-regulates activity”	XPA	binding
RAD23B	“up-regulates activity”	RPA1	binding
RAD23B	“up-regulates activity”	RPA2	binding
RAD23B	“up-regulates activity”	RPA3	binding
RAD23B	“up-regulates activity”	RPA4	binding
RAD23B	“up-regulates activity”	ERCC5	binding
RAD23B	“up-regulates activity”	ERCC1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 144 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
Regulation of activated PAK-2p34 by proteasome mediated degradation	10	27.6×	2e-10
Vpu mediated degradation of CD4	10	26.3×	2e-10
Autodegradation of the E3 ubiquitin ligase COP1	10	26.3×	2e-10
Ubiquitin-dependent degradation of Cyclin D	10	26.3×	2e-10
Degradation of DVL	11	25.9×	7e-11
Vif-mediated degradation of APOBEC3G	10	25.1×	3e-10
Formation of Incision Complex in GG-NER	10	25.1×	3e-10
NIK–>noncanonical NF-kB signaling	11	24.9×	7e-11

GO biological processes:

GO term	Partners	Fold	FDR
nucleotide-excision repair	6	18.2×	4e-04
proteasome-mediated ubiquitin-dependent protein catabolic process	14	5.8×	1e-04
ubiquitin-dependent protein catabolic process	9	5.3×	7e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1633 predictions. Top by Δscore:

Variant	Effect	Δscore
9:107283692:GACG:G	donor_gain	1.0000
9:107300136:TATA:T	acceptor_loss	1.0000
9:107300137:A:AG	acceptor_gain	1.0000
9:107300139:A:AC	acceptor_loss	1.0000
9:107300139:A:AG	acceptor_gain	1.0000
9:107300139:AG:A	acceptor_gain	1.0000
9:107300139:AGGT:A	acceptor_gain	1.0000
9:107300140:G:GA	acceptor_gain	1.0000
9:107300140:GG:G	acceptor_gain	1.0000
9:107300140:GGT:G	acceptor_gain	1.0000
9:107300140:GGTG:G	acceptor_gain	1.0000
9:107300222:GGT:G	donor_loss	1.0000
9:107300223:G:C	donor_loss	1.0000
9:107302025:A:AG	acceptor_gain	1.0000
9:107302027:T:G	acceptor_gain	1.0000
9:107302030:ATTAG:A	acceptor_gain	1.0000
9:107302031:T:G	acceptor_gain	1.0000
9:107302113:AA:A	donor_gain	1.0000
9:107302113:AAGTA:A	donor_loss	1.0000
9:107302114:AG:A	donor_loss	1.0000
9:107302115:G:GG	donor_gain	1.0000
9:107302116:TA:T	donor_loss	1.0000
9:107302117:AA:A	donor_loss	1.0000
9:107306368:A:AG	acceptor_gain	1.0000
9:107306377:A:AG	acceptor_gain	1.0000
9:107306378:G:GA	acceptor_gain	1.0000
9:107306378:GC:G	acceptor_gain	1.0000
9:107306378:GCC:G	acceptor_gain	1.0000
9:107306378:GCCC:G	acceptor_gain	1.0000
9:107306378:GCCCA:G	acceptor_gain	1.0000

AlphaMissense

2651 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:107283643:T:C	L5P	1.000
9:107283645:A:G	K6E	1.000
9:107283647:G:C	K6N	1.000
9:107283647:G:T	K6N	1.000
9:107283652:T:A	L8H	1.000
9:107283652:T:C	L8P	1.000
9:107300151:T:C	L26P	1.000
9:107300153:A:G	K27E	1.000
9:107300154:A:T	K27I	1.000
9:107300155:A:C	K27N	1.000
9:107300155:A:T	K27N	1.000
9:107300163:T:A	I30N	1.000
9:107300189:T:C	F39L	1.000
9:107300191:T:A	F39L	1.000
9:107300191:T:G	F39L	1.000
9:107300207:A:G	K45E	1.000
9:107300211:T:C	L46S	1.000
9:107300214:T:A	I47N	1.000
9:107300214:T:C	I47T	1.000
9:107300214:T:G	I47S	1.000
9:107300216:T:G	Y48D	1.000
9:107300219:G:C	A49P	1.000
9:107300222:G:C	G50R	1.000
9:107300222:G:T	G50C	1.000
9:107302035:G:A	G50D	1.000
9:107302035:G:T	G50V	1.000
9:107302041:T:A	I52N	1.000
9:107302041:T:G	I52S	1.000
9:107302044:T:A	L53H	1.000
9:107302044:T:C	L53P	1.000

dbSNP variants (sampled 300 via entrez): RS1000023130 (9:107307524 C>T), RS1000033488 (9:107321690 A>G), RS1000135528 (9:107328172 A>G), RS1000139911 (9:107315749 G>C), RS1000140766 (9:107288804 G>C,T), RS1000193414 (9:107289111 C>G), RS1000226483 (9:107291487 C>T), RS1000305296 (9:107283814 C>G,T), RS1000345145 (9:107332671 A>G), RS1000466478 (9:107283996 A>T), RS1000472484 (9:107287597 A>G), RS1000496408 (9:107303173 C>G), RS1000569298 (9:107296679 C>A,T), RS1000657022 (9:107291102 A>G), RS1000672289 (9:107329926 G>T)

Disease associations

OMIM: gene MIM:600062 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000840_1	Body mass index	7.000000e-06
GCST000952_9	Breast cancer	2.000000e-10
GCST001702_2	Prostate cancer	5.000000e-14
GCST003061_4	Cutaneous malignant melanoma	7.000000e-11
GCST004142_1	Melanoma	7.000000e-11
GCST007576_103	Chronotype	4.000000e-10
GCST010703_144	Brain morphology (MOSTest)	5.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008328	chronotype measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066866 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
RAD23B EXPRESSION	Vorinostat	Sarcoma	Sensitivity/Response	CIViC D	EID1597

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.59	Kd	2.593	nM	CHEMBL3752910
8.59	ED50	2.593	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149185: Binding affinity to human RAD23B incubated for 45 mins by Kinobead based pull down assay	kd	0.0026	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	3
Cadmium Chloride	increases expression, decreases expression	3
Cisplatin	increases expression, decreases response to substance, increases response to substance, decreases reaction	2
Doxorubicin	affects expression, decreases expression	2
Fluorouracil	increases expression, affects response to substance	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cyclosporine	increases expression	2
Particulate Matter	increases abundance, affects cotreatment, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
chlorophyllin	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
salinomycin	decreases expression	1
trichostatin A	affects expression	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	decreases expression	1
perfluorooctanoic acid	increases expression	1
cadmium acetate	decreases expression	1
coumarin	decreases phosphorylation	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
beta-methylcholine	affects expression	1
pinosylvin	decreases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
2,3-dimethoxy-1,4-naphthoquinone	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652227	Binding	Binding affinity to human RAD23B incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KT67	HeLa SilenciX HR23B	Cancer cell line	Female

Clinical trials (associated diseases)

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