RAD23A

Summary

RAD23A (RAD23 nucleotide excision repair protein A, HGNC:9812) is a protein-coding gene on chromosome 19p13.13, encoding Lysine-specific demethylase RAD23A (P54725). Multifunctional protein that participates in histone H4K20 demethylation, DNA repair, ubiquitin-dependent protein degradation, transcriptional regulation, and viral replication.

The protein encoded by this gene is one of two human homologs of Saccharomyces cerevisiae Rad23, a protein involved in nucleotide excision repair. Proteins in this family have a modular domain structure consisting of an ubiquitin-like domain (UbL), ubiquitin-associated domain 1 (UbA1), XPC-binding domain and UbA2. The protein encoded by this gene plays an important role in nucleotide excision repair and also in delivery of polyubiquitinated proteins to the proteasome. Alternative splicing results in multiple transcript variants encoding multiple isoforms.

Source: NCBI Gene 5886 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 25 total
• MANE Select transcript: NM_005053

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9812
Approved symbol	RAD23A
Name	RAD23 nucleotide excision repair protein A
Location	19p13.13
Locus type	gene with protein product
Status	Approved
Aliases	HHR23A, MGC111083
Ensembl gene	ENSG00000179262
Ensembl biotype	protein_coding
OMIM	600061
Entrez	5886

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 19 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000316856, ENST00000586375, ENST00000586534, ENST00000588329, ENST00000588826, ENST00000590881, ENST00000591467, ENST00000591499, ENST00000592268, ENST00000593114, ENST00000651137, ENST00000875550, ENST00000875551, ENST00000875552, ENST00000875553, ENST00000875554, ENST00000875555, ENST00000875556, ENST00000875557, ENST00000875558, ENST00000875559, ENST00000925763, ENST00000925764, ENST00000925765, ENST00000943230, ENST00000943231

RefSeq mRNA: 3 — MANE Select: NM_005053 NM_001270362, NM_001270363, NM_005053

CCDS: CCDS12289, CCDS59357, CCDS59358

Canonical transcript exons

ENST00000586534 — 9 exons

Exon	Start	End
ENSE00002776223	12945862	12946020
ENSE00002827039	12952936	12953642
ENSE00003477614	12952689	12952853
ENSE00003506967	12947848	12948009
ENSE00003557742	12949275	12949408
ENSE00003567362	12949081	12949159
ENSE00003580831	12948497	12948552
ENSE00003587266	12948686	12948813
ENSE00003625577	12948177	12948358

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 126.2467 / max 1246.9878, expressed in 1827 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174062	125.5539	1827
174070	0.4653	225
174071	0.2275	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	99.42	gold quality
gastrocnemius	UBERON:0001388	99.11	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.11	gold quality
gluteal muscle	UBERON:0002000	98.90	gold quality
triceps brachii	UBERON:0001509	98.80	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.77	gold quality
diaphragm	UBERON:0001103	98.70	gold quality
biceps brachii	UBERON:0001507	98.68	gold quality
muscle of leg	UBERON:0001383	98.46	gold quality
body of tongue	UBERON:0011876	98.30	gold quality
trabecular bone tissue	UBERON:0002483	97.84	gold quality
olfactory bulb	UBERON:0002264	97.82	gold quality
apex of heart	UBERON:0002098	97.81	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.72	gold quality
lower esophagus	UBERON:0013473	97.71	gold quality
type B pancreatic cell	CL:0000169	97.62	silver quality
popliteal artery	UBERON:0002250	97.58	gold quality
tibial artery	UBERON:0007610	97.58	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.47	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.40	gold quality
heart left ventricle	UBERON:0002084	97.39	gold quality
cardiac ventricle	UBERON:0002082	97.38	gold quality
muscle organ	UBERON:0001630	97.33	gold quality
tongue	UBERON:0001723	97.25	gold quality
aorta	UBERON:0000947	97.22	gold quality
right coronary artery	UBERON:0001625	97.18	gold quality
inferior olivary complex	UBERON:0002127	97.16	gold quality
prefrontal cortex	UBERON:0000451	97.14	gold quality
right atrium auricular region	UBERON:0006631	97.13	gold quality
left uterine tube	UBERON:0001303	97.12	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	42.99
E-MTAB-10042	yes	31.04
E-MTAB-9221	yes	14.76
E-HCAD-9	yes	10.25
E-MTAB-9388	yes	7.79
E-GEOD-106540	no	311.47
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting RAD23A, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-6846-5P	98.81	65.86	1121

Literature-anchored findings (GeneRIF, showing 24)

• involvement of rhp23, a Schizosaccharomyces pombe homolog of the human HHR23A and Saccharomyces cerevisiae RAD23 nucleotide excision repair genes, in cell cycle control and protein ubiquitination (PMID:11788722)
• structures of the UBA domains of HHR23A reveal a conserved hydrophobic surface for protein-protein interactions (PMID:12079361)
• the solution structures of the HHR23A Ubl domain (PMID:12970176)
• Adopts a closed conformation and binds to the proteasomal subunit S5a thereby changing its own conformation. (PMID:14557549)
• hHR23 binds to polyubiquitylated p53 via its carboxyl-terminal ubiquitin-associated (Uba) domain shielding p53 from deubiquitylation (PMID:14645509)
• Data suggest that the UBL domain of HHR23A negatively regulates polyubiquitin/UBA interactions and identify leucine 8 of ubiquitin as an important determinant of chain recognition. (PMID:15321727)
• hHR23A regulates the function of xeroderma pigmentosum C by its association with the nucleotide excision repair activator p53 (PMID:16105547)
• Ufd4, the E3 component of the UFD pathway, is involved in controlling the degradation of Rad4, and Ufd4 and Rad23 exhibit a synthetic inhibitory effect on Rad4 degradation (PMID:16430867)
• hHR23B thus plays a critical role in the activation and function of p53 after specific genotoxic exposures. (PMID:16924240)
• hHR23a and hPLIC2 interact via UBL/UBA domain interactions (PMID:17098253)
• UIM2 domain of S5a binds preferentially to hHR23a over polyubiquitin, and a model is provided for the ternary complex that represents one of the mechanisms used by the proteasome to capture ubiquitylated substrates. (PMID:17408689)
• Pyramidal crystals of the UbL domain of hHR23A were diffracted to beyond 2 A resolution and the structure was solved by molecular replacement. (PMID:19724136)
• Vpr promotes hHR23A-mediated protein-ubiquitination, and down-regulation of hHR23A using RNAi significantly reduced viral replication in non-proliferating MAGI-CCR5 cells and primary macrophages (PMID:20614012)
• Determined is the three-dimensional structure of its ubiquitin-like (UbL) domain by X-ray crystallography. (PMID:21047872)
• this study identified RAD23A as a novel negative regulator of RIG-I/MDA5 mediated anti-virus response. (PMID:23357418)
• Here, we show that hHR23A utilizes both the UBA2 and XPCB domains to form a stable complex with Vpr, linking Vpr directly to cellular DNA repair pathways and their probable exploitation by the virus. (PMID:24318982)
• Data indicate that phosphorylation provides a mechanism to regulate Rad23/proteasome interaction. (PMID:25311859)
• hHR23A associates with Chk1 through its ubiquitin-associated domains, and knockdown of hHR23A increases and stabilizes the protein level of Chk1 and its phosphorylation at S347. (PMID:26296656)
• Data indicate that HR23A protein-depleted cells exhibit enhanced autophagy when treated with DNA-damaging agents. (PMID:27613096)
• HR23A role in DNA reapair, in protein degradation and stability, tumorigenesis and neurodegenerative disorders [review] (PMID:27771451)
• The HR23A-knockdown cells appear to undergo epithelial-mesenchymal transition and take on certain attributes of cancer stemness. (PMID:31487504)
• Histone H4K20 Demethylation by Two hHR23 Proteins. (PMID:32209475)
• Kinetic Constraints in the Specific Interaction between Phosphorylated Ubiquitin and Proteasomal Shuttle Factors. (PMID:34356632)
• Structure of HIV-1 Vpr in complex with the human nucleotide excision repair protein hHR23A. (PMID:34824204)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rad23aa	ENSDARG00000020001
mus_musculus	Rad23a	ENSMUSG00000003813
rattus_norvegicus	Rad23a	ENSRNOG00000003026
drosophila_melanogaster	CG10694	FBGN0039147
caenorhabditis_elegans		WBGENE00013924

Paralogs (1): RAD23B (ENSG00000119318)

Protein

Protein identifiers

Lysine-specific demethylase RAD23A — P54725 (reviewed: P54725)

Alternative names: UV excision repair protein RAD23 homolog A

All UniProt accessions (6): A0A494C0B4, K7ELU6, K7ELW1, K7ENJ0, K7EQ16, P54725

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional protein that participates in histone H4K20 demethylation, DNA repair, ubiquitin-dependent protein degradation, transcriptional regulation, and viral replication. 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. Involved in modulation of proteasomal degradation. Binds to ‘Lys-48’-linked polyubiquitin chains in a length-dependent manner and with a lower affinity to ‘Lys-63’-linked 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. Involved in nucleotide excision repair, is considered functionally equivalent to RAD23B in global genome nucleotide excision repair (GG-NER) through its association with XPC. In vitro, the XPC-RAD23A complex demonstrates NER activity. Can stabilize XPC. (Microbial infection) Involved in -dependent replication of HIV-1 in non-proliferating cells and primary macrophages. Required for the association of HIV-1 Vpr with the host proteasome.

Subunit / interactions. Interacts with XPC; the interaction suggests the existence of a functional equivalent variant XPC complex composed of XPC, RAD23A and CETN2. RAD23A is expressed at a much higher level than RAD23B; consequently, most XPC complexes contain RAD23B. Interacts with PSMD4. Interacts with ATXN3. Interacts with UBQLN2. (Microbial infection) Interacts with HIV-1 Vpr.

Subcellular location. Nucleus.

Domain organisation. Both UBA domains are crucial for substrate binding and demethylase activity. The ubiquitin-like domain mediates interaction with ATXN3. The ubiquitin-like (UBL) and the UBA (ubiquitin-associated) domains interact intramolecularly in a highly dynamic manner, as each UBA domain competes for an overlapping UBL domain surface. Binding of ubiquitin or proteasome subunit PSMD4 disrupt the UBL-UBA domain interactions and drive RAD23A in to an open conformation.

Similarity. Belongs to the RAD23 family.

Isoforms (3)

UniProt ID	Names	Canonical?
P54725-1	1	yes
P54725-2	2
P54725-3	3

RefSeq proteins (3): NP_001257291, NP_001257292, NP_005044* (*=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 (72 total): mutagenesis site 15, helix 13, strand 12, modified residue 8, turn 8, domain 3, sequence variant 3, region of interest 3, compositionally biased region 3, splice variant 2, chain 1, cross-link 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
6W2G	X-RAY DIFFRACTION	1.1
7TGP	X-RAY DIFFRACTION	1.4
6W2I	X-RAY DIFFRACTION	1.45
6W2H	X-RAY DIFFRACTION	1.6
2WYQ	X-RAY DIFFRACTION	1.65
8Q06	X-RAY DIFFRACTION	1.9
6XQI	X-RAY DIFFRACTION	2.34
1DV0	SOLUTION NMR
1F4I	SOLUTION NMR
1IFY	SOLUTION NMR
1OQY	SOLUTION NMR
1P98	SOLUTION NMR
1P9D	SOLUTION NMR
1QZE	SOLUTION NMR
1TP4	SOLUTION NMR
5XBO	SOLUTION NMR
6XQJ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54725-F1	70.74	0.06

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 (9): 123, 128, 133, 136, 138, 205, 295, 357, 122

Mutagenesis-validated functional residues (15):

Position	Phenotype
8	no effect on interaction with eef1a1.
9	abolishes interaction with psmd4; when associated with t-49.
10	impairs ubl-uba domain interaction and enhances ubiquitin-binding; when associated with e-47.
47	no effect on ubl-uba domain interaction.
47	impairs ubl-uba domain interaction and enhances ubiquitin-binding; when associated with e-10. impairs ubl-uba domain int
49	impairs interaction with psmd4.
49	abolishes interaction with psmd4; when associated with a-9.
54	impairs interaction with psmd4.
71	impairs interaction with psmd4.
77	impairs ubl-uba domain interaction and enhances ubiquitin-binding; when associated with e-47.
77	no effect on interaction with psmd4.
79	increases interaction with psmd1 and psmc1.
192	decreases binding to ni(2+). abolishes binding to ni(2+); when associated with a-196.
196	decreases binding to ni(2+). abolishes binding to ni(2+); when associated with a-192.
333	abolishes interaction with hiv-1 vpr.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
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: 286 (showing top): REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, MORF_DNMT1, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, MORF_ESPL1, MORF_SMC1L1, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, MODULE_151, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MORF_HDAC1, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, MORF_UBE2N, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_VIRAL_GENOME_REPLICATION

GO Biological Process (12): nucleotide-excision repair (GO:0006289), protein destabilization (GO:0031648), regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032434), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), positive regulation of viral genome replication (GO:0045070), positive regulation of cell cycle (GO:0045787), UV-damage excision repair (GO:0070914), DNA repair (GO:0006281), DNA damage response (GO:0006974), cellular response to stress (GO:0033554), regulation of proteasomal protein catabolic process (GO:0061136)

GO Molecular Function (9): damaged DNA binding (GO:0003684), single-stranded DNA binding (GO:0003697), kinase binding (GO:0019900), polyubiquitin modification-dependent protein binding (GO:0031593), histone H4K20 demethylase activity (GO:0035575), ubiquitin binding (GO:0043130), proteasome binding (GO:0070628), ubiquitin-specific protease binding (GO:1990381), protein binding (GO:0005515)

GO Cellular Component (7): proteasome complex (GO:0000502), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Global Genome Nucleotide Excision Repair (GG-NER)	2
Deubiquitination	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA repair	2
proteasome-mediated ubiquitin-dependent protein catabolic process	2
proteasomal protein catabolic process	2
DNA binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
regulation of protein stability	1
regulation of proteasomal protein catabolic process	1
regulation of ubiquitin-dependent protein catabolic process	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
ubiquitin-dependent protein catabolic process	1
viral genome replication	1
regulation of viral genome replication	1
positive regulation of viral process	1
cell cycle	1
positive regulation of cellular process	1
regulation of cell cycle	1
cellular response to UV	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
response to stress	1
cellular response to stimulus	1
regulation of protein catabolic process	1
enzyme binding	1
modification-dependent protein binding	1
2-oxoglutarate-dependent dioxygenase activity	1
histone H4 demethylase activity	1
ubiquitin-like protein binding	1
protein-containing complex binding	1
protease binding	1
binding	1
intracellular protein-containing complex	1
endopeptidase complex	1
nuclear lumen	1
intracellular anatomical structure	1
endomembrane system	1

Protein interactions and networks

STRING

4482 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAD23A	ATXN3	P54252	985
RAD23A	ATXN3L	Q9H3M9	965
RAD23A	CETN2	P41208	962
RAD23A	XPC	Q01831	950
RAD23A	PSMD4	P55036	941
RAD23A	UBA2	Q9UBT2	855
RAD23A	ADRM1	Q16186	825
RAD23A	XPA	P23025	823
RAD23A	UBE4B	O95155	818
RAD23A	UBA1	P22314	809
RAD23A	UBE3A	P78355	809
RAD23A	UBQLN2	Q9UHD9	801
RAD23A	ERCC1	P07992	768
RAD23A	VCP	P55072	745
RAD23A	DDB1	Q16531	735

IntAct

336 interactions, top by confidence:

A	B	Type	Score
RAD23A	PSMD4	psi-mi:“MI:0407”(direct interaction)	0.950
PSMD4	RAD23A	psi-mi:“MI:2364”(proximity)	0.950
PSMD4	RAD23A	psi-mi:“MI:0915”(physical association)	0.950
RAD23A	PSMD4	psi-mi:“MI:0915”(physical association)	0.950
RAD23A	USP25	psi-mi:“MI:0915”(physical association)	0.890
USP25	RAD23A	psi-mi:“MI:0915”(physical association)	0.890
RAD23A	TRAF2	psi-mi:“MI:0915”(physical association)	0.870
TRAF2	RAD23A	psi-mi:“MI:0915”(physical association)	0.870
RAD23A		psi-mi:“MI:0407”(direct interaction)	0.860
	RAD23A	psi-mi:“MI:0915”(physical association)	0.860
	RAD23A	psi-mi:“MI:0407”(direct interaction)	0.860

BioGRID (468): TRAF2 (Two-hybrid), TRAF5 (Two-hybrid), TRIP6 (Two-hybrid), ZBTB44 (Two-hybrid), USP25 (Two-hybrid), NGLY1 (Two-hybrid), TRIM54 (Two-hybrid), FAM188A (Two-hybrid), ANKRD40 (Two-hybrid), ZBTB8A (Two-hybrid), RAD23A (Co-crystal Structure), RAD23A (Co-crystal Structure), RAD23A (Biochemical Activity), UBC (Reconstituted Complex), RAD23A (Reconstituted Complex)

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, D5LXJ0, G1SK22, G5EFF7, O14399, P0C032, P0C273, P0C275, P0C276

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
UBE3A	“down-regulates quantity by destabilization”	RAD23A	polyubiquitination
SMURF1	unknown	RAD23A	ubiquitination
DNA_damage	up-regulates	RAD23A
DDB1	up-regulates	RAD23A

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 62 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
TNFR1-induced NF-kappa-B signaling pathway	5	40.0×	1e-05
Ovarian tumor domain proteases	5	33.2×	2e-05
Regulation of TNFR1 signaling	5	26.7×	4e-05
TNFR2 non-canonical NF-kB pathway	6	25.9×	1e-05
Activation of NF-kappaB in B cells	5	23.4×	8e-05
Regulation of PTEN stability and activity	5	21.9×	9e-05
FCERI mediated NF-kB activation	5	18.6×	2e-04
UCH proteinases	6	17.7×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
regulation of canonical NF-kappaB signal transduction	5	43.8×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1516 predictions. Top by Δscore:

Variant	Effect	Δscore
19:12946017:GACG:G	donor_gain	1.0000
19:12946018:ACGGT:A	donor_loss	1.0000
19:12946021:G:GG	donor_gain	1.0000
19:12946021:GTGCG:G	donor_loss	1.0000
19:12947846:A:AG	acceptor_gain	1.0000
19:12947846:AG:A	acceptor_gain	1.0000
19:12947846:AGGT:A	acceptor_gain	1.0000
19:12947847:G:GT	acceptor_gain	1.0000
19:12947847:GG:G	acceptor_gain	1.0000
19:12947847:GGT:G	acceptor_gain	1.0000
19:12947847:GGTG:G	acceptor_gain	1.0000
19:12947847:GGTGA:G	acceptor_gain	1.0000
19:12948007:AAGGT:A	donor_loss	1.0000
19:12948008:AG:A	donor_gain	1.0000
19:12948008:AGGT:A	donor_loss	1.0000
19:12948008:AGGTG:A	donor_gain	1.0000
19:12948009:GG:G	donor_gain	1.0000
19:12948010:G:GA	donor_loss	1.0000
19:12948010:G:GG	donor_gain	1.0000
19:12948011:T:A	donor_loss	1.0000
19:12948169:T:A	acceptor_gain	1.0000
19:12948175:A:AG	acceptor_gain	1.0000
19:12948176:G:GG	acceptor_gain	1.0000
19:12948176:GACC:G	acceptor_gain	1.0000
19:12948176:GACCA:G	acceptor_gain	1.0000
19:12948357:GG:G	donor_gain	1.0000
19:12948358:GG:G	donor_gain	1.0000
19:12948681:CACAG:C	acceptor_loss	1.0000
19:12948682:A:AG	acceptor_gain	1.0000
19:12948682:ACAGT:A	acceptor_gain	1.0000

AlphaMissense

2359 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:12945972:A:C	K8N	1.000
19:12945972:A:T	K8N	1.000
19:12947858:T:C	L28P	1.000
19:12947862:G:C	K29N	1.000
19:12947862:G:T	K29N	1.000
19:12947918:T:A	L48H	1.000
19:12947918:T:C	L48P	1.000
19:12947921:T:A	I49N	1.000
19:12947921:T:C	I49T	1.000
19:12947921:T:G	I49S	1.000
19:12947926:G:C	A51P	1.000
19:12947929:G:C	G52R	1.000
19:12947930:G:A	G52D	1.000
19:12947930:G:T	G52V	1.000
19:12947939:T:C	L55S	1.000
19:12947939:T:G	L55W	1.000
19:12947986:T:C	F71L	1.000
19:12947988:T:A	F71L	1.000
19:12947988:T:G	F71L	1.000
19:12947990:T:A	V72E	1.000
19:12947993:T:A	V73D	1.000
19:12947996:T:A	V74D	1.000
19:12948733:G:C	G174R	1.000
19:12948752:T:A	V180D	1.000
19:12948761:C:A	A183D	1.000
19:12948764:T:C	L184P	1.000
19:12948772:A:C	S187R	1.000
19:12948774:C:A	S187R	1.000
19:12948774:C:G	S187R	1.000
19:12948791:G:C	R193P	1.000

dbSNP variants (sampled 300 via entrez): RS1000094984 (19:12951957 C>A,T), RS1000184497 (19:12947562 C>T), RS1000786637 (19:12946427 G>A), RS1000867927 (19:12945610 G>A), RS1000920495 (19:12945761 C>G,T), RS1001042824 (19:12950523 G>A), RS1001114173 (19:12946585 A>G), RS1001147989 (19:12950655 C>G,T), RS1002001403 (19:12948080 G>A), RS1002269239 (19:12945869 G>A,C,T), RS1002537978 (19:12950670 C>G,T), RS1002698833 (19:12945175 T>G), RS1002750912 (19:12945395 A>G), RS1003137036 (19:12949691 G>A), RS1003238203 (19:12945242 T>A,G)

Disease associations

OMIM: gene MIM:600061 | 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
GCST002595_9	Clozapine-induced agranulocytosis	1.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases methylation, increases expression	3
Cyclosporine	increases expression	3
methylmercuric chloride	increases expression	2
sodium arsenite	increases expression	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	increases oxidation, increases abundance, affects cotreatment	2
Arsenic	increases expression	2
Methylnitronitrosoguanidine	decreases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
pyrithione zinc	increases expression	1
trichostatin A	affects expression	1
coumarin	decreases phosphorylation	1
cupric oxide	decreases phosphorylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
epigallocatechin gallate	decreases expression	1
CPG-oligonucleotide	decreases expression	1
indirubin-3’-monoxime	decreases expression	1
pomiferin	decreases expression	1
osajin	decreases expression	1
bisphenol B	increases expression	1
rosavin	decreases expression	1
eprenetapopt	affects reaction, affects expression	1
bisphenol S	increases expression	1
6-OH-BDE-47	decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3FQ	Abcam HEK293T RAD23A KO	Transformed cell line	Female
CVCL_KT66	HeLa SilenciX HR23A	Cancer cell line	Female

Clinical trials (associated diseases)

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