UBE2O

Summary

UBE2O (ubiquitin conjugating enzyme E2 O, HGNC:29554) is a protein-coding gene on chromosome 17q25.1, encoding (E3-independent) E2 ubiquitin-conjugating enzyme (Q9C0C9). E2/E3 hybrid ubiquitin-protein ligase that displays both E2 and E3 ligase activities and mediates monoubiquitination of target proteins. It is a selective cancer dependency (DepMap: 12.2% of cell lines).

Enables ubiquitin conjugating enzyme activity and ubiquitin protein ligase activity. Involved in positive regulation of BMP signaling pathway; protein ubiquitination; and retrograde transport, endosome to Golgi. Located in cytoplasm and nuclear body.

Source: NCBI Gene 63893 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 152 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 12.2% of screened cell lines
• MANE Select transcript: NM_022066

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29554
Approved symbol	UBE2O
Name	ubiquitin conjugating enzyme E2 O
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	E2-230K
Ensembl gene	ENSG00000175931
Ensembl biotype	protein_coding
OMIM	617649
Entrez	63893

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000319380, ENST00000586409, ENST00000586505, ENST00000587127, ENST00000587581, ENST00000590658, ENST00000915130, ENST00000915131, ENST00000915132, ENST00000915133, ENST00000942172

RefSeq mRNA: 1 — MANE Select: NM_022066 NM_022066

CCDS: CCDS32742

Canonical transcript exons

ENST00000319380 — 18 exons

Exon	Start	End
ENSE00001259635	76391756	76391813
ENSE00001259641	76391910	76392113
ENSE00001259652	76396128	76396821
ENSE00001259731	76389456	76391613
ENSE00001259738	76452725	76453152
ENSE00001506932	76395725	76395861
ENSE00003475675	76401011	76401154
ENSE00003534559	76398472	76398584
ENSE00003536651	76398255	76398383
ENSE00003544101	76399449	76399921
ENSE00003566304	76402602	76402699
ENSE00003580622	76400147	76400297
ENSE00003598812	76398837	76398991
ENSE00003604631	76402064	76402127
ENSE00003606790	76400441	76400550
ENSE00003640196	76405206	76405316
ENSE00003646065	76397799	76397888
ENSE00003657834	76405513	76405572

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 90.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.0589 / max 130.9046, expressed in 1790 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168210	9.5049	1728
168211	6.9318	1688
168212	0.6221	360

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	90.69	gold quality
right frontal lobe	UBERON:0002810	90.22	gold quality
cerebellar hemisphere	UBERON:0002245	90.20	gold quality
cerebellar cortex	UBERON:0002129	90.12	gold quality
cortical plate	UBERON:0005343	89.87	gold quality
apex of heart	UBERON:0002098	89.41	gold quality
prefrontal cortex	UBERON:0000451	88.97	gold quality
gastrocnemius	UBERON:0001388	88.96	gold quality
cerebellum	UBERON:0002037	88.75	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.10	gold quality
ganglionic eminence	UBERON:0004023	88.07	gold quality
muscle of leg	UBERON:0001383	87.92	gold quality
stromal cell of endometrium	CL:0002255	87.70	gold quality
frontal cortex	UBERON:0001870	87.68	gold quality
islet of Langerhans	UBERON:0000006	87.53	gold quality
right lobe of thyroid gland	UBERON:0001119	87.39	gold quality
neocortex	UBERON:0001950	87.37	gold quality
cingulate cortex	UBERON:0003027	87.21	gold quality
anterior cingulate cortex	UBERON:0009835	87.21	gold quality
right atrium auricular region	UBERON:0006631	87.18	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.17	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.72	gold quality
sural nerve	UBERON:0015488	86.53	gold quality
ventricular zone	UBERON:0003053	86.42	gold quality
bone marrow cell	CL:0002092	86.34	gold quality
left lobe of thyroid gland	UBERON:0001120	86.27	gold quality
cardiac atrium	UBERON:0002081	86.03	gold quality
adenohypophysis	UBERON:0002196	85.84	gold quality
heart left ventricle	UBERON:0002084	85.72	gold quality
granulocyte	CL:0000094	85.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

87 targeting UBE2O, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 12.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 18)

• UBE2O negatively regulates TRAF6-mediated NF-kappaB activation by inhibiting TRAF6 polyubiquitination. (PMID:23381138)
• monoubiquitinated SMAD6 impairs the binding affinity of non-modified SMAD6 to the BMP type I receptor. Moreover, UBE2O and SMAD6 cooperated in the regulation of BMP7-induced adipogenesis (PMID:23455153)
• UBE2O defines an atypical ubiquitin-signaling pathway that coordinates the function of BAP1. (PMID:24703950)
• UBE2O specifically targets AMPKalpha2 for ubiquitination and degradation, and thereby promotes activation of the mTOR-HIF1alpha pathway. (PMID:28162974)
• UBE2O mediates c-Maf polyubiquitination and degradation, induces MM cell apoptosis, and suppresses myeloma tumor growth, which provides a novel insight in understanding myelomagenesis and UBE2O biology. (PMID:28673317)
• UBE2O is a self-contained quality control factor that comprises substrate recognition and ubiquitin transfer activities within a single protein to efficiently target orphans of multiprotein complexes for degradation. (PMID:28774922)
• UBE2O is critical for P-TEFb recruitment to the HIV-1 promoter. (PMID:29845934)
• This work identifies UBE2O as a critical regulator in the ubiquitin-proteasome system, which modulates BMAL1 transcriptional activity and circadian function by promoting BMAL1 ubiquitination and degradation under normal physiological conditions. (PMID:29871923)
• UBE2O directly mediates the ubiquitination of many substrates, including AMPKalpha2, BAP1, MLL protein SMAD6, c-Maf, ARNTL, and free ribosomal proteins. UBE2O is frequently amplified or mutated in multiple cancers, and its high expression is associated with low survival rate of gastric, lung, breast, and prostate cancer patients. Review. (PMID:30468556)
• Study found that UBE2O is markedly upregulated in obese subjects with type 2 diabetes. (PMID:31292296)
• UBE2O promotes the proliferation, EMT and stemness properties of breast cancer cells through the UBE2O/AMPKalpha2/mTORC1-MYC positive feedback loop. (PMID:31907353)
• Saliva exosomes-derived UBE2O mRNA promotes angiogenesis in cutaneous wounds by targeting SMAD6. (PMID:32375794)
• UBE2O targets Mxi1 for ubiquitination and degradation to promote lung cancer progression and radioresistance. (PMID:32901121)
• UBE2O promotes hepatocellular carcinoma cell proliferation and invasion by regulating the AMPKalpha2/mTOR pathway. (PMID:34790050)
• UBE2O and USP7 co-regulate RECQL4 ubiquitinylation and homologous recombination-mediated DNA repair. (PMID:34921745)
• Mechanism of client selection by the protein quality-control factor UBE2O. (PMID:35915257)
• High Level of Ubiquitin Conjugate Enzyme E2O Indicates Poor Prognosis of Patients with Hepatocellular Carcinoma. (PMID:36269535)
• Age-Associated UBE2O Reduction Promotes Neuronal Death in Alzheimer’s Disease. (PMID:37182872)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	UBE2O	ENSDARG00000100674
mus_musculus	Ube2o	ENSMUSG00000020802
rattus_norvegicus	Ube2o	ENSRNOG00000011007

Paralogs (24): UBE2T (ENSG00000077152), UBE2A (ENSG00000077721), UBE2K (ENSG00000078140), CDC34 (ENSG00000099804), UBE2I (ENSG00000103275), UBE2W (ENSG00000104343), UBE2R2 (ENSG00000107341), UBE2S (ENSG00000108106), UBE2B (ENSG00000119048), UBE2G1 (ENSG00000132388), UBE2Z (ENSG00000159202), UBE2J2 (ENSG00000160087), AKTIP (ENSG00000166971), UBE2V2 (ENSG00000169139), UBE2C (ENSG00000175063), UBE2U (ENSG00000177414), UBE2N (ENSG00000177889), UBE2F (ENSG00000184182), UBE2G2 (ENSG00000184787), UBE2H (ENSG00000186591), UBE2J1 (ENSG00000198833), PEDS1 (ENSG00000240849), UBE2V1 (ENSG00000244687), UBE2NL (ENSG00000276380)

Protein

Protein identifiers

(E3-independent) E2 ubiquitin-conjugating enzyme — Q9C0C9 (reviewed: Q9C0C9)

Alternative names: E2/E3 hybrid ubiquitin-protein ligase UBE2O, Ubiquitin carrier protein O, Ubiquitin-conjugating enzyme E2 O, Ubiquitin-conjugating enzyme E2 of 230 kDa, Ubiquitin-protein ligase O

All UniProt accessions (3): Q9C0C9, K7EQ12, K7ES11

UniProt curated annotations — full annotation on UniProt →

Function. E2/E3 hybrid ubiquitin-protein ligase that displays both E2 and E3 ligase activities and mediates monoubiquitination of target proteins. Negatively regulates TRAF6-mediated NF-kappa-B activation independently of its E2 activity. Acts as a positive regulator of BMP7 signaling by mediating monoubiquitination of SMAD6, thereby regulating adipogenesis. Mediates monoubiquitination at different sites of the nuclear localization signal (NLS) of BAP1, leading to cytoplasmic retention of BAP1. Also able to monoubiquitinate the NLS of other chromatin-associated proteins, such as INO80 and CXXC1, affecting their subcellular location. Acts as a regulator of retrograde transport by assisting the TRIM27:MAGEL2 E3 ubiquitin ligase complex to mediate ‘Lys-63’-linked ubiquitination of WASHC1, leading to promote endosomal F-actin assembly.

Subunit / interactions. Interacts with CPNE1 (via VWFA domain) and CPNE4 (via VWFA domain). Interacts with UBR2.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Predominantly expressed in skeletal muscle and heart.

Post-translational modifications. Phosphorylated. Phosphorylation affects subcellular location. Ubiquitinated: autoubiquitinates, possibly affecting its subcellular location.

Activity regulation. inhibited by phenylarsine oxide (PAO).

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the ubiquitin-conjugating enzyme family.

RefSeq proteins (1): NP_071349* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000608	UBC	Domain
IPR016135	UBQ-conjugating_enzyme/RWD	Homologous_superfamily
IPR057732	SH3-A_UBE2O	Domain
IPR057733	UBE2O-like_SH3-B	Domain
IPR057734	UBE2O-like_SH3-C	Domain
IPR057735	UBE2O-like_tSH3-B	Domain

Pfam: PF00179, PF23043, PF23044, PF23046, PF23048

Enzyme classification (BRENDA):

• EC 2.3.2.24 — (E3-independent) E2 ubiquitin-conjugating enzyme (BRENDA: 5 organisms, 56 substrates, 7 inhibitors, 6 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[HISTONE H2A]-L-LYSINE	0.0008–0.0028	2
[HISTONE H2B]-L-LYSINE	0.0015–0.012	2
[CYTOCHROME C]-L-LYSINE	0.125	1
[HISTONE H3]-L-LYSINE	0.0013	1

UniProt features (104 total): strand 43, helix 14, modified residue 13, compositionally biased region 7, region of interest 7, sequence conflict 7, turn 6, chain 1, domain 1, short sequence motif 1, active site 1, sequence variant 1, mutagenesis site 1, coiled-coil region 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
9QUG	X-RAY DIFFRACTION	1.8
9MC5	ELECTRON MICROSCOPY	3.29
7UN6	ELECTRON MICROSCOPY	3.3
9MC4	ELECTRON MICROSCOPY	3.32
9MC6	ELECTRON MICROSCOPY	3.32
9MC7	ELECTRON MICROSCOPY	3.34
9MC9	ELECTRON MICROSCOPY	3.37
9MCB	ELECTRON MICROSCOPY	3.42
7UN3	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C0C9-F1	66.88	0.33

Functional residue map

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

Catalytic / active sites (1): 1040 (glycyl thioester intermediate)

Post-translational modifications (13): 50, 87, 89, 399, 401, 441, 488, 491, 515, 836, 838, 839, 896

Mutagenesis-validated functional residues (1):

Position	Phenotype
1040	loss of function.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 159 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GCANCTGNY_MYOD_Q6, SP3_Q3, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, CAGGTCC_MIR492, CAGCTG_AP4_Q5, SP1_Q2_01, GTGCCTT_MIR506, GOBP_POSITIVE_REGULATION_OF_BMP_SIGNALING_PATHWAY, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY

GO Biological Process (5): protein monoubiquitination (GO:0006513), positive regulation of BMP signaling pathway (GO:0030513), retrograde transport, endosome to Golgi (GO:0042147), protein K63-linked ubiquitination (GO:0070534), protein ubiquitination (GO:0016567)

GO Molecular Function (8): RNA binding (GO:0003723), ubiquitin-protein transferase activity (GO:0004842), ATP binding (GO:0005524), ubiquitin protein ligase activity (GO:0061630), ubiquitin conjugating enzyme activity (GO:0061631), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
ubiquitin-protein transferase activity	2
protein ubiquitination	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
intercellular transport	1
endosomal transport	1
cytosolic transport	1
protein polyubiquitination	1
protein modification by small protein conjugation	1
nucleic acid binding	1
ubiquitin-like protein transferase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ubiquitin-like protein ligase activity	1
ubiquitin-like protein conjugating enzyme activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2917 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBE2O	UBE2H	P37286	548
UBE2O	MAGEL2	Q9UJ55	527
UBE2O	TRIM27	P14373	514
UBE2O	UBE2J2	Q8N2K1	501
UBE2O	UBA1	P22314	493
UBE2O	MEPCE	Q7L2J0	480
UBE2O	LARP7	Q4G0J3	472
UBE2O	SUMO2	P55855	464
UBE2O	PSMA2	P25787	462
UBE2O	ASXL1	Q8IXJ9	458
UBE2O	HERC4	Q5GLZ8	457
UBE2O	UBE2J1	Q9Y385	454
UBE2O	MYCBP2	O75592	433
UBE2O	UBE2G1	P62253	433
UBE2O	ANKRD17	O75179	430
UBE2O	UBE2W	Q96B02	430

IntAct

303 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
INO80E	TFPT	psi-mi:“MI:0914”(association)	0.790
PIP4K2A	AHCYL1	psi-mi:“MI:0914”(association)	0.730
BAP1	OGT	psi-mi:“MI:0914”(association)	0.730
UBE2O	APPL1	psi-mi:“MI:0915”(physical association)	0.720
APPL1	UBE2O	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RIOK1	PRMT5	psi-mi:“MI:0914”(association)	0.710
UBA52	UBE2O	psi-mi:“MI:0915”(physical association)	0.660
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
NOL12	RRP8	psi-mi:“MI:0914”(association)	0.640
CHEK2	PPM1G	psi-mi:“MI:0914”(association)	0.560
SFMBT2	UBE2O	psi-mi:“MI:0915”(physical association)	0.560
UBE2O	GNB2	psi-mi:“MI:0915”(physical association)	0.560
GNB2	UBE2O	psi-mi:“MI:0915”(physical association)	0.560
UBE2O	PRKN	psi-mi:“MI:0915”(physical association)	0.560
VHL	UBE2O	psi-mi:“MI:0915”(physical association)	0.560
YBX1	UBE2O	psi-mi:“MI:0915”(physical association)	0.550
ZNF707	ZNF316	psi-mi:“MI:0914”(association)	0.530

BioGRID (986): UBE2O (Two-hybrid), UBE2O (Affinity Capture-RNA), UBE2O (Co-fractionation), UBE2O (Affinity Capture-MS), UBE2O (Affinity Capture-MS), UBE2O (Affinity Capture-MS), UBE2O (Affinity Capture-MS), UBE2O (Affinity Capture-MS), UBE2O (Affinity Capture-MS), UBE2O (Affinity Capture-MS), UBE2O (Affinity Capture-MS), UBE2O (Affinity Capture-MS), UBE2O (Affinity Capture-MS), UBE2O (Affinity Capture-MS), UBE2O (Affinity Capture-MS)

ESM2 similar proteins: A0JMK9, A0JMT0, A2BIL7, A8DZJ1, D4AEC2, F4IDY7, O60268, O88379, P13864, P61406, Q03111, Q12830, Q24K09, Q3T8J9, Q4R707, Q4V7A6, Q535K8, Q5R8B0, Q5RAK6, Q5S003, Q63ZP1, Q640I9, Q6DD45, Q6P1G2, Q6ZRS2, Q7TNN8, Q80Y56, Q86US8, Q86W92, Q8BMD7, Q8BRB7, Q8BZ21, Q8C1B1, Q8R0A7, Q8WML3, Q8WUB8, Q92539, Q92794, Q96KC8, Q98TA5

Diamond homologs: A5PKP9, F4HPP7, O74196, O88738, P15732, P25867, P35129, P46595, P50623, P51965, P52482, P52483, P52485, P52487, P52490, P61077, P61078, P61079, P62837, P62838, P62839, P62840, P70711, Q02159, Q06AA9, Q11076, Q1RMX2, Q2T9X7, Q3B7D1, Q3UE37, Q3ZCF7, Q4R5N4, Q5R4V7, Q5UQ88, Q5ZKX6, Q66KB0, Q6DG60, Q6PCF7, Q6ZPJ3, Q6ZWY6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
UBE2O	down-regulates	SMAD6	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 209 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
Dengue Virus Genome Translation and Replication	5	10.8×	4e-03
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	13	10.4×	1e-07
Peptide chain elongation	12	10.4×	2e-07
Viral mRNA Translation	12	10.4×	2e-07
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	12	10.2×	2e-07
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	5	10.2×	5e-03
Formation of a pool of free 40S subunits	13	9.9×	2e-07
Selenocysteine synthesis	12	9.8×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	13	12.6×	4e-08
ribosomal small subunit biogenesis	7	8.3×	5e-03
translation	13	7.0×	3e-05
rRNA processing	9	6.7×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	132
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3293 predictions. Top by Δscore:

Variant	Effect	Δscore
17:76391609:CAGAC:C	acceptor_gain	1.0000
17:76391614:C:CA	acceptor_loss	1.0000
17:76391614:C:CC	acceptor_gain	1.0000
17:76391751:TGTA:T	donor_loss	1.0000
17:76391752:GTAC:G	donor_loss	1.0000
17:76391753:TA:T	donor_loss	1.0000
17:76391754:A:C	donor_loss	1.0000
17:76391755:C:CG	donor_loss	1.0000
17:76391812:CCCT:C	acceptor_loss	1.0000
17:76391814:C:A	acceptor_loss	1.0000
17:76391815:T:G	acceptor_loss	1.0000
17:76391907:CACCT:C	donor_loss	1.0000
17:76391909:C:CG	donor_loss	1.0000
17:76395858:TTTG:T	acceptor_gain	1.0000
17:76395862:C:CC	acceptor_gain	1.0000
17:76396122:ACTC:A	donor_loss	1.0000
17:76396124:TCACA:T	donor_loss	1.0000
17:76396125:CA:C	donor_loss	1.0000
17:76396126:A:AC	donor_gain	1.0000
17:76396127:C:CC	donor_gain	1.0000
17:76396127:CA:C	donor_gain	1.0000
17:76396127:CAGG:C	donor_gain	1.0000
17:76396817:AAGTG:A	acceptor_gain	1.0000
17:76396818:AGTG:A	acceptor_gain	1.0000
17:76396819:GTG:G	acceptor_gain	1.0000
17:76396820:TG:T	acceptor_gain	1.0000
17:76396822:C:CC	acceptor_gain	1.0000
17:76397793:CCTCA:C	donor_loss	1.0000
17:76397794:CTCAC:C	donor_loss	1.0000
17:76397795:TCA:T	donor_loss	1.0000

AlphaMissense

8494 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:76391032:C:G	G1264R	1.000
17:76391037:G:A	S1262F	1.000
17:76391517:T:A	E1102V	1.000
17:76391545:C:G	G1093R	1.000
17:76391570:G:C	F1084L	1.000
17:76391570:G:T	F1084L	1.000
17:76391572:A:G	F1084L	1.000
17:76391592:G:T	P1077Q	1.000
17:76391604:A:G	L1073P	1.000
17:76391610:A:G	L1071P	1.000
17:76391756:C:G	G1070R	1.000
17:76391770:A:G	L1065P	1.000
17:76391779:A:G	L1062P	1.000
17:76391799:C:A	W1055C	1.000
17:76391799:C:G	W1055C	1.000
17:76391800:C:G	W1055S	1.000
17:76391801:A:G	W1055R	1.000
17:76391801:A:T	W1055R	1.000
17:76391914:C:T	G1049E	1.000
17:76391919:C:A	W1047C	1.000
17:76391919:C:G	W1047C	1.000
17:76391921:A:G	W1047R	1.000
17:76391921:A:T	W1047R	1.000
17:76391926:C:A	G1045V	1.000
17:76391926:C:T	G1045D	1.000
17:76391927:C:G	G1045R	1.000
17:76391929:A:G	L1044P	1.000
17:76391932:A:G	L1043P	1.000
17:76391932:A:T	L1043H	1.000
17:76391934:G:C	S1042R	1.000

dbSNP variants (sampled 300 via entrez): RS1000048822 (17:76400869 C>T), RS1000086364 (17:76444400 A>G,T), RS1000119220 (17:76423373 C>G), RS1000166377 (17:76422330 C>T), RS1000171761 (17:76428325 T>C), RS1000212197 (17:76390842 T>C,G), RS1000268942 (17:76431819 T>C), RS1000284253 (17:76412739 G>A), RS1000290085 (17:76395502 T>A), RS1000431117 (17:76434413 C>T), RS1000532086 (17:76439896 G>A), RS1000649812 (17:76402285 C>A,T), RS1000687362 (17:76445777 A>G,T), RS1000778233 (17:76408107 A>G), RS1000794556 (17:76451074 G>A)

Disease associations

OMIM: gene MIM:617649 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST002616_12	Mitochondrial DNA levels	9.000000e-06
GCST004627_178	Lymphocyte count	3.000000e-11
GCST004632_10	Lymphocyte percentage of white cells	4.000000e-11
GCST90002386_196	High light scatter reticulocyte percentage of red cells	4.000000e-09
GCST90002389_243	Lymphocyte percentage of white cells	5.000000e-22
GCST90002399_252	Neutrophil percentage of white cells	2.000000e-14
GCST90002401_556	Platelet distribution width	8.000000e-16
GCST90002405_392	Reticulocyte count	3.000000e-13
GCST90002405_393	Reticulocyte count	6.000000e-15
GCST90002406_472	Reticulocyte fraction of red cells	8.000000e-15
GCST90002406_473	Reticulocyte fraction of red cells	5.000000e-18
GCST90002407_151	White blood cell count	1.000000e-15

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006312	mitochondrial DNA measurement
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007984	platelet component distribution width
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295940 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
bisphenol A	decreases expression	2
Cyclosporine	increases expression	2
Copper Sulfate	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
chloroacetaldehyde	decreases expression	1
triphenyl phosphate	affects expression	1
cobaltous chloride	increases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
adefovir dipivoxil	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Cidofovir	affects expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Caffeine	affects phosphorylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Clodronic Acid	decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Lead	increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Oxygen	increases 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
CHEMBL4118969	Binding	Binding affinity to UBE2O in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2K8	Abcam HeLa UBE2O KO	Cancer cell line	Female
CVCL_TV82	HAP1 UBE2O (-) 1	Cancer cell line	Male
CVCL_TV83	HAP1 UBE2O (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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