UBE2V2

Summary

UBE2V2 (ubiquitin conjugating enzyme E2 V2, HGNC:12495) is a protein-coding gene on chromosome 8q11.21, encoding Ubiquitin-conjugating enzyme E2 variant 2 (Q15819). Has no ubiquitin ligase activity on its own.

Ubiquitin-conjugating enzyme E2 variant proteins constitute a distinct subfamily within the E2 protein family. They have sequence similarity to other ubiquitin-conjugating enzymes but lack the conserved cysteine residue that is critical for the catalytic activity of E2s. The protein encoded by this gene also shares homology with ubiquitin-conjugating enzyme E2 variant 1 and yeast MMS2 gene product. It may be involved in the differentiation of monocytes and enterocytes.

Source: NCBI Gene 7336 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_003350

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12495
Approved symbol	UBE2V2
Name	ubiquitin conjugating enzyme E2 V2
Location	8q11.21
Locus type	gene with protein product
Status	Approved
Aliases	UEV-2, DDVit-1, EDPF-1, MMS2, UEV2, EDPF1, DDVIT1, EDAF-1
Ensembl gene	ENSG00000169139
Ensembl biotype	protein_coding
OMIM	603001
Entrez	7336

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000517630, ENST00000518360, ENST00000520595, ENST00000520809, ENST00000521346, ENST00000521628, ENST00000523111, ENST00000523432, ENST00000851852

RefSeq mRNA: 1 — MANE Select: NM_003350 NM_003350

CCDS: CCDS43738

Canonical transcript exons

ENST00000523111 — 4 exons

Exon	Start	End
ENSE00002110020	48008431	48008470
ENSE00002116163	48060682	48064708
ENSE00003500674	48043033	48043181
ENSE00003967657	48049853	48049978

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.4588 / max 2171.6600, expressed in 1819 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88783	66.7408	1819
88788	0.4016	148
88789	0.3164	128

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.17	gold quality
ganglionic eminence	UBERON:0004023	97.37	gold quality
adrenal tissue	UBERON:0018303	97.17	gold quality
ventricular zone	UBERON:0003053	96.87	gold quality
prefrontal cortex	UBERON:0000451	96.67	gold quality
pons	UBERON:0000988	96.50	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.42	gold quality
embryo	UBERON:0000922	96.39	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.97	gold quality
islet of Langerhans	UBERON:0000006	95.86	gold quality
calcaneal tendon	UBERON:0003701	95.39	gold quality
cartilage tissue	UBERON:0002418	95.35	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.24	gold quality
oral cavity	UBERON:0000167	95.21	gold quality
right frontal lobe	UBERON:0002810	95.15	gold quality
amygdala	UBERON:0001876	95.09	gold quality
tibial artery	UBERON:0007610	95.00	gold quality
popliteal artery	UBERON:0002250	94.99	gold quality
frontal cortex	UBERON:0001870	94.95	gold quality
neocortex	UBERON:0001950	94.84	gold quality
esophagus squamous epithelium	UBERON:0006920	94.74	gold quality
cerebral cortex	UBERON:0000956	94.67	gold quality
orbitofrontal cortex	UBERON:0004167	94.64	gold quality
nucleus accumbens	UBERON:0001882	94.63	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.59	gold quality
superior vestibular nucleus	UBERON:0007227	94.55	gold quality
substantia nigra	UBERON:0002038	94.47	gold quality
tendon	UBERON:0000043	94.41	gold quality
telencephalon	UBERON:0001893	94.41	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.41	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.15
E-MTAB-6678	no	3.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

119 targeting UBE2V2, 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-4795-3P	100.00	74.62	4024
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-340-5P	100.00	72.50	4437
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
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-6772-5P	99.94	67.01	577

Literature-anchored findings (GeneRIF, showing 17)

• Ubc13-Mms2 and Lys63-polyubiquitin chains are associated with signaling cellular stress (PMID:14562038)
• UBE2v2 signalling through PCNA ubiquitination is not required for immunoglobulin diversification in DT40 cells. (PMID:15725630)
• The results in this study allowed identification of important residues of the Ubc13-Mms2 interface, determine a correlation between heterodimer formation and function, and conclude why Mms2 forms a specific complex with Ubc13 but not other Ubc proteins. (PMID:15749714)
• Insight into the influence of protein dynamics on the affinity of ubiquitin for Mms2. (PMID:15952783)
• Data demonstrate that divergent activities of Ubc13 rely on its pairing with either of two Uevs, Uev1A or Mms2. (PMID:16129784)
• Mms2 physical association with ubiquitin is correlated with its ability to promote Lys63-linked ubiquitin chain assembly (PMID:17964296)
• These results point to a high level of redundancy in the DNA damage tolerance pathway and suggest the existence of another hMMS2 variant (hMMSv) or complex that can compensate for its loss. (PMID:18284681)
• entire coding region and splice junctions of RNF8, UBC13 and MMS2 genes were screened for mutations in affected index cases from 123 Northern Finnish breast cancer families (PMID:21774837)
• Data show RING finger (RNF) E3 ubiquitin ligase RNF8 dimerizes and binds to E2 ubiquitin-conjugating complex Ubc13/Mms2 with formation of Lys-63 ubiquitin chains, whereas the RNF168 RING domain is a monomer and does not catalyze Lys-6 ubiquitylation. (PMID:22589545)
• the crystal structure of human OTUB1 in complex with human UBC13 and MMS2 (PMID:22679021)
• suppression of hMMS2 reverses L-OHP tolerance in differentiated human colorectal carcinoma cells by promoting apoptosis (PMID:24846979)
• Functional analysis of selected regulated proteins revealed that knockdown of HNRPD, PHB2 and UB2V2 can increase HCMV replication, while knockdown of A4 and KSRP resulted in decreased HCMV replication. (PMID:25910425)
• Data suggest that ubiquitin-conjugating enzyme E2 variant 2 (Ube2V2) and ring finger protein 4 (RNF4) together induce an active conformation of the ubiquitin-conjugating enzyme Ubc13-ubiquitin (Ubc13~Ub) thioester. (PMID:26148049)
• Ubc13-Mms2 cooperates with a family of RING E3 proteins in budding yeast membrane protein sorting. (PMID:32265276)
• Uev1A amino terminus stimulates poly-ubiquitin chain assembly and is required for NF-kappaB activation. (PMID:32659264)
• UBE2V2 Positively Correlates With PD-L1 Expression and Confers Poor Patient Survival in Lung Adenocarcinoma. (PMID:33734107)
• UBE2V2 promotes metastasis by regulating EMT and predicts a poor prognosis in lung adenocarcinoma. (PMID:37755128)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ube2v2	ENSDARG00000028198
mus_musculus	Ube2v2	ENSMUSG00000022674
rattus_norvegicus		ENSRNOG00000056621
drosophila_melanogaster	Uev1A	FBGN0035601
caenorhabditis_elegans	uev-1	WBGENE00006730

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), UBE2C (ENSG00000175063), UBE2O (ENSG00000175931), UBE2U (ENSG00000177414), UBE2N (ENSG00000177889), UBE2F (ENSG00000184182), UBE2G2 (ENSG00000184787), UBE2H (ENSG00000186591), UBE2J1 (ENSG00000198833), PEDS1 (ENSG00000240849), UBE2V1 (ENSG00000244687), UBE2NL (ENSG00000276380)

Protein

Protein identifiers

Ubiquitin-conjugating enzyme E2 variant 2 — Q15819 (reviewed: Q15819)

Alternative names: DDVit 1, Enterocyte differentiation-associated factor 1, Enterocyte differentiation-promoting factor 1, MMS2 homolog, Vitamin D3-inducible protein

All UniProt accessions (5): Q15819, A0M8W4, E5RIF1, G3V113, H0YBX6

UniProt curated annotations — full annotation on UniProt →

Function. Has no ubiquitin ligase activity on its own. The UBE2V2/UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through ‘Lys-63’. This type of poly-ubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage.

Subunit / interactions. Heterodimer with UBE2N. Binds CHFR.

Tissue specificity. Detected in placenta, colon, liver and skin. Detected at very low levels in most tissues.

Induction. Up-regulated in cultured fresh blood cells upon treatment with vitamin D3.

Similarity. Belongs to the ubiquitin-conjugating enzyme family.

RefSeq proteins (1): NP_003341* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000608	UBC	Domain
IPR016135	UBQ-conjugating_enzyme/RWD	Homologous_superfamily

Pfam: PF00179

Enzyme classification (BRENDA):

• EC 2.3.2.23 — E2 ubiquitin-conjugating enzyme (BRENDA: 20 organisms, 93 substrates, 28 inhibitors, 12 Km, 8 kcat entries)
• 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)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[UBIQUITIN-CARRIER-PROTEIN UBC2B]-L-CYSTEINE	0.0001	5
[UBE2W]-S-UBIQUITINYL-L-CYSTEINE	0.2203–0.3014	2
[HISTONE H2A]-L-LYSINE	0.0008–0.0028	2
[HISTONE H2B]-L-LYSINE	0.0015–0.012	2
S-UBIQUITINYL-[E1 UBIQUITIN-ACTIVATING ENZYME]-L	1	1
[UBIQUITIN CARRIER PROTEIN UBC4]-L-CYSTEINE	0.0019	1
[CYTOCHROME C]-L-LYSINE	0.125	1
[HISTONE H3]-L-LYSINE	0.0013	1

UniProt features (19 total): strand 5, helix 5, turn 3, sequence variant 2, initiator methionine 1, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
4ONL	X-RAY DIFFRACTION	1.35
4ONM	X-RAY DIFFRACTION	1.35
4ONN	X-RAY DIFFRACTION	1.5
9BIV	X-RAY DIFFRACTION	1.68
9LHJ	X-RAY DIFFRACTION	1.68
8WR5	X-RAY DIFFRACTION	1.7
4NR3	X-RAY DIFFRACTION	1.8
1J7D	X-RAY DIFFRACTION	1.85
1J74	X-RAY DIFFRACTION	1.9
4NRG	X-RAY DIFFRACTION	1.95
9N1F	X-RAY DIFFRACTION	2.1
7BBD	X-RAY DIFFRACTION	2.2
4NRI	X-RAY DIFFRACTION	2.3
7BBF	X-RAY DIFFRACTION	2.54
3VON	X-RAY DIFFRACTION	3.15
5AIT	X-RAY DIFFRACTION	3.4
4ORH	X-RAY DIFFRACTION	4.8
1ZGU	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15819-F1	94.86	0.92

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): 2

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693571	Nonhomologous End-Joining (NHEJ)
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-5696395	Formation of Incision Complex in GG-NER
R-HSA-69473	G2/M DNA damage checkpoint
R-HSA-8866654	E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 217 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_DNA_DAMAGE_TOLERANCE, KAUFFMANN_DNA_REPAIR_GENES, GOBP_REGULATION_OF_DNA_REPAIR, ATGTTAA_MIR302C

GO Biological Process (9): protein polyubiquitination (GO:0000209), DNA double-strand break processing (GO:0000729), regulation of DNA repair (GO:0006282), DNA damage tolerance (GO:0006301), protein ubiquitination (GO:0016567), error-free postreplication DNA repair (GO:0042275), protein K63-linked ubiquitination (GO:0070534), positive regulation of protein K63-linked ubiquitination (GO:1902523), positive regulation of double-strand break repair (GO:2000781)

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

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), ubiquitin conjugating enzyme complex (GO:0031371), UBC13-MMS2 complex (GO:0031372), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
DNA Double Strand Break Response	1
DNA Double-Strand Break Repair	1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1
Global Genome Nucleotide Excision Repair (GG-NER)	1
G2/M Checkpoints	1
Protein ubiquitination	1
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	2
double-strand break repair	2
cellular anatomical structure	2
protein ubiquitination	1
5’-3’ DNA exonuclease activity	1
DNA repair	1
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
DNA replication	1
DNA damage response	1
protein modification by small protein conjugation	1
DNA damage tolerance	1
protein polyubiquitination	1
protein K63-linked ubiquitination	1
regulation of protein K63-linked ubiquitination	1
positive regulation of protein polyubiquitination	1
positive regulation of DNA repair	1
regulation of double-strand break repair	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
intracellular protein-containing complex	1
transferase complex	1
ubiquitin conjugating enzyme complex	1
extracellular vesicle	1

Protein interactions and networks

STRING

2774 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBE2V2	UBE2N	P61088	999
UBE2V2	RAD18	Q9NS91	983
UBE2V2	SHPRH	Q149N8	965
UBE2V2	HLTF	Q14527	913
UBE2V2	RAD52	P43351	883
UBE2V2	UBE2I	P50550	874
UBE2V2	UBB	P02248	850
UBE2V2	UBE2D2	P51669	829
UBE2V2	REV1	Q9UBZ9	818
UBE2V2	SUMO4	Q6EEV6	806
UBE2V2	UBE2A	P49459	788
UBE2V2	REV3L	O60673	771
UBE2V2	UBE2W	Q96B02	771
UBE2V2	RAD51	Q06609	764
UBE2V2	UBE2B	P23567	757

IntAct

70 interactions, top by confidence:

A	B	Type	Score
UBE2V1	UBE2N	psi-mi:“MI:0914”(association)	0.910
UBE2N	UBE2V2	psi-mi:“MI:0407”(direct interaction)	0.810
UBE2V2	UBE2N	psi-mi:“MI:0915”(physical association)	0.810
UBE2N	UBE2V2	psi-mi:“MI:0915”(physical association)	0.810
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HLTF	UBE2N	psi-mi:“MI:0914”(association)	0.680
UBE2N	UBA1	psi-mi:“MI:0914”(association)	0.640
HLTF	PCNA	psi-mi:“MI:0914”(association)	0.560
EGFR	UBE2V2	psi-mi:“MI:0915”(physical association)	0.550
MSRB2	BLTP3B	psi-mi:“MI:0914”(association)	0.530
UBE2V2	UBC35	psi-mi:“MI:0915”(physical association)	0.510
UBC35	UBE2V2	psi-mi:“MI:0915”(physical association)	0.510
SHPRH	UBE2N	psi-mi:“MI:0914”(association)	0.500
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
SBDS	DNM1L	psi-mi:“MI:0914”(association)	0.480
LMTK3	GPI	psi-mi:“MI:0914”(association)	0.420
UBE2V2		psi-mi:“MI:0915”(physical association)	0.370
UBE2V2	iglC2	psi-mi:“MI:0915”(physical association)	0.370
SNTA1	UBE2V2	psi-mi:“MI:0915”(physical association)	0.370
USP14	UBE2V2	psi-mi:“MI:0915”(physical association)	0.370
UBE2V2	MALSU1	psi-mi:“MI:0915”(physical association)	0.370
UBE2V2	XIAP	psi-mi:“MI:0915”(physical association)	0.370
UBE2V2	RNF2	psi-mi:“MI:0915”(physical association)	0.370
SIAH1	UBE2V2	psi-mi:“MI:0915”(physical association)	0.370
MKRN3	UBE2V2	psi-mi:“MI:0915”(physical association)	0.370
DZIP3	UBE2V2	psi-mi:“MI:0915”(physical association)	0.370
UBE2V2	RNF144A	psi-mi:“MI:0915”(physical association)	0.370
ZNRF1	UBE2V2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (160): ube2nb (Two-hybrid), ube2nb (Reconstituted Complex), UBE2N (Reconstituted Complex), UBE2V2 (Reconstituted Complex), UBE2V2 (Reconstituted Complex), UBE2V2 (Reconstituted Complex), UBE2V2 (Affinity Capture-Western), UBE2V2 (Reconstituted Complex), UBC (Reconstituted Complex), UBE2N (Co-crystal Structure), UBE2N (Co-fractionation), UBE2V2 (Co-fractionation), UBE2V2 (Affinity Capture-MS), UBE2V2 (Affinity Capture-MS), UBE2V2 (Affinity Capture-MS)

ESM2 similar proteins: A6H795, B3RTL9, B5DEI4, B5X1G6, B9EM04, C1BKD1, C1BZU2, C3ZDX5, O23239, P42743, Q02384, Q07889, Q07890, Q13404, Q15819, Q1JPX4, Q28FC1, Q28IA3, Q32L27, Q3SZ43, Q3SZ52, Q498F8, Q4R5E1, Q4VBH4, Q5E953, Q5F3Z3, Q5R4Z6, Q5R6C9, Q5RE48, Q5XGV8, Q5ZJJ5, Q6BBI8, Q6DEN0, Q6DJ78, Q6PEH5, Q7M767, Q7ZYX1, Q8VDW4, Q90879, Q96B02

Diamond homologs: A5PJC4, A5PKP9, C4R826, D3ZDK2, O45495, O60015, O74196, O74983, P0CS16, P0CS17, P15731, P15732, P23566, P25153, P25866, P25867, P25868, P35129, P35134, P42747, P43102, P46595, P49428, P51668, P51965, P52482, P52483, P52485, P52486, P52493, P53152, P61077, P61078, P61079, P61080, P61085, P61086, P61087, P62837, P62838

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
“Ub:E1 (UBA1 substrate)”	“up-regulates activity”	UBE2V2	ubiquitination
“Ub:E1 (UBA6 substrate)”	“up-regulates activity”	UBE2V2	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 82 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
E3 ubiquitin ligases ubiquitinate target proteins	5	16.7×	1e-03
Antigen processing: Ubiquitination & Proteasome degradation	9	5.8×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein K63-linked ubiquitination	6	22.0×	7e-05
protein polyubiquitination	10	15.8×	5e-07
positive regulation of canonical NF-kappaB signal transduction	10	9.9×	2e-05
DNA damage response	10	7.3×	2e-04
protein ubiquitination	10	5.7×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1473 predictions. Top by Δscore:

Variant	Effect	Δscore
8:48043027:GTATA:G	acceptor_loss	1.0000
8:48043030:TA:T	acceptor_loss	1.0000
8:48043031:A:AG	acceptor_gain	1.0000
8:48043032:G:GG	acceptor_gain	1.0000
8:48043032:GGA:G	acceptor_gain	1.0000
8:48043063:T:A	acceptor_gain	1.0000
8:48043160:C:T	donor_gain	1.0000
8:48043180:GG:G	donor_gain	1.0000
8:48043181:GG:G	donor_gain	1.0000
8:48049848:TCCA:T	acceptor_loss	1.0000
8:48049849:CCA:C	acceptor_loss	1.0000
8:48049850:CA:C	acceptor_loss	1.0000
8:48049851:A:AG	acceptor_gain	1.0000
8:48049851:A:G	acceptor_loss	1.0000
8:48049852:G:GG	acceptor_gain	1.0000
8:48049852:GAC:G	acceptor_gain	1.0000
8:48049852:GACA:G	acceptor_gain	1.0000
8:48049852:GACAA:G	acceptor_gain	1.0000
8:48049974:GGATG:G	donor_gain	1.0000
8:48049975:GATG:G	donor_gain	1.0000
8:48049975:GATGG:G	donor_gain	1.0000
8:48049976:ATGG:A	donor_loss	1.0000
8:48049977:TGGTA:T	donor_loss	1.0000
8:48049978:GGTAA:G	donor_loss	1.0000
8:48049979:G:GG	donor_gain	1.0000
8:48049979:G:T	donor_loss	1.0000
8:48049980:TAA:T	donor_loss	1.0000
8:48060676:TTTCA:T	acceptor_loss	1.0000
8:48060677:TTCA:T	acceptor_loss	1.0000
8:48060678:TCA:T	acceptor_loss	1.0000

AlphaMissense

955 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:48043053:T:C	F13L	1.000
8:48043054:T:C	F13S	1.000
8:48043055:T:A	F13L	1.000
8:48043055:T:G	F13L	1.000
8:48043060:T:C	L15S	1.000
8:48043072:T:C	L19P	1.000
8:48043080:G:A	G22R	1.000
8:48043080:G:C	G22R	1.000
8:48043108:T:A	V31D	1.000
8:48043113:T:A	W33R	1.000
8:48043113:T:C	W33R	1.000
8:48043116:G:C	G34R	1.000
8:48043120:T:A	L35H	1.000
8:48043152:T:A	W46R	1.000
8:48043152:T:C	W46R	1.000
8:48043153:G:C	W46S	1.000
8:48043154:G:C	W46C	1.000
8:48043154:G:T	W46C	1.000
8:48043159:G:A	G48D	1.000
8:48043165:T:A	I50N	1.000
8:48043170:G:A	G52R	1.000
8:48043170:G:C	G52R	1.000
8:48043170:G:T	G52W	1.000
8:48043171:G:A	G52E	1.000
8:48060715:T:A	W109R	1.000
8:48060715:T:C	W109R	1.000
8:48043054:T:G	F13C	0.999
8:48043060:T:G	L15W	0.999
8:48043063:T:C	L16S	0.999
8:48043068:G:A	E18K	0.999

dbSNP variants (sampled 300 via entrez): RS1000068058 (8:48030676 G>A), RS1000145372 (8:48038234 A>G), RS1000165907 (8:48057069 T>C), RS1000187444 (8:48013361 G>A,T), RS1000264835 (8:48001114 C>T), RS1000265918 (8:48063473 A>G), RS1000304216 (8:48036681 C>T), RS1000310552 (8:48023835 C>T), RS1000322850 (8:48056778 C>T), RS1000350458 (8:48007231 T>G), RS1000350872 (8:48010702 T>G), RS1000360738 (8:48049856 A>T), RS1000381491 (8:48054981 T>C), RS1000414125 (8:48054562 A>G), RS1000414279 (8:48007120 C>A,T)

Disease associations

OMIM: gene MIM:603001 | 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
GCST008839_406	Height	6.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	3
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
bufotalin	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
2,3-dimethoxy-1,4-naphthoquinone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
bisphenol B	increases expression	1
bisphenol S	decreases methylation	1
jinfukang	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cannabidiol	increases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Phenylmercuric Acetate	decreases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Testosterone	increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	decreases expression	1
Sodium Selenite	increases expression	1
Antirheumatic Agents	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TV90	HAP1 UBE2V2 (-) 1	Cancer cell line	Male
CVCL_TV91	HAP1 UBE2V2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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