UBE2G2

Summary

UBE2G2 (ubiquitin conjugating enzyme E2 G2, HGNC:12483) is a protein-coding gene on chromosome 21q22.3, encoding Ubiquitin-conjugating enzyme E2 G2 (P60604). Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. It is a selective cancer dependency (DepMap: 20.0% of cell lines).

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. The encoded protein shares 100% sequence identity with the mouse counterpart. This gene is ubiquitously expressed, with high expression seen in adult muscle. Three alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 7327 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 23 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 20.0% of screened cell lines
• MANE Select transcript: NM_003343

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12483
Approved symbol	UBE2G2
Name	ubiquitin conjugating enzyme E2 G2
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	UBC7
Ensembl gene	ENSG00000184787
Ensembl biotype	protein_coding
OMIM	603124
Entrez	7327

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 5 protein_coding_CDS_not_defined, 4 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000330942, ENST00000345496, ENST00000462569, ENST00000477954, ENST00000478200, ENST00000481546, ENST00000490091, ENST00000490450, ENST00000491513, ENST00000496395, ENST00000497630, ENST00000497664, ENST00000907888, ENST00000914956

RefSeq mRNA: 3 — MANE Select: NM_003343 NM_001202489, NM_003343, NM_182688

CCDS: CCDS13714, CCDS33586

Canonical transcript exons

ENST00000345496 — 6 exons

Exon	Start	End
ENSE00001810483	44801706	44801820
ENSE00003461738	44788060	44788095
ENSE00003513720	44777299	44777417
ENSE00003540326	44768580	44771489
ENSE00003545838	44787920	44787965
ENSE00003611843	44773547	44773687

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.6038 / max 290.2317, expressed in 1826 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190764	35.7615	1820
190765	14.1242	1799
190763	7.6258	1761
190760	0.0769	25
190761	0.0154	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.05	gold quality
middle frontal gyrus	UBERON:0002702	97.50	gold quality
medial globus pallidus	UBERON:0002477	96.87	gold quality
body of pancreas	UBERON:0001150	96.80	gold quality
paraflocculus	UBERON:0005351	96.71	gold quality
colonic epithelium	UBERON:0000397	96.60	gold quality
right coronary artery	UBERON:0001625	96.25	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.02	gold quality
lower esophagus	UBERON:0013473	96.00	gold quality
gastrocnemius	UBERON:0001388	95.82	gold quality
endothelial cell	CL:0000115	95.79	gold quality
globus pallidus	UBERON:0001875	95.76	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.70	gold quality
cardia of stomach	UBERON:0001162	95.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.69	gold quality
right ovary	UBERON:0002118	95.65	gold quality
coronary artery	UBERON:0001621	95.56	gold quality
superior surface of tongue	UBERON:0007371	95.56	gold quality
fundus of stomach	UBERON:0001160	95.46	gold quality
left adrenal gland cortex	UBERON:0035825	95.46	gold quality
left coronary artery	UBERON:0001626	95.45	gold quality
lymph node	UBERON:0000029	95.44	gold quality
body of uterus	UBERON:0009853	95.43	gold quality
left uterine tube	UBERON:0001303	95.42	gold quality
muscle of leg	UBERON:0001383	95.42	gold quality
adrenal cortex	UBERON:0001235	95.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.41	gold quality
left ovary	UBERON:0002119	95.30	gold quality
left adrenal gland	UBERON:0001234	95.29	gold quality
body of tongue	UBERON:0011876	95.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6142	no	176.30
E-CURD-112	no	2.59
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

98 targeting UBE2G2, 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-4673	100.00	66.64	1490
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-6883-5P	99.69	68.05	3785

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 20.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• Ubc7 mediates inositol 1,4,5-trisphosphate receptor ubiquitination and is a component of the endoplasmic reticulum-associated degradation pathway (PMID:12869571)
• interrupting a specific E2-E3 interaction can selectively inhibit endoplasmic reticulum -associated degradation (PMID:16407162)
• Structural comparison of human UBE2G2 with yeast Ubc7 indicated that the overall structures are similar except for the long loop region and the C-terminal helix. (PMID:16582478)
• Results report the solution structure and backbone dynamics of Ube2g2 solved by nuclear magnetic resonance spectroscopy. (PMID:20014027)
• Lys-48-linked polyubiquitin chains may be designed to bind certain proteins like Ube2g2 such that the terminal ubiquitin subunit carrying the reactive Lys-48 side chain can be positioned properly for chain elongation regardless of chain length. (PMID:21098018)
• The presence of the AUP1-Ube2g2 complex at LDs provides a direct molecular link between LDs and the cellular ubiquitination machinery. (PMID:21127063)
• These results reveal an unanticipated mode of Ube2g2 self-association that allows Ube2g2 to effectively engage two ubiquitins to specifically synthesize Lys48-linked ubiquitin chains. (PMID:24366945)
• Further study discovered that the gp78 CUE domain works as a proofreading machine during the growth of K48-linked polyubiquitin chains to ensure the linkage specificity. Together, our studies uncover a novel mechanism underlying the linkage specificity determination of longer polyubiquitin chains. (PMID:27067047)
• UBE2G2 was crucial for the degradation of various immunoreceptors. UBE2J2, on the other hand, counteracted US2-induced endoplasmic reticulum-associated protein degradation by downregulating TRC8 expression. (PMID:28743740)
• A structurally conserved site in AUP1 binds the E2 enzyme UBE2G2 and is essential for ER-associated degradation. (PMID:34879065)
• Proinsulin degradation and presentation of a proinsulin B-chain autoantigen involves ER-associated protein degradation (ERAD)-enzyme UBE2G2. (PMID:38787820)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ube2g2	ENSDARG00000025404
mus_musculus	Ube2g2	ENSMUSG00000009293
rattus_norvegicus	Ube2g2	ENSRNOG00000001222
drosophila_melanogaster	Ubc7	FBGN0267384
caenorhabditis_elegans	ubc-14	WBGENE00006709

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

Protein

Protein identifiers

Ubiquitin-conjugating enzyme E2 G2 — P60604 (reviewed: P60604)

Alternative names: E2 ubiquitin-conjugating enzyme G2, Ubiquitin carrier protein G2, Ubiquitin-protein ligase G2

All UniProt accessions (3): P60604, F8WCB9, F8WDB1

UniProt curated annotations — full annotation on UniProt →

Function. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes ‘Lys-48’-linked polyubiquitination. Involved in endoplasmic reticulum-associated degradation (ERAD). Required for sterol-induced ubiquitination of 3-hydroxy-3-methylglutaryl coenzyme A reductase and its subsequent proteasomal degradation.

Subunit / interactions. Interacts with AUP1 (via C-terminus); the interaction recruits UBE2G2 to lipid droplets. Interacts with ubiquitin ligases AMFR/gp78 and RNF139/TRC8; recruitment to lipid droplets by AUP1 facilitates interaction of UBE2G2 with AMFR and RNF139, leading to sterol-induced ubiquitination of 3-hydroxy-3-methylglutaryl coenzyme A reductase and its subsequent proteasomal degradation.

Subcellular location. Endoplasmic reticulum. Lipid droplet.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the ubiquitin-conjugating enzyme family.

Isoforms (2)

UniProt ID	Names	Canonical?
P60604-1	1	yes
P60604-2	2

RefSeq proteins (3): NP_001189418, NP_003334, NP_872630 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000608	UBC	Domain
IPR016135	UBQ-conjugating_enzyme/RWD	Homologous_superfamily
IPR023313	UBQ-conjugating_AS	Active_site
IPR050113	Ub_conjugating_enzyme-E2-like	Family

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 (22 total): helix 7, strand 5, turn 2, sequence conflict 2, initiator methionine 1, chain 1, domain 1, active site 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7LEW	X-RAY DIFFRACTION	1.74
3H8K	X-RAY DIFFRACTION	1.8
8T0S	X-RAY DIFFRACTION	1.95
4LAD	X-RAY DIFFRACTION	2.3
2CYX	X-RAY DIFFRACTION	2.56
2KLY	SOLUTION NMR
2LXP	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60604-F1	94.67	0.87

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): 89 (glycyl thioester intermediate)

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8866652	Synthesis of active ubiquitin: roles of E1 and E2 enzymes
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 183 (showing top): GOBP_ENDOPLASMIC_RETICULUM_TO_CYTOSOL_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MITSIADES_RESPONSE_TO_APLIDIN_DN, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_RESPONSE_TO_INTERFERON_BETA, RODRIGUES_NTN1_TARGETS_DN

GO Biological Process (8): protein polyubiquitination (GO:0000209), ubiquitin-dependent protein catabolic process (GO:0006511), cellular response to interferon-beta (GO:0035458), ERAD pathway (GO:0036503), protein K48-linked ubiquitination (GO:0070936), negative regulation of retrograde protein transport, ER to cytosol (GO:1904153), protein ubiquitination (GO:0016567), protein modification by small protein conjugation (GO:0032446)

GO Molecular Function (7): ubiquitin-protein transferase activity (GO:0004842), ATP binding (GO:0005524), identical protein binding (GO:0042802), ubiquitin conjugating enzyme activity (GO:0061631), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), lipid droplet (GO:0005811), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein ubiquitination	1
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	2
cytoplasm	2
modification-dependent protein catabolic process	1
response to interferon-beta	1
cellular response to cytokine stimulus	1
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
protein polyubiquitination	1
retrograde protein transport, ER to cytosol	1
negative regulation of protein exit from endoplasmic reticulum	1
regulation of retrograde protein transport, ER to cytosol	1
protein modification by small protein conjugation	1
protein modification by small protein conjugation or removal	1
ubiquitin-like protein transferase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein conjugating enzyme activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
endomembrane system	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

93 interactions, top by confidence:

A	B	Type	Score
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
UBE2G2	AMFR	psi-mi:“MI:0407”(direct interaction)	0.840
AMFR	UBE2G2	psi-mi:“MI:0407”(direct interaction)	0.840
AMFR	UBE2G2	psi-mi:“MI:0915”(physical association)	0.840
UBE2G2	AUP1	psi-mi:“MI:0915”(physical association)	0.750
AUP1	UBE2G2	psi-mi:“MI:0914”(association)	0.750
UBC	UBE2G2	psi-mi:“MI:0915”(physical association)	0.560
PIK3R1	UBE2G2	psi-mi:“MI:0915”(physical association)	0.560
	VAPB	psi-mi:“MI:0914”(association)	0.500
BIRC8	UBE2G2	psi-mi:“MI:0915”(physical association)	0.370
MDM2	UBE2G2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (608): UBE2G2 (Two-hybrid), UBE2G2 (Biochemical Activity), UBE2G2 (Reconstituted Complex), UBE2G2 (Biochemical Activity), UBE2G2 (Reconstituted Complex), UBE2G2 (Biochemical Activity), UBE2G2 (Reconstituted Complex), UBE2G2 (Affinity Capture-MS), UBE2G2 (Affinity Capture-MS), UBE2G2 (Affinity Capture-MS), UBE2G2 (Affinity Capture-Western), UBE2G2 (Reconstituted Complex), UBE2G2 (Biochemical Activity), UBE2G2 (Affinity Capture-MS), HNRNPAB (Co-fractionation)

ESM2 similar proteins: A0A1B0GUS4, A5PJC4, A5PKP9, D3ZDK2, O13685, O14933, O74196, O74549, P15731, P15732, P25867, P35129, P35131, P35132, P35133, P35134, P35135, P43102, P51668, P52487, P60604, P60605, P61080, P62837, P62838, P62839, P62840, P68036, P68037, P70711, Q17QG5, Q1RMX2, Q21633, Q2TA10, Q3MHP1, Q3ZCF7, Q4V8J2, Q5R5I4, Q5RF84, Q6C9W0

Diamond homologs: A5PKP9, D3ZDK2, O13685, O74196, O74201, O74810, P06104, P15731, P15732, P21734, P23566, P25153, P25865, P25866, P25867, P35128, P35129, P35130, P35131, P35132, P35133, P35134, P35135, P42745, P42746, P43102, P46595, P49459, P51668, P51965, P52478, P52482, P52483, P52485, P52490, P52493, P60604, P60605, P61077, P61078

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
UBE2G2	“down-regulates quantity by destabilization”	DIO2	ubiquitination
UBE2G2	“down-regulates quantity by destabilization”	DIO	ubiquitination
“Ub:E1 (UBA1 substrate)”	“up-regulates activity”	UBE2G2	ubiquitination
“Ub:E1 (UBA6 substrate)”	“up-regulates activity”	UBE2G2	ubiquitination
UBE2G2	“up-regulates activity”	SYVN1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 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
Defective CFTR causes cystic fibrosis	6	22.7×	5e-05
Degradation of AXIN	5	21.4×	3e-04
Hh mutants are degraded by ERAD	5	20.9×	3e-04
Regulation of RUNX3 expression and activity	5	20.1×	3e-04
Hedgehog ligand biogenesis	5	18.2×	4e-04
Downstream TCR signaling	8	17.7×	7e-06
Activation of NF-kappaB in B cells	5	17.0×	4e-04
Degradation of CDH1	5	17.0×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	6	14.3×	1e-03
ubiquitin-dependent protein catabolic process	11	10.7×	3e-06
protein polyubiquitination	6	9.1×	1e-02
proteasome-mediated ubiquitin-dependent protein catabolic process	8	5.5×	1e-02
protein ubiquitination	9	4.9×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1607 predictions. Top by Δscore:

Variant	Effect	Δscore
21:44771485:GGGCT:G	acceptor_gain	1.0000
21:44771486:GGCTC:G	acceptor_loss	1.0000
21:44771488:CT:C	acceptor_gain	1.0000
21:44771489:TCTG:T	acceptor_loss	1.0000
21:44771490:C:CC	acceptor_gain	1.0000
21:44771490:CT:C	acceptor_loss	1.0000
21:44773544:TAC:T	donor_loss	1.0000
21:44773546:C:CT	donor_loss	1.0000
21:44773684:TAGA:T	acceptor_gain	1.0000
21:44773685:AGA:A	acceptor_gain	1.0000
21:44773686:GA:G	acceptor_gain	1.0000
21:44773687:AC:A	acceptor_loss	1.0000
21:44773688:C:CA	acceptor_loss	1.0000
21:44773688:C:CC	acceptor_gain	1.0000
21:44773689:T:A	acceptor_loss	1.0000
21:44777297:A:AC	donor_gain	1.0000
21:44777298:C:CC	donor_gain	1.0000
21:44798232:ATGAG:A	donor_gain	1.0000
21:44801704:A:AC	donor_gain	1.0000
21:44801705:C:CC	donor_gain	1.0000
21:44771486:GGCT:G	acceptor_gain	0.9900
21:44773562:C:CT	donor_gain	0.9900
21:44773683:GTAGA:G	acceptor_gain	0.9900
21:44786111:TCA:T	donor_gain	0.9900
21:44787918:A:AC	donor_gain	0.9900
21:44787919:C:CC	donor_gain	0.9900
21:44801699:GACTC:G	donor_loss	0.9900
21:44801700:ACTC:A	donor_loss	0.9900
21:44801701:CTCA:C	donor_loss	0.9900
21:44801702:TCAC:T	donor_loss	0.9900

AlphaMissense

1104 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:44773602:C:A	W110C	1.000
21:44773602:C:G	W110C	1.000
21:44773604:A:G	W110R	1.000
21:44773604:A:T	W110R	1.000
21:44787936:A:G	W37R	1.000
21:44787936:A:T	W37R	1.000
21:44771441:C:G	R145P	0.999
21:44771468:G:T	A136D	0.999
21:44771486:G:T	P130H	0.999
21:44773552:A:G	L127P	0.999
21:44773573:A:G	L120P	0.999
21:44773603:C:G	W110S	0.999
21:44773606:C:G	R109P	0.999
21:44773650:G:C	H94Q	0.999
21:44773650:G:T	H94Q	0.999
21:44773652:G:C	H94D	0.999
21:44773654:A:G	L93P	0.999
21:44773654:A:T	L93H	0.999
21:44773657:A:T	I92N	0.999
21:44773660:G:A	S91F	0.999
21:44773660:G:T	S91Y	0.999
21:44773663:A:T	I90N	0.999
21:44773665:G:C	C89W	0.999
21:44773666:C:T	C89Y	0.999
21:44773667:A:G	C89R	0.999
21:44773669:A:T	V88D	0.999
21:44773675:C:A	G86V	0.999
21:44777300:G:C	N81K	0.999
21:44777300:G:T	N81K	0.999
21:44777307:T:C	H79R	0.999

dbSNP variants (sampled 300 via entrez): RS1000054107 (21:44791987 A>G), RS1000057767 (21:44797817 C>A), RS1000150315 (21:44783477 A>G), RS1000292866 (21:44780645 T>C), RS1000335181 (21:44803688 C>A,T), RS1000405270 (21:44792116 T>C), RS1000419312 (21:44786072 C>G,T), RS1000511358 (21:44769011 C>G), RS1000637200 (21:44774319 G>T), RS1000647707 (21:44780379 A>G), RS1000691194 (21:44774713 A>C), RS1000833935 (21:44796216 C>A,T), RS1000911333 (21:44768809 T>C), RS1000930899 (21:44802058 T>C), RS1000934730 (21:44790877 G>C)

Disease associations

OMIM: gene MIM:603124 | disease phenotypes: MIM:240300

GenCC curated gene-disease

Mondo (1): autoimmune polyendocrine syndrome type 1 (MONDO:0009411)

Orphanet (1): Autoimmune polyendocrinopathy type 1 (Orphanet:3453)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90011898_166	Alanine aminotransferase levels	3.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523256 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.38	Kd	4.161	nM	CHEMBL3752910
8.38	ED50	4.161	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 44 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	2149957: Binding affinity to human UBE2G2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0042	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	5
Cadmium Chloride	decreases expression, increases expression	3
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
arsenic trichloride	affects binding, increases abundance, increases reaction, increases expression	1
CGP 52608	increases reaction, affects binding	1
bisphenol B	increases expression	1
abrine	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Cidofovir	increases expression	1
Arsenic	affects binding, increases abundance, increases reaction, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Clodronic Acid	increases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Gold	decreases expression	1
Ifosfamide	increases expression	1
Methyl Methanesulfonate	decreases expression	1
Oxygen	decreases expression	1
Serine	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4369194	Binding	Binding affinity to recombinant TEV cleavage site-fused-His6-tagged Ube2g2 (unknown origin) expressed in Escherichia coli Rosetta2 (DE3) assessed as compound-protein complex formation at 5 uL measured after overnight incubation at pH 7.4 by	Design, synthesis, and anticancer activity evaluation of irreversible allosteric inhibitors of the ubiquitin-conjugating enzyme Ube2g2. — Medchemcomm

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TV70	HAP1 UBE2G2 (-) 1	Cancer cell line	Male
CVCL_TV71	HAP1 UBE2G2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00743782	PHASE2	COMPLETED	Comparing Pump With Subcutaneous Injection Delivery of PTH 1-34 in the Management of Chronic Hypoparathyroidism
NCT05398809	PHASE2	RECRUITING	Evaluate the Efficacy and Safety of Ruxolitinib on Hair Regrowth in Patients With Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED)-Associated Alopecia Areata