UBE2T

Summary

UBE2T (ubiquitin conjugating enzyme E2 T, HGNC:25009) is a protein-coding gene on chromosome 1q32.1, encoding Ubiquitin-conjugating enzyme E2 T (Q9NPD8). Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins.

The protein encoded by this gene catalyzes the covalent attachment of ubiquitin to protein substrates. Defects in this gene have been associated with Fanconi anemia of complementation group T. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 29089 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Fanconi anemia complementation group T (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 82 total — 11 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 115
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_014176

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25009
Approved symbol	UBE2T
Name	ubiquitin conjugating enzyme E2 T
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	HSPC150, FANCT
Ensembl gene	ENSG00000077152
Ensembl biotype	protein_coding
OMIM	610538
Entrez	29089

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay

ENST00000460852, ENST00000487227, ENST00000643045, ENST00000646595, ENST00000646651, ENST00000699423, ENST00000699424, ENST00000699425, ENST00000699426, ENST00000699427, ENST00000699428, ENST00000699429, ENST00000852163, ENST00000934398, ENST00000934399, ENST00000934400, ENST00000934401, ENST00000934402

RefSeq mRNA: 2 — MANE Select: NM_014176 NM_001310326, NM_014176

CCDS: CCDS1425

Canonical transcript exons

ENST00000646651 — 7 exons

Exon	Start	End
ENSE00000415302	202333237	202333335
ENSE00000791436	202333010	202333093
ENSE00003504498	202334989	202335058
ENSE00003602536	202335646	202335818
ENSE00003684618	202333450	202333555
ENSE00003976531	202331657	202331960
ENSE00003976544	202341895	202341936

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 96.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.3473 / max 798.9066, expressed in 1720 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16712	45.3939	1709
16714	3.3106	1087
16713	2.6428	1058

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	96.94	gold quality
ventricular zone	UBERON:0003053	96.55	gold quality
ganglionic eminence	UBERON:0004023	96.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.01	gold quality
secondary oocyte	CL:0000655	91.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.28	gold quality
mucosa of transverse colon	UBERON:0004991	89.42	gold quality
cortical plate	UBERON:0005343	89.20	gold quality
rectum	UBERON:0001052	87.56	gold quality
right testis	UBERON:0004534	87.23	gold quality
biceps brachii	UBERON:0001507	87.21	gold quality
left testis	UBERON:0004533	87.00	gold quality
testis	UBERON:0000473	86.70	gold quality
bone marrow	UBERON:0002371	86.04	gold quality
prefrontal cortex	UBERON:0000451	85.64	gold quality
thymus	UBERON:0002370	85.01	gold quality
trabecular bone tissue	UBERON:0002483	84.58	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.39	gold quality
islet of Langerhans	UBERON:0000006	84.03	gold quality
anterior cingulate cortex	UBERON:0009835	83.96	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.72	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	83.66	gold quality
stromal cell of endometrium	CL:0002255	83.43	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.40	gold quality
vermiform appendix	UBERON:0001154	83.39	gold quality
heart left ventricle	UBERON:0002084	82.83	gold quality
gastrocnemius	UBERON:0001388	82.69	gold quality
cardiac ventricle	UBERON:0002082	82.31	gold quality
smooth muscle tissue	UBERON:0001135	82.23	gold quality
adrenal tissue	UBERON:0018303	82.19	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	486.90
E-MTAB-8530	yes	457.16
E-MTAB-5061	yes	424.23
E-GEOD-93593	yes	366.22
E-HCAD-24	yes	301.92
E-HCAD-10	yes	43.50
E-CURD-112	yes	40.17
E-GEOD-125970	yes	23.24
E-HCAD-13	yes	22.30
E-HCAD-5	yes	18.32
E-ANND-3	yes	7.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting UBE2T, 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-1277-5P	100.00	73.95	5056
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-212-5P	96.83	67.43	950
HSA-MIR-6806-5P	96.37	68.74	587

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• UBE2T is the ubiquitin-conjugating enzyme (E2) in the Fanconi anemia pathway and has a self-inactivation mechanism that could be important for negative regulation of the Fanconi anemia pathway. (PMID:16916645)
• UBE2T was significantly upregulated in lung cancer tissue and cell lines, suggesting involvement of UBE2T in the malignant cell phenotype. (PMID:18667844)
• This work therefore establishes a system that provides mechanistic insight into the functions of FANCL and FANCI in the catalysis of FANCD2 monoubiquitination. (PMID:19111657)
• Upon the occurrence of DNA damage, FANCI becomes monoubiquitinated on Lys-523 by the UBE2T-FANCL pair. (PMID:19589784)
• Our data imply a critical role of UBE2T in development and/or progression of breast cancer through the interaction with and the regulation of the BRCA1/BARD1 complex. (PMID:19887602)
• hypoxic conditions down-regulate UBE2T expression which correlates with an increased sensitivity to crosslinking agents consistent with a defective Fanconi anemia pathway (PMID:21722982)
• Mutations in the gene encoding the E2 conjugating enzyme UBE2T cause Fanconi anemia (PMID:26046368)
• we identified UBE2T as a bona fide FA gene (FANCT) that also may be a rare cancer susceptibility gene. (PMID:26085575)
• UBE2T is the primary E2 of the FA pathway required for FANCD2 and FANCI activation. (PMID:26119737)
• Identify critical roles of UBE2T in prostate cancer development and progression. (PMID:26308072)
• High UBE2T expression is associated with nasopharyngeal carcinoma. (PMID:26943030)
• UBE2T plays an important role in the tumorigenesis of gastric cancer and could act as a potential independent prognostic factor for cancer therapy. (PMID:27020591)
• Results showed that UBE2T was overexpressed in osteosarcoma tissues and cell lines. Moreover, UBE2T knockdown inhibited osteosarcoma cell proliferation, migration, and invasion. (PMID:27712593)
• Results show that UBE2T expression was increased in gastric tumors. Its suppression altered the expression of epithelial-mesenchymal transition factors and inhibited growth and colony formation, increased G2/M phase cell cycle arrest, and promoted apoptosis in gastric cancer cells. These findings provide evidence that UBE2T plays a critical role in gastric cancer. (PMID:28427240)
• report the identification of a new allosteric pocket on Ube2T through a fragment screening using biophysical methods. Several fragments binding to this site inhibit ubiquitin conjugation in vitro (PMID:28437106)
• Collectively, our findings suggest UBE2T serves as a promising prognostic factor for HCC and functions as an oncogene. The newly identified miR-543/UBE2T/p53 axis may represent a new potential therapeutic target for HCC intervention. (PMID:28935368)
• we studied the relationship between UBE2T and MM. UBE2T is a predictor of MM survival, higher the expression of UBE2T, worse the prognosis and survival of MM patients. UBE2T increases with the exasperation of MM. UBE2T are probably affecting MM through the cell division pathway, which could be a meaningful biomarker for MM. (PMID:30622320)
• RISPR/Cas9-mediated genetic knockout of UBE2T only partially reduced HR, demonstrating that UBE2T-independent pathways can compensate for the recombination defect in UBE2T/FANCT null cells. (PMID:30715513)
• UBE2T promoted the proliferation of renal cell carcinoma cells by regulating PI3K/Akt signaling. (PMID:31173226)
• High UBE2T expression is associated with osteosarcoma. (PMID:31355678)
• disrupting UBE2T-dependent DNA repair and leading to the accumulation of DNA damage and genome instability (PMID:31481791)
• important role in cell cycle progression, apoptosis, and hepatocelluar carcinoma development (PMID:31798276)
• UBE2T promotes glioblastoma invasion and migration via stabilizing GRP78 and regulating EMT. (PMID:32491994)
• UBE2T promotes radiation resistance in non-small cell lung cancer via inducing epithelial-mesenchymal transition and the ubiquitination-mediated FOXO1 degradation. (PMID:32590022)
• A homozygous missense variant in UBE2T is associated with a mild Fanconi anemia phenotype. (PMID:32646888)
• Ubiquitin-conjugating enzyme E2T regulates cell proliferation and migration in cholangiocarcinoma. (PMID:32796405)
• UBE2T-regulated H2AX monoubiquitination induces hepatocellular carcinoma radioresistance by facilitating CHK1 activation. (PMID:33087136)
• Increased Expression of UBE2T Predicting Poor Survival of Epithelial Ovarian Cancer: Based on Comprehensive Analysis of UBE2s, Clinical Samples, and the GEO Database. (PMID:33180631)
• A novel UBE2T inhibitor suppresses Wnt/beta-catenin signaling hyperactivation and gastric cancer progression by blocking RACK1 ubiquitination. (PMID:33323973)
• UBE2T promotes proliferation, invasion and glycolysis of breast cancer cells by regualting the PI3K/AKT signaling pathway. (PMID:33435787)
• The interplay of UBE2T and Mule in regulating Wnt/beta-catenin activation to promote hepatocellular carcinoma progression. (PMID:33542213)
• Identification of Biomarkers Based on Bioinformatics Analysis: The Expression of Ubiquitin-Conjugating Enzyme E2T (UBE2T) in the Carcinogenesis and Progression of Hepatocellular Carcinoma. (PMID:33658475)
• UBE2T Contributes to the Prognosis of Esophageal Squamous Cell Carcinoma. (PMID:34257599)
• DEPDC1B regulates the progression of human chordoma through UBE2T-mediated ubiquitination of BIRC5. (PMID:34330893)
• UBE2T promotes autophagy via the p53/AMPK/mTOR signaling pathway in lung adenocarcinoma. (PMID:34461934)
• E2F5 promotes proliferation and invasion of gastric cancer through directly upregulating UBE2T transcription. (PMID:34583905)
• miR-543 impairs breast cancer cell phenotypes by targeting and suppressing ubiquitin-conjugating enzyme E2T (UBE2T). (PMID:34787051)
• MiR-182-5p inhibits the tumorigenesis of clear cell renal cell carcinoma by repressing UBE2T. (PMID:35129808)
• UBE2T is upregulated, predicts poor prognosis, and promotes cell proliferation and invasion by promoting epithelial-mesenchymal transition via inhibiting autophagy in an AKT/mTOR dependent manner in ovarian cancer. (PMID:35130130)
• UBE2T-mediated Akt ubiquitination and Akt/beta-catenin activation promotes hepatocellular carcinoma development by increasing pyrimidine metabolism. (PMID:35169125)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ube2t	ENSDARG00000063285
mus_musculus	Ube2t	ENSMUSG00000026429
rattus_norvegicus	Ube2t	ENSRNOG00000005038

Paralogs (24): 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), UBE2G2 (ENSG00000184787), UBE2H (ENSG00000186591), UBE2J1 (ENSG00000198833), PEDS1 (ENSG00000240849), UBE2V1 (ENSG00000244687), UBE2NL (ENSG00000276380)

Protein

Protein identifiers

Ubiquitin-conjugating enzyme E2 T — Q9NPD8 (reviewed: Q9NPD8)

Alternative names: Cell proliferation-inducing gene 50 protein, E2 ubiquitin-conjugating enzyme T, Ubiquitin carrier protein T, Ubiquitin-protein ligase T

All UniProt accessions (6): Q9NPD8, A0A2R8Y812, A0A8V8TN93, A0A8V8TNE2, A0A8V8TPM9, A0A8V8TQ15

UniProt curated annotations — full annotation on UniProt →

Function. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes monoubiquitination. Involved in mitomycin-C (MMC)-induced DNA repair. Acts as a specific E2 ubiquitin-conjugating enzyme for the Fanconi anemia complex by associating with E3 ubiquitin-protein ligase FANCL and catalyzing monoubiquitination of FANCD2, a key step in the DNA damage pathway. Also mediates monoubiquitination of FANCL and FANCI. May contribute to ubiquitination and degradation of BRCA1. In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, but may prefer ‘Lys-11’-, ‘Lys-27’-, ‘Lys-48’- and ‘Lys-63’-linked polyubiquitination.

Subunit / interactions. Directly interacts with FANCL. Interacts with BRCA1.

Subcellular location. Nucleus.

Post-translational modifications. Auto-ubiquitinated. Effects of auto-monoubiquitination at Lys-91 and Lys-182 are unclear: according to a report, monoubiquitination inactivates E2 enzyme activity. In contrast, according to another report, autoubiquitination does not affect E2 enzyme activity.

Disease relevance. Fanconi anemia complementation group T (FANCT) [MIM:616435] A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. The disease is caused by variants affecting the gene represented in this entry.

Induction. Down-regulated following hypoxia. Up-regulated in breast cancers.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the ubiquitin-conjugating enzyme family.

RefSeq proteins (2): NP_001297255, NP_054895* (*=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 (31 total): mutagenesis site 8, helix 5, strand 5, cross-link 4, turn 3, chain 1, domain 1, region of interest 1, active site 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
8JUC	X-RAY DIFFRACTION	1.54
8JVD	X-RAY DIFFRACTION	1.7
8JVE	X-RAY DIFFRACTION	1.76
5OJJ	X-RAY DIFFRACTION	1.85
1YH2	X-RAY DIFFRACTION	2
6R75	X-RAY DIFFRACTION	2
8JVL	X-RAY DIFFRACTION	2.06
4CCG	X-RAY DIFFRACTION	2.4
5NGZ	X-RAY DIFFRACTION	2.4
7KZS	ELECTRON MICROSCOPY	4.2
7KZT	ELECTRON MICROSCOPY	4.2
7KZV	ELECTRON MICROSCOPY	4.2
7KZR	ELECTRON MICROSCOPY	4.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPD8-F1	86.36	0.74

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): 86 (glycyl thioester intermediate)

Post-translational modifications (5): 184, 91, 182, 191, 192

Mutagenesis-validated functional residues (8):

Position	Phenotype
5	no effect on fancl-binding, nor on fancl-dependent monoubiquitination of fancd2.
60	loss of fancl-binding and of fancl-dependent monoubiquitination of fancd2.
63	decreased binding to fancl.
73	decreased fancd2 ubiquitination.
86	loss of e2 enzyme activity.
91	decreased monoubiquitination.
99–101	no effect on fancl-binding, nor on fancl-dependent monoubiquitination of fancd2.
182–191	decreased monoubiquitination.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6783310	Fanconi Anemia Pathway
R-HSA-8866652	Synthesis of active ubiquitin: roles of E1 and E2 enzymes

MSigDB gene sets: 459 (showing top): PID_FANCONI_PATHWAY, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, WONG_PROTEASOME_GENE_MODULE, KONG_E2F3_TARGETS, GOLDRATH_ANTIGEN_RESPONSE, PATIL_LIVER_CANCER, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_PROTEIN_K11_LINKED_UBIQUITINATION, LE_EGR2_TARGETS_UP, GOBP_PROTEIN_AUTOUBIQUITINATION, GOBP_PROTEIN_MONOUBIQUITINATION, GOBP_DNA_DAMAGE_RESPONSE

GO Biological Process (13): protein polyubiquitination (GO:0000209), DNA repair (GO:0006281), protein monoubiquitination (GO:0006513), DNA damage response (GO:0006974), protein K29-linked ubiquitination (GO:0035519), protein K27-linked ubiquitination (GO:0044314), protein autoubiquitination (GO:0051865), protein K63-linked ubiquitination (GO:0070534), protein K48-linked ubiquitination (GO:0070936), protein K11-linked ubiquitination (GO:0070979), protein K6-linked ubiquitination (GO:0085020), protein ubiquitination (GO:0016567), protein modification by small protein conjugation (GO:0032446)

GO Molecular Function (9): chromatin binding (GO:0003682), ubiquitin-protein transferase activity (GO:0004842), ATP binding (GO:0005524), ubiquitin protein ligase binding (GO:0031625), ubiquitin conjugating enzyme activity (GO:0061631), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740), ubiquitin-like protein transferase activity (GO:0019787)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
DNA Repair	1
Protein ubiquitination	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein polyubiquitination	6
protein ubiquitination	3
binding	2
nuclear lumen	2
cellular anatomical structure	2
DNA metabolic process	1
DNA damage response	1
cellular response to stress	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
ubiquitin-like protein ligase binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein conjugating enzyme activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
aminoacyltransferase activity	1
catalytic activity, acting on a protein	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

3498 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBE2T	FANCL	Q9NW38	999
UBE2T	FANCD2	Q9BXW9	940
UBE2T	FANCA	O15360	925
UBE2T	FAAP100	Q0VG06	875
UBE2T	FANCG	O15287	859
UBE2T	FAAP24	Q9BTP7	857
UBE2T	FANCB	Q8NB91	857
UBE2T	FANCF	Q9NPI8	854
UBE2T	FANCC	Q00597	853
UBE2T	FANCI	Q9NVI1	846
UBE2T	FANCE	Q9HB96	843
UBE2T	FANCM	Q8IYD8	843
UBE2T	F6S8H2	F6S8H2	752
UBE2T	SLX4	Q8IY92	717
UBE2T	BRCA1	P38398	712

IntAct

54 interactions, top by confidence:

A	B	Type	Score
UBE2T	FANCL	psi-mi:“MI:0407”(direct interaction)	0.560
UBE2T	GNB2	psi-mi:“MI:0915”(physical association)	0.560
MAPT	DENR	psi-mi:“MI:0914”(association)	0.560
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
CDK5R1	DENR	psi-mi:“MI:0914”(association)	0.530
UBE2T	FAAP100	psi-mi:“MI:0914”(association)	0.530
MFI	LASP1	psi-mi:“MI:0914”(association)	0.530
ZNF277	RNF123	psi-mi:“MI:0914”(association)	0.530
FSD1	UBFD1	psi-mi:“MI:0914”(association)	0.530
ARL6IP6	YKT6	psi-mi:“MI:0914”(association)	0.530
OIP5	CYTH3	psi-mi:“MI:0914”(association)	0.530
RDH12	NME2P1	psi-mi:“MI:0914”(association)	0.530
MOK	H1-3	psi-mi:“MI:0914”(association)	0.530
ARIH2	UBE2T	psi-mi:“MI:0915”(physical association)	0.490
UBE2T	E2	psi-mi:“MI:0915”(physical association)	0.370
UBE2T	AMFR	psi-mi:“MI:0915”(physical association)	0.370
UBE2T	PCGF2	psi-mi:“MI:0915”(physical association)	0.370
UBE2T	SNURF	psi-mi:“MI:0915”(physical association)	0.370
UBE2T	TRIM27	psi-mi:“MI:0915”(physical association)	0.370
MGRN1	UBE2T	psi-mi:“MI:0915”(physical association)	0.370
UBE2T	MARCHF5	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (154): UBE2T (Reconstituted Complex), UBE2T (Affinity Capture-MS), UBE2T (Affinity Capture-MS), UBE2T (Affinity Capture-MS), UBE2T (Affinity Capture-MS), UBE2T (Affinity Capture-MS), UBE2T (Affinity Capture-MS), UBE2T (Affinity Capture-MS), FANCL (PCA), GNB2L1 (Co-fractionation), PRDX2 (Co-fractionation), SRA1 (Co-fractionation), UBE2T (Biochemical Activity), FANCL (Two-hybrid), UBE2T (Two-hybrid)

ESM2 similar proteins: A3KN22, O74549, P0C8G3, P21734, P25869, P27949, P49427, P51965, P52482, P52491, P61081, P61082, P62253, P62254, P62255, Q08BH7, Q1RMW1, Q29503, Q3UWQ3, Q42540, Q42541, Q54TI6, Q55EY8, Q5M8Y2, Q5U203, Q5ZKX6, Q6C9W0, Q6CSW8, Q6DCZ9, Q6FVQ8, Q6IRC7, Q6NY82, Q6P8D9, Q6ZWZ2, Q712K3, Q75AF2, Q7ZY08, Q8CFI2, Q91W82, Q95017

Diamond homologs: A0A1B0GUS4, A5PJC4, A5PKP9, D3ZDK2, O13685, O14933, O74196, O74810, P0C8G3, P0C8G4, P0C8G5, P15731, P15732, P21734, P25867, P25869, P27949, P35128, P35129, P35131, P35132, P35133, P35134, P35135, P43102, P46595, P49427, P51668, P51965, P52482, P52483, P52485, P52487, P52490, P52492, P61077, P61078, P61079, P61080, P61088

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
“Ub:E1 (UBA1 substrate)”	“up-regulates activity”	UBE2T	ubiquitination
“Ub:E1 (UBA6 substrate)”	“up-regulates activity”	UBE2T	ubiquitination
FANCL	“down-regulates quantity”	UBE2T	ubiquitination
UBE2T	“up-regulates activity”	FANCL	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 59 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
Antigen processing: Ubiquitination & Proteasome degradation	9	8.0×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein K63-linked ubiquitination	5	25.2×	3e-04
protein polyubiquitination	6	13.1×	7e-04
ubiquitin-dependent protein catabolic process	7	9.8×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	4
Uncertain significance	29
Likely benign	30
Benign	5

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
1069857	NC_000001.10:g.(?202302138)(202304882_?)del	Pathogenic
1076158	NM_014176.4(UBE2T):c.368dup (p.Leu124fs)	Pathogenic
199436	NM_014176.4(UBE2T):c.4C>G (p.Gln2Glu)	Pathogenic
199437	NM_014176.4(UBE2T):c.179+5G>A	Pathogenic
2425911	NC_000001.10:g.(?202302118)(202304882_?)del	Pathogenic
3658483	NM_014176.4(UBE2T):c.167del (p.Ile56fs)	Pathogenic
3675445	NM_014176.4(UBE2T):c.109C>T (p.Gln37Ter)	Pathogenic
3700682	NM_014176.4(UBE2T):c.205C>T (p.Arg69Ter)	Pathogenic
3713143	NM_014176.4(UBE2T):c.134del (p.Pro45fs)	Pathogenic
929628	NM_014176.4(UBE2T):c.110-280_468+264del	Pathogenic
929629	NM_014176.4(UBE2T):c.110-280_468+264dup	Pathogenic
2882001	NM_014176.4(UBE2T):c.110-1G>T	Likely pathogenic
3613846	NM_014176.4(UBE2T):c.109+1G>A	Likely pathogenic
4281601	GRCh37/hg19 1q32.1(chr1:202302132-202304882)x1	Likely pathogenic
806425	GRCh37/hg19 1q32.1(chr1:202302138-202304946)x1	Likely pathogenic

SpliceAI

560 predictions. Top by Δscore:

Variant	Effect	Δscore
1:202331961:C:CC	acceptor_gain	1.0000
1:202333092:GA:G	acceptor_gain	1.0000
1:202333094:C:CC	acceptor_gain	1.0000
1:202333099:A:AC	acceptor_gain	1.0000
1:202333099:A:C	acceptor_gain	1.0000
1:202333235:A:AC	donor_gain	1.0000
1:202333236:C:CC	donor_gain	1.0000
1:202333335:CCTA:C	acceptor_gain	1.0000
1:202333442:CAA:C	donor_gain	1.0000
1:202333442:CAACT:C	donor_gain	1.0000
1:202333444:ACT:A	donor_loss	1.0000
1:202333447:CA:C	donor_loss	1.0000
1:202333448:A:AC	donor_gain	1.0000
1:202333448:A:T	donor_loss	1.0000
1:202333449:C:CT	donor_gain	1.0000
1:202333449:CT:C	donor_gain	1.0000
1:202333449:CTT:C	donor_gain	1.0000
1:202333551:GGTAC:G	acceptor_gain	1.0000
1:202333552:GTAC:G	acceptor_gain	1.0000
1:202333553:TAC:T	acceptor_gain	1.0000
1:202333554:AC:A	acceptor_gain	1.0000
1:202333554:ACC:A	acceptor_loss	1.0000
1:202333555:CC:C	acceptor_gain	1.0000
1:202333556:C:CC	acceptor_gain	1.0000
1:202333556:C:CG	acceptor_loss	1.0000
1:202333558:A:AC	acceptor_gain	1.0000
1:202333558:A:C	acceptor_gain	1.0000
1:202333566:A:AC	acceptor_gain	1.0000
1:202333566:A:C	acceptor_gain	1.0000
1:202335060:T:C	acceptor_gain	1.0000

AlphaMissense

1294 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:202333329:A:G	W98R	0.999
1:202333329:A:T	W98R	0.999
1:202333327:C:A	W98C	0.998
1:202333327:C:G	W98C	0.998
1:202333501:G:C	N78K	0.998
1:202333501:G:T	N78K	0.998
1:202333050:G:T	A143D	0.997
1:202333061:G:C	F139L	0.997
1:202333061:G:T	F139L	0.997
1:202333063:A:G	F139L	0.997
1:202333280:A:G	L114P	0.997
1:202333487:C:A	G83V	0.997
1:202335015:A:C	F51L	0.997
1:202335015:A:T	F51L	0.997
1:202335016:A:G	F51S	0.997
1:202335017:A:G	F51L	0.997
1:202333487:C:T	G83E	0.996
1:202333507:A:C	H76Q	0.996
1:202333507:A:T	H76Q	0.996
1:202333525:A:C	F70L	0.996
1:202333525:A:T	F70L	0.996
1:202333526:A:G	F70S	0.996
1:202333527:A:G	F70L	0.996
1:202333250:A:G	L124P	0.995
1:202333479:A:G	C86R	0.995
1:202333508:T:C	H76R	0.995
1:202333509:G:C	H76D	0.995
1:202333250:A:T	L124H	0.994
1:202333256:T:C	D122G	0.994
1:202333298:A:G	L108S	0.994

dbSNP variants (sampled 300 via entrez): RS1000418710 (1:202334189 C>A), RS1000474381 (1:202334489 T>G), RS1000571613 (1:202339797 T>C), RS1000625407 (1:202340080 G>A), RS1000822331 (1:202343202 A>G), RS1001068108 (1:202332875 T>C), RS1001307840 (1:202340801 C>T), RS1001415808 (1:202332765 G>A), RS1001465837 (1:202339411 T>A,C), RS1001497068 (1:202339860 G>A), RS1001636656 (1:202334177 A>G,T), RS1001696064 (1:202332337 G>C), RS1002239552 (1:202332722 A>C), RS1002315263 (1:202338912 A>C), RS1002592028 (1:202332460 G>A,C)

Disease associations

OMIM: gene MIM:610538 | disease phenotypes: MIM:616435

GenCC curated gene-disease

Disease	Classification	Inheritance
Fanconi anemia complementation group T	Strong	Autosomal recessive
Fanconi anemia	Supportive	Autosomal recessive

Mondo (2): Fanconi anemia complementation group T (MONDO:0014638), Fanconi anemia (MONDO:0019391)

Orphanet (1): Fanconi anemia (Orphanet:84)

HPO phenotypes

115 total (30 of 115 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000035	Abnormal testis morphology
HP:0000047	Hypospadias
HP:0000072	Hydroureter
HP:0000079	Abnormality of the urinary system
HP:0000083	Renal insufficiency
HP:0000130	Abnormality of the uterus
HP:0000135	Hypogonadism
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000324	Facial asymmetry
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000364	Hearing abnormality
HP:0000365	Hearing impairment
HP:0000377	Abnormal pinna morphology
HP:0000453	Choanal atresia
HP:0000478	Abnormality of the eye
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000492	Abnormal eyelid morphology
HP:0000504	Abnormality of vision

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001930_15	Breast cancer	1.000000e-08
GCST002112_2	Celiac disease	3.000000e-07

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D005199	Fanconi Anemia	C15.378.050.085.080.280; C15.378.190.223.500.500.280; C16.320.077.280; C18.452.284.280

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4105763 (SINGLE PROTEIN), CHEMBL4742320 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 411,454 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1200679	ZINC CHLORIDE	4	411,454

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression	3
Estradiol	decreases expression, increases expression	3
Cyclosporine	decreases expression	3
Benzo(a)pyrene	decreases expression, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Fluorouracil	affects expression, affects response to substance	2
Testosterone	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Valproic Acid	affects expression, increases expression	2
Aflatoxin B1	affects expression, increases expression	2
bisphenol F	affects cotreatment, increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
cupric chloride	increases expression	1
cupric oxide	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluoro-n-nonanoic acid	decreases expression	1
corosolic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1

ChEMBL screening assays

15 unique, capped per target: 15 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4020060	Binding	Binding affinity to N-terminally 6xHis-Smt3 tagged human Ube2T C86K/K91R/K95R mutant expressed in Escherichia coli by ITC method	Mind the Metal: A Fragment Library-Derived Zinc Impurity Binds the E2 Ubiquitin-Conjugating Enzyme Ube2T and Induces Structural Rearrangements. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1R7	Abcam K-562 UBE2T KO	Cancer cell line	Female
CVCL_D2MU	Abcam Raji UBE2T KO	Cancer cell line	Male
CVCL_TV89	HAP1 UBE2T (-)	Cancer cell line	Male
CVCL_WQ76	Abcam Jurkat UBE2T KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06519786	PHASE3	UNKNOWN	Safety and Efficacy of Metformin for Treatment of Cytopenia in Children and Adolescents With Fanconi Anemia
NCT00000603	PHASE2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00001749	PHASE2	COMPLETED	Medical Treatment for Diamond Blackfan Anemia
NCT00004787	PHASE2	COMPLETED	Phase II Pilot Study of Granulocyte Colony-Stimulating Factor for Inherited Bone Marrow Failure Syndromes
NCT00053989	PHASE2	COMPLETED	NMA Allogeneic Hematopoietic Cell Transplant in Hematologic Cancer/Disorders
NCT00084695	PHASE2	UNKNOWN	Umbilical Cord Blood for Stem Cell Transplantation in Treating Young Patients With Malignant or Nonmalignant Diseases
NCT00258427	PHASE2	COMPLETED	Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia
NCT00453388	PHASE2	COMPLETED	Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia
NCT01071239	PHASE2	COMPLETED	Hematopoietic Stem Cell Transplant for Fanconi Anemia
NCT02143830	PHASE2	RECRUITING	HSCT for Patients With Fanconi Anemia Using Risk-Adjusted Chemotherapy
NCT02931071	PHASE2	COMPLETED	Clinical Phase II Trial to Evaluate CD34+ Cells Mobilization and Collection in Patients With Fanconi Anemia for Subsequent Transduction With a Lentiviral Vector Carring FANCA Gene. FANCOSTEM-1
NCT03206086	PHASE2	ACTIVE_NOT_RECRUITING	Eltrombopag for People With Fanconi Anemia
NCT03398824	PHASE2	COMPLETED	Pilot Study of Metformin for Patients With Fanconi Anemia
NCT03476330	PHASE2	COMPLETED	Quercetin Chemoprevention for Squamous Cell Carcinoma in Patients With Fanconi Anemia
NCT03579875	PHASE2	RECRUITING	Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders
NCT03600909	PHASE2	TERMINATED	A Study of the Effect of Blood Stem Cell Transplant After Chemotherapy Alone in Patients With Fanconi Anemia
NCT04232085	PHASE2	RECRUITING	Regenerative Medicine to Restore Hematopoiesis and Immune Function in Immunodeficiencies and Inherited Bone Marrow Failures
NCT06045052	PHASE2	COMPLETED	Eltrombopag for Treatment of Fanconi Anemia
NCT00001399	PHASE1	COMPLETED	Gene Therapy for the Treatment of Fanconi’s Anemia Type C
NCT00005896	PHASE1	UNKNOWN	Phase I Pilot Study of CD34 Enriched, Fanconi’s Anemia Complementation Group C Gene Transduced Autologous Peripheral Blood Stem Cell Transplantation in Patients With Fanconi’s Anemia
NCT00006127	PHASE1	UNKNOWN	Phase I Study of Amifostine in Patients With Bone Marrow Failure Related to Fanconi’s Anemia
NCT00093743	PHASE1	COMPLETED	Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed by Unrelated Donor Stem Cell Transplant in Treating Patients With Fanconi Anemia
NCT00243399	PHASE1	COMPLETED	Oxandrolone for the Treatment of Bone Marrow Aplasia in Fanconi Anemia
NCT00272857	PHASE1	COMPLETED	Bone Marrow Cell Gene Transfer in Individuals With Fanconi Anemia
NCT00317876	PHASE1	COMPLETED	Cyclophosphamide in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant for Fanconi’s Anemia
NCT00586274	PHASE1	TERMINATED	Use of Rft5-Dga to Deplete Alloreactive Cells for Pts With Fanconi Anemia After Haploidentical SCT
NCT01331018	PHASE1	TERMINATED	Gene Therapy for Fanconi Anemia
NCT01720147	PHASE1	COMPLETED	Quercetin in Children With Fanconi Anemia; a Pilot Study
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT00352976	PHASE2/PHASE3	COMPLETED	TBI Dose De-escalation for Fanconi Anemia
NCT01019876	PHASE2/PHASE3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT00005898	PHASE1/PHASE2	COMPLETED	Phase I/II Study of Total Body Irradiation, Cyclophosphamide, and Fludarabine Followed by Alternate Donor Hematopoietic Cell Transplantation in Patients With Fanconi’s Anemia
NCT00167206	PHASE1/PHASE2	TERMINATED	Stem Cell Transplantation for Fanconi Anemia
NCT00305708	PHASE1/PHASE2	COMPLETED	Busulfan, Antithymocyte Globulin, and Fludarabine Followed By a Donor Stem Cell Transplant in Treating Young Patients With Blood Disorders, Bone Marrow Disorders, Chronic Myelogenous Leukemia in First Chronic Phase, or Acute Myeloid Leukemia in First Remission
NCT00479115	PHASE1/PHASE2	COMPLETED	Mobilization and Collection of Peripheral Blood Stem Cells in Patients With Fanconi Anemia Using G-CSF and AMD3100
NCT00590460	PHASE1/PHASE2	TERMINATED	Antibody Conditioning Regimen For Allogeneic Donor Stem Cell Transplantation Of Patients With Fanconi Anemia
NCT00630253	PHASE1/PHASE2	COMPLETED	Cytoxan, Fludara, and Antithymocyte Globulin Conditioning Followed By Stem Cell Transplant in Treating Fanconi Anemia
NCT01001598	PHASE1/PHASE2	TERMINATED	Safety and Efficacy Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita
NCT02065869	PHASE1/PHASE2	TERMINATED	Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant
NCT02678533	PHASE1/PHASE2	COMPLETED	Mobilization and Collection of Peripheral Blood Stem Cells in Patients With Fanconi Anemia Using G-CSF and Plerixafor