UBE2L6

Summary

UBE2L6 (ubiquitin conjugating enzyme E2 L6, HGNC:12490) is a protein-coding gene on chromosome 11q12.1, encoding Ubiquitin/ISG15-conjugating enzyme E2 L6 (O14933). Catalyzes the covalent attachment of ubiquitin or ISG15 to other proteins.

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 (E1s), ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s). This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is highly similar in primary structure to the enzyme encoded by the UBE2L3 gene. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 9246 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 31 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004223

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12490
Approved symbol	UBE2L6
Name	ubiquitin conjugating enzyme E2 L6
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Aliases	UBCH8
Ensembl gene	ENSG00000156587
Ensembl biotype	protein_coding
OMIM	603890
Entrez	9246

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000287156, ENST00000340573, ENST00000526659, ENST00000527022, ENST00000528275

RefSeq mRNA: 2 — MANE Select: NM_004223 NM_004223, NM_198183

CCDS: CCDS7960, CCDS7961

Canonical transcript exons

ENST00000287156 — 4 exons

Exon	Start	End
ENSE00001106587	57567585	57567672
ENSE00002184446	57551662	57552509
ENSE00003482457	57554437	57554623
ENSE00003678270	57560337	57560432

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 72.2055 / max 711.2140, expressed in 1804 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119799	67.1917	1794
119800	1.5891	771
119803	1.4808	687
119801	1.3427	682
119802	0.4994	261
119798	0.1018	48

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.57	gold quality
monocyte	CL:0000576	98.40	gold quality
leukocyte	CL:0000738	98.35	gold quality
mononuclear cell	CL:0000842	98.33	gold quality
tendon of biceps brachii	UBERON:0008188	97.27	gold quality
palpebral conjunctiva	UBERON:0001812	97.17	gold quality
ganglionic eminence	UBERON:0004023	97.17	gold quality
lymph node	UBERON:0000029	97.12	gold quality
spleen	UBERON:0002106	96.97	gold quality
vermiform appendix	UBERON:0001154	96.86	gold quality
gall bladder	UBERON:0002110	96.76	gold quality
stromal cell of endometrium	CL:0002255	96.69	gold quality
cortical plate	UBERON:0005343	96.44	gold quality
blood	UBERON:0000178	96.23	gold quality
right lung	UBERON:0002167	96.21	gold quality
right lobe of liver	UBERON:0001114	96.09	gold quality
right adrenal gland	UBERON:0001233	96.08	gold quality
upper lobe of left lung	UBERON:0008952	96.06	gold quality
right adrenal gland cortex	UBERON:0035827	95.93	gold quality
upper lobe of lung	UBERON:0008948	95.84	gold quality
smooth muscle tissue	UBERON:0001135	95.82	gold quality
caecum	UBERON:0001153	95.72	gold quality
peritoneum	UBERON:0002358	95.71	gold quality
omental fat pad	UBERON:0010414	95.71	gold quality
left adrenal gland	UBERON:0001234	95.58	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.29	gold quality
left adrenal gland cortex	UBERON:0035825	95.23	gold quality
right coronary artery	UBERON:0001625	95.22	gold quality
pericardium	UBERON:0002407	95.20	gold quality
thymus	UBERON:0002370	95.00	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	22.88
E-HCAD-13	yes	12.92
E-MTAB-7052	no	448.69
E-MTAB-7037	no	425.10
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting UBE2L6, 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-8485	100.00	77.57	4731
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-6894-5P	98.70	63.78	809
HSA-MIR-6840-3P	98.68	65.95	1923

Literature-anchored findings (GeneRIF, showing 14)

• Quantitative-PCR and Northern analysis confirmed down-regulation of UCRP and UBE2L6 with BRCA2 knockdown, respectively. (PMID:15670748)
• Ube1L was required for transfer of ISG15 to UbcH8 and for binding of Ube1L to UbcH8 (PMID:18583345)
• The structure of UbcH8 does not undergo a significant conformational change upon forming a complex with ubiquitin. (PMID:19928833)
• gain and loss-of-function approaches show that UBCH8 and the ubiquitin-ligase SIAH1 physically interact with and target FLT3-ITD for proteasomal degradation (PMID:20508617)
• study reports that UBCH8 and UBE2G1 and UBE2G2 cooperate with CRL4Cdt2 in promoting the polyubiquitylation and subsequent degradation of p21 and Cdt1, respectively (PMID:21628527)
• Data indicate that reduced expression of the ubiquitin-conjugating enzyme UbcH8 protein correlated with poor outcome in nasopharyngeal carcinoma (NPC) patients. (PMID:26506425)
• Depletion of either ISG15 or UBE2L6/UBCH8 resulted in enhanced endogenous autophagic flux. (PMID:28186990)
• hese findings establish UBE2L6 as a novel target of UHRF1 that regulates the apoptosis function of UHRF1. (PMID:29157076)
• TNF-alpha, similar to the response by IFN-beta, could directly induce expression of ISG15 and its conjugation machinery, UbE1L and UbcH8, in human lung carcinoma. (PMID:31428903)
• Inhibition of UBE2L6 attenuates ISGylation and impedes ATRA-induced differentiation of leukemic cells. (PMID:31820845)
• UBE2L6 is Involved in Cisplatin Resistance by Regulating the Transcription of ABCB6. (PMID:32329696)
• An integrative analysis identifying transcriptional features and key genes involved in COVID-19. (PMID:33242255)
• Increased UBE2L6 regulated by type 1 interferon as potential marker in TB. (PMID:34773365)
• Association of UBE2L6 and ABCB6 Expression With Platinum Resistance in Serous Ovarian Carcinoma. (PMID:37500176)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ube2l6	ENSMUSG00000027078
rattus_norvegicus	Ube2l6	ENSRNOG00000030467
drosophila_melanogaster	Ubc84D	FBGN0017456
drosophila_melanogaster	CG2924	FBGN0023528
drosophila_melanogaster	Ubc10	FBGN0026316
drosophila_melanogaster	CG17030	FBGN0035584
caenorhabditis_elegans		WBGENE00006713
caenorhabditis_elegans	ubc-25	WBGENE00006720

Paralogs (12): UBE2D1 (ENSG00000072401), UBE2D4 (ENSG00000078967), UBE2D3 (ENSG00000109332), UBE2D2 (ENSG00000131508), UBE2Q2 (ENSG00000140367), UBE2Q1 (ENSG00000160714), UBE2E3 (ENSG00000170035), UBE2E1 (ENSG00000170142), UBE2E2 (ENSG00000182247), UBE2L3 (ENSG00000185651), UBE2QL1 (ENSG00000215218), UBE2L5 (ENSG00000236444)

Protein

Protein identifiers

Ubiquitin/ISG15-conjugating enzyme E2 L6 — O14933 (reviewed: O14933)

Alternative names: E2 ubiquitin-conjugating enzyme L6, Retinoic acid-induced gene B protein, UbcH8, Ubiquitin carrier protein L6, Ubiquitin-protein ligase L6

All UniProt accessions (3): O14933, E9PKW8, E9PQT7

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the covalent attachment of ubiquitin or ISG15 to other proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Promotes ubiquitination and subsequent proteasomal degradation of FLT3.

Subunit / interactions. Interacts with RNF19A, RNF19B and RNF144B. Interacts with FLT3 (tyrosine phosphorylated).

Tissue specificity. Present in natural killer cells (at protein level).

Post-translational modifications. ISGylated.

Induction. By IFNB1/IFN-beta.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the ubiquitin-conjugating enzyme family.

Isoforms (2)

UniProt ID	Names	Canonical?
O14933-1	1	yes
O14933-2	2

RefSeq proteins (2): NP_004214, NP_937826 (=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)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. 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
S-UBIQUITINYL-[E1 UBIQUITIN-ACTIVATING ENZYME]-L	1	1
[UBIQUITIN CARRIER PROTEIN UBC4]-L-CYSTEINE	0.0019	1

UniProt features (19 total): strand 7, helix 6, turn 2, chain 1, domain 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
1WZV	X-RAY DIFFRACTION	2.1
1WZW	X-RAY DIFFRACTION	2.4
8SE9	ELECTRON MICROSCOPY	3.2
8SEB	ELECTRON MICROSCOPY	3.24
8SV8	ELECTRON MICROSCOPY	3.38
8SEA	ELECTRON MICROSCOPY	3.4
8OIF	ELECTRON MICROSCOPY	3.5
2KJH	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14933-F1	95.28	0.96

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)

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-168928	DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-5656169	Termination of translesion DNA synthesis
R-HSA-936440	Negative regulators of DDX58/IFIH1 signaling
R-HSA-977225	Amyloid fiber formation
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-9833110	RSV-host interactions
R-HSA-9833482	PKR-mediated signaling
R-HSA-9909505	Modulation of host responses by IFN-stimulated genes

MSigDB gene sets: 325 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, MODULE_45, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, RIZKI_TUMOR_INVASIVENESS_3D_DN, WIELAND_UP_BY_HBV_INFECTION, MISSIAGLIA_REGULATED_BY_METHYLATION_UP, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, KOYAMA_SEMA3B_TARGETS_UP, RADAEVA_RESPONSE_TO_IFNA1_UP

GO Biological Process (8): protein polyubiquitination (GO:0000209), ubiquitin-dependent protein catabolic process (GO:0006511), ISG15-protein conjugation (GO:0032020), protein modification process (GO:0036211), innate immune response (GO:0045087), protein ubiquitination (GO:0016567), modification-dependent protein catabolic process (GO:0019941), protein modification by small protein conjugation (GO:0032446)

GO Molecular Function (9): ubiquitin-protein transferase activity (GO:0004842), ISG15 transferase activity (GO:0042296), ubiquitin binding (GO:0043130), ubiquitin conjugating enzyme activity (GO:0061631), nucleotide binding (GO:0000166), protein binding (GO:0005515), ATP binding (GO:0005524), transferase activity (GO:0016740), ubiquitin-like protein transferase activity (GO:0019787)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Antimicrobial mechanism of IFN-stimulated genes	2
Innate Immune System	1
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	1
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1
Metabolism of proteins	1
Class I MHC mediated antigen processing & presentation	1
Respiratory Syncytial Virus Infection Pathway	1
Interferon Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein ubiquitination	2
protein modification by small protein conjugation	2
ubiquitin-like protein transferase activity	2
modification-dependent protein catabolic process	1
protein metabolic process	1
macromolecule modification	1
immune response	1
defense response to symbiont	1
protein catabolic process	1
protein modification process	1
modification-dependent macromolecule catabolic process	1
protein modification by small protein conjugation or removal	1
ubiquitin-like 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
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
catalytic activity	1
aminoacyltransferase activity	1
catalytic activity, acting on a protein	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

2390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBE2L6	UBA7	P41226	951
UBE2L6	PRKN	O60260	939
UBE2L6	HERC5	Q9UII4	901
UBE2L6	ARIH1	Q9Y4X5	880
UBE2L6	ISG15	P05161	872
UBE2L6	USP18	Q9UMW8	824
UBE2L6	TRIM25	Q14258	811
UBE2L6	SIAH1	Q8IUQ4	805
UBE2L6	RNF8	O76064	748
UBE2L6	UBE3A	P78355	724
UBE2L6	RNF125	Q96EQ8	668
UBE2L6	HERC6	Q8IVU3	661
UBE2L6	RNF19A	Q9NV58	650
UBE2L6	RIGI	O95786	635
UBE2L6	SNCAIP	Q9Y6H5	613
UBE2L6	IFIH1	Q9BYX4	613

IntAct

96 interactions, top by confidence:

A	B	Type	Score
ARIH2	UBE2L6	psi-mi:“MI:0915”(physical association)	0.880
UBE2L6	ARIH2	psi-mi:“MI:0915”(physical association)	0.880
LONRF1	UBE2L6	psi-mi:“MI:0915”(physical association)	0.780
UBE2L6	RBCK1	psi-mi:“MI:0915”(physical association)	0.780
RBCK1	UBE2L6	psi-mi:“MI:0915”(physical association)	0.780
UBE2L6	LONRF1	psi-mi:“MI:0915”(physical association)	0.780
RNF144B	UBE2L6	psi-mi:“MI:0915”(physical association)	0.680
UBE2L6	RNF144B	psi-mi:“MI:0915”(physical association)	0.680
DTX3	UBE2L6	psi-mi:“MI:0915”(physical association)	0.670
UBE2L6	TRIM8	psi-mi:“MI:0915”(physical association)	0.670
UBE2L6	DTX3	psi-mi:“MI:0915”(physical association)	0.670
UBE2L6	TRIM62	psi-mi:“MI:0915”(physical association)	0.560
UBE2L6	RNF216	psi-mi:“MI:0915”(physical association)	0.560
UBE2L6	MID1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (153): UBE2L6 (Reconstituted Complex), ARIH2 (Two-hybrid), RBCK1 (Two-hybrid), LONRF1 (Two-hybrid), UBE2L6 (Biochemical Activity), UBE2L6 (Biochemical Activity), UBE3A (Biochemical Activity), UBE2L6 (Biochemical Activity), UBE2L6 (Two-hybrid), UBE2L6 (Affinity Capture-Western), UBE2L6 (Affinity Capture-Western), UBE2L6 (Reconstituted Complex), UBE2L6 (Affinity Capture-Western), UBE2L6 (Affinity Capture-MS), UBE2L6 (Affinity Capture-MS)

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: 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

2 interactions.

A	Effect	B	Mechanism
“Ub:E1 (UBA1 substrate)”	“up-regulates activity”	UBE2L6	ubiquitination
“Ub:E1 (UBA6 substrate)”	“up-regulates activity”	UBE2L6	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 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	13	16.7×	2e-11
Class I MHC mediated antigen processing & presentation	6	14.5×	2e-04
Adaptive Immune System	6	6.2×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein K63-linked ubiquitination	6	48.6×	2e-07
protein autoubiquitination	5	35.5×	9e-06
protein K48-linked ubiquitination	6	30.6×	2e-06
ubiquitin-dependent protein catabolic process	13	29.2×	4e-14
protein polyubiquitination	6	21.0×	1e-05
protein ubiquitination	13	16.3×	4e-11
positive regulation of canonical NF-kappaB signal transduction	7	15.4×	9e-06
proteasome-mediated ubiquitin-dependent protein catabolic process	9	14.2×	5e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

692 predictions. Top by Δscore:

Variant	Effect	Δscore
11:57552505:CAGGA:C	acceptor_gain	1.0000
11:57552506:AGGA:A	acceptor_gain	1.0000
11:57552507:GGA:G	acceptor_gain	1.0000
11:57552508:GACTG:G	acceptor_loss	1.0000
11:57552510:C:CC	acceptor_gain	1.0000
11:57554461:T:TA	donor_gain	1.0000
11:57554462:C:A	donor_gain	1.0000
11:57554471:A:AC	donor_gain	1.0000
11:57554472:C:CC	donor_gain	1.0000
11:57554472:CTG:C	donor_gain	1.0000
11:57554619:TGGTC:T	acceptor_gain	1.0000
11:57554620:GGTC:G	acceptor_gain	1.0000
11:57554621:GTC:G	acceptor_gain	1.0000
11:57554621:GTCC:G	acceptor_loss	1.0000
11:57554622:TC:T	acceptor_gain	1.0000
11:57554623:CC:C	acceptor_gain	1.0000
11:57554623:CCTGT:C	acceptor_loss	1.0000
11:57554624:C:CC	acceptor_gain	1.0000
11:57554626:G:C	acceptor_gain	1.0000
11:57554626:G:GC	acceptor_gain	1.0000
11:57554629:C:CT	acceptor_gain	1.0000
11:57560335:A:AC	donor_gain	1.0000
11:57560335:A:C	donor_loss	1.0000
11:57560336:C:A	donor_loss	1.0000
11:57560336:C:CA	donor_gain	1.0000
11:57560336:CG:C	donor_gain	1.0000
11:57560336:CGG:C	donor_gain	1.0000
11:57560336:CGGG:C	donor_gain	1.0000
11:57560336:CGGGT:C	donor_gain	1.0000
11:57560428:AGCTC:A	acceptor_gain	1.0000

AlphaMissense

1007 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:57554462:C:A	W95C	0.986
11:57554462:C:G	W95C	0.986
11:57554594:G:C	F51L	0.985
11:57554594:G:T	F51L	0.985
11:57554596:A:G	F51L	0.985
11:57554464:A:G	W95R	0.977
11:57554464:A:T	W95R	0.977
11:57560357:A:G	W35R	0.977
11:57560357:A:T	W35R	0.977
11:57554538:A:G	F70S	0.974
11:57552402:C:G	A140P	0.973
11:57554519:G:C	H76Q	0.970
11:57554519:G:T	H76Q	0.970
11:57552412:G:C	F136L	0.968
11:57552412:G:T	F136L	0.968
11:57552414:A:G	F136L	0.968
11:57554595:A:G	F51S	0.968
11:57554520:T:C	H76R	0.967
11:57554537:G:C	F70L	0.965
11:57554537:G:T	F70L	0.965
11:57554539:A:G	F70L	0.965
11:57552377:C:T	G148E	0.962
11:57554583:A:G	I55T	0.961
11:57554521:G:C	H76D	0.960
11:57554576:G:C	F57L	0.960
11:57554576:G:T	F57L	0.960
11:57554578:A:G	F57L	0.960
11:57552401:G:T	A140D	0.958
11:57554463:C:G	W95S	0.954
11:57554577:A:G	F57S	0.954

dbSNP variants (sampled 300 via entrez): RS1000182583 (11:57568997 A>C), RS1000318636 (11:57553782 C>T), RS1000517398 (11:57566038 T>C), RS1000540300 (11:57565590 C>T), RS1000646333 (11:57559473 T>C), RS1001024247 (11:57560163 A>G), RS1001074663 (11:57559773 G>T), RS1001131451 (11:57566369 G>A), RS1001189894 (11:57559428 T>C), RS1001279900 (11:57562046 C>T), RS1001375227 (11:57553694 C>A), RS1002188220 (11:57567398 C>T), RS1002282517 (11:57560783 G>A), RS1002334856 (11:57560994 G>C), RS1002753148 (11:57569426 G>A)

Disease associations

OMIM: gene MIM:603890 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725040 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179010: Inhibition of UBE2L6 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects expression, affects cotreatment, increases expression	3
Estradiol	affects expression, affects cotreatment, decreases expression, increases expression	3
Tretinoin	affects cotreatment, increases expression	3
Cyclosporine	decreases expression, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	increases expression, affects expression, affects cotreatment	2
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
terbufos	increases methylation	1
pyrrolidine dithiocarbamic acid	affects cotreatment, increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
bathocuproine sulfonate	affects cotreatment, increases expression	1
ferrous chloride	increases expression	1
epigallocatechin gallate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
bisphenol S	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
picoxystrobin	decreases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	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
CHEMBL5697740	Binding	Inhibition of UBE2L6 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TV80	HAP1 UBE2L6 (-) 1	Cancer cell line	Male
CVCL_TV81	HAP1 UBE2L6 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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