ELOC

Summary

ELOC (elongin C, HGNC:11617) is a protein-coding gene on chromosome 8q21.11, encoding Elongin-C (Q15369). SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. It is a common-essential gene (DepMap: required in 99.4% of cancer cell lines).

This gene encodes the protein elongin C, which is a subunit of the transcription factor B (SIII) complex. The SIII complex is composed of elongins A/A2, B and C. It activates elongation by RNA polymerase II by suppressing transient pausing of the polymerase at many sites within transcription units. Elongin A functions as the transcriptionally active component of the SIII complex, whereas elongins B and C are regulatory subunits. Elongin A2 is specifically expressed in the testis, and capable of forming a stable complex with elongins B and C. The von Hippel-Lindau tumor suppressor protein binds to elongins B and C, and thereby inhibits transcription elongation. Multiple alternatively spliced transcript variants encoding two distinct isoforms have been identified.

Source: NCBI Gene 6921 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 24 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_005648

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11617
Approved symbol	ELOC
Name	elongin C
Location	8q21.11
Locus type	gene with protein product
Status	Approved
Aliases	SIII
Ensembl gene	ENSG00000154582
Ensembl biotype	protein_coding
OMIM	600788
Entrez	6921

Gene structure

Transcript identifiers

Ensembl transcripts: 85 — 83 protein_coding, 2 retained_intron

ENST00000284811, ENST00000518127, ENST00000519082, ENST00000519487, ENST00000520210, ENST00000520242, ENST00000522337, ENST00000523815, ENST00000602840, ENST00000622804, ENST00000685250, ENST00000685938, ENST00000687224, ENST00000688584, ENST00000692141, ENST00000906596, ENST00000906597, ENST00000906598, ENST00000906599, ENST00000906600, ENST00000906601, ENST00000906602, ENST00000906603, ENST00000906604, ENST00000906605, ENST00000906606, ENST00000906607, ENST00000906608, ENST00000906609, ENST00000906610, ENST00000906611, ENST00000906612, ENST00000927258, ENST00000927259, ENST00000927260, ENST00000927261, ENST00000927262, ENST00000927263, ENST00000927264, ENST00000927265, ENST00000927266, ENST00000927267, ENST00000927268, ENST00000927269, ENST00000927270, ENST00000927271, ENST00000927272, ENST00000927273, ENST00000927274, ENST00000927275, ENST00000927276, ENST00000927277, ENST00000927278, ENST00000927279, ENST00000927280, ENST00000927281, ENST00000927282, ENST00000927283, ENST00000927284, ENST00000927285, ENST00000927286, ENST00000927287, ENST00000927288, ENST00000927289, ENST00000927290, ENST00000927291, ENST00000927292, ENST00000927293, ENST00000927294, ENST00000927295, ENST00000927296, ENST00000927297, ENST00000927298, ENST00000927299, ENST00000927300, ENST00000927301, ENST00000927302, ENST00000927303, ENST00000927304, ENST00000927305, ENST00000927306, ENST00000927307, ENST00000953077, ENST00000953078, ENST00000953079

RefSeq mRNA: 9 — MANE Select: NM_005648 NM_001204857, NM_001204858, NM_001204859, NM_001204860, NM_001204861, NM_001204862, NM_001204863, NM_001204864, NM_005648

CCDS: CCDS34910, CCDS56539

Canonical transcript exons

ENST00000520242 — 4 exons

Exon	Start	End
ENSE00002108274	73945119	73946820
ENSE00002120521	73972077	73972191
ENSE00003658204	73955911	73956054
ENSE00003937944	73959765	73959818

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.6626 / max 686.9537, expressed in 1826 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93620	26.4542	1824
93619	16.8518	1792
93625	7.3198	1735
93624	3.1926	1466
93621	1.5053	1041
93622	1.3020	924
93623	1.0368	694

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.97	gold quality
sperm	CL:0000019	98.87	gold quality
heart right ventricle	UBERON:0002080	98.86	gold quality
male germ cell	CL:0000015	98.78	gold quality
gingival epithelium	UBERON:0001949	98.56	gold quality
esophagus squamous epithelium	UBERON:0006920	98.43	gold quality
palpebral conjunctiva	UBERON:0001812	98.39	gold quality
left testis	UBERON:0004533	98.38	gold quality
right testis	UBERON:0004534	98.36	gold quality
tendon of biceps brachii	UBERON:0008188	98.34	gold quality
gingiva	UBERON:0001828	98.26	gold quality
biceps brachii	UBERON:0001507	98.12	gold quality
amniotic fluid	UBERON:0000173	98.08	gold quality
adult organism	UBERON:0007023	98.08	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.96	gold quality
eye	UBERON:0000970	97.89	gold quality
squamous epithelium	UBERON:0006914	97.87	gold quality
prefrontal cortex	UBERON:0000451	97.86	gold quality
gastrocnemius	UBERON:0001388	97.84	gold quality
epithelium of esophagus	UBERON:0001976	97.82	gold quality
oral cavity	UBERON:0000167	97.81	gold quality
cortical plate	UBERON:0005343	97.80	gold quality
cardiac ventricle	UBERON:0002082	97.72	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.72	gold quality
heart left ventricle	UBERON:0002084	97.70	gold quality
anterior cingulate cortex	UBERON:0009835	97.69	gold quality
cingulate cortex	UBERON:0003027	97.68	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.63	gold quality
right atrium auricular region	UBERON:0006631	97.55	gold quality
parietal pleura	UBERON:0002400	97.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	266.97
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

114 targeting ELOC, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 25)

• These findings suggest that Elongin c may be one of the target genes for amplification of 8q21 (PMID:12004003)
• findings report that HIV-1 Vif interacts with cellular proteins Cul5, elongins B and C, and Rbx1 to form an Skp1-cullin-F-box (SCF)-like complex (PMID:14564014)
• specific Elongin C and Skp1 sequences determine Cullin selection (PMID:15280393)
• show that ASB2, by interacting with the Elongin BC complex, can assemble with Cullin5.Rbx1 to form an E3 ubiquitin ligase complex that stimulates polyubiquitination by the E2 ubiquitin-conjugating enzyme Ubc5 (PMID:15590664)
• the E3 ubiquitin ligase activity of the Vif-BC-Cul5 complex is essential for Vif function against APOBEC3G (PMID:15781449)
• Results describe the 1.9-A crystal structure of the ternary complex of SOCS2 with elongin C and elongin B. (PMID:16675548)
• Elongin B/C recruitment regulates substrate binding by CIS (PMID:18508766)
• TCEB1 promotes invasion of prostate cancer cells and is involved in development of hormone-refractory prostate cancer (PMID:18844214)
• Recombinant full-length Vif interacted with the Elongin BC complex in vitro with a K(d) of 1.9 muM and resulted in observable changes in deuterium uptake in both Elongin C and B. (PMID:20728451)
• Functional interaction of Notch4(ICD) and Elongin C provides novel insight into regulation of Notch signaling in epithelial cell biology and disease. (PMID:22001063)
• TCEB1 and SELC14L1 are good candidate markers for predicting prognosis and progression of prostate cancer. (PMID:23083832)
• PRAME expression in leukaemic cell lines is upregulated by IFN gamma and LPS, suggesting a possible role in immune responses. PRAME associates with Elongin BC complexes by binding Elongin C. (PMID:23460923)
• ASB9 is unstable alone but forms a stable ternary complex with EloBC that binds with high affinity to the Cullin 5 N-terminal domain. (PMID:23837592)
• Vif interaction with EloB-EloC may contribute to recruitment of CBF-beta to Vif, demonstrating that the EloB C-teminus may play a role in improving Vif function and that the over-expression of EloB results in Vif stabilization. (PMID:23988114)
• AFF1 is a ubiquitous P-TEFb partner; full Tat transactivation requires the complete super elongation complexes (PMID:24367103)
• The crystal structure of VHL bound to a Cul2 N-terminal domain, Elongin B, and Elongin C. (PMID:25661653)
• TCEB1-mutated renal cell carcinoma is a distinct entity with recurrent hotspot mutations, specific copy number alterations, pathway activation, and characteristic morphological features. (PMID:25676555)
• crystals of SOCS2 in complex with its adaptor proteins, Elongin C and Elongin B, underwent a change in crystallographic parameters when treated with dimethyl sulfoxide during soaking experiments. (PMID:26121586)
• CRL4(AMBRA)(1) modulates interleukin-6/STAT3 signaling and HIV-1 infectivity that are regulated by CRL5(SOCS)(3) and CRL5(VIF), respectively. Thus, by discovering a substrate of CRL4(AMBRA)(1), ELOC, the shared adapter of CRL5 ubiquitin ligases, we uncovered a novel CRL cross-regulation pathway. (PMID:30166453)
• Putative Drivers of Aggressiveness in TCEB1-mutant Renal Cell Carcinoma: An Emerging Entity with Variable Clinical Course. (PMID:31813809)
• Renal cell carcinomas with leiomyomatous stroma harbor recurrent mutations of TSC1/TSC2, MTOR, and/or ELOC. (PMID:31850909)
• Elongin C Contributes to RNA Polymerase II Degradation by the Interferon Antagonist NSs of La Crosse Orthobunyavirus. (PMID:31941775)
• Novel genetic characterisation and phenotype correlation in von Hippel-Lindau (VHL) disease based on the Elongin C binding site: a large retrospective study. (PMID:32303605)
• NF-kappaB-activated SPRY4-IT1 promotes cancer cell metastasis by downregulating TCEB1 mRNA via Staufen1-mediated mRNA decay. (PMID:34163032)
• [Clinicopathological and molecular genetic characteristics of ELOC mutated renal cell carcinoma]. (PMID:38058035)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	elocb	ENSDARG00000045359
mus_musculus	Eloc	ENSMUSG00000079658
rattus_norvegicus	LOC134482331	ENSRNOG00000051063
drosophila_melanogaster	EloC	FBGN0266711
caenorhabditis_elegans		WBGENE00001236
caenorhabditis_elegans		WBGENE00001237
caenorhabditis_elegans		WBGENE00077680

Protein

Protein identifiers

Elongin-C — Q15369 (reviewed: Q15369)

Alternative names: Elongin 15 kDa subunit, RNA polymerase II transcription factor SIII subunit C, SIII p15, Transcription elongation factor B polypeptide 1

All UniProt accessions (5): Q15369, A0A8I5KYG1, A0A8J9AD82, E5RHG8, R4GMY8

UniProt curated annotations — full annotation on UniProt →

Function. SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex). In embryonic stem cells, the elongin BC complex is recruited by EPOP to Polycomb group (PcG) target genes in order generate genomic region that display both active and repressive chromatin properties, an important feature of pluripotent stem cells. Core component of multiple cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins. By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes. Component the von Hippel-Lindau ubiquitination complex CBC(VHL). A number of ECS complexes (containing either KLHDC2, KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B or FEM1C as substrate-recognition component) are part of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The ECS(ASB9) complex mediates ubiquitination and degradation of CKB. As part of a multisubunit ubiquitin ligase complex, polyubiquitinates monoubiquitinated POLR2A. ECS(LRR1) ubiquitinates MCM7 and promotes CMG replisome disassembly by VCP and chromatin extraction during S-phase. As part of the ECS(RAB40C) complex, mediates ANKRD28 ubiquitination and degradation, thereby inhibiting protein phosphatase 6 (PP6) complex activity and focal adhesion assembly during cell migration. The ECS(ASB7) complex acts a negative regulator of H3K9me3 histone mark by mediating ubiquitination and degradation of SUV39H1. (Microbial infection) Following infection by HIV-1 virus, component of a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) hijacked by the HIV-1 Vif protein, which catalyzes ubiquitination and degradation of APOBEC3F and APOBEC3G. The complex can also ubiquitinate APOBEC3H to some extent.

Subunit / interactions. Heterotrimer of an A (ELOA, ELOA2 or ELOA3P), ELOB and ELOC subunit. The elongin BC complex interacts with EPOP; leading to recruit the elongin BC complex to Polycomb group (PcG) target genes, thereby restricting excessive activity of the PRC2/EED-EZH2 complex. Component of multiple cullin-RING E3 ubiquitin-protein ligase complexes composed of Elongin BC (ELOB and ELOC), a cullin (CUL2 or CUL5), a catalytic subunit (RBX1 or RNF7/RBX2), as well as a substrate adapter protein that can be either ASB2, ASB7, ASB9, ASB11, KLHDC2, KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B, FEM1C, LRR1, PCMTD1, SOCS1, SOCS2, SOCS5, SPSB1, SPSB3, ELOA, VHL, WSB1, ZYG11B or RAB40C. Interacts with TMF1. As part of the Elongin BC E3 ubiquitin ligase complex; interacts with NRBP1. May form oligomers as a KLHDC2/KLHDC3-ELOB-ELOC complex; this interaction is autoinhibitory for the E3 ligase complex as the substrate-binding site of KLHDC2/KLHDC3 is blocked in the oligomer. (Microbial infection) Interacts with HIV-1 Vif; forming an active cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex). (Microbial infection) Substrate adapter protein can be a viral protein such as HIV Vif. (Microbial infection) Interacts with human respiratory syncytial virus (HRSV) protein NS1. (Microbial infection) Interacts with molluscum contagiosum virus MC132. (Microbial infection) Interacts with herpes virus 8 virus protein LANA1.

Subcellular location. Nucleus.

Tissue specificity. Overexpressed in prostate cancer cell line PC-3 and breast cancer cell line SK-BR-3.

Post-translational modifications. Ubiquitinated by the DCX(AMBRA1) complex, leading to its degradation by the proteasome.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the SKP1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15369-1	1	yes
Q15369-2	2

RefSeq proteins (9): NP_001191786, NP_001191787, NP_001191788, NP_001191789, NP_001191790, NP_001191791, NP_001191792, NP_001191793, NP_005639* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001232	SKP1-like	Family
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR016073	Skp1_comp_POZ	Domain
IPR039948	ELC1	Family

Pfam: PF03931

UniProt features (17 total): helix 7, strand 7, chain 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

225 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7Z76	X-RAY DIFFRACTION	1.32
9GIO	X-RAY DIFFRACTION	1.49
7JTO	X-RAY DIFFRACTION	1.7
8BDS	X-RAY DIFFRACTION	1.72
4AJY	X-RAY DIFFRACTION	1.73
6GMR	X-RAY DIFFRACTION	1.75
6HR2	X-RAY DIFFRACTION	1.76
7ZLM	X-RAY DIFFRACTION	1.79
8BB3	X-RAY DIFFRACTION	1.8
6GFX	X-RAY DIFFRACTION	1.83
1LM8	X-RAY DIFFRACTION	1.85
9D1Z	X-RAY DIFFRACTION	1.88
2C9W	X-RAY DIFFRACTION	1.9
6ZHC	X-RAY DIFFRACTION	1.92
7ZLS	X-RAY DIFFRACTION	1.92
6GMN	X-RAY DIFFRACTION	1.94
7ZLP	X-RAY DIFFRACTION	1.94
6I7R	X-RAY DIFFRACTION	1.95
7Z77	X-RAY DIFFRACTION	1.97
6I5N	X-RAY DIFFRACTION	1.98
8P0F	X-RAY DIFFRACTION	1.98
9BOL	X-RAY DIFFRACTION	1.99
1LQB	X-RAY DIFFRACTION	2
4B9K	X-RAY DIFFRACTION	2
9D1I	X-RAY DIFFRACTION	2
6BVB	X-RAY DIFFRACTION	2
7ZLR	X-RAY DIFFRACTION	2.01
8BDJ	X-RAY DIFFRACTION	2.02
8BDM	X-RAY DIFFRACTION	2.02
8BB2	X-RAY DIFFRACTION	2.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15369-F1	90.10	0.76

Function

Pathways and Gene Ontology

Reactome pathways

20 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-1234176	Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-167152	Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167200	Formation of HIV-1 elongation complex containing HIV-1 Tat
R-HSA-167238	Pausing and recovery of Tat-mediated HIV elongation
R-HSA-167243	Tat-mediated HIV elongation arrest and recovery
R-HSA-167246	Tat-mediated elongation of the HIV-1 transcript
R-HSA-167287	HIV elongation arrest and recovery
R-HSA-167290	Pausing and recovery of HIV elongation
R-HSA-180585	Vif-mediated degradation of APOBEC3G
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-75955	RNA Polymerase II Transcription Elongation
R-HSA-8951664	Neddylation
R-HSA-9010553	Regulation of expression of SLITs and ROBOs
R-HSA-9705462	Inactivation of CSF3 (G-CSF) signaling
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-9833109	Evasion by RSV of host interferon responses
R-HSA-9954709	Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide
R-HSA-9820841	M-decay: degradation of maternal mRNAs by maternally stored factors

MSigDB gene sets: 340 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, LEE_NEURAL_CREST_STEM_CELL_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, KAAB_FAILED_HEART_ATRIUM_DN, BASSO_B_LYMPHOCYTE_NETWORK, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, MODULE_151, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MODULE_150

GO Biological Process (6): regulation of transcription by RNA polymerase II (GO:0006357), transcription initiation at RNA polymerase II promoter (GO:0006367), ubiquitin-dependent protein catabolic process (GO:0006511), protein ubiquitination (GO:0016567), ubiquitin-dependent protein catabolic process via the C-end degron rule pathway (GO:0140627), target-directed miRNA degradation (GO:0140958)

GO Molecular Function (3): transcription corepressor binding (GO:0001222), protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515)

GO Cellular Component (8): nucleoplasm (GO:0005654), cytosol (GO:0005829), Cul2-RING ubiquitin ligase complex (GO:0031462), Cul5-RING ubiquitin ligase complex (GO:0031466), elongin complex (GO:0070449), ubiquitin ligase complex (GO:0000151), nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Transcription of the HIV genome	5
RNA Polymerase II Transcription	2
RNA Polymerase II Transcription Elongation	1
Cellular response to hypoxia	1
Tat-mediated elongation of the HIV-1 transcript	1
HIV Transcription Elongation	1
Host Interactions of HIV factors	1
Transcriptional Regulation by TP53	1
Post-translational protein modification	1
Signaling by ROBO receptors	1
Signaling by CSF3 (G-CSF)	1
Class I MHC mediated antigen processing & presentation	1
RSV-host interactions	1
Ribosome-associated quality control	1
Maternal to zygotic transition (MZT)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
transcription by RNA polymerase II	2
cullin-RING ubiquitin ligase complex	2
regulation of DNA-templated transcription	1
DNA-templated transcription initiation	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
protein modification by small protein conjugation	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
miRNA catabolic process	1
post-transcriptional gene silencing	1
negative regulation of miRNA-mediated gene silencing	1
transcription coregulator binding	1
protein binding	1
molecular adaptor activity	1
binding	1
nuclear lumen	1
cytoplasm	1
transcription elongation factor complex	1
intracellular protein-containing complex	1
transferase complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3078 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELOC	VHL	P40337	999
ELOC	ELOB	Q15370	999
ELOC	CUL2	Q13617	999
ELOC	RBX1	P62877	998
ELOC	CUL5	Q93034	998
ELOC	RNF7	Q9UBF6	997
ELOC	CBFB	Q13951	992
ELOC	ELOA2	Q8IYF1	989
ELOC	ELOA	Q14241	987
ELOC	HIF1A	Q16665	987
ELOC	CUL1	Q13616	979
ELOC	CISH	Q9NSE2	976
ELOC	NEDD8	Q15843	974
ELOC	RACK1	P25388	923
ELOC	SKP1	P34991	920

IntAct

310 interactions, top by confidence:

A	B	Type	Score
COMMD1	CCDC22	psi-mi:“MI:0914”(association)	0.970
ELOB	VHL	psi-mi:“MI:0915”(physical association)	0.960
ELOC	ELOB	psi-mi:“MI:0915”(physical association)	0.950
ELOB	ELOC	psi-mi:“MI:0915”(physical association)	0.950
ELOB	ELOC	psi-mi:“MI:0914”(association)	0.950
CUL2	VHL	psi-mi:“MI:0914”(association)	0.940
NEDD8	UBE2M	psi-mi:“MI:0914”(association)	0.940
VHL	ELOC	psi-mi:“MI:0914”(association)	0.920
VHL	ELOC	psi-mi:“MI:0915”(physical association)	0.920
CUL5	SOCS2	psi-mi:“MI:0914”(association)	0.880
PRAME	CUL2	psi-mi:“MI:0914”(association)	0.830
CUL2	ELOC	psi-mi:“MI:0914”(association)	0.800
CUL4B	COPS2	psi-mi:“MI:0914”(association)	0.790
ELOC	METTL21C	psi-mi:“MI:0915”(physical association)	0.780
METTL21C	ELOC	psi-mi:“MI:0915”(physical association)	0.780
KLHDC3	CUL2	psi-mi:“MI:0914”(association)	0.770

BioGRID (656): TCEB1 (Affinity Capture-MS), TCEB1 (Co-purification), TCEB2 (Two-hybrid), METTL21C (Two-hybrid), vif (Co-purification), TCEB1 (Co-purification), TCEB1 (Reconstituted Complex), TCEB1 (Affinity Capture-Western), TCEB2 (Co-purification), TCEB1 (Co-purification), TCEB1 (Affinity Capture-Western), TCEB1 (Affinity Capture-MS), TCEB1 (Affinity Capture-MS), TCEB1 (Affinity Capture-MS), TCEB1 (Affinity Capture-MS)

ESM2 similar proteins: A0PGB3, A1C9U5, A1CZG3, B0Y3B5, B6QGB9, B8MDP8, B8NSJ0, C5FHU9, D4ARL8, G5ECU1, O49484, O65674, O81055, O81057, P52285, P52286, P63208, P63209, Q0CA59, Q15369, Q1PEL7, Q2KII4, Q39255, Q3ZCF3, Q4R5B9, Q4WTT8, Q557E4, Q5BAX8, Q5KU00, Q5R512, Q5ZKF5, Q651E8, Q6H4D6, Q6PEC4, Q6PL11, Q71U00, Q8NK13, Q8TGW7, Q9FHW7, Q9LNT9

Diamond homologs: P83940, P83941, Q03071, Q15369, Q2KII4, Q54Q05, Q751F9, Q9USX9, P52285, Q557E4, Q6PL11, O49484, O65674, Q39255, Q6H4D6, Q9LNT9

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ELOC	up-regulates	H1-1	phosphorylation
ELOC	down-regulates	NOTCH4	ubiquitination
ELOC	“form complex”	“BAF250b E3 ligase”	binding
ELOC	“form complex”	VCB-Cul2	binding
ELOC	“form complex”	“Elongin E3-Cul-5”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 141 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
DNA Damage Recognition in GG-NER	6	16.5×	2e-04
Formation of TC-NER Pre-Incision Complex	7	14.2×	7e-05
Neddylation	31	14.1×	6e-25
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	5	9.5×	1e-02
Class I MHC mediated antigen processing & presentation	12	8.1×	5e-06
Antigen processing: Ubiquitination & Proteasome degradation	20	7.2×	9e-10
Adaptive Immune System	15	4.3×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
ubiquitin-dependent protein catabolic process via the C-end degron rule pathway	6	53.1×	2e-07
protein neddylation	7	38.7×	9e-08
regulation of protein neddylation	5	36.9×	3e-05
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	7	11.6×	3e-04
proteasome-mediated ubiquitin-dependent protein catabolic process	28	11.5×	2e-19
protein ubiquitination	33	10.8×	5e-22
protein polyubiquitination	7	6.4×	9e-03
intracellular signal transduction	20	6.0×	4e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

921 predictions. Top by Δscore:

Variant	Effect	Δscore
8:73946816:CTGAC:C	acceptor_gain	1.0000
8:73955905:GCTTA:G	donor_loss	1.0000
8:73955906:CTTA:C	donor_loss	1.0000
8:73955907:TTACC:T	donor_loss	1.0000
8:73955908:TACC:T	donor_loss	1.0000
8:73955910:C:A	donor_loss	1.0000
8:73956055:C:CC	acceptor_gain	1.0000
8:73972199:T:TA	donor_gain	1.0000
8:73972200:C:A	donor_gain	1.0000
8:73946817:TGACC:T	acceptor_loss	0.9900
8:73946819:ACCTG:A	acceptor_loss	0.9900
8:73946820:CCT:C	acceptor_loss	0.9900
8:73946821:C:CC	acceptor_gain	0.9900
8:73946821:C:T	acceptor_loss	0.9900
8:73946822:T:A	acceptor_loss	0.9900
8:73955909:A:AC	donor_gain	0.9900
8:73955910:C:CC	donor_gain	0.9900
8:73956050:TCCAT:T	acceptor_gain	0.9900
8:73956051:CCAT:C	acceptor_gain	0.9900
8:73956051:CCATC:C	acceptor_gain	0.9900
8:73956052:CAT:C	acceptor_gain	0.9900
8:73956052:CATC:C	acceptor_gain	0.9900
8:73956055:CTAA:C	acceptor_loss	0.9900
8:73956060:G:GC	acceptor_gain	0.9900
8:73972159:G:GA	donor_gain	0.9900
8:73972196:A:AC	donor_gain	0.9900
8:73972197:C:CC	donor_gain	0.9900
8:73972241:GTA:G	donor_loss	0.9900
8:73972242:TACCT:T	donor_loss	0.9900
8:73972244:C:CA	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000063465 (8:73956440 G>T), RS1000114311 (8:73949926 C>G), RS1000122974 (8:73960753 A>G), RS1000328793 (8:73954978 G>A,C), RS1000406209 (8:73972083 G>A), RS1000558111 (8:73948019 C>T), RS1000628038 (8:73949401 A>G), RS1000666632 (8:73953841 A>G), RS1000667507 (8:73954849 T>C), RS1000716583 (8:73948312 C>T), RS1000758621 (8:73953558 A>C), RS1000843861 (8:73958875 T>C), RS1000873833 (8:73966743 C>G,T), RS1000911711 (8:73971225 T>C), RS1000963650 (8:73970891 G>A,C)

Disease associations

OMIM: gene MIM:600788 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000751_4	Attention deficit hyperactivity disorder	7.000000e-06
GCST002932_29	Manganese levels	2.000000e-06
GCST006614_93	Total cholesterol levels	4.000000e-09
GCST010725_15	Malaria	2.000000e-07
GCST010725_27	Malaria	4.000000e-07
GCST010725_69	Malaria	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004574	total cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (7): CHEMBL3259469 (SINGLE PROTEIN), CHEMBL3301400 (PROTEIN COMPLEX), CHEMBL4296117 (PROTEIN COMPLEX), CHEMBL4296148 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296149 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296150 (PROTEIN-PROTEIN INTERACTION), CHEMBL5169077 (PROTEIN-PROTEIN INTERACTION)

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

Binding affinities (BindingDB)

3 measured of 4 human assays (4 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
8-(3,5-difluoro-2-pyridinyl)-N-[5-[[5-[(2S)-1-[(2R,4R)-4-hydroxy-2-[4-methyl-4-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]-5-oxo-1H-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]-1,2-oxazol-3-yl]oxy]pentyl]-15-methyl-4-(methylsulfonylmethyl)-14-oxo-8,12,15-triazatetracyclo[8.6.1.02,7.013,17]heptadeca-1(16),2(7),3,5,10,13(17)-hexaene-5-carboxamide	IC50	795 nM	US-11242344: (4-hydroxypyrrolidin-2-yl)-heterocyclic compounds and methods of use thereof
8-(3,5-difluoro-2-pyridinyl)-N-[5-[[5-[(2R)-1-[(4R)-4-hydroxy-2-[(4S)-4-methyl-4-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]-5-oxo-1H-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]-1,2-oxazol-3-yl]oxy]pentyl]-15-methyl-4-(methylsulfonylmethyl)-14-oxo-8,12,15-triazatetracyclo[8.6.1.02,7.013,17]heptadeca-1(16),2(7),3,5,10,13(17)-hexaene-5-carboxamide	IC50	16900 nM	US-11242344: (4-hydroxypyrrolidin-2-yl)-heterocyclic compounds and methods of use thereof
4-(3,5-difluoropyridin-2-yl)-N-(11-(((2S)-1-((4R)-4-hydroxy-2-((S)-5-methyl-5-(4-(4-methylthiazol-5-yl)phenyl)-4-oxo-4,5-dihydro-1H-imidazol-2-yl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-11-oxoundecyl)-10-methyl-7-((methylsulfonyl)methyl)-11-oxo-3,4,10,11-tetrahydro-1H-1,4,10-triazadibenzo[cd,f]azulene-6-carboxamide (2 Single Diastereomers)	IC50	255000 nM	US-11242344: (4-hydroxypyrrolidin-2-yl)-heterocyclic compounds and methods of use thereof

ChEMBL bioactivities

243 potent at pChembl≥5 of 321 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.30	Kd	5	nM	CHEMBL4244103
8.17	Kd	6.7	nM	CHEMBL4241500
8.17	IC50	6.8	nM	CHEMBL5184620
8.05	Kd	9	nM	CHEMBL4226570
7.82	Kd	15	nM	CHEMBL4227226
7.80	Kd	16	nM	CHEMBL4225470
7.62	Kd	24	nM	CHEMBL4225470
7.62	Kd	24	nM	CHEMBL5274606
7.60	Kd	25	nM	CHEMBL5421220
7.58	Kd	26	nM	CHEMBL4227158
7.58	Kd	26	nM	CHEMBL5182441
7.57	Kd	27	nM	CHEMBL5182441
7.53	Kd	29.3	nM	CHEMBL6035425
7.47	Kd	34	nM	CHEMBL5425050
7.47	Kd	34	nM	CHEMBL5592905
7.46	Kd	35	nM	CHEMBL5182441
7.43	Kd	37	nM	CHEMBL5421220
7.43	Kd	37	nM	CHEMBL5595966
7.41	Ki	39	nM	CHEMBL4740486
7.39	Kd	41	nM	CHEMBL5405990
7.39	Kd	41	nM	CHEMBL5403921
7.36	Kd	44	nM	CHEMBL4225470
7.36	Kd	44	nM	CHEMBL5425778
7.36	Kd	43.8	nM	CHEMBL6035425
7.35	Kd	45	nM	CHEMBL5398197
7.28	Kd	52	nM	CHEMBL4225537
7.28	Kd	53	nM	CHEMBL5403921
7.25	Kd	56	nM	CHEMBL5205396
7.22	Kd	60	nM	CHEMBL5274502
7.21	Kd	62	nM	CHEMBL5592812
7.20	Kd	63	nM	CHEMBL5425778
7.20	IC50	62.8	nM	CHEMBL6063790
7.18	Kd	66	nM	CHEMBL5412800
7.16	Kd	69	nM	CHEMBL4226570
7.16	Kd	70	nM	CHEMBL5274502
7.15	Ki	71	nM	CHEMBL5176799
7.14	Kd	73	nM	CHEMBL4227226
7.14	Kd	73	nM	CHEMBL5398197
7.14	Kd	72	nM	CHEMBL5422221
7.10	Kd	80	nM	CHEMBL4225537
7.10	Kd	80	nM	CHEMBL5422221
7.08	Kd	83	nM	CHEMBL5274502
7.07	Kd	86	nM	CHEMBL5416084
7.06	Kd	87	nM	CHEMBL5274502
7.05	Kd	90	nM	CHEMBL4225470
7.05	Kd	90	nM	CHEMBL4225537
7.04	Ki	91	nM	CHEMBL4226570
7.01	Kd	97	nM	CHEMBL4228950
7.01	Kd	98	nM	CHEMBL5274606
7.01	Kd	97	nM	CHEMBL5423283

PubChem BioAssay actives

185 with measured affinity, of 386 total; 50 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-pyrrol-1-ylphenyl)methanol	1398315: Binding affinity to N-terminal His6 tagged VHL (54 to 213 residues)/ELoC (17 to 112 residues)/EloB (1 to 120 residues) (unknown origin) complex expressed in Escherichia coli BL21(DE3) assessed as dissociation constant by ITC method	kd	0.0050	uM
6-chloro-2,3-dihydrothiochromen-4-one	1398315: Binding affinity to N-terminal His6 tagged VHL (54 to 213 residues)/ELoC (17 to 112 residues)/EloB (1 to 120 residues) (unknown origin) complex expressed in Escherichia coli BL21(DE3) assessed as dissociation constant by ITC method	kd	0.0067	uM
(2S,4R)-1-[(2S)-2-[[2-[4-[4-[3-[2,6-difluoro-3-(propylsulfonylamino)benzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl]phenyl]piperazin-1-yl]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	2119304: Inhibition of 6xHis-tagged VHL (1 to 213 residues)/Elongin B/Elogin C (unknown origin) expressed in Escherichia coli BL21 cells by fluorescence polarization assay	ic50	0.0068	uM
(2S,4R)-1-[(2S)-2-[[2-[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1387966: Induction of interaction of N-terminal His6-tagged recombinant human VHL (54 to 213 residues)/elongin C (17 to 112 residues)/elongin B (1 to 104 residues) co-expressed in Escherichia coli BL21 (DE3) with recombinant human Brd4 BD2 assessed as VCB/BRD4/compound ternary complex formation by isothermal titration calorimetry-based assay	kd	0.0090	uM
(2S,4R)-1-[(2S)-2-[[2-[2-[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1387966: Induction of interaction of N-terminal His6-tagged recombinant human VHL (54 to 213 residues)/elongin C (17 to 112 residues)/elongin B (1 to 104 residues) co-expressed in Escherichia coli BL21 (DE3) with recombinant human Brd4 BD2 assessed as VCB/BRD4/compound ternary complex formation by isothermal titration calorimetry-based assay	kd	0.0150	uM
(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388333: Binding affinity to VBC (unknown origin) at 50 uM at 20 degC by surface plasmon resonance assay	kd	0.0160	uM
(2S,4R)-1-[(2S)-2-[[2-[2-[2-[4-[[2,6-dimethoxy-4-(2-methyl-1-oxo-2,7-naphthyridin-4-yl)phenyl]methyl]piperazin-1-yl]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1960422: Binding affinity to 6His-tagged human VHL/ElonginC/ElonginB expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant using FAM-DEALAHypYIPMDDDFQLRSF peptide as substrate by fluorescence polarisation	kd	0.0240	uM
(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[2-methyl-4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide	2014880: Binding affinity to biotinylated VHL/Elongin B/Elongin C (unknown origin) immobilized in SA sensor chip assessed as dissociation constant by SPR analysis	kd	0.0250	uM
(2S,4R)-1-[(2S)-2-[[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1387966: Induction of interaction of N-terminal His6-tagged recombinant human VHL (54 to 213 residues)/elongin C (17 to 112 residues)/elongin B (1 to 104 residues) co-expressed in Escherichia coli BL21 (DE3) with recombinant human Brd4 BD2 assessed as VCB/BRD4/compound ternary complex formation by isothermal titration calorimetry-based assay	kd	0.0260	uM
(2S,4R)-N-[[2-[5-[4-[[2,6-dimethoxy-4-(2-methyl-1-oxo-2,7-naphthyridin-4-yl)phenyl]methyl]piperazin-1-yl]pentoxy]-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxamide	1960409: Binding affinity to 6His-tagged human VHL/ElonginC/ElonginB expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant by ITC analysis	kd	0.0260	uM
(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-N-[[5-fluoro-2-methoxy-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-hydroxypyrrolidine-2-carboxamide	2014880: Binding affinity to biotinylated VHL/Elongin B/Elongin C (unknown origin) immobilized in SA sensor chip assessed as dissociation constant by SPR analysis	kd	0.0340	uM
[4-[[1-[5-[2-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-2-oxoethoxy]pentyl]triazol-4-yl]methoxy]phenyl]methyl N-[(2S)-4-methyl-1-oxo-1-[[(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]pentan-2-yl]carbamate	2116888: Binding affinity to human VHL (54 to 213 residues)/Elongin B (1 to104 residues)/Elongin C (17 to 112 residues) assessed as dissociation constant measured upto 120 sec by SPR method	kd	0.0340	uM
sodium (2S)-1-hydroxy-2-[[(2S)-2-[[4-[[1-[5-[2-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-2-oxoethoxy]pentyl]triazol-4-yl]methoxy]phenyl]methoxycarbonylamino]-4-methylpentanoyl]amino]-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonate	2116888: Binding affinity to human VHL (54 to 213 residues)/Elongin B (1 to104 residues)/Elongin C (17 to 112 residues) assessed as dissociation constant measured upto 120 sec by SPR method	kd	0.0370	uM
(2S,4R)-4-hydroxy-1-[(2S)-2-[[2-[2-[2-[2-[2-[2-[2-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-2-oxoethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1853529: Displacement of (2S,4R)-N-(4-bromobenzyl)-4-hydroxy-1-(3,3,3-trifluoropropanoyl)pyrrolidine-2-carboxamide from dual VBC E3 ligase (unknown origin) ternary complex assessed as inhibition constant by 19F NMR assay	ki	0.0390	uM
(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[2-methyl-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	2014880: Binding affinity to biotinylated VHL/Elongin B/Elongin C (unknown origin) immobilized in SA sensor chip assessed as dissociation constant by SPR analysis	kd	0.0410	uM
(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-N-[(1S)-1-[5-fluoro-2-methyl-4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]-4-hydroxypyrrolidine-2-carboxamide	2014880: Binding affinity to biotinylated VHL/Elongin B/Elongin C (unknown origin) immobilized in SA sensor chip assessed as dissociation constant by SPR analysis	kd	0.0410	uM
(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-N-[(1S)-1-[5-fluoro-2-methoxy-4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]-4-hydroxypyrrolidine-2-carboxamide	2014880: Binding affinity to biotinylated VHL/Elongin B/Elongin C (unknown origin) immobilized in SA sensor chip assessed as dissociation constant by SPR analysis	kd	0.0440	uM
(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-N-[(1S)-1-[3-fluoro-4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]-4-hydroxypyrrolidine-2-carboxamide	2014880: Binding affinity to biotinylated VHL/Elongin B/Elongin C (unknown origin) immobilized in SA sensor chip assessed as dissociation constant by SPR analysis	kd	0.0450	uM
(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388333: Binding affinity to VBC (unknown origin) at 50 uM at 20 degC by surface plasmon resonance assay	kd	0.0520	uM
(2S,4R)-1-[(2S)-2-[9-[4-[6-chloro-2-(2,6-diazaspiro[3.3]heptan-2-yl)-1-[(4-fluoro-3,5-dimethylphenyl)methyl]benzimidazol-4-yl]piperazin-1-yl]nonanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide	1903595: Binding affinity to VCB E3 ligase (unknown origin) assessed as binary equilibrium dissociation constant by surface plasmon resonance analysis	kd	0.0560	uM
(2S,4R)-N-[[2-[2-[2-[2-[4-[[2,6-dimethoxy-4-(2-methyl-1-oxo-2,7-naphthyridin-4-yl)phenyl]methyl]piperazin-1-yl]ethoxy]ethoxy]ethoxy]-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxamide	1960424: Co-operative binding affinity to 6His-tagged human VHL/ElonginC/ElonginB expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant in the presence of BRD9-BD as complex with compound using FAM-DEALAHypYIPMDDDFQLRSF peptide as substrate by fluorescence polarization assay	kd	0.0600	uM
[4-[[1-[5-[2-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-2-oxoethoxy]pentyl]triazol-4-yl]methoxy]phenyl]methyl N-[(2S)-1-[[(2S)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	2116888: Binding affinity to human VHL (54 to 213 residues)/Elongin B (1 to104 residues)/Elongin C (17 to 112 residues) assessed as dissociation constant measured upto 120 sec by SPR method	kd	0.0620	uM
(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-N-[[3-fluoro-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-hydroxypyrrolidine-2-carboxamide	2014880: Binding affinity to biotinylated VHL/Elongin B/Elongin C (unknown origin) immobilized in SA sensor chip assessed as dissociation constant by SPR analysis	kd	0.0660	uM
(2R,3S,4S)-1-[(2S)-2-[[2-[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-3-fluoro-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1853501: Displacement of (2S,4R)-N-(4-bromobenzyl)-4-hydroxy-1-(3,3,3-trifluoropropanoyl)pyrrolidine-2-carboxamide from BRD4 bromodomain 2/VBC E3 ligase (unknown origin) ternary complex assessed as inhibition constant by 19F NMR assay	ki	0.0710	uM
(2S,4R)-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-N-[[5-fluoro-2-methyl-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-hydroxypyrrolidine-2-carboxamide	2014880: Binding affinity to biotinylated VHL/Elongin B/Elongin C (unknown origin) immobilized in SA sensor chip assessed as dissociation constant by SPR analysis	kd	0.0720	uM
(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[2-methyl-4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide	2014877: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.0860	uM
(2S,4R)-1-[(2S)-2-[(1-acetylcyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388333: Binding affinity to VBC (unknown origin) at 50 uM at 20 degC by surface plasmon resonance assay	kd	0.0970	uM
(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-N-[[3-fluoro-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-hydroxypyrrolidine-2-carboxamide	2014877: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.0970	uM
(2S,4R)-1-[(2S)-2-[[2-[2-[2-[2-[[4-[(2S,4R)-1-acetyl-4-(4-chloroanilino)-2-methyl-3,4-dihydro-2H-quinolin-6-yl]benzoyl]amino]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1387965: Binding affinity to N-terminal His6-tagged recombinant human VHL (54 to 213 residues)/elongin C (17 to 112 residues)/elongin B (1 to 104 residues) expressed in Escherichia coli BL21 (DE3) assessed as compound binary complex formation by isothermal titration calorimetry-based assay	kd	0.1050	uM
(2S,4R)-4-hydroxy-1-[(2S)-2-[(2-hydroxyacetyl)amino]-3,3-dimethylbutanoyl]-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388319: Binding affinity to VHL (unknown origin)/elongin C (unknown origin)/elongin B (unknown origin) by isothermal titration calorimetry-based assay	kd	0.1050	uM
(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388333: Binding affinity to VBC (unknown origin) at 50 uM at 20 degC by surface plasmon resonance assay	kd	0.1070	uM
(2S,4R)-1-[(2S)-2-[[2-[2-[2-[2-[2-[[4-[(2S,4R)-1-acetyl-4-(4-chloroanilino)-2-methyl-3,4-dihydro-2H-quinolin-6-yl]benzoyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1387965: Binding affinity to N-terminal His6-tagged recombinant human VHL (54 to 213 residues)/elongin C (17 to 112 residues)/elongin B (1 to 104 residues) expressed in Escherichia coli BL21 (DE3) assessed as compound binary complex formation by isothermal titration calorimetry-based assay	kd	0.1090	uM
(2S,4R)-1-[(2S)-2-[[2-[2-[2-[[4-[(2S,4R)-1-acetyl-4-(4-chloroanilino)-2-methyl-3,4-dihydro-2H-quinolin-6-yl]benzoyl]amino]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1387965: Binding affinity to N-terminal His6-tagged recombinant human VHL (54 to 213 residues)/elongin C (17 to 112 residues)/elongin B (1 to 104 residues) expressed in Escherichia coli BL21 (DE3) assessed as compound binary complex formation by isothermal titration calorimetry-based assay	kd	0.1160	uM
2-cyclopentyl-4-[7-[10-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-10-oxodecoxy]quinazolin-4-yl]benzoic acid	2023220: Binding affinity to N-terminal 6 his tagged VHL (54 to 213 residues)/truncated ElonginC (17 to 122 residues) /full length ElonginB (unknown origin) expressed in Escherichia coli assessed as dissociation constant measured upto 300 secs by SPR analysis	kd	0.1300	uM
(2S,4R)-1-[(2S)-2-(cyclopropanecarbonylamino)-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388319: Binding affinity to VHL (unknown origin)/elongin C (unknown origin)/elongin B (unknown origin) by isothermal titration calorimetry-based assay	kd	0.1320	uM
(2S,4R)-1-[(2S)-2-[(1-acetamidocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388319: Binding affinity to VHL (unknown origin)/elongin C (unknown origin)/elongin B (unknown origin) by isothermal titration calorimetry-based assay	kd	0.1380	uM
(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-N-[[3-fluoro-2-hydroxy-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-hydroxypyrrolidine-2-carboxamide	2014877: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.1410	uM
(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[2-methyl-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	2014877: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.1490	uM
(2S,4R)-1-[(2R)-3-[[4-[[4-[4-[[5-chloro-4-(methylamino)pyrimidin-2-yl]amino]-3-methoxybenzoyl]piperazin-1-yl]methyl]cyclohexyl]methylsulfanyl]-2-[(1-fluorocyclopropanecarbonyl)amino]-3-methylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	2120188: Binding affinity to VHL/Elongin C/Elogin B (unknown origin) using FAM-DEALA-Hyp-YIPMDDDFQLRSF as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.1600	uM
(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[3-methoxy-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	2014877: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.1630	uM
(2S,4R)-1-[(2R)-2-[(1-fluorocyclopropanecarbonyl)amino]-3-methyl-3-[[4-(morpholin-4-ylmethyl)cyclohexyl]methylsulfanyl]butanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	2120195: Binding affinity to VHL/Elongin C/Elogin B (unknown origin) assessed as dissociation constant at 20 uM by ITC analysis	kd	0.1650	uM
(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[2-methoxy-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	2014877: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.1830	uM
(2S,4R)-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-N-[(1S)-1-[3-fluoro-4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]-4-hydroxypyrrolidine-2-carboxamide	2014877: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.1860	uM
(2S,4R)-1-[(2S)-2-amino-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	2116888: Binding affinity to human VHL (54 to 213 residues)/Elongin B (1 to104 residues)/Elongin C (17 to 112 residues) assessed as dissociation constant measured upto 120 sec by SPR method	kd	0.1890	uM
(2S,4R)-1-[(2S)-3,3-dimethyl-2-[(2,2,2-trichloroacetyl)amino]butanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388318: Displacement of FAM-labeled HIF-1alpha peptide from VBC (unknown origin) by fluorescence polarization assay	kd	0.2000	uM
(2S,4R)-1-[(2S)-2-(cyclobutanecarbonylamino)-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388319: Binding affinity to VHL (unknown origin)/elongin C (unknown origin)/elongin B (unknown origin) by isothermal titration calorimetry-based assay	kd	0.2100	uM
(2S,4R)-N-[[3-chloro-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxamide	2014877: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.2200	uM
(2S,4R)-1-[(2S)-3,3-dimethyl-2-(oxetane-3-carbonylamino)butanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1388319: Binding affinity to VHL (unknown origin)/elongin C (unknown origin)/elongin B (unknown origin) by isothermal titration calorimetry-based assay	kd	0.2300	uM
(2R,3R,4S)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-3-fluoro-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	2014875: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B (1 to 104 residues)/Elongin C (17 to 112 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) cells assessed as dissociation constant by ITC analysis	kd	0.2440	uM
(2S,4R)-N-[[2-chloro-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2S)-2-[(1-cyanocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxamide	2014877: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay	kd	0.2450	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases expression, affects expression	2
Valproic Acid	decreases methylation, increases expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
potassium perchlorate	increases expression	1
arsenite	affects binding, increases reaction	1
tetrabromobisphenol A	increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
4-hydroxy-2-nonenal	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
dinophysistoxin 1	increases expression	1
chloropicrin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
dorsomorphin	affects cotreatment, increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Dactinomycin	affects cotreatment, increases secretion	1
Doxorubicin	increases expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

97 unique, capped per target: 97 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652603	Binding	Binding affinity to human TCEB1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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