PSMB7

Summary

PSMB7 (proteasome 20S subunit beta 7, HGNC:9544) is a protein-coding gene on chromosome 9q33.3, encoding Proteasome subunit beta type-7 (Q99436). Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. It is a common-essential gene (DepMap: required in 96.8% of cancer cell lines).

The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. The encoded protein is a member of the proteasome B-type family, also known as the T1B family, and is a 20S core beta subunit in the proteasome. Expression of this catalytic subunit is downregulated by gamma interferon, and proteolytic processing is required to generate a mature subunit. A pseudogene of this gene is located on the long arm of chromosome 14.

Source: NCBI Gene 5695 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 16 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 96.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_002799

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9544
Approved symbol	PSMB7
Name	proteasome 20S subunit beta 7
Location	9q33.3
Locus type	gene with protein product
Status	Approved
Aliases	Z
Ensembl gene	ENSG00000136930
Ensembl biotype	protein_coding
OMIM	604030
Entrez	5695

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000259457, ENST00000441097, ENST00000466951, ENST00000474081, ENST00000478817, ENST00000498485, ENST00000894502, ENST00000894503, ENST00000894504, ENST00000916856, ENST00000916857, ENST00000916858, ENST00000916859, ENST00000916860, ENST00000916861

RefSeq mRNA: 1 — MANE Select: NM_002799 NM_002799

CCDS: CCDS6855

Canonical transcript exons

ENST00000259457 — 8 exons

Exon	Start	End
ENSE00000726881	124405317	124405432
ENSE00001866322	124415364	124415442
ENSE00003474631	124356764	124356915
ENSE00003516673	124414842	124414935
ENSE00003539655	124353465	124353709
ENSE00003648784	124412352	124412492
ENSE00003677239	124384598	124384656
ENSE00003677426	124413908	124414005

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 150.5938 / max 1109.3557, expressed in 1823 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102425	150.5938	1823

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.28	gold quality
cortical plate	UBERON:0005343	99.10	gold quality
ventricular zone	UBERON:0003053	98.98	gold quality
left testis	UBERON:0004533	98.82	gold quality
right testis	UBERON:0004534	98.82	gold quality
embryo	UBERON:0000922	98.81	gold quality
right adrenal gland	UBERON:0001233	98.65	gold quality
left adrenal gland	UBERON:0001234	98.59	gold quality
skin of leg	UBERON:0001511	98.54	gold quality
right adrenal gland cortex	UBERON:0035827	98.53	gold quality
left adrenal gland cortex	UBERON:0035825	98.50	gold quality
adrenal tissue	UBERON:0018303	98.47	gold quality
skin of abdomen	UBERON:0001416	98.44	gold quality
stromal cell of endometrium	CL:0002255	98.39	gold quality
apex of heart	UBERON:0002098	98.36	gold quality
zone of skin	UBERON:0000014	98.31	gold quality
adrenal gland	UBERON:0002369	98.30	gold quality
body of pancreas	UBERON:0001150	98.29	gold quality
right frontal lobe	UBERON:0002810	98.29	gold quality
adrenal cortex	UBERON:0001235	98.25	gold quality
adult organism	UBERON:0007023	98.21	gold quality
prefrontal cortex	UBERON:0000451	98.19	gold quality
testis	UBERON:0000473	98.16	gold quality
rectum	UBERON:0001052	98.15	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.13	gold quality
nucleus accumbens	UBERON:0001882	98.11	gold quality
islet of Langerhans	UBERON:0000006	98.08	gold quality
caudate nucleus	UBERON:0001873	98.08	gold quality
right lobe of liver	UBERON:0001114	98.07	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-53	no	647.30
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting PSMB7, 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-449B-3P	99.20	67.24	1047
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-550A-3P	98.37	69.61	632
HSA-MIR-4704-5P	96.13	68.67	608

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 8)

• Low protein Z levels but not protein Z gene G79A polymorphism are a risk factor for ischemic stroke. (PMID:18378283)
• A previously unreported sporadic missense mutation within exon 8 is described in a patient with very low protein Z levels. (PMID:18462727)
• PSB7, PRDX1, and SRP9 up-regulation as candidate biomarkers of colon cancer is discovered (PMID:18549262)
• ZPI functions like other serpins to regulate the activity of FXa but in a manner uniquely dependent on protein Z, procoagulant membranes, and pH (PMID:18768472)
• we have identified and characterized a new phosphorylated isoform of the human 20S proteasome b7 subunit and showed its differential expression in tumor vs. normal cell lines (PMID:19645816)
• high PSMB7 expression is associated with anthracycline resistance in breast cancer. (PMID:20010949)
• reduced protein levels in patients with rheumatoid arthritis in association with disease progression (PMID:21713324)
• Studied the associations of Protein Z (PROZ G79A) and Endothelin-1 (EDN1 G5665T) polymorphisms with the clinical features of sickle cell disease (SCD) in a cohort of Egyptian children with SCD. (PMID:28548215)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmb7	ENSDARG00000037962
mus_musculus	Psmb7	ENSMUSG00000026750
rattus_norvegicus	Psmb7	ENSRNOG00000011732
drosophila_melanogaster	Prosbeta1	FBGN0010590
caenorhabditis_elegans		WBGENE00003947

Paralogs (18): PSMB1 (ENSG00000008018), PSMA4 (ENSG00000041357), PSMA3 (ENSG00000100567), PSMB5 (ENSG00000100804), PSMA6 (ENSG00000100902), PSMA7 (ENSG00000101182), PSMA2 (ENSG00000106588), PSMB2 (ENSG00000126067), PSMA1 (ENSG00000129084), PSMB6 (ENSG00000142507), PSMA5 (ENSG00000143106), PSMA8 (ENSG00000154611), PSMB4 (ENSG00000159377), PSMB8 (ENSG00000204264), PSMB10 (ENSG00000205220), PSMB11 (ENSG00000222028), PSMB9 (ENSG00000240065), PSMB3 (ENSG00000277791)

Protein

Protein identifiers

Proteasome subunit beta type-7 — Q99436 (reviewed: Q99436)

Alternative names: Macropain chain Z, Multicatalytic endopeptidase complex chain Z, Proteasome subunit Z, Proteasome subunit beta-2

All UniProt accessions (3): E9KL30, Q99436, Q5TBG5

UniProt curated annotations — full annotation on UniProt →

Function. Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB7 displays a trypsin-like activity.

Subunit / interactions. The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. (Microbial infection) Interacts with HIV-1 Tat protein.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed at a low level in colonic mucosa. Up-regulated in colorectal cancer tissues.

Similarity. Belongs to the peptidase T1B family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99436-1	1	yes
Q99436-2	2

RefSeq proteins (1): NP_002790* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000243	Pept_T1A_subB	Family
IPR001353	Proteasome_sua/b	Family
IPR016050	Proteasome_bsu_CS	Conserved_site
IPR023333	Proteasome_suB-type	Family
IPR024689	Proteasome_bsu_C	Domain
IPR029055	Ntn_hydrolases_N	Homologous_superfamily

Pfam: PF00227, PF12465

UniProt features (28 total): strand 16, helix 5, splice variant 2, propeptide 1, chain 1, turn 1, active site 1, sequence variant 1

Structure

Experimental structures (PDB)

162 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5LE5	X-RAY DIFFRACTION	1.8
5LEY	X-RAY DIFFRACTION	1.9
5LF4	X-RAY DIFFRACTION	1.99
5LF1	X-RAY DIFFRACTION	2
5LF7	X-RAY DIFFRACTION	2
8UD9	ELECTRON MICROSCOPY	2.04
5LF6	X-RAY DIFFRACTION	2.07
5LF3	X-RAY DIFFRACTION	2.1
8BZL	X-RAY DIFFRACTION	2.14
5LEZ	X-RAY DIFFRACTION	2.19
5LEX	X-RAY DIFFRACTION	2.2
5LF0	X-RAY DIFFRACTION	2.41
9K53	ELECTRON MICROSCOPY	2.5
9HMN	ELECTRON MICROSCOPY	2.55
4R3O	X-RAY DIFFRACTION	2.6
6HTR	X-RAY DIFFRACTION	2.6
6RGQ	ELECTRON MICROSCOPY	2.6
9YUZ	ELECTRON MICROSCOPY	2.6
8QYL	ELECTRON MICROSCOPY	2.67
6HTB	X-RAY DIFFRACTION	2.7
8CVR	ELECTRON MICROSCOPY	2.7
6KWY	ELECTRON MICROSCOPY	2.72
8QYJ	ELECTRON MICROSCOPY	2.73
8QYM	ELECTRON MICROSCOPY	2.73
8USB	ELECTRON MICROSCOPY	2.73
9MBP	ELECTRON MICROSCOPY	2.75
6HTC	X-RAY DIFFRACTION	2.8
6HUU	X-RAY DIFFRACTION	2.8
7NAN	ELECTRON MICROSCOPY	2.8
8TM6	ELECTRON MICROSCOPY	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99436-F1	90.42	0.73

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): 44 (nucleophile)

Function

Pathways and Gene Ontology

Reactome pathways

69 pathways

ID	Pathway
R-HSA-1169091	Activation of NF-kappaB in B cells
R-HSA-1234176	Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-1236974	ER-Phagosome pathway
R-HSA-1236978	Cross-presentation of soluble exogenous antigens (endosomes)
R-HSA-174084	Autodegradation of Cdh1 by Cdh1:APC/C
R-HSA-174113	SCF-beta-TrCP mediated degradation of Emi1
R-HSA-174154	APC/C:Cdc20 mediated degradation of Securin
R-HSA-174178	APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
R-HSA-174184	Cdc20:Phospho-APC/C mediated degradation of Cyclin A
R-HSA-180534	Vpu mediated degradation of CD4
R-HSA-180585	Vif-mediated degradation of APOBEC3G
R-HSA-187577	SCF(Skp2)-mediated degradation of p27/p21
R-HSA-195253	Degradation of beta-catenin by the destruction complex
R-HSA-202424	Downstream TCR signaling
R-HSA-211733	Regulation of activated PAK-2p34 by proteasome mediated degradation
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-349425	Autodegradation of the E3 ubiquitin ligase COP1
R-HSA-350562	Regulation of ornithine decarboxylase (ODC)
R-HSA-382556	ABC-family protein mediated transport
R-HSA-450408	AUF1 (hnRNP D0) binds and destabilizes mRNA
R-HSA-4608870	Asymmetric localization of PCP proteins
R-HSA-4641257	Degradation of AXIN
R-HSA-4641258	Degradation of DVL
R-HSA-5358346	Hedgehog ligand biogenesis
R-HSA-5362768	Hh mutants are degraded by ERAD
R-HSA-5607761	Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-5610780	Degradation of GLI1 by the proteasome
R-HSA-5610783	Degradation of GLI2 by the proteasome

MSigDB gene sets: 388 (showing top): REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, BASSO_B_LYMPHOCYTE_NETWORK, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, KEGG_PROTEASOME, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOCC_SECRETORY_GRANULE, ENK_UV_RESPONSE_KERATINOCYTE_UP, REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21

GO Biological Process (3): proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), proteolysis (GO:0006508), obsolete proteolysis involved in protein catabolic process (GO:0051603)

GO Molecular Function (5): endopeptidase activity (GO:0004175), threonine-type endopeptidase activity (GO:0004298), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (12): proteasome complex (GO:0000502), extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), proteasome core complex (GO:0005839), cilium (GO:0005929), nuclear body (GO:0016604), proteasome core complex, beta-subunit complex (GO:0019774), secretory granule lumen (GO:0034774), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
Antigen processing-Cross presentation	2
APC/C-mediated degradation of cell cycle proteins	2
Host Interactions of HIV factors	2
Downstream signaling events of B Cell Receptor (BCR)	1
Cellular response to hypoxia	1
Regulation of APC/C activators between G1/S and early anaphase	1
APC/C:Cdc20 mediated degradation of mitotic proteins	1
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	1
Cyclin E associated events during G1/S transition	1
Cyclin A:Cdk2-associated events at S phase entry	1
Signaling by WNT	1
TCR signaling	1
Regulation of Apoptosis	1
Mitotic Anaphase	1
Fc epsilon receptor (FCERI) signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular protein-containing complex	2
intracellular anatomical structure	2
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
protein metabolic process	1
peptidase activity	1
endopeptidase activity	1
threonine-type peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
endopeptidase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
proteasome complex	1
catalytic complex	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
nucleoplasm	1
intracellular membraneless organelle	1
proteasome core complex	1
protein-containing complex	1
secretory granule	1
cytoplasmic vesicle lumen	1
intracellular organelle lumen	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

2984 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMB7	PSMB6	P28072	982
PSMB7	PSMB5	P28074	979
PSMB7	PSMB1	P20618	941
PSMB7	PSMA5	P28066	886
PSMB7	PSMB2	P31145	881
PSMB7	PSMA6	P34062	837
PSMB7	PSMB4	P28070	812
PSMB7	PSMB3	P31147	794
PSMB7	PSMA3	P25788	780
PSMB7	PSMC2	P35998	771
PSMB7	PSMC3	P17980	749
PSMB7	PSMA4	P25789	744
PSMB7	PSMD1	Q99460	735
PSMB7	PSMA1	P25786	716
PSMB7	PSMD7	P51665	713

IntAct

162 interactions, top by confidence:

A	B	Type	Score
PSMA1	PSMA7	psi-mi:“MI:0915”(physical association)	0.950
PSMA1	PSMA7	psi-mi:“MI:0914”(association)	0.950
PSMA1	PSMA7	psi-mi:“MI:2364”(proximity)	0.950
POMP	PSMB7	psi-mi:“MI:0915”(physical association)	0.910
PSMB7	POMP	psi-mi:“MI:0915”(physical association)	0.910
PSMB7	PSMB1	psi-mi:“MI:0914”(association)	0.900
PSMB1	PSMB7	psi-mi:“MI:0915”(physical association)	0.900
PSMB7	PSMB1	psi-mi:“MI:0915”(physical association)	0.900
PSMB7	PSMB5	psi-mi:“MI:0915”(physical association)	0.890
PSMB5	PSMB7	psi-mi:“MI:0915”(physical association)	0.890
PSMA2	PSMA7	psi-mi:“MI:0914”(association)	0.850
PSMG2	PSMG1	psi-mi:“MI:0914”(association)	0.850
PSMA6	PSMA7	psi-mi:“MI:0914”(association)	0.850

BioGRID (529): PSMB7 (Affinity Capture-MS), PSMB7 (Affinity Capture-MS), PSMB7 (Affinity Capture-MS), PSMB7 (Affinity Capture-MS), PSMB7 (Affinity Capture-MS), PSMB7 (Affinity Capture-MS), PSMA2 (Affinity Capture-MS), PSMA3 (Affinity Capture-MS), PSMB1 (Affinity Capture-MS), PSMA6 (Affinity Capture-MS), PSME4 (Affinity Capture-MS), PSMA8 (Affinity Capture-MS), PSMA7 (Affinity Capture-MS), PSMD11 (Affinity Capture-MS), PSMC6 (Affinity Capture-MS)

ESM2 similar proteins: A1XQU1, A2YXU2, A2Z3I9, A7KE01, A7KII6, O23710, O23712, O24030, O24361, O24362, O35955, O42265, O43063, O55234, P25043, P28062, P28063, P28064, P28074, P28075, P30655, P30656, P38624, P40306, P70195, P93395, Q09841, Q0J006, Q10329, Q2TBP0, Q3MHN0, Q3T0T1, Q3T112, Q4KM35, Q54BC8, Q54QR2, Q55GJ6, Q5R8S2, Q5RDH8, Q5W416

Diamond homologs: A0RXV1, A1RSJ8, A1RWY6, A1RX71, A1XQU1, A2BN27, A2SS78, A3CUS9, A3DN27, A3MS44, A3MXQ6, A4FYA5, A4WH05, A4WMZ0, A4YIE0, A5LHX3, A6UT20, A6VK02, A7I841, A8M8R5, A8MBW0, A9A2U7, A9A788, B1L6S7, B1YDJ0, B5IEE5, B6YSW2, B6YXV3, B8D683, B8GG66, B9LTS6, C3MRE5, C3MY41, C3MZI0, C3N7K2, C3NFX2, C4KIR0, C5A2D5, C5A7L1, C6A459

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PSMB7	“form complex”	“26S Proteasome”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 111 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: Ub, ATP-independent proteasomal degradation	15	99.6×	5e-28
Regulation of activated PAK-2p34 by proteasome mediated degradation	23	74.5×	2e-37
Cross-presentation of soluble exogenous antigens (endosomes)	25	73.8×	1e-40
Proteasome assembly	30	71.1×	2e-48
Vpu mediated degradation of CD4	23	71.0×	6e-37
Regulation of ornithine decarboxylase (ODC)	22	69.6×	2e-35
Autodegradation of the E3 ubiquitin ligase COP1	22	67.9×	3e-35
Ubiquitin-dependent degradation of Cyclin D	22	67.9×	3e-35

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	31	16.2×	2e-26

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2064 predictions. Top by Δscore:

Variant	Effect	Δscore
9:124356760:TCAC:T	donor_loss	1.0000
9:124356761:CACCT:C	donor_loss	1.0000
9:124356762:A:AC	donor_gain	1.0000
9:124356762:A:T	donor_loss	1.0000
9:124356763:C:CC	donor_gain	1.0000
9:124356763:C:G	donor_loss	1.0000
9:124356913:CTC:C	acceptor_gain	1.0000
9:124356916:C:CC	acceptor_gain	1.0000
9:124384593:CATA:C	donor_gain	1.0000
9:124412347:CTTA:C	donor_loss	1.0000
9:124412348:TTAC:T	donor_loss	1.0000
9:124412349:TAC:T	donor_loss	1.0000
9:124412350:A:AC	donor_gain	1.0000
9:124412350:A:T	donor_loss	1.0000
9:124412351:C:CC	donor_gain	1.0000
9:124412351:C:CT	donor_loss	1.0000
9:124412490:CAA:C	acceptor_gain	1.0000
9:124412493:C:CC	acceptor_gain	1.0000
9:124413902:ACTT:A	donor_loss	1.0000
9:124413903:CTT:C	donor_loss	1.0000
9:124413904:TTA:T	donor_loss	1.0000
9:124413905:TAC:T	donor_loss	1.0000
9:124413906:A:AC	donor_gain	1.0000
9:124413906:AC:A	donor_loss	1.0000
9:124413907:C:CA	donor_gain	1.0000
9:124413907:CT:C	donor_gain	1.0000
9:124413907:CTA:C	donor_gain	1.0000
9:124413907:CTAA:C	donor_gain	1.0000
9:124413907:CTAAA:C	donor_gain	1.0000
9:124414001:CCATC:C	acceptor_gain	1.0000

AlphaMissense

1804 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:124384650:C:T	G173D	1.000
9:124405317:C:G	G171R	1.000
9:124405349:C:T	G160E	1.000
9:124405397:C:T	G144E	1.000
9:124412479:C:A	G90W	1.000
9:124412486:A:C	C87W	1.000
9:124412489:A:C	C86W	1.000
9:124413935:T:A	K76I	1.000
9:124413995:A:T	V56D	1.000
9:124356848:C:T	G213E	0.999
9:124356859:G:C	D209E	0.999
9:124356859:G:T	D209E	0.999
9:124356860:T:A	D209V	0.999
9:124356860:T:C	D209G	0.999
9:124356860:T:G	D209A	0.999
9:124356872:C:T	G205D	0.999
9:124356873:C:G	G205R	0.999
9:124356885:C:G	A201P	0.999
9:124384638:G:T	A177E	0.999
9:124384650:C:A	G173V	0.999
9:124384651:C:G	G173R	0.999
9:124384656:C:A	G171V	0.999
9:124384656:C:T	G171D	0.999
9:124405317:C:A	G171C	0.999
9:124405349:C:A	G160V	0.999
9:124405350:C:G	G160R	0.999
9:124405350:C:T	G160R	0.999
9:124405394:C:T	G145E	0.999
9:124405398:C:A	G144W	0.999
9:124405398:C:G	G144R	0.999

dbSNP variants (sampled 300 via entrez): RS1000063063 (9:124362316 G>A), RS1000070141 (9:124387762 A>C), RS1000072534 (9:124354779 G>A,T), RS1000318172 (9:124378876 G>A), RS1000326448 (9:124380274 C>T), RS1000336710 (9:124400339 T>C), RS1000344738 (9:124356875 G>A), RS1000399072 (9:124369000 T>C), RS1000442687 (9:124384740 G>A,T), RS1000469805 (9:124360669 C>T), RS1000532126 (9:124365159 C>A,G,T), RS1000562708 (9:124385167 C>T), RS1000706977 (9:124371451 C>A,G), RS1000791475 (9:124408046 C>T), RS1000800816 (9:124395781 C>T)

Disease associations

OMIM: gene MIM:604030 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006061_113	Atrial fibrillation	7.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3347256 (SINGLE PROTEIN), CHEMBL3831201 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 41,720 (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
CHEMBL325041	BORTEZOMIB	4	13,120
CHEMBL451887	CARFILZOMIB	4	12,508
CHEMBL2141296	IXAZOMIB	3	6,022
CHEMBL371405	MARIZOMIB	3	7,332
CHEMBL2103884	OPROZOMIB	2	2,738

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

ChEMBL bioactivities

315 potent at pChembl≥5 of 340 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.22	IC50	0.6	nM	CINNABARAMIDE G
9.22	Ki	0.6	nM	CHEMBL5624541
9.22	Ki	0.6	nM	BORTEZOMIB
9.04	IC50	0.92	nM	CHEMBL4102324
9.00	IC50	1	nM	CINNABARAMIDE A
8.89	IC50	1.3	nM	MARIZOMIB
8.82	IC50	1.5	nM	CHEMBL4460323
8.70	IC50	2	nM	CHEMBL307387
8.66	IC50	2.2	nM	CHEMBL5419917
8.62	IC50	2.4	nM	CHEMBL4517600
8.62	IC50	2.4	nM	BORTEZOMIB
8.62	IC50	2.4	nM	CHEMBL5413513
8.60	IC50	2.5	nM	CHEMBL4587036
8.59	IC50	2.56	nM	BORTEZOMIB
8.57	IC50	2.7	nM	CHEMBL3237863
8.57	IC50	2.7	nM	CHEMBL5394365
8.52	IC50	3	nM	BORTEZOMIB
8.47	IC50	3.4	nM	CHEMBL4444107
8.47	IC50	3.4	nM	CHEMBL6143686
8.46	IC50	3.43	nM	CHEMBL5197285
8.44	IC50	3.6	nM	CHEMBL4541038
8.41	IC50	3.9	nM	CHEMBL3237862
8.41	IC50	3.9	nM	CHEMBL4547405
8.40	IC50	4	nM	CHEMBL5406440
8.39	IC50	4.1	nM	CHEMBL3237864
8.39	IC50	4.1	nM	CHEMBL3237867
8.39	IC50	4.03	nM	CHEMBL5171225
8.37	IC50	4.28	nM	CHEMBL4581126
8.34	IC50	4.6	nM	CHEMBL4542373
8.34	IC50	4.6	nM	CHEMBL4558648
8.32	IC50	4.8	nM	CHEMBL3237873
8.32	IC50	4.8	nM	CHEMBL4467618
8.30	IC50	5	nM	CHEMBL5398681
8.29	IC50	5.1	nM	CHEMBL3237865
8.29	IC50	5.15	nM	CHEMBL5186240
8.28	IC50	5.2	nM	CHEMBL5429323
8.28	IC50	5.2	nM	CHEMBL5431451
8.25	IC50	5.6	nM	CHEMBL5423645
8.24	IC50	5.7	nM	CHEMBL3237866
8.24	IC50	5.7	nM	CHEMBL3237860
8.23	IC50	5.9	nM	CHEMBL3237868
8.22	IC50	6	nM	CINNABARAMIDE F
8.22	IC50	6	nM	CHEMBL5412037
8.22	IC50	6	nM	CHEMBL74336
8.20	IC50	6.3	nM	CHEMBL5440712
8.19	IC50	6.4	nM	CHEMBL4447701
8.19	IC50	6.4	nM	CHEMBL4435814
8.19	IC50	6.5	nM	CHEMBL4436430
8.19	IC50	6.5	nM	IXAZOMIB
8.16	IC50	6.91	nM	BORTEZOMIB

PubChem BioAssay actives

282 with measured affinity, of 817 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
methyl (2R)-2-acetamido-3-[(2R,3S,4R)-2-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-4-hexyl-3-hydroxy-3-methyl-5-oxopyrrolidine-2-carbonyl]sulfanylpropanoate	277357: Inhibition of human 20S proteasome	ic50	0.0006	uM
[(1R)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-(pyrazine-2-carbonyl)amino]-3-methylbutyl]boronic acid	2131634: Binding affinity to 20s proteosome (unknown origin) assessed as inhibition constant	ki	0.0006	uM
1-N-[(2S)-1-[[(2S)-1-[(2-chlorophenyl)methylamino]-1-oxo-4-phenylbutan-2-yl]amino]-4-(2,2-dimethylpropylamino)-1,4-dioxobutan-2-yl]-4-N-(1,3-thiazol-2-yl)piperidine-1,4-dicarboxamide	1903224: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu Leu-Val-Tyr-AMC as substrate preincubated for 15 mins followed by substrate addition measured by fluorescence assay	ic50	0.0009	uM
(1R,4R,5S)-1-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-4-hexyl-5-methyl-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione	277357: Inhibition of human 20S proteasome	ic50	0.0010	uM
(1R,4R,5S)-4-(2-chloroethyl)-1-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-5-methyl-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione	1853759: Inhibition of 20S proteasome (unknown origin) by fluorescence based assay	ic50	0.0013	uM
1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]-4-N-(1,3-thiazol-2-yl)piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0015	uM
N-[5-[[amino(nitramido)methylidene]amino]-1-[(4-methyl-1-oxopentan-2-yl)amino]-1-oxopentan-2-yl]-2-cyclopentyl-10-(1,3-dioxoisoindol-2-yl)decanamide	3028: Compound was evaluated for inhibitory activity against 20S proteasome from human liver and brain	ic50	0.0020	uM
4-[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-3-cyclopropylpropanoyl]amino]-3-methylbutyl]-2-methyl-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0022	uM
4-N-(4-benzoylphenyl)-1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0024	uM
4-[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-2-cyclopentylacetyl]amino]-3-methylbutyl]-2-methyl-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0024	uM
Bortezomib	1985684: Inhibition of 26S proteasome (unknown origin)	ic50	0.0024	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-N-[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[2-[[2-[[2-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]pentanediamide	1559513: Inhibition of human 20S proteasome using Suc-LLVY-AMC as substrate measured every 5 mins for 120 mins by fluorescence based assay	ic50	0.0025	uM
4-[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-2-cyclopropylacetyl]amino]-3-methylbutyl]-2-methyl-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0027	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0027	uM
4-N-(4-fluorophenyl)-1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0034	uM
1-N-[(2S)-4-(2,2-dimethylpropylamino)-1,4-dioxo-1-[[(2S)-1-oxo-4-phenyl-1-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-yl]amino]butan-2-yl]-4-N-methyl-4-N-(1,3-thiazol-2-yl)piperidine-1,4-dicarboxamide	1903224: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu Leu-Val-Tyr-AMC as substrate preincubated for 15 mins followed by substrate addition measured by fluorescence assay	ic50	0.0034	uM
1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]-4-N-pyridin-3-ylpiperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0036	uM
4-N-(1,3-benzothiazol-2-yl)-1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0039	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[3-phenylmethoxy-2-(phenylmethoxymethyl)propyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0039	uM
[(1R)-1-[[2-[(2,5-dibromobenzoyl)amino]acetyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0040	uM
1-N-[(2S)-4-(2,2-dimethylpropylamino)-1,4-dioxo-1-[[(2S)-1-oxo-4-phenyl-1-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-yl]amino]butan-2-yl]-4-N-pyridin-3-ylpiperidine-1,4-dicarboxamide	1903224: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu Leu-Val-Tyr-AMC as substrate preincubated for 15 mins followed by substrate addition measured by fluorescence assay	ic50	0.0040	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[5-phenylmethoxy-4-(phenylmethoxymethyl)pentyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0041	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[5-phenylmethoxy-4-(phenylmethoxymethyl)pentyl]pentanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0041	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-N-[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[2-[[2-[[2-[[(2S)-3-(4-hydroxyphenyl)-1-[[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]pentanediamide	1559513: Inhibition of human 20S proteasome using Suc-LLVY-AMC as substrate measured every 5 mins for 120 mins by fluorescence based assay	ic50	0.0043	uM
1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]-4-N-(1,3,4-thiadiazol-2-yl)piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0046	uM
4-N-(4-chlorophenyl)-1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0046	uM
4-N-(4-methoxyphenyl)-1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0048	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-(4-phenylmethoxybutyl)butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0048	uM
[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-3-cyclopropylpropanoyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0050	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[3-phenylmethoxy-2-(phenylmethoxymethyl)propyl]pentanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0051	uM
(2S)-N’-(2,2-dimethylpropyl)-2-[[4-[methyl(pyridine-3-carbonyl)amino]piperidine-1-carbonyl]amino]-N-[(2S)-1-oxo-4-phenyl-1-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-yl]butanediamide	1903224: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu Leu-Val-Tyr-AMC as substrate preincubated for 15 mins followed by substrate addition measured by fluorescence assay	ic50	0.0052	uM
4-[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]-2-methyl-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0052	uM
[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]acetyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0052	uM
[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-2-cyclopropylacetyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0056	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]pentanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0057	uM
benzyl N-[(2S)-1-[[(2R)-1-[(1R,2S)-2-[[(2R,3S)-3-[(2S)-butan-2-yl]-4-oxooxetane-2-carbonyl]amino]cyclopropyl]-4-phenylbutan-2-yl]amino]-1-oxopropan-2-yl]carbamate	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0057	uM
(2S)-2-[(2,5-dichlorobenzoyl)amino]-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0059	uM
(2R)-2-acetamido-3-[(2R,3S,4R)-2-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-4-hexyl-3-hydroxy-3-methyl-5-oxopyrrolidine-2-carbonyl]sulfanylpropanoic acid	277357: Inhibition of human 20S proteasome	ic50	0.0060	uM
[(1R)-1-[[2-[[2,5-bis(trifluoromethyl)benzoyl]amino]-2-cyclopentylacetyl]amino]-3-methylbutyl]boronic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0060	uM
N-[5-[[amino(nitramido)methylidene]amino]-1-[(4-methyl-1-oxopentan-2-yl)amino]-1-oxopentan-2-yl]-10-cyano-2-cyclopentyldecanamide	3028: Compound was evaluated for inhibitory activity against 20S proteasome from human liver and brain	ic50	0.0060	uM
4-[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]-3,5,10-trioxa-4-boratricyclo[5.2.1.02,6]decane-8-carboxylic acid	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0063	uM
1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]-4-N-(1,2-oxazol-3-yl)piperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0064	uM
(2S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-4-methyl-N-[(2S)-1-[[(2S)-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]pentanamide	1559513: Inhibition of human 20S proteasome using Suc-LLVY-AMC as substrate measured every 5 mins for 120 mins by fluorescence based assay	ic50	0.0064	uM
1-N-[(2S)-4-methyl-1-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]-4-N-pyrazin-2-ylpiperidine-1,4-dicarboxamide	1624025: Inhibition of human 20S proteasome preincubated for 15 mins followed by substrate addition	ic50	0.0065	uM
Ixazomib	2033891: Inhibition of human 20S proteasome chymotrypsin-like activity using Suc-Leu-Leu-Val-Tyr-AMC as fluorogenic peptide pre-incubated for 10 mins with compound followed by substrate addition for 60 mins by spectrofluorimetric analysis	ic50	0.0065	uM
4-N-(4-chlorophenyl)-1-N-[(2S)-4-(2,2-dimethylpropylamino)-1,4-dioxo-1-[[(2S)-1-oxo-4-phenyl-1-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]butan-2-yl]amino]butan-2-yl]-4-N-methylpiperidine-1,4-dicarboxamide	1903224: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu Leu-Val-Tyr-AMC as substrate preincubated for 15 mins followed by substrate addition measured by fluorescence assay	ic50	0.0069	uM
(2S)-N-[(2S,3R,4R)-3-hydroxy-5-[[(2S)-1-[(2-hydroxy-4-methoxyphenyl)methylamino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxo-1-phenyl-4-[(3,4,5-trimethoxyphenyl)methylamino]pentan-2-yl]-3,3-dimethyl-2-[(2-naphthalen-1-ylacetyl)amino]butanamide	3027: Tested in vitro for inhibition of chymotrypsin like activity of purified human 20S proteasome	ic50	0.0070	uM
Carfilzomib	1770085: Inhibition of human 20S proteasome chymotrypsin-like activity in human RPMI-8226 cells using Suc-LLVY-AMC as fluorogenic substrate incubated for 3 hrs by fluorescence assay	ic50	0.0070	uM
(2S)-2-[[(2S)-3-(4-hydroxyphenyl)-2-[(2-naphthalen-1-ylacetyl)amino]propanoyl]amino]-N-[1-(4-hydroxyphenyl)-3-oxopropan-2-yl]-3-methylbutanamide	248827: Inhibitory concentration to inhibit chymotrypsin-like activity of 20S proteasome prepared from human leukemia HL-60 cells was determined	ic50	0.0070	uM
(2S)-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]-2-(pyrazine-2-carbonylamino)butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0071	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment	4
sodium arsenite	affects binding, increases reaction, increases expression	3
bisphenol A	decreases expression	2
Vehicle Emissions	affects cotreatment, decreases expression, affects expression, increases reaction	2
Doxorubicin	increases expression, increases metabolic processing	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
salinomycin	decreases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
cupric chloride	increases expression	1
arsenic trichloride	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
chloropicrin	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
stattic	decreases expression	1
bisphenol S	increases expression	1
EGFR tyrosine kinase inhibitor 324674	increases expression, decreases reaction	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1

ChEMBL screening assays

171 unique, capped per target: 162 binding, 6 admet, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3222879	Binding	Inhibition of human 20S proteasome using Suc-LLVY-AMC as substrate preincubated for 30 mins followed by substrate addition measured after 90 mins by fluorescence assay	Oxathiazole-2-one derivative of bortezomib: Synthesis, stability and proteasome inhibition activity — Medchemcomm
CHEMBL4736581	ADMET	Inhibition of human 20S proteasome stably expressed in HEK293 cells at 5 to 50 uM using succinyl-LLVY-AMC as substrate preincubated for 30 mins followed by substrate addition and measured at 3 mins interval for 30 mins by fluorescence assay	A covalent p97/VCP ATPase inhibitor can overcome resistance to CB-5083 and NMS-873 in colorectal cancer cells. — Eur J Med Chem
CHEMBL834792	Functional	Inhibitory concentration to inhibit trypsin-like activity of 20S proteasome from human leukemia HL-60 cells was determined	Structure-based design of derivatives of tyropeptin A as the potent and selective inhibitors of mammalian 20S proteasome. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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