PSMB9

Summary

PSMB9 (proteasome 20S subunit beta 9, HGNC:9546) is a protein-coding gene on chromosome 6p21.32, encoding Proteasome subunit beta type-9 (P28065). The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH.

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. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. This gene is located in the class II region of the MHC (major histocompatibility complex). Expression of this gene is induced by gamma interferon and this gene product replaces catalytic subunit 1 (proteasome beta 6 subunit) in the immunoproteasome. Proteolytic processing is required to generate a mature subunit.

Source: NCBI Gene 5698 — RefSeq curated summary.

At a glance

• Gene–disease (curated): proteasome-associated autoinflammatory syndrome 6 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 16
• Clinical variants (ClinVar): 63 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 42
• Druggable target: yes — 7 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002800

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9546
Approved symbol	PSMB9
Name	proteasome 20S subunit beta 9
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Aliases	RING12, beta1i, PSMB6i
Ensembl gene	ENSG00000240065
Ensembl biotype	protein_coding
OMIM	177045
Entrez	5698

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 retained_intron

ENST00000374859, ENST00000395330, ENST00000414474, ENST00000464863, ENST00000467593, ENST00000892971, ENST00000892972

RefSeq mRNA: 1 — MANE Select: NM_002800 NM_002800

CCDS: CCDS4759

Canonical transcript exons

ENST00000374859 — 6 exons

Exon	Start	End
ENSE00001659845	32854192	32854289
ENSE00001727868	32858364	32858505
ENSE00003576541	32856138	32856205
ENSE00003643042	32858005	32858134
ENSE00003691069	32857263	32857394
ENSE00003844539	32859405	32859851

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 99.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.9303 / max 656.0366, expressed in 1594 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67184	26.6089	1551
67179	5.4975	563
67183	2.0990	819
67185	0.7250	343

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.08	gold quality
leukocyte	CL:0000738	98.52	gold quality
monocyte	CL:0000576	98.50	gold quality
lymph node	UBERON:0000029	98.15	gold quality
vermiform appendix	UBERON:0001154	97.93	gold quality
blood	UBERON:0000178	97.84	gold quality
spleen	UBERON:0002106	97.82	gold quality
duodenum	UBERON:0002114	96.83	gold quality
mucosa of transverse colon	UBERON:0004991	94.40	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.16	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.96	gold quality
small intestine	UBERON:0002108	93.77	gold quality
right lung	UBERON:0002167	93.71	gold quality
bone marrow cell	CL:0002092	93.37	gold quality
gall bladder	UBERON:0002110	93.22	gold quality
upper lobe of left lung	UBERON:0008952	92.94	gold quality
rectum	UBERON:0001052	92.90	gold quality
bone marrow	UBERON:0002371	92.55	gold quality
omental fat pad	UBERON:0010414	91.66	gold quality
smooth muscle tissue	UBERON:0001135	91.32	gold quality
adipose tissue	UBERON:0001013	91.24	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.89	gold quality
apex of heart	UBERON:0002098	90.82	gold quality
lung	UBERON:0002048	90.19	gold quality
fallopian tube	UBERON:0003889	89.94	gold quality
thoracic mammary gland	UBERON:0005200	89.46	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.08	gold quality
intestine	UBERON:0000160	88.97	gold quality
transverse colon	UBERON:0001157	88.90	gold quality
left adrenal gland	UBERON:0001234	88.89	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	201.99
E-MTAB-10287	yes	31.38
E-MTAB-6701	yes	18.93
E-HCAD-1	yes	18.89
E-HCAD-10	yes	13.78
E-CURD-88	yes	8.54
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX1, CDX2, EGR1, IRF1, IRF6, NFKB1, RELA, SEC14L2, STAT1

miRNA regulators (miRDB)

21 targeting PSMB9, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-628-5P	98.36	67.74	844
HSA-MIR-138-1-3P	98.25	67.89	867
HSA-MIR-5088-5P	97.97	64.28	487
HSA-MIR-1302	97.92	67.27	844
HSA-MIR-3661	97.83	67.30	705
HSA-MIR-517-5P	97.13	68.43	781
HSA-MIR-631	97.05	66.93	602
HSA-MIR-3059-3P	96.71	67.08	606
HSA-MIR-2114-5P	96.00	64.56	617
HSA-MIR-1251-5P	95.78	64.10	374
HSA-MIR-328-3P	92.82	64.37	521

Literature-anchored findings (GeneRIF, showing 40)

• a high-frequency TAP1/LMP2 promoter polymorphism in human tumors (PMID:11788900)
• Impaired expression of proteasome subunits is involved in the loss of HLA class I expression in human colon cancer cells. (PMID:12519221)
• caspase inhibition led to elevated levels of LMP2 and oxidized proteins; results suggest an age-related loss in capacity to carry out apoptosis might contribute to the observed accumulation of oxidized proteins during aging and in age-related diseases. (PMID:15284441)
• These data suggest that LMP2 contributes to IkappaBalpha degradation and p50 generation, and that inhibition of LMP2 suppresses expression and activities of MMP-2 and MMP-9 by blocking the transfer of active NF-kappaB heterodimers into the nucleus. (PMID:16222703)
• LMP2-associated proteasome is recruited to the entire sequence of ER target genes, implicating a role for the proteasome in both transcription initiation and elongation. (PMID:16957778)
• two inducible subunits of the proteasome, lmp2 and lmp7, are transcriptionally up-regulated by heat shock; heat-shocked cells show enhanced presentation of immunoproteasome-dependent MHC I antigenic epitopes, but not immunoproteasome-independent epitopes (PMID:17142736)
• study found strong associations of psoriasis with variant alleles of LMP and TAP (PMID:17581627)
• These data reveal a novel “feed-forward” mechanism induced by NF-kappaB which ensures that acutely synthesized IRF-1 operates in concert with NF-kappaB to amplify the immunoproteasome and antigen-processing functions of CD40. (PMID:18694960)
• Downregulation of LMP2 is associated with acute myeloid leukaemic blasts. (PMID:19148137)
• Obtained data suggest the LMP2 and PSMA6 gene polymorphism significance as the risk factors of essential hypertension in adolescents. (PMID:19526842)
• data show that the proteasomal ss1i subunit is dysregulated in peripheral white blood cells and in inflammatory infiltrates of minor salivary glands in patients with Sjogren’s syndrome (PMID:19833746)
• Data show that LMP2 60HH variant reduces the risk to develop MS amongst Italian HLA-A*02+ females. (PMID:20174631)
• downregulation of expression in PBMC of chronic hepatitis B patients (PMID:20300807)
• In a southern Spanish population, no differences were observed in the frequencies of the LMP and TAP genotypes between brucellosis patients and controls. (PMID:20470844)
• the genetic variant within the LMP2/LMP7 gene would increase the risk of intestinal M. tuberculosis infection. (PMID:21303409)
• In patients with primary Sjogren’s syndrome, the expression of LMP7 (but not LMP2) is up-regulated in the labial gland. (PMID:21529441)
• This is the first study to demonstrate that LMP2 variants can affect radiographic severity in ankylosing spondylitis. (PMID:22034108)
• High expression of LMP2 and low expression of PPM1A might play an important role in the motility and invasiveness of trophoblast cells and malignant transformation of hydatidiform mole. (PMID:22041443)
• The polymorphic site is unique in the Chinese population of Han nationality at the LMP2 codon 60 loci (Arg60Cys), but a lack of association with lung cancer exists. (PMID:22261389)
• LMP2 expression in nasopharyngeal carcinoma is associated with poor prognosis. (PMID:22287277)
• LMP2 has a role as a tumor-suppressor and may have a role in uterine leiomyosarcoma therapy (PMID:22355695)
• LMP2 may negatively regulate LMS independently of its role in the proteasome. (PMID:22659265)
• study reports expression of LMP2 in patients with renal oncocytomas (RO) and eosinophilic variant of chromophobe renal cell carcinomas (CHRCC-EO); all CHRCC-EO cases (7 of 7) strongly showed nuclear LMP2 staining, as opposed to only 2 of 56 ROs; suggest its use as an aid in differential diagnosis of these neoplasias (PMID:22705098)
• The MAGE-C(2336-344) antigenic peptide is produced by the immunoproteasome and intermediate proteasome beta1i-beta5i, but not by the standard proteasome nor intermediate proteasome beta5i. (PMID:22925930)
• Data indicate that treatment-emergent resistance to single-agent bortezomib was independent of variants in the proteasome genes PSMB1, PSMB5, PSMB6, PSMB8, PSMB9, and PSMB10. (PMID:23018640)
• functional variants in PSMB9 may contribute to melanoma susceptibility. (PMID:23360169)
• Genetic polymorphisms of rs17587 of PSMB9 appeared to be associated with rheumatoid arthritis in ethnic Han Chinese from Yunnan. (PMID:23568741)
• Data indicate that the codon 60 Arg/His polymorphism does not significantly alter the expression and activity of beta1i among the cell lines tested and clinical samples from colon and pancreatic cancer. (PMID:24040045)
• study found prevalence of LMP2-AA genotype was higher in acute myeolid leukemia (AML) patients while it was significantly lower in multiple myeloma (MM) cases than in the control subjects; results suggestLMP2 polymorphisms could play a role in the development of AML and MM (PMID:24377540)
• The data show that LMP2 and PSMA6 gene polymorphism is not a risk factor of ischemic stroke in Ukrainian population. (PMID:24809174)
• Comparison with reference profiles of sorted immune cells and healthy muscle confirmed upregulation of PSMB8 and -9 in myositis biopsies beyond infiltration related changes. (PMID:25098831)
• The TAP1-rs1135216 and PSMB9-rs17587 variants are significantly associated with vitiligo, and even one copy of these mutant alleles can influence the risk among Saudis. (PMID:25548428)
• designed siRNAs that efficiently silence LMP2, LMP7 and MECL-1 gene expression. (PMID:26944796)
• Chinese females carrying the rs17587-G/G genotype in PSMB9 may increase a higher risk for Parkinson’s disease. (PMID:27098790)
• Data show that tight junction protein 1 (TJP1) suppressed expression of the catalytically proteasome subunits LMP7 and LMP2, decreased proteasome activity, and enhanced proteasome inhibitor sensitivity in vitro and in vivo through suppression of EGFR/JAK1/STAT3 signaling. (PMID:27132469)
• single nucleotide polymorphism in PSMB9 are associated with hand dermatitis (PMID:27258892)
• Defective PSMB9/beta1i expression is likely to be one of the risk factors for the development of human uterine neoplasm. (PMID:28482675)
• co-inhibition of LMP2 and LMP7 appears to be synergistic and advantageous for the treatment of autoimmune diseases. (PMID:30279279)
• the allelic model of LMP2 CfoI might be a protective factor for ankylosing spondylitis in the Caucasian population (Meta-Analysis) (PMID:31702633)
• The dominant model of LMP2 CfoI might be a risk factor for IDDM in Asian population. Whereas, the allelic and dominant models of LMP7 G37360T might be protective factors for IDDM in Caucasian population (PMID:32221071)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmb9a	ENSDARG00000000656
mus_musculus	Psmb9	ENSMUSG00000096727
rattus_norvegicus	Psmb9	ENSRNOG00000000459
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), PSMB7 (ENSG00000136930), PSMB6 (ENSG00000142507), PSMA5 (ENSG00000143106), PSMA8 (ENSG00000154611), PSMB4 (ENSG00000159377), PSMB8 (ENSG00000204264), PSMB10 (ENSG00000205220), PSMB11 (ENSG00000222028), PSMB3 (ENSG00000277791)

Protein

Protein identifiers

Proteasome subunit beta type-9 — P28065 (reviewed: P28065)

Alternative names: Low molecular mass protein 2, Macropain chain 7, Multicatalytic endopeptidase complex chain 7, Proteasome chain 7, Proteasome subunit beta-1i, Really interesting new gene 12 protein

All UniProt accessions (4): A0A1U9X8D7, A2ACR0, A2ACR1, P28065

UniProt curated annotations — full annotation on UniProt →

Function. The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Replacement of PSMB6 by PSMB9 increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues.

Subunit / interactions. The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Component of the immunoproteasome, where it displaces the equivalent housekeeping subunit PSMB6. Component of the spermatoproteasome, a form of the proteasome specifically found in testis. (Microbial infection) Interacts with HIV-1 TAT protein.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity.

Disease relevance. Proteasome-associated autoinflammatory syndrome 3 (PRAAS3) [MIM:617591] An autoinflammatory disorder characterized by onset in early infancy and recurrent fever, nodular dermatitis, myositis, panniculitis-induced lipodystrophy, lymphadenopathy, and immune dysregulation. Variable accompanying features may include joint contractures, hepatosplenomegaly, anemia, thrombocytopenia, recurrent infections, autoantibodies, and hypergammaglobulinemia. Some patients may have intracranial calcifications. PRAAS3 inheritance is autosomal recessive or digenic. The disease may be caused by variants affecting distinct genetic loci, including the gene represented in this entry. Proteasome-associated autoinflammatory syndrome 6 (PRAAS6) [MIM:620796] An autosomal dominant, autoinflammatory disorder characterized by recurrent fever, skin rash, myositis, liver dysfunction, splenomegaly, pulmonary hypertension, and basal ganglia calcifications. Disease onset is in early infancy. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated by interferon gamma (at protein level). Up-regulated by IRF1. Up-regulated by tumor necrosis factor-alpha (at protein level). Up-regulated by tetrodotoxin (TTX) in glial cells. Up-regulated in Crohn’s bowel disease (CD). Up-regulated by heat shock treatment. Up-regulated by CD40L via the NFKB1 pathway in cancer cells.

Miscellaneous. Encoded in the MHC class II region. A model for self-activation in which residue Thr-21 serves as nucleophile and Lys-53 as proton donor/acceptor has been proposed. Subunit processing of mammalian beta-subunits proceeds via a novel ordered two-step mechanism involving autocatalysis.

Similarity. Belongs to the peptidase T1B family.

Isoforms (2)

UniProt ID	Names	Canonical?
P28065-1	LMP2.L	yes
P28065-2	LMP2.S

RefSeq proteins (1): NP_002791* (*=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
IPR029055	Ntn_hydrolases_N	Homologous_superfamily

Pfam: PF00227

UniProt features (37 total): strand 12, sequence variant 6, helix 6, mutagenesis site 3, turn 3, modified residue 2, propeptide 1, chain 1, active site 1, site 1, splice variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7AWE	X-RAY DIFFRACTION	2.29
7B12	X-RAY DIFFRACTION	2.43
9FST	X-RAY DIFFRACTION	2.75
9FSU	X-RAY DIFFRACTION	2.75
6E5B	X-RAY DIFFRACTION	2.77
9FRW	X-RAY DIFFRACTION	2.85
6AVO	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28065-F1	91.41	0.86

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 (2): 21 (nucleophile); 20–21 (cleavage; by autolysis)

Post-translational modifications (2): 53, 109

Mutagenesis-validated functional residues (3):

Position	Phenotype
20	impairs correct processing at the consensus site.
21	impairs correct processing at the consensus site.
53	impairs correct processing at the consensus site.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-1236978	Cross-presentation of soluble exogenous antigens (endosomes)
R-HSA-9907900	Proteasome assembly
R-HSA-9912633	Antigen processing: Ub, ATP-independent proteasomal degradation

MSigDB gene sets: 568 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, MODULE_172, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, WALLACE_PROSTATE_CANCER_RACE_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, JI_RESPONSE_TO_FSH_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, KEGG_PROTEASOME, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_THYMIC_T_CELL_SELECTION, MODULE_45, GOBP_T_CELL_HOMEOSTASIS

GO Biological Process (4): immune system process (GO:0002376), 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 (8): proteasome complex (GO:0000502), nucleus (GO:0005634), cytosol (GO:0005829), proteasome core complex (GO:0005839), proteasome core complex, beta-subunit complex (GO:0019774), extracellular exosome (GO:0070062), spermatoproteasome complex (GO:1990111), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Antigen processing-Cross presentation	2
Post-translational protein modification	1
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular protein-containing complex	2
cellular anatomical structure	2
proteasome complex	2
intracellular anatomical structure	2
biological_process	1
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
cytoplasm	1
catalytic complex	1
proteasome core complex	1
protein-containing complex	1
extracellular vesicle	1

Protein interactions and networks

STRING

2558 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMB9	PSMB10	P40306	988
PSMB9	PSMB8	P28062	988
PSMB9	PSMB11	A5LHX3	939
PSMB9	PSMB2	P31145	935
PSMB9	PSMB4	P28070	895
PSMB9	PSME1	Q06323	884
PSMB9	POMP	Q9Y244	876
PSMB9	IFNG	P01579	875
PSMB9	PSMA3	P25788	870
PSMB9	TAP2	Q03519	859
PSMB9	TAP1	Q03518	852
PSMB9	TAPBP	O15533	846
PSMB9	PSME2	Q9UL46	844
PSMB9	PDLIM7	Q9NR12	839
PSMB9	HLA-DOB	P13765	839

IntAct

71 interactions, top by confidence:

A	B	Type	Score
PSMA1	PSMA7	psi-mi:“MI:0914”(association)	0.950
PSMB7	PSMB1	psi-mi:“MI:0914”(association)	0.900
PSMA2	PSMA7	psi-mi:“MI:0914”(association)	0.850
PSMG2	PSMG1	psi-mi:“MI:0914”(association)	0.850
PSMB9	PSMB7	psi-mi:“MI:0915”(physical association)	0.840
PSMA5	PSMA7	psi-mi:“MI:0914”(association)	0.800
PSMB7	PSMA7	psi-mi:“MI:0914”(association)	0.790
PSMB9	POMP	psi-mi:“MI:0915”(physical association)	0.740
PSMB4	PSMA7	psi-mi:“MI:0914”(association)	0.730
PSMB3	PSMD11	psi-mi:“MI:0914”(association)	0.640
PSMB7	PSMD11	psi-mi:“MI:0914”(association)	0.640
PSMB1	PSMA7	psi-mi:“MI:0914”(association)	0.640
PSMB9	LAGE3	psi-mi:“MI:0915”(physical association)	0.600
PSMB9	GRIP1	psi-mi:“MI:0915”(physical association)	0.580
NCOA3	PSMB9	psi-mi:“MI:0915”(physical association)	0.580
NCOA1	PSMB9	psi-mi:“MI:0915”(physical association)	0.580
PSMB9	NCOA3	psi-mi:“MI:0915”(physical association)	0.580
GRIP1	PSMB9	psi-mi:“MI:0915”(physical association)	0.580

BioGRID (267): SRC (Reconstituted Complex), NCOA2 (Reconstituted Complex), NCOA3 (Reconstituted Complex), NCOA2 (Two-hybrid), SRC (Affinity Capture-Western), NCOA2 (Affinity Capture-Western), NCOA3 (Affinity Capture-Western), PSMB9 (Co-localization), PSMB9 (Co-localization), ESR1 (Co-localization), SRC (Co-localization), POLR2B (Co-localization), POLR2C (Co-localization), POLR2D (Co-localization), POLR2E (Co-localization)

ESM2 similar proteins: A1XQU1, A2YXU2, A2Z3I9, A7KE01, A7KII6, O23710, O23715, O24030, O24362, O35521, O35522, O35523, O35524, O43063, O94517, P22769, P25043, P28065, P28072, P28073, P28075, P28076, P28077, P38624, P60900, P60901, P70195, P93395, Q09841, Q0J006, Q10329, Q2TBP0, Q2YDE4, Q3MHN0, Q3SZC2, Q54QR2, Q55GJ6, Q5RDH8, Q60692, Q6YT00

Diamond homologs: A0B5B1, A0RXV1, A1RSJ8, A1RWY6, A1RX71, A1XQU1, A2BN24, A2BN27, A2SS78, A3CUS9, A3DN21, A3DN27, A3MXQ6, A4FYA5, A4WMZ0, A4YIE0, A5LHX3, A6VK02, A7I841, A7KE01, A7KII6, A8AA46, A8AB58, A8M8R5, A9A2U7, A9A788, B1L6S7, B1L6X8, B1YDJ0, B6YSW2, B6YXV3, B8GG66, C5A2D5, C7P6N4, C9REN7, D0KRX1, D0KTH0, D1Z199, D3S8M7, O23717

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
carfilzomib	“down-regulates activity”	PSMB9	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 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	9	171.3×	1e-17
Proteasome assembly	14	95.2×	2e-23
Cross-presentation of soluble exogenous antigens (endosomes)	11	93.0×	4e-18
Regulation of activated PAK-2p34 by proteasome mediated degradation	10	92.8×	1e-16
Regulation of ornithine decarboxylase (ODC)	10	90.6×	1e-16
Vpu mediated degradation of CD4	10	88.5×	1e-16
Autodegradation of the E3 ubiquitin ligase COP1	10	88.5×	1e-16
Ubiquitin-dependent degradation of Cyclin D	10	88.5×	1e-16

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	13	20.6×	3e-12

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	33
Likely benign	11
Benign	6

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1299361	NM_002800.5(PSMB9):c.467G>A (p.Gly156Asp)	Pathogenic
4526757	NM_002800.5(PSMB9):c.128+1G>A	Likely pathogenic

SpliceAI

2413 predictions. Top by Δscore:

Variant	Effect	Δscore
6:32845782:CCAC:C	acceptor_gain	1.0000
6:32845783:CACC:C	acceptor_gain	1.0000
6:32845785:CCTGA:C	acceptor_loss	1.0000
6:32845786:C:CA	acceptor_loss	1.0000
6:32845786:C:CC	acceptor_gain	1.0000
6:32847063:CTCA:C	donor_loss	1.0000
6:32847064:TCACC:T	donor_loss	1.0000
6:32847066:A:AC	donor_gain	1.0000
6:32847067:C:CA	donor_loss	1.0000
6:32847067:C:CC	donor_gain	1.0000
6:32847200:TACCT:T	acceptor_gain	1.0000
6:32847203:CT:C	acceptor_gain	1.0000
6:32847204:TC:T	acceptor_loss	1.0000
6:32847205:C:CC	acceptor_gain	1.0000
6:32847206:T:C	acceptor_loss	1.0000
6:32847507:GAGTA:G	donor_loss	1.0000
6:32847508:AGTAC:A	donor_loss	1.0000
6:32847509:GTA:G	donor_loss	1.0000
6:32847510:TA:T	donor_loss	1.0000
6:32847511:AC:A	donor_loss	1.0000
6:32847512:C:CT	donor_loss	1.0000
6:32847522:AGC:A	donor_gain	1.0000
6:32847566:A:AC	donor_gain	1.0000
6:32847567:C:CC	donor_gain	1.0000
6:32847672:CCAC:C	acceptor_gain	1.0000
6:32847673:CAC:C	acceptor_gain	1.0000
6:32847673:CACC:C	acceptor_gain	1.0000
6:32847674:ACC:A	acceptor_loss	1.0000
6:32847676:C:CC	acceptor_gain	1.0000
6:32847677:T:G	acceptor_loss	1.0000

AlphaMissense

1396 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:32856159:T:C	F28L	0.995
6:32856161:T:A	F28L	0.995
6:32856161:T:G	F28L	0.995
6:32857293:G:C	K53N	0.994
6:32857293:G:T	K53N	0.994
6:32856187:A:T	D37V	0.993
6:32859437:A:C	S189R	0.993
6:32859439:C:A	S189R	0.993
6:32859439:C:G	S189R	0.993
6:32856142:C:T	T22I	0.992
6:32856189:T:C	S38P	0.992
6:32858505:G:C	A178P	0.992
6:32859426:G:C	R185P	0.992
6:32856183:T:C	S36P	0.991
6:32856186:G:C	D37H	0.991
6:32856190:C:T	S38F	0.991
6:32856150:G:C	A25P	0.990
6:32856187:A:C	D37A	0.990
6:32858040:C:A	A99D	0.990
6:32858106:C:A	A121D	0.990
6:32859405:C:A	A178D	0.990
6:32856139:C:T	T21I	0.989
6:32856180:G:C	G35R	0.989
6:32859417:C:A	A182D	0.989
6:32856151:C:A	A25E	0.988
6:32857292:A:T	K53M	0.988
6:32858042:G:C	A100P	0.988
6:32858494:T:C	F174S	0.988
6:32856187:A:G	D37G	0.987
6:32856193:G:C	R39P	0.987

dbSNP variants (sampled 300 via entrez): RS1000072525 (6:32855413 T>C), RS1000709566 (6:32853996 G>T), RS1001065885 (6:32860137 T>A), RS1001073856 (6:32853755 G>A), RS1001339551 (6:32854447 G>A,T), RS1001764117 (6:32857470 G>A,C,T), RS1002362051 (6:32855747 G>A,C), RS1002851803 (6:32857973 C>A), RS1004640079 (6:32854169 T>C), RS1005094831 (6:32853817 T>C), RS1005385486 (6:32859395 C>A,T), RS1005586837 (6:32853181 G>A), RS1006055007 (6:32852864 C>T), RS1007395765 (6:32858582 A>T), RS1007433984 (6:32852335 C>T)

Disease associations

OMIM: gene MIM:177045 | disease phenotypes: MIM:620796, MIM:617591

GenCC curated gene-disease

Disease	Classification	Inheritance
proteasome-associated autoinflammatory syndrome 6	Strong	Autosomal dominant
proteasome-associated autoinflammatory syndrome 3	Limited	Unknown

Mondo (2): proteasome-associated autoinflammatory syndrome 6 (MONDO:0968983), proteasome-associated autoinflammatory syndrome 3 (MONDO:0054699)

Orphanet (0):

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000988	Skin rash
HP:0001250	Seizure
HP:0001394	Cirrhosis
HP:0001409	Portal hypertension
HP:0001640	Cardiomegaly
HP:0001744	Splenomegaly
HP:0001876	Pancytopenia
HP:0001888	Decreased total lymphocyte count
HP:0001945	Fever
HP:0001974	Increased total leukocyte count
HP:0002090	Pneumonia
HP:0002092	Pulmonary arterial hypertension
HP:0002135	Basal ganglia calcification
HP:0002922	Increased CSF protein concentration
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003281	Increased circulating ferritin concentration
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0004315	Decreased circulating IgG concentration
HP:0008151	Prolonged prothrombin time
HP:0011171	Simple febrile seizure
HP:0011227	Elevated circulating C-reactive protein concentration
HP:0025435	Increased circulating lactate dehydrogenase concentration
HP:0030149	Cardiogenic shock
HP:0030356	Increased circulating interferon-gamma concentration
HP:0030783	Increased circulating interleukin 6 concentration
HP:0031185	Elevated circulating NT-proBNP concentration
HP:0031545	Abnormally low T cell receptor excision circle level
HP:0031956	Elevated circulating aspartate aminotransferase concentration

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001009_2	Nephropathy	2.000000e-12
GCST001687_2	Disc degeneration (lumbar)	3.000000e-08
GCST001785_9	Crohn’s disease	9.000000e-59
GCST002655_18	IgA nephropathy	2.000000e-09
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_150	Autism spectrum disorder or schizophrenia	2.000000e-08
GCST004521_170	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_296	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST004616_20	Platelet distribution width	1.000000e-11
GCST005542_4	Sarcoidosis (non-Lofgren’s syndrome without extrapulmonary manifestations)	2.000000e-06
GCST005790_66	Rosacea symptom severity	2.000000e-15
GCST008916_27	Asthma	5.000000e-31
GCST008916_90	Asthma	4.000000e-15
GCST011426_20	Systemic lupus erythematosus	4.000000e-07
GCST012227_935	Hip circumference adjusted for BMI	5.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width
EFO:0009180	rosacea severity measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1944495 (SINGLE PROTEIN), CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3831201 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 43,732 (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
CHEMBL270515	DELANZOMIB	2	1,883
CHEMBL4297468	ZETOMIPZOMIB	2	129
CHEMBL2103884	OPROZOMIB	2	2,738

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — T1: Proteasome

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
zetomipzomib	Inhibition	6.88	pIC50

ChEMBL bioactivities

477 potent at pChembl≥5 of 517 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
9.21	IC50	0.623	nM	ZETOMIPZOMIB
9.04	IC50	0.92	nM	CHEMBL4102324
9.00	IC50	1	nM	CINNABARAMIDE A
9.00	IC50	1	nM	DELANZOMIB
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	CHEMBL5171825
8.57	IC50	2.7	nM	CHEMBL5394365
8.54	IC50	2.9	nM	BORTEZOMIB
8.52	IC50	3	nM	BORTEZOMIB
8.52	IC50	3	nM	CHEMBL4437785
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
8.40	IC50	4	nM	BORTEZOMIB
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	CHEMBL4749207
8.30	IC50	5	nM	BORTEZOMIB
8.30	IC50	5	nM	CHEMBL5398681
8.30	IC50	5	nM	CHEMBL5566401
8.30	IC50	5	nM	CHEMBL5566972
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
8.26	IC50	5.5	nM	BORTEZOMIB
8.25	IC50	5.6	nM	CHEMBL5423645
8.24	IC50	5.7	nM	CHEMBL3237866

PubChem BioAssay actives

449 with measured affinity, of 1152 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
(2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide	1604183: Inhibition of 20S proteasome beta 1i (unknown origin) after 1 hr by fluorescence based assay	ic50	0.0006	uM
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)-1-[[(2S,3R)-3-hydroxy-2-[(6-phenylpyridine-2-carbonyl)amino]butanoyl]amino]-3-methylbutyl]boronic acid	1604183: Inhibition of 20S proteasome beta 1i (unknown origin) after 1 hr by fluorescence based assay	ic50	0.0010	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
[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]boronic acid;2-hydroxypropane-1,2,3-tricarboxylic acid	1895435: Inhibition of human 20S immunoproteasome beta-1i subunit using (Ac-PAL)2R110 as substrate preincubated for 2 hrs followed by substrate addition and measured after 1 hr by fluorescence intensity assay	ic50	0.0027	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
[(1R)-1-[(1-cyclohexyltriazole-4-carbonyl)amino]-3-methylbutyl]boronic acid	2109704: Inhibition of human LMP2 beta-1i subunit using Ac-PAL-AMC as substrate preincubated with compound for 30 mins followed by substrate addition and measured after 1 hr by fluorescence based analysis	ic50	0.0030	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-[[(2S)-2-[[2-(4-hydroxyphenyl)acetyl]amino]-3-phenylpropanoyl]amino]-3-methylbutyl]boronic acid	1687108: Inhibition of human 20S immunoproteasome beta 1 subunit caspase-like activity using fluorogenic peptide Ac-nLPnLD-AMC as substrate in presence of PA28alpha incubated for 1 to 2 hrs by fluorescence microplate reader assay	ic50	0.0050	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
[(1R)-1-[(3-cyclohexyl-1,2-oxazole-5-carbonyl)amino]-3-methylbutyl]boronic acid	2109704: Inhibition of human LMP2 beta-1i subunit using Ac-PAL-AMC as substrate preincubated with compound for 30 mins followed by substrate addition and measured after 1 hr by fluorescence based analysis	ic50	0.0050	uM
[(1R)-2-cyclobutyl-1-[(1-cyclohexyltriazole-4-carbonyl)amino]ethyl]boronic acid	2109704: Inhibition of human LMP2 beta-1i subunit using Ac-PAL-AMC as substrate preincubated with compound for 30 mins followed by substrate addition and measured after 1 hr by fluorescence based analysis	ic50	0.0050	uM
[(1R)-1-[(1-cyclohexyltriazole-4-carbonyl)amino]-2-cyclopentylethyl]boronic acid	2109704: Inhibition of human LMP2 beta-1i subunit using Ac-PAL-AMC as substrate preincubated with compound for 30 mins followed by substrate addition and measured after 1 hr by fluorescence based analysis	ic50	0.0050	uM
[(1R)-1-[(1-cyclohexyltriazole-4-carbonyl)amino]-2-phenylethyl]boronic acid	2109704: Inhibition of human LMP2 beta-1i subunit using Ac-PAL-AMC as substrate preincubated with compound for 30 mins followed by substrate addition and measured after 1 hr by fluorescence based analysis	ic50	0.0050	uM
[(R)-cyclobutyl-[(1-cyclohexyltriazole-4-carbonyl)amino]methyl]boronic acid	2109704: Inhibition of human LMP2 beta-1i subunit using Ac-PAL-AMC as substrate preincubated with compound for 30 mins followed by substrate addition and measured after 1 hr by fluorescence based 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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Tretinoin	increases expression	5
Cisplatin	affects cotreatment, increases expression, decreases response to substance	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
Smoke	decreases expression, increases abundance	3
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	increases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	affects expression, increases methylation	2
Antirheumatic Agents	affects cotreatment, decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
sotorasib	affects cotreatment, increases expression	1
aminomethylphosphonic acid (AMPA)	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
2,2,2-trichloroethanol	affects cotreatment, increases expression, decreases reaction	1
tolfenamic acid	increases expression	1
quercitrin	decreases expression	1
trichostatin A	decreases expression, increases expression	1
arsenite	affects binding, increases reaction	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
sodium arsenite	affects acetylation, affects methylation	1
pyrrolidine dithiocarbamic acid	affects cotreatment, decreases expression, decreases reaction, increases expression	1
aflatoxin G1	decreases expression	1
nickel sulfate	increases expression	1
1-nitropyrene	decreases expression	1
tamibarotene	increases expression	1
microcystin RR	decreases expression	1

ChEMBL screening assays

220 unique, capped per target: 210 binding, 7 admet, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1948737	Binding	Binding affinity to LMP2/beta1i in human PC3 cells at 10 to 80 uM after 1.5 hrs by Western blotting	A bright approach to the immunoproteasome: development of LMP2/β1i-specific imaging probes. — Bioorg Med Chem
CHEMBL5056062	ADMET	Inhibition of human 20S immunoproteasome beta-1i subunit at 100 uM using Z-LLE-AMC as substrate measured over 1.5 to 2 hrs by plate reader assay relative to control	Macrocyclic Peptides that Selectively Inhibit the Mycobacterium tuberculosis Proteasome. — 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

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C7DG	Abcam A-549 PSMB9 KO	Cancer cell line	Male
CVCL_C7E6	Abcam HCT 116 PSMB9 KO	Cancer cell line	Male
CVCL_C7EM	Abcam THP-1 PSMB9 KO	Cancer cell line	Male
CVCL_E7B2	THP-1 PSMB9-eGFP-His	Cancer cell line	Male
CVCL_TH33	HAP1 PSMB9 (-) 1	Cancer cell line	Male
CVCL_TH34	HAP1 PSMB9 (-) 2	Cancer cell line	Male
CVCL_TH35	HAP1 PSMB9 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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