PSMB10

Summary

PSMB10 (proteasome 20S subunit beta 10, HGNC:9538) is a protein-coding gene on chromosome 16q22.1, encoding Proteasome subunit beta type-10 (P40306). 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. Proteolytic processing is required to generate a mature subunit. Expression of this gene is induced by gamma interferon, and this gene product replaces catalytic subunit 2 (proteasome beta 7 subunit) in the immunoproteasome.

Source: NCBI Gene 5699 — RefSeq curated summary.

At a glance

• Gene–disease (curated): proteasome-associated autoinflammatory syndrome 5 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 49 total — 6 pathogenic
• Phenotypes (HPO): 28
• Druggable target: yes — 7 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002801

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9538
Approved symbol	PSMB10
Name	proteasome 20S subunit beta 10
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	LMP10, MGC1665, beta2i
Ensembl gene	ENSG00000205220
Ensembl biotype	protein_coding
OMIM	176847
Entrez	5699

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 3 retained_intron

ENST00000358514, ENST00000570304, ENST00000570985, ENST00000574576, ENST00000575556, ENST00000864458, ENST00000947595

RefSeq mRNA: 1 — MANE Select: NM_002801 NM_002801

CCDS: CCDS10853

Canonical transcript exons

ENST00000358514 — 8 exons

Exon	Start	End
ENSE00000946613	67936694	67936850
ENSE00001404410	67934506	67934671
ENSE00003525915	67934797	67934948
ENSE00003571534	67936398	67936485
ENSE00003609213	67935420	67935478
ENSE00003612463	67936215	67936312
ENSE00003663051	67935963	67936103
ENSE00003670463	67935582	67935697

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.5851 / max 462.0173, expressed in 1802 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157832	44.9082	1748
157831	1.6769	855

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.10	gold quality
leukocyte	CL:0000738	98.31	gold quality
monocyte	CL:0000576	98.28	gold quality
blood	UBERON:0000178	97.88	gold quality
spleen	UBERON:0002106	97.87	gold quality
mucosa of transverse colon	UBERON:0004991	97.71	gold quality
duodenum	UBERON:0002114	97.56	gold quality
putamen	UBERON:0001874	97.48	gold quality
vermiform appendix	UBERON:0001154	97.35	gold quality
substantia nigra	UBERON:0002038	97.27	gold quality
apex of heart	UBERON:0002098	97.26	gold quality
amygdala	UBERON:0001876	97.22	gold quality
temporal lobe	UBERON:0001871	97.20	gold quality
caudate nucleus	UBERON:0001873	97.17	gold quality
body of pancreas	UBERON:0001150	97.13	gold quality
lymph node	UBERON:0000029	97.07	gold quality
nucleus accumbens	UBERON:0001882	97.00	gold quality
Ammon’s horn	UBERON:0001954	96.79	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.72	gold quality
hypothalamus	UBERON:0001898	96.61	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.56	gold quality
small intestine	UBERON:0002108	96.24	gold quality
prefrontal cortex	UBERON:0000451	96.04	gold quality
anterior cingulate cortex	UBERON:0009835	96.03	gold quality
transverse colon	UBERON:0001157	96.02	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.92	gold quality
right uterine tube	UBERON:0001302	95.76	gold quality
heart left ventricle	UBERON:0002084	95.55	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.35	gold quality
bone marrow cell	CL:0002092	95.12	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	12.04
E-MTAB-6379	no	1795.67
E-MTAB-7606	no	1286.70
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF1, NFKB1, RELA

Literature-anchored findings (GeneRIF, showing 8)

• Impaired expression of proteasome subunits is involved in the loss of HLA class I expression in human colon cancer cells. (PMID:12519221)
• Multicatalytic endopeptidase complex subunit is involved in antigen presentation and is an important candidate gene for initial exploration of relationships between antigen processing genes and disease resistance. (PMID:17541830)
• 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)
• Adenovirus E1A causes down-regulation of MECL1 expression (PMID:22018786)
• 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)
• LMP10 nuclear expression in the Human Papillomavirus (HPV)-positive group and LMP10 cytoplasmic expression in the HPV-negative group of patients correlated to better clinical outcome. (PMID:24752327)
• designed siRNAs that efficiently silence LMP2, LMP7 and MECL-1 gene expression. (PMID:26944796)
• this study provided novel evidence demonstrating that LMP10 is a positive regulator of NF-kB signaling, which contributes to Ang II-induced retinopathy. (PMID:29499566)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmb10	ENSDARG00000043781
mus_musculus	Psmb10	ENSMUSG00000031897
rattus_norvegicus	Psmb10	ENSRNOG00000078638
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), PSMB11 (ENSG00000222028), PSMB9 (ENSG00000240065), PSMB3 (ENSG00000277791)

Protein

Protein identifiers

Proteasome subunit beta type-10 — P40306 (reviewed: P40306)

Alternative names: Low molecular mass protein 10, Macropain subunit MECl-1, Multicatalytic endopeptidase complex subunit MECl-1, Proteasome MECl-1, Proteasome subunit beta-2i

All UniProt accessions (2): P40306, J3QQN1

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.

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 PSMB7. 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 5 (PRAAS5) [MIM:619175] An autosomal recessive, autoinflammatory disorder characterized by recurrent, polymorphic disseminated cutaneous rash with annular lesions, non-specific lymphocytic infiltration in the skin, fever, failure to thrive, and persistent hepatosplenomegaly. Disease onset is in early infancy. The disease may be caused by variants affecting the gene represented in this entry. Immunodeficiency 121 with autoinflammation (IMD121) [MIM:620807] An autosomal dominant immunologic disorder characterized by severe combined immunodeficiency with T- and B-cell lymphopenia and low-normal NK cell numbers, failure to thrive, diarrhea, alopecia, and desquamating erythematous rash. Remaining T cells have limited T-cell receptor repertoires, a skewed memory phenotype, and an elevated CD4/CD8 ratio. Bone marrow examination indicates severely impaired B-cell maturation with limited V(D)J recombination. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated by IFNG/IFN-gamma (at protein level). Up-regulated by IRF1. Up-regulated by TNF (at protein level). Up-regulated by tetrodotoxin (TTX) in glial cells. Up-regulated in Crohn’s bowel disease (CD). Up-regulated by CD40L via the NFKB1 pathway in cancer cells.

Similarity. Belongs to the peptidase T1B family.

RefSeq proteins (1): NP_002792* (*=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 13, helix 4, sequence variant 3, turn 2, modified residue 2, propeptide 1, chain 1, active site 1, site 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
7AWE	X-RAY DIFFRACTION	2.29
7B12	X-RAY DIFFRACTION	2.43
6HV3	X-RAY DIFFRACTION	2.7
6HVR	X-RAY DIFFRACTION	2.7
6HVV	X-RAY DIFFRACTION	2.7
9FSV	X-RAY DIFFRACTION	2.75
6E5B	X-RAY DIFFRACTION	2.77
6HVA	X-RAY DIFFRACTION	2.9
6HVT	X-RAY DIFFRACTION	2.9
6HVU	X-RAY DIFFRACTION	2.9
6HV4	X-RAY DIFFRACTION	3
6HV5	X-RAY DIFFRACTION	3
6HVW	X-RAY DIFFRACTION	3
6HVS	X-RAY DIFFRACTION	3.1
6HV7	X-RAY DIFFRACTION	3.4
6AVO	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40306-F1	90.66	0.74

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 40 (nucleophile); 39–40 (cleavage; by autolysis)

Post-translational modifications (2): 1, 230

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: 495 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, KOBAYASHI_EGFR_SIGNALING_24HR_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, chr16q22, 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, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP

GO Biological Process (8): cell morphogenesis (GO:0000902), antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent (GO:0002479), humoral immune response (GO:0006959), proteasomal ubiquitin-independent protein catabolic process (GO:0010499), T cell proliferation (GO:0042098), 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 (7): proteasome complex (GO:0000502), nucleus (GO:0005634), cytosol (GO:0005829), proteasome core complex (GO:0005839), proteasome core complex, beta-subunit complex (GO:0019774), 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
proteasomal protein catabolic process	2
intracellular protein-containing complex	2
cellular anatomical structure	2
proteasome complex	2
intracellular anatomical structure	2
anatomical structure morphogenesis	1
antigen processing and presentation of exogenous peptide antigen via MHC class I	1
immune response	1
T cell activation	1
lymphocyte proliferation	1
ubiquitin-dependent 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

Protein interactions and networks

STRING

2414 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMB10	PSMB8	P28062	990
PSMB10	PSMB9	P28065	988
PSMB10	PSMB11	A5LHX3	962
PSMB10	PSME1	Q06323	935
PSMB10	PSME2	Q9UL46	925
PSMB10	PSMB2	P31145	905
PSMB10	CTRL	P40313	861
PSMB10	PSMA8	Q8TAA3	801
PSMB10	TAPBP	O15533	794
PSMB10	PSKH1	P11801	780
PSMB10	LCAT	P04180	765
PSMB10	IFNG	P01579	740
PSMB10	PSMB4	P28070	735
PSMB10	CTRB2	Q6GPI1	677
PSMB10	TMBIM4	Q9HC24	669

IntAct

52 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
PSMA5	PSMA7	psi-mi:“MI:0914”(association)	0.800
PSMA2	PSMB1	psi-mi:“MI:0914”(association)	0.790
PSMB3	PSMA7	psi-mi:“MI:0914”(association)	0.770
PSMB10	CCNDBP1	psi-mi:“MI:0915”(physical association)	0.740
CCNDBP1	PSMB10	psi-mi:“MI:0915”(physical association)	0.740
PSMB4	PSMA7	psi-mi:“MI:0914”(association)	0.730
PSMB3	PSMB10	psi-mi:“MI:0915”(physical association)	0.660
PSMB10	PSMB3	psi-mi:“MI:0915”(physical association)	0.660
PSMB3	PSMD11	psi-mi:“MI:0914”(association)	0.640
PSMB10	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
PSMB10	CRX	psi-mi:“MI:0915”(physical association)	0.560
CRX	PSMB10	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	PSMB10	psi-mi:“MI:0915”(physical association)	0.560
PSMB10	DMWD	psi-mi:“MI:0915”(physical association)	0.560
GRN	PSMB10	psi-mi:“MI:0915”(physical association)	0.560
PSMB10	PRKN	psi-mi:“MI:0915”(physical association)	0.560
PSMB10	RNF11	psi-mi:“MI:0915”(physical association)	0.560
PSMB10	SPRED1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (122): PSMB10 (Two-hybrid), PSMB10 (Two-hybrid), CCNDBP1 (Two-hybrid), PSMB10 (Affinity Capture-MS), PSMB10 (Co-fractionation), PSMB3 (Co-fractionation), PSMB4 (Co-fractionation), PSMB5 (Co-fractionation), PSMD5 (Co-fractionation), PSMB10 (Two-hybrid), PSMB10 (Affinity Capture-MS), PSMB10 (Affinity Capture-MS), PSMB10 (Affinity Capture-MS), PTN (Two-hybrid), PSMB10 (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
carfilzomib	“down-regulates activity”	PSMB10	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 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	285.5×	1e-19
Cross-presentation of soluble exogenous antigens (endosomes)	10	141.0×	1e-18
Regulation of activated PAK-2p34 by proteasome mediated degradation	9	139.3×	5e-17
Regulation of ornithine decarboxylase (ODC)	9	135.9×	5e-17
Vpu mediated degradation of CD4	9	132.8×	5e-17
Autodegradation of the E3 ubiquitin ligase COP1	9	132.8×	5e-17
Ubiquitin-dependent degradation of Cyclin D	9	132.8×	5e-17
Vif-mediated degradation of APOBEC3G	9	126.9×	6e-17

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	11	26.1×	2e-11

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	0
Uncertain significance	26
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
3241964	NM_002801.4(PSMB10):c.40_42del (p.Phe14del)	Pathogenic
3241966	NM_002801.4(PSMB10):c.247dup (p.Cys83fs)	Pathogenic
3241967	NM_002801.4(PSMB10):c.710+1G>C	Pathogenic
3241968	NM_002801.4(PSMB10):c.601G>A (p.Gly201Arg)	Pathogenic
3241969	NM_002801.4(PSMB10):c.601G>C (p.Gly201Arg)	Pathogenic
997016	NM_002801.4(PSMB10):c.41T>C (p.Phe14Ser)	Pathogenic

SpliceAI

973 predictions. Top by Δscore:

Variant	Effect	Δscore
16:67934562:A:AC	donor_gain	1.0000
16:67934563:C:CC	donor_gain	1.0000
16:67934792:CTCA:C	donor_loss	1.0000
16:67934793:TCAC:T	donor_loss	1.0000
16:67934794:CA:C	donor_loss	1.0000
16:67934796:C:T	donor_loss	1.0000
16:67934796:CCT:C	donor_gain	1.0000
16:67935959:GCACC:G	donor_loss	1.0000
16:67935960:CACCT:C	donor_loss	1.0000
16:67935961:ACCTG:A	donor_loss	1.0000
16:67935962:C:CA	donor_loss	1.0000
16:67936189:A:AC	donor_gain	1.0000
16:67936190:C:CC	donor_gain	1.0000
16:67936213:A:AC	donor_gain	1.0000
16:67936214:C:CC	donor_gain	1.0000
16:67936308:CCGTC:C	acceptor_gain	1.0000
16:67936309:CGTC:C	acceptor_gain	1.0000
16:67936309:CGTCC:C	acceptor_gain	1.0000
16:67936310:GTCCT:G	acceptor_loss	1.0000
16:67936311:TC:T	acceptor_gain	1.0000
16:67936311:TCCT:T	acceptor_loss	1.0000
16:67936312:CC:C	acceptor_gain	1.0000
16:67936312:CCTG:C	acceptor_loss	1.0000
16:67936313:C:CC	acceptor_gain	1.0000
16:67936313:CTGAG:C	acceptor_loss	1.0000
16:67936314:T:C	acceptor_loss	1.0000
16:67936396:A:AC	donor_gain	1.0000
16:67936397:C:CC	donor_gain	1.0000
16:67936399:TGGA:T	donor_gain	1.0000
16:67934558:G:C	donor_gain	0.9900

AlphaMissense

1726 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:67934906:C:A	G201W	0.984
16:67936294:C:G	A55P	0.983
16:67934918:C:G	A197P	0.981
16:67936401:G:C	F47L	0.981
16:67936401:G:T	F47L	0.981
16:67936403:A:G	F47L	0.981
16:67935592:G:C	F163L	0.980
16:67935592:G:T	F163L	0.980
16:67935594:A:G	F163L	0.980
16:67936097:A:C	C83W	0.977
16:67936102:A:G	C82R	0.975
16:67935435:G:C	F181L	0.974
16:67935435:G:T	F181L	0.974
16:67935437:A:G	F181L	0.974
16:67936100:G:C	C82W	0.972
16:67935662:C:T	G140D	0.969
16:67936296:C:T	G54D	0.967
16:67936411:C:T	G44D	0.967
16:67935614:C:T	G156D	0.966
16:67935460:G:T	A173D	0.964
16:67936284:C:G	R58P	0.964
16:67936230:A:T	I76N	0.963
16:67936098:C:T	C83Y	0.961
16:67936291:C:G	D56H	0.961
16:67934917:G:T	A197D	0.959
16:67935635:A:T	L149H	0.957
16:67934909:C:G	A200P	0.956
16:67934914:A:T	V198D	0.956
16:67935965:G:C	F127L	0.955
16:67935965:G:T	F127L	0.955

dbSNP variants (sampled 300 via entrez): RS1001085577 (16:67935995 C>T), RS1001271194 (16:67935771 C>A,G,T), RS1001769119 (16:67936207 A>C), RS1003119222 (16:67937766 C>G,T), RS1003665921 (16:67938318 T>C), RS1003709163 (16:67937912 C>T), RS1003865622 (16:67936407 C>G,T), RS1005053439 (16:67935307 C>T), RS1005518146 (16:67936308 C>A,G), RS1006085384 (16:67936663 G>A), RS1007217054 (16:67937573 T>C), RS1007660361 (16:67937205 G>A,T), RS1009220020 (16:67937848 G>A), RS1009244917 (16:67937609 C>T), RS1010514807 (16:67938266 C>G)

Disease associations

OMIM: gene MIM:176847 | disease phenotypes: MIM:619175, MIM:620807

GenCC curated gene-disease

Disease	Classification	Inheritance
proteasome-associated autoinflammatory syndrome 5	Strong	Autosomal recessive
immunodeficiency 121 with autoinflammation	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
immunodeficiency 121 with autoinflammation	Limited	AD

Mondo (2): proteasome-associated autoinflammatory syndrome 5 (MONDO:0030924), immunodeficiency 121 with autoinflammation (MONDO:0971001)

Orphanet (0):

HPO phenotypes

28 total (28 of 28 shown, HPO-id order):

HPO	Term
HP:0000100	Nephrotic syndrome
HP:0000821	Hypothyroidism
HP:0000944	Abnormal metaphysis morphology
HP:0000958	Dry skin
HP:0000969	Edema
HP:0000989	Pruritus
HP:0001019	Erythroderma
HP:0001072	Thickened skin
HP:0001508	Failure to thrive
HP:0001596	Alopecia
HP:0001744	Splenomegaly
HP:0001831	Short toe
HP:0001880	Increased total eosinophil count
HP:0001903	Anemia
HP:0001945	Fever
HP:0001974	Increased total leukocyte count
HP:0002028	Chronic diarrhea
HP:0002090	Pneumonia
HP:0002240	Hepatomegaly
HP:0002665	Lymphoma
HP:0002716	Lymphadenopathy
HP:0002960	Autoimmunity
HP:0004332	Abnormal lymphocyte morphology
HP:0004430	Severe combined immunodeficiency
HP:0007549	Desquamation of skin soon after birth
HP:0100646	Thyroiditis
HP:0100806	Sepsis
HP:0100840	Aplasia/Hypoplasia of the eyebrow

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001438_13	Crohn’s disease	2.000000e-07
GCST002539_84	Schizophrenia	2.000000e-08
GCST006803_42	Schizophrenia	4.000000e-08
GCST010002_113	Refractive error	2.000000e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3317334 (SINGLE PROTEIN), 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)

ChEMBL bioactivities

407 potent at pChembl≥5 of 448 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.88	IC50	0.131	nM	ZETOMIPZOMIB
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

PubChem BioAssay actives

375 with measured affinity, of 1070 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	1604185: Inhibition of 20S proteasome beta 2i (unknown origin) after 1 hr by fluorescence based assay	ic50	0.0001	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,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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects cotreatment, increases expression, affects expression	6
Acetaminophen	decreases expression, increases expression, affects response to substance	4
Cyclosporine	decreases expression, increases expression	3
sodium arsenite	increases expression	2
(+)-JQ1 compound	decreases expression	2
Cisplatin	increases expression, decreases response to substance	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Tretinoin	increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
OTX015	decreases expression	1
FR900359	increases phosphorylation	1
mivebresib	decreases expression	1
sotorasib	affects cotreatment, increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
tolfenamic acid	increases expression	1
trichostatin A	increases expression	1
arsenite	affects binding, increases reaction	1
potassium chromate(VI)	decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	increases expression, affects cotreatment	1
Temozolomide	increases expression	1
Vorinostat	affects cotreatment, increases expression	1

ChEMBL screening assays

206 unique, capped per target: 195 binding, 8 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
CHEMBL5056063	ADMET	Inhibition of human 20S immunoproteasome beta-2i subunit at 100 uM using Z-VLR-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

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2CF	Abcam HeLa PSMB10 KO	Cancer cell line	Female
CVCL_TH28	HAP1 PSMB10 (-) 1	Cancer cell line	Male
CVCL_TH29	HAP1 PSMB10 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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