PSMD3

Summary

PSMD3 (proteasome 26S subunit, non-ATPase 3, HGNC:9560) is a protein-coding gene on chromosome 17q21.1, encoding 26S proteasome non-ATPase regulatory subunit 3 (O43242). Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core 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. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase 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. This gene encodes a member of the proteasome subunit S3 family that functions as one of the non-ATPase subunits of the 19S regulator lid. Single nucleotide polymorphisms in this gene are associated with neutrophil count.

Source: NCBI Gene 5709 — RefSeq curated summary.

At a glance

• GWAS associations: 30
• Clinical variants (ClinVar): 74 total — 1 likely-pathogenic
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_002809

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9560
Approved symbol	PSMD3
Name	proteasome 26S subunit, non-ATPase 3
Location	17q21.1
Locus type	gene with protein product
Status	Approved
Aliases	S3, P58, Rpn3
Ensembl gene	ENSG00000108344
Ensembl biotype	protein_coding
OMIM	617676
Entrez	5709

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000264639, ENST00000415039, ENST00000485835, ENST00000540504, ENST00000580980, ENST00000871888, ENST00000871889, ENST00000871890, ENST00000871891, ENST00000916285, ENST00000916286, ENST00000916287, ENST00000916288, ENST00000916289, ENST00000916290

RefSeq mRNA: 1 — MANE Select: NM_002809 NM_002809

CCDS: CCDS11356

Canonical transcript exons

ENST00000264639 — 12 exons

Exon	Start	End
ENSE00001388354	39997504	39997959
ENSE00001410218	39980807	39981190
ENSE00001729071	39984294	39984484
ENSE00003470448	39997330	39997380
ENSE00003496437	39986575	39986712
ENSE00003496673	39989739	39989929
ENSE00003520326	39995424	39995527
ENSE00003531197	39995176	39995295
ENSE00003533949	39994954	39995068
ENSE00003565435	39990094	39990197
ENSE00003574285	39988683	39988819
ENSE00003628239	39996183	39996338

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 126.3006 / max 836.0630, expressed in 1828 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160654	102.4532	1827
160653	23.8474	1815

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	98.18	gold quality
muscle of leg	UBERON:0001383	97.62	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.35	gold quality
skin of leg	UBERON:0001511	97.05	gold quality
cortical plate	UBERON:0005343	96.83	gold quality
mucosa of transverse colon	UBERON:0004991	96.80	gold quality
skin of abdomen	UBERON:0001416	96.60	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.58	gold quality
stromal cell of endometrium	CL:0002255	96.53	gold quality
ganglionic eminence	UBERON:0004023	96.48	gold quality
body of uterus	UBERON:0009853	96.28	gold quality
cerebellar hemisphere	UBERON:0002245	96.23	gold quality
cerebellar cortex	UBERON:0002129	96.18	gold quality
mucosa of stomach	UBERON:0001199	96.15	gold quality
ectocervix	UBERON:0012249	96.12	gold quality
apex of heart	UBERON:0002098	96.05	gold quality
left uterine tube	UBERON:0001303	95.99	gold quality
transverse colon	UBERON:0001157	95.96	gold quality
right frontal lobe	UBERON:0002810	95.93	gold quality
muscle organ	UBERON:0001630	95.91	gold quality
endocervix	UBERON:0000458	95.90	gold quality
right lobe of liver	UBERON:0001114	95.90	gold quality
ventricular zone	UBERON:0003053	95.90	gold quality
right ovary	UBERON:0002118	95.83	gold quality
left adrenal gland	UBERON:0001234	95.80	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.80	gold quality
left ovary	UBERON:0002119	95.68	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.68	gold quality
right adrenal gland	UBERON:0001233	95.67	gold quality
lower esophagus	UBERON:0013473	95.67	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-53	no	1694.27
E-MTAB-9689	no	265.83
E-GEOD-124858	no	17.71
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BRCA2

miRNA regulators (miRDB)

23 targeting PSMD3, 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-3613-3P	100.00	76.36	7965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-4718	98.55	68.61	814
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-556-5P	97.75	66.17	473
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-10398-5P	97.12	64.94	1051

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 11)

• The significant contribution of PSMD3-CSF3 and PLCB4 loci to the regulation of neutrophil count, is demonstrated. (PMID:20172861)
• Study identified significantly white blood cell count (WBC) level associated SNPs of three separate genes GSDMA, MED24, and PSMD3 in European continent (EA) subjects. (PMID:22037903)
• HNF1A gene was associated with C-reactive protein, and the region including PSMD3 and CSF3 genes was associated with white blood cell count. (PMID:22788528)
• Our study suggests that PSMD3 variants are associated with insulin resistance in populations of different ancestries and that these relationships may also be modified by dietary factors. (PMID:23303871)
• A strong association between genetic variant rs2305482 in PSMD3 on chromosome 17 and IFN-induced neutropenia. (PMID:25515861)
• this study shows that haplotypes consisting of single nucleotide polymorphisms harboring PSMD3, CSF3 and MED24 genes are associated with asthma in Slovenian patients (PMID:27163155)
• In thyroid hemiagenesis, genomic examinations revealed the presence of four recurrent defects (three deletions and one duplication) affecting highly conservative proteasome genes PSMA1, PSMA3, and PSMD3. (PMID:28390009)
• Proteasome 26S subunit, non-ATPases 1 (PSMD1) and 3 (PSMD3), play an oncogenic role in chronic myeloid leukemia by stabilizing nuclear factor-kappa B. (PMID:33712704)
• 26S Proteasome Non-ATPase Regulatory Subunits 1 (PSMD1) and 3 (PSMD3) as Putative Targets for Cancer Prognosis and Therapy. (PMID:34572038)
• PSMD3 gene mutations cause pathological myopia. (PMID:36948574)
• PSMD3-ILF3 signaling cascade drives lung cancer cell proliferation and migration. (PMID:37337223)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmd3	ENSDARG00000018124
mus_musculus	Psmd3	ENSMUSG00000017221
rattus_norvegicus	Psmd3	ENSRNOG00000028103
drosophila_melanogaster	Rpn3	FBGN0261396
caenorhabditis_elegans		WBGENE00004460

Paralogs (1): COPS3 (ENSG00000141030)

Protein

Protein identifiers

26S proteasome non-ATPase regulatory subunit 3 — O43242 (reviewed: O43242)

Alternative names: 26S proteasome regulatory subunit RPN3, 26S proteasome regulatory subunit S3, Proteasome subunit p58

All UniProt accessions (3): O43242, F5H8K4, H0YGV8

UniProt curated annotations — full annotation on UniProt →

Function. Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.

Subunit / interactions. Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD3, a base containing 6 ATPases and few additional components. Interacts with UBQLN1 (via ubiquitin-like domain). Interacts with ERCC6.

Similarity. Belongs to the proteasome subunit S3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O43242-1	1	yes
O43242-2	2

RefSeq proteins (1): NP_002800* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR013586	PSMD3_C	Domain
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR050756	CSN3	Family
IPR057985	TPR_PSMD3_N	Domain

Pfam: PF01399, PF08375, PF25573

UniProt features (46 total): helix 23, turn 4, sequence conflict 3, strand 3, compositionally biased region 3, cross-link 2, splice variant 2, region of interest 2, modified residue 2, chain 1, domain 1

Structure

Experimental structures (PDB)

118 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9K53	ELECTRON MICROSCOPY	2.5
8USB	ELECTRON MICROSCOPY	2.73
9MBP	ELECTRON MICROSCOPY	2.75
9NKG	ELECTRON MICROSCOPY	2.8
9E8I	ELECTRON MICROSCOPY	2.87
9BV3	ELECTRON MICROSCOPY	2.9
9E8H	ELECTRON MICROSCOPY	2.9
9K4J	ELECTRON MICROSCOPY	2.9
9NKF	ELECTRON MICROSCOPY	2.9
9U3L	ELECTRON MICROSCOPY	2.91
9NKI	ELECTRON MICROSCOPY	2.94
6MSB	ELECTRON MICROSCOPY	3
7W37	ELECTRON MICROSCOPY	3
8CVT	ELECTRON MICROSCOPY	3
9E8G	ELECTRON MICROSCOPY	3.01
9MBQ	ELECTRON MICROSCOPY	3.08
7W38	ELECTRON MICROSCOPY	3.1
8USC	ELECTRON MICROSCOPY	3.1
9BV1	ELECTRON MICROSCOPY	3.1
9E8O	ELECTRON MICROSCOPY	3.1
9K4R	ELECTRON MICROSCOPY	3.1
9E8Q	ELECTRON MICROSCOPY	3.16
6MSD	ELECTRON MICROSCOPY	3.2
6MSK	ELECTRON MICROSCOPY	3.2
7W39	ELECTRON MICROSCOPY	3.2
7W3G	ELECTRON MICROSCOPY	3.2
7W3H	ELECTRON MICROSCOPY	3.2
9K4M	ELECTRON MICROSCOPY	3.2
9K4Y	ELECTRON MICROSCOPY	3.2
9K50	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43242-F1	73.25	0.05

Functional residue map

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

Post-translational modifications (4): 38, 418, 430, 38

Function

Pathways and Gene Ontology

Reactome pathways

68 pathways

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

MSigDB gene sets: 342 (showing top): REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, SHEPARD_BMYB_MORPHOLINO_UP, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, WHITEHURST_PACLITAXEL_SENSITIVITY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, KEGG_PROTEASOME, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOCC_SECRETORY_GRANULE, GCANCTGNY_MYOD_Q6, REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21

GO Biological Process (3): ubiquitin-dependent protein catabolic process (GO:0006511), regulation of protein catabolic process (GO:0042176), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

GO Molecular Function (2): enzyme regulator activity (GO:0030234), protein binding (GO:0005515)

GO Cellular Component (12): proteasome complex (GO:0000502), extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), proteasome regulatory particle, lid subcomplex (GO:0008541), membrane (GO:0016020), proteasome accessory complex (GO:0022624), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813), proteasome regulatory particle (GO:0005838)

Reactome top-level categories

Rollup of top-18 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein-containing complex	3
protein ubiquitination	1
modification-dependent protein catabolic process	1
regulation of catabolic process	1
protein catabolic process	1
regulation of protein metabolic process	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
catalytic activity	1
molecular function regulator activity	1
binding	1
intracellular protein-containing complex	1
endopeptidase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
proteasome regulatory particle	1
proteasome complex	1
intracellular anatomical structure	1
secretory granule	1
cytoplasmic vesicle lumen	1
extracellular vesicle	1
intracellular organelle lumen	1
ficolin-1-rich granule	1
proteasome accessory complex	1

Protein interactions and networks

STRING

2310 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMD3	PSMD12	O00232	998
PSMD3	PSMD8	P48556	997
PSMD3	PSMD11	O00231	997
PSMD3	PSMD6	Q15008	997
PSMD3	PSMD13	Q9UNM6	997
PSMD3	PSMD7	P51665	996
PSMD3	PSMD14	O00487	996
PSMD3	SEM1	Q6ZVN7	993
PSMD3	PSMD4	P55036	962
PSMD3	PSMD2	Q13200	940
PSMD3	PSMD1	Q99460	926
PSMD3	ADRM1	Q16186	881
PSMD3	PSMC4	P43686	870
PSMD3	PSMC2	P35998	818
PSMD3	PSMC3	P17980	783

IntAct

282 interactions, top by confidence:

A	B	Type	Score
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
PSMD3	ZBTB43	psi-mi:“MI:0915”(physical association)	0.780
ZBTB43	PSMD3	psi-mi:“MI:0915”(physical association)	0.780
PSMD13	PSMD11	psi-mi:“MI:0914”(association)	0.750
PSMD7	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMC5	PSMD3	psi-mi:“MI:0914”(association)	0.730
PSMD11	PSMD12	psi-mi:“MI:0915”(physical association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PSMD3	SEM1	psi-mi:“MI:0915”(physical association)	0.670
PSMD3	PSMA6	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (1196): PSMD3 (Affinity Capture-MS), SHFM1 (Two-hybrid), ZBTB43 (Two-hybrid), CEP44 (Two-hybrid), PSMD3 (Affinity Capture-RNA), PSMD3 (Affinity Capture-RNA), PSMD3 (Affinity Capture-MS), PSMD3 (Affinity Capture-MS), PSMD3 (Affinity Capture-MS), PSMD3 (Affinity Capture-MS), PSMD3 (Affinity Capture-MS), PSMD3 (Affinity Capture-MS), PSMD3 (Affinity Capture-MS), PSMD3 (Affinity Capture-MS), PSMD3 (Affinity Capture-MS)

ESM2 similar proteins: A0JNN3, A2AWA9, B1H2N3, B5DEN9, B5DGH9, O43242, O60941, O76031, P14685, P60228, P60229, Q05AY2, Q06364, Q07866, Q0IIL1, Q13330, Q1LUA8, Q28FE2, Q2KJ46, Q3B8M3, Q3T102, Q4QR03, Q4R6G8, Q503N9, Q5F428, Q5R7N3, Q5R8K9, Q5R8N4, Q5RAN1, Q5U2U0, Q5ZLA5, Q62599, Q641X8, Q6DH26, Q6DRI1, Q6GQA1, Q6P6Q9, Q6P7L9, Q7Z3J2, Q8K4B0

Diamond homologs: O42897, O43242, O61470, P14685, P25161, P40016, P93768, Q04908, Q06364, Q1ZXD3, Q2KJ46, Q9LNU4, Q9LQR8, Q9U5Z8, Q8SRT7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PSMD3	“form complex”	“26S Proteasome”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 152 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Antigen processing: Ub, ATP-independent proteasomal degradation	15	86.5×	4e-27
Proteasome assembly	40	82.4×	7e-71
Regulation of activated PAK-2p34 by proteasome mediated degradation	29	81.6×	2e-50
Regulation of ornithine decarboxylase (ODC)	29	79.7×	5e-50
Cross-presentation of soluble exogenous antigens (endosomes)	31	79.5×	2e-53
Vpu mediated degradation of CD4	29	77.8×	8e-50
Autodegradation of the E3 ubiquitin ligase COP1	29	77.8×	8e-50
Ubiquitin-dependent degradation of Cyclin D	29	77.8×	8e-50

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of proteasomal protein catabolic process	5	40.0×	4e-05
regulation of proteasomal protein catabolic process	5	30.9×	9e-05
proteasome-mediated ubiquitin-dependent protein catabolic process	36	15.2×	9e-30
ubiquitin-dependent protein catabolic process	10	6.0×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	48
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
369988	GRCh37/hg19 17q21.1(chr17:38146929-38153473)x1	Likely pathogenic

SpliceAI

1627 predictions. Top by Δscore:

Variant	Effect	Δscore
17:39981088:G:GT	donor_gain	1.0000
17:39984281:T:TA	acceptor_gain	1.0000
17:39984292:A:AG	acceptor_gain	1.0000
17:39984293:G:GA	acceptor_gain	1.0000
17:39984293:GA:G	acceptor_gain	1.0000
17:39984293:GAC:G	acceptor_gain	1.0000
17:39984293:GACA:G	acceptor_gain	1.0000
17:39984293:GACAT:G	acceptor_gain	1.0000
17:39984482:GAG:G	donor_gain	1.0000
17:39984485:G:A	donor_loss	1.0000
17:39984485:GTGA:G	donor_gain	1.0000
17:39984486:T:G	donor_loss	1.0000
17:39986570:CCTA:C	acceptor_loss	1.0000
17:39986571:CTA:C	acceptor_loss	1.0000
17:39986573:A:AG	acceptor_gain	1.0000
17:39986574:G:GA	acceptor_gain	1.0000
17:39986574:GCC:G	acceptor_gain	1.0000
17:39986574:GCCC:G	acceptor_gain	1.0000
17:39986574:GCCCA:G	acceptor_gain	1.0000
17:39986710:G:GT	donor_gain	1.0000
17:39986721:G:GT	donor_gain	1.0000
17:39986727:G:GG	donor_gain	1.0000
17:39988679:CCA:C	acceptor_loss	1.0000
17:39988681:A:AG	acceptor_gain	1.0000
17:39988681:AG:A	acceptor_gain	1.0000
17:39988682:G:A	acceptor_loss	1.0000
17:39988682:G:GA	acceptor_gain	1.0000
17:39988682:GG:G	acceptor_gain	1.0000
17:39988682:GGC:G	acceptor_gain	1.0000
17:39988682:GGCAC:G	acceptor_gain	1.0000

AlphaMissense

3479 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:39989756:T:C	L235P	1.000
17:39989852:C:A	A267D	1.000
17:39989909:C:A	A286D	1.000
17:39989912:G:T	R287M	1.000
17:39989929:G:A	G293R	1.000
17:39989929:G:C	G293R	1.000
17:39989929:G:T	G293W	1.000
17:39990094:G:A	G293E	1.000
17:39990105:G:C	A297P	1.000
17:39990115:T:C	L300P	1.000
17:39990120:T:C	Y302H	1.000
17:39990121:A:G	Y302C	1.000
17:39990129:G:C	A305P	1.000
17:39990150:G:C	A312P	1.000
17:39990151:C:A	A312D	1.000
17:39990159:A:G	K315E	1.000
17:39990161:G:C	K315N	1.000
17:39990161:G:T	K315N	1.000
17:39990163:C:A	A316D	1.000
17:39990178:C:A	A321D	1.000
17:39990186:T:C	F324L	1.000
17:39990187:T:C	F324S	1.000
17:39990188:C:A	F324L	1.000
17:39990188:C:G	F324L	1.000
17:39994982:T:C	L337P	1.000
17:39994985:T:C	L338S	1.000
17:39994985:T:G	L338W	1.000
17:39994990:G:A	G340R	1.000
17:39994990:G:C	G340R	1.000
17:39994990:G:T	G340W	1.000

dbSNP variants (sampled 300 via entrez): RS1000001914 (17:39994789 T>A), RS1000113588 (17:39994969 A>G), RS1000235500 (17:39997050 C>G,T), RS1000319285 (17:39983011 A>G), RS1000677681 (17:39992197 T>C), RS1000770539 (17:39991876 C>T), RS1001065462 (17:39980821 C>G,T), RS1001098319 (17:39980613 G>A,C), RS1001403979 (17:39981920 A>G), RS1001434902 (17:39981653 C>T), RS1001506661 (17:39998249 A>T), RS1001865207 (17:39991556 A>G), RS1002079921 (17:39996528 C>T), RS1002345490 (17:39993576 G>A), RS1002441904 (17:39993196 G>T)

Disease associations

OMIM: gene MIM:617676 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): thyroid hemiagenesis (MONDO:0019860)

Orphanet (1): Thyroid hemiagenesis (Orphanet:95719)

HPO phenotypes

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

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST000589_4	White blood cell count	3.000000e-14
GCST000600_2	Neutrophil count	6.000000e-10
GCST001134_16	White blood cell types	4.000000e-16
GCST001137_10	White blood cell count	9.000000e-35
GCST001137_8	White blood cell count	2.000000e-31
GCST001302_2	White blood cell count	2.000000e-12
GCST001302_4	White blood cell count	1.000000e-12
GCST002556_12	White blood cell count	3.000000e-23
GCST002556_13	White blood cell count	3.000000e-12
GCST002556_6	White blood cell count	3.000000e-19
GCST002557_3	Neutrophil count	9.000000e-25
GCST002557_7	Neutrophil count	4.000000e-23
GCST002557_8	Neutrophil count	7.000000e-11
GCST004128_2	White blood cell count (neutrophil)	5.000000e-11
GCST004618_20	White blood cell count (basophil)	2.000000e-47
GCST004624_12	Sum eosinophil basophil counts	2.000000e-14
GCST004632_3	Lymphocyte percentage of white cells	2.000000e-108
GCST005038_120	Allergic disease (asthma, hay fever or eczema)	8.000000e-22
GCST005056_1	Neutrophil count	2.000000e-10
GCST005973_15	White blood cell count	9.000000e-62
GCST006014_25	Creatine kinase levels	3.000000e-09
GCST007395_3	Mitochondrial DNA copy number	7.000000e-07
GCST007399_2	Mitochondrial DNA copy number	2.000000e-07
GCST008103_61	Bipolar disorder	6.000000e-07
GCST008916_21	Asthma	2.000000e-62
GCST008916_36	Asthma	6.000000e-13
GCST008916_85	Asthma	2.000000e-12
GCST012232_28	Lipoprotein (a) levels	1.000000e-08
GCST90002389_228	Lymphocyte percentage of white cells	2.000000e-118
GCST90002394_399	Monocyte percentage of white cells	3.000000e-82

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count
EFO:0005090	basophil count
EFO:0004842	eosinophil count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004534	creatine kinase measurement
EFO:0006312	mitochondrial DNA measurement
EFO:0006925	lipoprotein A measurement
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3831210 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 25,628 (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

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

ChEMBL bioactivities

66 potent at pChembl≥5 of 67 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.62	IC50	2.4	nM	BORTEZOMIB
8.59	IC50	2.56	nM	BORTEZOMIB
8.57	IC50	2.7	nM	CHEMBL3237863
8.47	IC50	3.4	nM	CHEMBL6143686
8.41	IC50	3.9	nM	CHEMBL3237862
8.39	IC50	4.1	nM	CHEMBL3237864
8.39	IC50	4.1	nM	CHEMBL3237867
8.32	IC50	4.8	nM	CHEMBL3237873
8.29	IC50	5.1	nM	CHEMBL3237865
8.24	IC50	5.7	nM	CHEMBL3237866
8.24	IC50	5.7	nM	CHEMBL3237860
8.23	IC50	5.9	nM	CHEMBL3237868
8.15	IC50	7	nM	BORTEZOMIB
8.15	IC50	7.1	nM	CHEMBL3237870
8.15	IC50	7.14	nM	BORTEZOMIB
8.12	IC50	7.5	nM	CHEMBL3237871
8.11	IC50	7.7	nM	CHEMBL3237874
8.11	IC50	7.8	nM	CHEMBL3237869
8.07	IC50	8.6	nM	CARFILZOMIB
7.71	Kd	19.67	nM	CHEMBL5653589
7.71	ED50	19.67	nM	CHEMBL5653589
7.54	IC50	29	nM	CHEMBL3237861
7.34	IC50	46	nM	CHEMBL3237867
7.27	IC50	54	nM	CHEMBL3237872
7.12	IC50	75	nM	CHEMBL3237865
7.12	IC50	76	nM	CHEMBL3237866
6.96	IC50	110	nM	CHEMBL3262766
6.92	IC50	120	nM	CHEMBL3237864
6.92	IC50	120	nM	BORTEZOMIB
6.89	IC50	130	nM	CHEMBL3237869
6.85	IC50	140	nM	CHEMBL3237862
6.82	IC50	150	nM	CHEMBL3237863
6.77	IC50	170	nM	CHEMBL3237873
6.77	IC50	170	nM	CHEMBL3262765
6.72	IC50	190	nM	CHEMBL3262758
6.68	IC50	210	nM	CHEMBL3237870
6.66	IC50	220	nM	CHEMBL3262756
6.60	IC50	250	nM	CHEMBL3237868
6.47	IC50	340	nM	CHEMBL3262752
6.47	IC50	340	nM	CHEMBL3262755
6.44	IC50	360	nM	CHEMBL3262757
6.42	IC50	380	nM	CHEMBL3262754
6.36	IC50	440	nM	CHEMBL3262753
6.30	IC50	500	nM	CHEMBL3237872
6.20	IC50	630	nM	CHEMBL3262762
6.02	IC50	950	nM	CHEMBL3262761
6.00	IC50	1000	nM	CHEMBL3237871
5.96	IC50	1100	nM	CHEMBL3237862
5.85	IC50	1400	nM	BELACTOSIN A
5.84	IC50	1440	nM	BELACTOSIN A

PubChem BioAssay actives

62 with measured affinity, of 137 total; 34 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
Bortezomib	1985684: Inhibition of 26S proteasome (unknown origin)	ic50	0.0024	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
(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
(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-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
(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)-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
(2S)-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]-2-(pyrazine-2-carbonylamino)butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0071	uM
(2S)-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]-2-[(6-phenylpyridine-2-carbonyl)amino]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0075	uM
[(1R)-1-[[(2S)-2-acetamido-4-oxo-4-[[3-phenylmethoxy-2-(phenylmethoxymethyl)propyl]amino]butanoyl]amino]-3-methylbutyl]boronic acid	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0077	uM
(2S)-2-benzamido-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	0.0078	uM
Carfilzomib	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.0086	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149127: Binding affinity to human PSMD3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0197	uM
(2R,3S)-3-[(2S)-butan-2-yl]-4-oxo-N-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]oxetane-2-carboxamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0290	uM
(2S)-2-acetamido-N’-methyl-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]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0540	uM
N-[(1R)-3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]naphthalene-2-carboxamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.1100	uM
N-[(1R)-3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]-4-(trifluoromethyl)benzamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.1700	uM
N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]naphthalene-2-carboxamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.1900	uM
N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]-4-(trifluoromethyl)benzamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.2200	uM
N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]pyridine-3-carboxamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.3400	uM
4-methoxy-N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]benzamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.3400	uM
4-cyano-N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]benzamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.3600	uM
4-fluoro-N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]benzamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.3800	uM
N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]benzamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.4400	uM
N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]oxane-4-carboxamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.6300	uM
N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]thiophene-2-carboxamide	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.9500	uM
(2S)-2-[[(2S)-2-aminopropanoyl]amino]-3-[(1S,2S)-2-[[(2R,3S)-3-[(2S)-butan-2-yl]-4-oxooxetane-2-carbonyl]amino]cyclopropyl]propanoic acid	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	1.4000	uM
(2S)-2-acetamido-N-[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]butanediamide	1152964: Inhibition of chymotrypsin-like of human 20S proteasome using chromophoric Suc-LLVY-AMC as substrate after 60 mins by fluorescence assay	ic50	2.3000	uM
N-[3-(2-oxo-1,3,4-oxathiazol-5-yl)phenyl]acetamide	1137840: Inhibition of chymotrypsin-like activity of 26S proteasome in intact human Karpas 1106p cells assessed as substrate hydrolysis using Suc-LLVY-(D)-aminoluciferin as substrate after 3 hrs by cell-based Proteasome-Glo assay	ec50	4.2000	uM
(2S)-2-acetamido-N-[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]-N’-(4-phenylmethoxybutyl)butanediamide	1152964: Inhibition of chymotrypsin-like of human 20S proteasome using chromophoric Suc-LLVY-AMC as substrate after 60 mins by fluorescence assay	ic50	5.7000	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149127: Binding affinity to human PSMD3 incubated for 45 mins by Kinobead based pull down assay	kd	6.2161	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	4
sodium arsenite	decreases expression, increases expression	3
Cyclosporine	increases expression	3
Arsenic Trioxide	affects binding, decreases reaction, increases expression	2
Smoke	decreases expression	2
Tobacco Smoke Pollution	increases expression, affects expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
kojic acid	decreases expression	1
cobaltous chloride	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
bisphenol AF	increases expression	1
Arbutin	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Diazinon	increases methylation	1
Environmental Pollutants	affects expression	1
Furaldehyde	increases expression, affects cotreatment, affects localization	1
Hydralazine	decreases expression, affects cotreatment	1
Ivermectin	decreases expression	1

ChEMBL screening assays

27 unique, capped per target: 27 binding

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

Clinical trials (associated diseases)

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