PSMD11

Summary

PSMD11 (proteasome 26S subunit, non-ATPase 11, HGNC:9556) is a protein-coding gene on chromosome 17q11.2, encoding 26S proteasome non-ATPase regulatory subunit 11 (O00231). 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 99.2% 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 S9 family that functions as a non-ATPase subunit of the 19S regulator and is phosphorylated by AMP-activated protein kinase. Alternatively spliced transcript variants have been observed for this gene.

Source: NCBI Gene 5717 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 59 total — 2 pathogenic, 1 likely-pathogenic
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_002815

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9556
Approved symbol	PSMD11
Name	proteasome 26S subunit, non-ATPase 11
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	S9, p44.5, MGC3844, Rpn6
Ensembl gene	ENSG00000108671
Ensembl biotype	protein_coding
OMIM	604449
Entrez	5717

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 39 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000261712, ENST00000457654, ENST00000469475, ENST00000481992, ENST00000493026, ENST00000578213, ENST00000578397, ENST00000579451, ENST00000580904, ENST00000584340, ENST00000585265, ENST00000649012, ENST00000899312, ENST00000899313, ENST00000899314, ENST00000899315, ENST00000899316, ENST00000899317, ENST00000899318, ENST00000899319, ENST00000899320, ENST00000925957, ENST00000925958, ENST00000925959, ENST00000925960, ENST00000925961, ENST00000925962, ENST00000925963, ENST00000925964, ENST00000925965, ENST00000925966, ENST00000925967, ENST00000925968, ENST00000925969, ENST00000925970, ENST00000925971, ENST00000925972, ENST00000925973, ENST00000966387, ENST00000966388, ENST00000966389, ENST00000966390, ENST00000966391, ENST00000966392, ENST00000966393

RefSeq mRNA: 2 — MANE Select: NM_002815 NM_001270482, NM_002815

CCDS: CCDS11272

Canonical transcript exons

ENST00000261712 — 14 exons

Exon	Start	End
ENSE00000868001	32480146	32480197
ENSE00000868002	32479851	32479886
ENSE00001278105	32479251	32479376
ENSE00001951556	32480753	32483319
ENSE00002713989	32444510	32444614
ENSE00003458854	32464521	32464578
ENSE00003492106	32464049	32464120
ENSE00003531008	32474764	32474824
ENSE00003578339	32480489	32480631
ENSE00003583255	32468999	32469193
ENSE00003617754	32446945	32447046
ENSE00003627079	32473801	32473945
ENSE00003663635	32454495	32454619
ENSE00003668538	32477521	32477583

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 97.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.0445 / max 336.6392, expressed in 1822 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160236	47.0445	1822

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	97.67	gold quality
gastrocnemius	UBERON:0001388	97.53	gold quality
muscle of leg	UBERON:0001383	97.18	gold quality
islet of Langerhans	UBERON:0000006	96.82	gold quality
adrenal tissue	UBERON:0018303	96.34	gold quality
cartilage tissue	UBERON:0002418	96.26	gold quality
tibialis anterior	UBERON:0001385	96.25	gold quality
nipple	UBERON:0002030	96.21	gold quality
secondary oocyte	CL:0000655	96.16	gold quality
muscle organ	UBERON:0001630	96.15	gold quality
skeletal muscle organ	UBERON:0014892	96.15	gold quality
body of tongue	UBERON:0011876	95.89	gold quality
upper leg skin	UBERON:0004262	95.88	gold quality
pharyngeal mucosa	UBERON:0000355	95.83	gold quality
penis	UBERON:0000989	95.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.75	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.65	gold quality
ganglionic eminence	UBERON:0004023	95.59	gold quality
ventricular zone	UBERON:0003053	95.56	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.29	gold quality
esophagus mucosa	UBERON:0002469	95.24	gold quality
stromal cell of endometrium	CL:0002255	95.22	gold quality
colonic epithelium	UBERON:0000397	95.11	gold quality
cerebellar vermis	UBERON:0004720	95.11	gold quality
embryo	UBERON:0000922	94.98	gold quality
biceps brachii	UBERON:0001507	94.96	gold quality
right testis	UBERON:0004534	94.96	gold quality
skin of hip	UBERON:0001554	94.91	gold quality
left testis	UBERON:0004533	94.90	gold quality
deltoid	UBERON:0001476	94.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	447.85
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO4

miRNA regulators (miRDB)

112 targeting PSMD11, 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-1277-5P	100.00	73.95	5056
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-12119	99.87	68.35	1653

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.2% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 11)

• interaction with ubiquitinated NF-kappaB2/p100 (PMID:12185077)
• AMP-activated protein kinase is able to interact physically with this subunit and modify its phosphorylation status. (PMID:19616115)
• human embryonic stem cells (hESCs) exhibit high proteasome activity that is correlated with increased levels of the 19S proteasome subunit PSMD11 (known as RPN-6 in Caenorhabditis elegans) and a corresponding increased assembly of the 26S/30S proteasome (PMID:22972301)
• Data show that activated PKA phosphorylates the 19S subunit, Rpn6/PSMD11 (regulatory particle non-ATPase 6/proteasome subunit D11) at Ser14. (PMID:26669444)
• These results suggest that quick induction of PSMD11 or other acute apoptosis inhibitors through activation of the MEK1/ERK1/2 signaling pathway may be one of the important surviving mechanism which can help pancreatic cancer cells avoid acute apoptosis. (PMID:29665121)
• MicroRNA-451 inhibits inflammation and proliferation of glomerular mesangial cells through down-regulating PSMD11 and NF-kappaB p65. (PMID:31652441)
• PSMD11, PTPRM and PTPRB as novel biomarkers of pancreatic cancer progression. (PMID:32663515)
• Relationship between the Expression Level of PSMD11 and Other Proteasome Proteins with the Activity of Ricin and Viscumin. (PMID:32894464)
• Prognostic Value and Molecular Mechanisms of Proteasome 26S Subunit, Non-ATPase Family Genes for Pancreatic Ductal Adenocarcinoma Patients after Pancreaticoduodenectomy. (PMID:33525943)
• PSMD11 modulates circadian clock function through PER and CRY nuclear translocation. (PMID:36961772)
• PSMD11 loss-of-function variants correlate with a neurobehavioral phenotype, obesity, and increased interferon response. (PMID:38866022)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmd11b	ENSDARG00000005134
danio_rerio	psmd11a	ENSDARG00000060150
mus_musculus	Psmd11	ENSMUSG00000017428
rattus_norvegicus	Psmd11	ENSRNOG00000005538
drosophila_melanogaster	Rpn6	FBGN0028689
caenorhabditis_elegans		WBGENE00004462
caenorhabditis_elegans		WBGENE00010309

Paralogs (1): COPS2 (ENSG00000166200)

Protein

Protein identifiers

26S proteasome non-ATPase regulatory subunit 11 — O00231 (reviewed: O00231)

Alternative names: 26S proteasome regulatory subunit RPN6, 26S proteasome regulatory subunit S9, 26S proteasome regulatory subunit p44.5

All UniProt accessions (4): O00231, J3KSW3, J3QRY4, J3QS13

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. In the complex, PSMD11 is required for proteasome assembly. Plays a key role in increased proteasome activity in embryonic stem cells (ESCs): its high expression in ESCs promotes enhanced assembly of the 26S proteasome, followed by higher proteasome activity.

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 PSMD11, a base containing 6 ATPases and few additional components.

Subcellular location. Nucleus. Cytoplasm. Cytosol.

Tissue specificity. Highly expressed in embryonic stem cells (ESCs). Expression decreases as ESCs differentiate.

Post-translational modifications. Phosphorylated by AMPK.

Induction. By FOXO4; expression in embryonic stem cells (ESCs) is mediated by FOXO4.

Similarity. Belongs to the proteasome subunit S9 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00231-1	1	yes
O00231-2	2

RefSeq proteins (2): NP_001257411, NP_002806* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR040773	Rpn6_N	Domain
IPR040780	Rpn6_C_helix	Domain
IPR050871	26S_Proteasome/COP9_Components	Family

Pfam: PF01399, PF18055, PF18503

UniProt features (38 total): helix 19, turn 4, mutagenesis site 3, modified residue 3, strand 3, initiator methionine 1, chain 1, sequence conflict 1, domain 1, cross-link 1, splice variant 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
9E8H	ELECTRON MICROSCOPY	2.9
9NKF	ELECTRON MICROSCOPY	2.9
9BV3	ELECTRON MICROSCOPY	2.9
9K4J	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
9E8O	ELECTRON MICROSCOPY	3.1
9BV1	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-O00231-F1	82.84	0.20

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): 2, 14, 23, 274

Mutagenesis-validated functional residues (3):

Position	Phenotype
272	does not affect phosphorylation by ampk; when associated with a14- and a-79.
14	does not affect phosphorylation by ampk; when associated with a-79 and a-272.
79	does not affect phosphorylation by ampk; when associated with a-14 and a-272.

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: 393 (showing top): REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, RRAGTTGT_UNKNOWN, AP1_01, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, KEGG_PROTEASOME, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOCC_SECRETORY_GRANULE, REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN

GO Biological Process (4): ubiquitin-dependent protein catabolic process (GO:0006511), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), proteasome assembly (GO:0043248), stem cell differentiation (GO:0048863)

GO Molecular Function (2): structural molecule activity (GO:0005198), protein binding (GO:0005515)

GO Cellular Component (13): 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), ficolin-1-rich granule lumen (GO:1904813), cytoplasm (GO:0005737), proteasome regulatory particle (GO:0005838), protein-containing complex (GO:0032991)

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	5
protein-containing complex	3
intracellular anatomical structure	2
protein ubiquitination	1
modification-dependent protein catabolic process	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
protein-containing complex assembly	1
cell differentiation	1
molecular_function	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
secretory granule	1
cytoplasmic vesicle lumen	1
intracellular organelle lumen	1
ficolin-1-rich granule	1
proteasome accessory complex	1
cellular_component	1

Protein interactions and networks

STRING

2570 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMD11	PSMD12	O00232	997
PSMD11	PSMD3	O43242	997
PSMD11	PSMD8	P48556	996
PSMD11	PSMD7	P51665	996
PSMD11	PSMD6	Q15008	996
PSMD11	PSMD13	Q9UNM6	996
PSMD11	PSMD14	O00487	995
PSMD11	PSMD4	P55036	949
PSMD11	PSMC4	P43686	897
PSMD11	ADRM1	Q16186	895
PSMD11	PSMD1	Q99460	875
PSMD11	PSMD2	Q13200	822
PSMD11	PSMC1	P49014	804
PSMD11	USP14	P54578	794
PSMD11	IQGAP1	P46940	789

IntAct

295 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
PSMD13	PSMD11	psi-mi:“MI:0914”(association)	0.750
PSMD4	PSMD11	psi-mi:“MI:0914”(association)	0.750
PSMB2	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMD7	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMD11	PSMD12	psi-mi:“MI:0915”(physical association)	0.730
PSMD12	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMD2	PSMD11	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710

BioGRID (652): PSMD11 (Affinity Capture-MS), PSMD11 (Affinity Capture-MS), PSMD11 (Affinity Capture-MS), PSMD11 (Affinity Capture-MS), PSMD11 (Affinity Capture-MS), PSMD11 (Affinity Capture-MS), PSMD11 (Affinity Capture-MS), PSMD11 (Affinity Capture-MS), PSMD11 (Affinity Capture-MS), PSMD11 (Affinity Capture-MS), PSMD11 (Affinity Capture-MS), ADRM1 (Co-fractionation), COPS3 (Co-fractionation), COX5A (Co-fractionation), DCTN1 (Co-fractionation)

ESM2 similar proteins: A7Y521, B0BN93, B5DGH9, F1LMZ8, F1QGH9, F6P3G4, F6XBL2, O00231, O35142, O43242, O55029, O88544, P14685, P35605, P35606, P60228, P60229, P84169, Q05AY2, Q13098, Q1LUA8, Q2KI42, Q2KJ46, Q3B8M3, Q3SZA0, Q3T102, Q4R5E6, Q4R6G8, Q5E964, Q5R648, Q5R664, Q5R8K9, Q5RF54, Q5ZLA5, Q641X8, Q68FS2, Q6DRI1, Q6NRT5, Q6P0H6, Q6P4Z9

Diamond homologs: A8X379, F1LMZ8, F1QGH9, F6P3G4, F6XBL2, O00231, P34481, Q12377, Q20938, Q2KI42, Q54UB5, Q7KLV9, Q8BG32, Q9LP45, Q9P7S2, Q54HL6, Q6IQT4, Q6IR75

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PSMD11	“form complex”	“26S Proteasome”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 135 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
Regulation of activated PAK-2p34 by proteasome mediated degradation	27	82.6×	2e-46
Regulation of ornithine decarboxylase (ODC)	27	80.7×	3e-46
Vpu mediated degradation of CD4	27	78.8×	5e-46
Autodegradation of the E3 ubiquitin ligase COP1	27	78.8×	5e-46
Ubiquitin-dependent degradation of Cyclin D	27	78.8×	5e-46
Proteasome assembly	35	78.4×	1e-59
Cross-presentation of soluble exogenous antigens (endosomes)	28	78.1×	4e-47
Vif-mediated degradation of APOBEC3G	27	75.3×	3e-45

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of proteasomal protein catabolic process	5	42.4×	3e-05
proteasome-mediated ubiquitin-dependent protein catabolic process	33	14.7×	1e-26
ubiquitin-dependent protein catabolic process	10	6.3×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	41
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3902349	NM_002815.4(PSMD11):c.559C>T (p.Arg187Ter)	Pathogenic
599582	NM_002815.3(PSMD11):c.850-3_850delCAGA	Pathogenic
3901200	NM_002815.4(PSMD11):c.572C>T (p.Thr191Ile)	Likely pathogenic

SpliceAI

2297 predictions. Top by Δscore:

Variant	Effect	Δscore
17:32446940:CCCA:C	acceptor_loss	1.0000
17:32446941:CCA:C	acceptor_loss	1.0000
17:32446943:A:AG	acceptor_gain	1.0000
17:32446943:AGT:A	acceptor_gain	1.0000
17:32446944:G:GA	acceptor_gain	1.0000
17:32446944:GT:G	acceptor_gain	1.0000
17:32446944:GTG:G	acceptor_gain	1.0000
17:32446944:GTGA:G	acceptor_gain	1.0000
17:32446944:GTGAA:G	acceptor_gain	1.0000
17:32446945:T:TA	acceptor_gain	1.0000
17:32447042:TGCAG:T	donor_gain	1.0000
17:32447043:GCAG:G	donor_gain	1.0000
17:32447043:GCAGG:G	donor_gain	1.0000
17:32447044:CAG:C	donor_gain	1.0000
17:32447045:AG:A	donor_gain	1.0000
17:32447045:AGG:A	donor_loss	1.0000
17:32447046:GG:G	donor_gain	1.0000
17:32447046:GGTA:G	donor_loss	1.0000
17:32447047:G:GA	donor_loss	1.0000
17:32447047:G:GG	donor_gain	1.0000
17:32454476:T:TA	acceptor_gain	1.0000
17:32454479:ATT:A	acceptor_gain	1.0000
17:32454481:T:A	acceptor_gain	1.0000
17:32454490:TACA:T	acceptor_loss	1.0000
17:32454490:TACAG:T	acceptor_gain	1.0000
17:32454491:A:AG	acceptor_gain	1.0000
17:32454491:ACAG:A	acceptor_gain	1.0000
17:32454492:C:G	acceptor_gain	1.0000
17:32454492:CAG:C	acceptor_gain	1.0000
17:32454493:A:AG	acceptor_gain	1.0000

AlphaMissense

2744 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:32464076:T:A	W116R	1.000
17:32464076:T:C	W116R	1.000
17:32464078:G:C	W116C	1.000
17:32464078:G:T	W116C	1.000
17:32464079:G:C	A117P	1.000
17:32464100:T:C	F124L	1.000
17:32464102:C:A	F124L	1.000
17:32464102:C:G	F124L	1.000
17:32464528:T:C	L133P	1.000
17:32469062:T:C	L171P	1.000
17:32469070:A:C	S174R	1.000
17:32469072:C:A	S174R	1.000
17:32469072:C:G	S174R	1.000
17:32469106:G:C	A186P	1.000
17:32469115:G:C	A189P	1.000
17:32469127:G:C	A193P	1.000
17:32469128:C:A	A193D	1.000
17:32469193:G:C	G215R	1.000
17:32473801:G:A	G215D	1.000
17:32473801:G:T	G215V	1.000
17:32473860:G:C	A235P	1.000
17:32479342:T:C	L335P	1.000
17:32480180:T:C	L370P	1.000
17:32480489:G:A	G376E	1.000
17:32447011:T:C	L53P	0.999
17:32447023:T:C	L57P	0.999
17:32454547:G:C	K82N	0.999
17:32454547:G:T	K82N	0.999
17:32454549:C:A	A83D	0.999
17:32454576:T:C	L92P	0.999

dbSNP variants (sampled 300 via entrez): RS1000009688 (17:32449843 T>C), RS1000060861 (17:32472073 G>T), RS1000075697 (17:32465146 A>G), RS1000126734 (17:32481333 G>A), RS1000147289 (17:32463086 T>C), RS1000311614 (17:32446770 C>A,T), RS1000372440 (17:32456782 C>A,T), RS1000433129 (17:32471762 A>G), RS1000468144 (17:32444342 C>T), RS1000529302 (17:32466675 T>C), RS1000577801 (17:32483256 T>A), RS1000608821 (17:32460094 C>G), RS1000660735 (17:32456404 C>T), RS1000670997 (17:32460525 A>T), RS1000781943 (17:32453496 C>T)

Disease associations

OMIM: gene MIM:604449 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Strong	Autosomal dominant
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (2): complex neurodevelopmental disorder (MONDO:0100038), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST011769_23	Schizophrenia	1.000000e-08

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3831212 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 27,166 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

67 potent at pChembl≥5 of 68 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
7.54	IC50	29	nM	CHEMBL3237861
7.34	IC50	46	nM	CHEMBL3237867
7.27	IC50	54	nM	CHEMBL3237872
7.22	IC50	60	nM	MOLIBRESIB
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
6.84	Kd	144.7	nM	CHEMBL5653589
6.84	ED50	144.7	nM	CHEMBL5653589
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
5.86	Kd	1380	nM	CHEMBL5200541

PubChem BioAssay actives

64 with measured affinity, of 143 total; 36 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
(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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178652: Inhibition of PSMD11 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0600	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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149122: Binding affinity to human PSMD11 incubated for 45 mins by Kinobead based pull down assay	kd	0.1447	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
6-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-N-[5-fluoro-2-[3-(6-methyl-3-pyridinyl)-1,2,4-oxadiazol-5-yl]phenyl]hexanamide	1904231: Binding affinity to biotinylated recombinant Rpn6 (unknown origin) assessed as dissociation constant by biolayer interferometry analysis	kd	1.3800	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
3-(3H-benzimidazol-5-yl)-5-(4-fluorophenyl)-1,2,4-oxadiazole	1904231: Binding affinity to biotinylated recombinant Rpn6 (unknown origin) assessed as dissociation constant by biolayer interferometry analysis	kd	8.5300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	6
Arsenic Trioxide	increases expression	3
Tobacco Smoke Pollution	affects expression, increases expression	3
Cyclosporine	increases expression	3
sodium arsenite	increases abundance, increases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance, affects expression, affects cotreatment	2
Arsenic	decreases expression, increases abundance, affects cotreatment, increases expression	2
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	2
Tretinoin	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
TAK-243	decreases sumoylation	1
methylmercuric chloride	increases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	increases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
arsenite	increases reaction, affects binding	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
ochratoxin A	increases expression	1
butylidenephthalide	decreases expression	1
cupric chloride	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
arsenic trichloride	decreases expression, increases abundance	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment, increases expression	1
dimethylarsinous acid	decreases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
bisphenol S	increases expression	1
(+)-JQ1 compound	decreases expression	1

ChEMBL screening assays

34 unique, capped per target: 34 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)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism