PSMC5

Summary

PSMC5 (proteasome 26S subunit, ATPase 5, HGNC:9552) is a protein-coding gene on chromosome 17q23.3, encoding 26S proteasome regulatory subunit 8 (P62195). 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 99.8% 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. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes one of the ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. In addition to participation in proteasome functions, this subunit may participate in transcriptional regulation since it has been shown to interact with the thyroid hormone receptor and retinoid X receptor-alpha. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5705 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• Clinical variants (ClinVar): 56 total — 2 pathogenic, 1 likely-pathogenic
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_002805

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9552
Approved symbol	PSMC5
Name	proteasome 26S subunit, ATPase 5
Location	17q23.3
Locus type	gene with protein product
Status	Approved
Aliases	SUG1, p45/SUG, TBP10, p45, S8, TRIP1, SUG-1, RPT6
Ensembl gene	ENSG00000087191
Ensembl biotype	protein_coding
OMIM	601681
Entrez	5705

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 21 protein_coding, 8 retained_intron, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000310144, ENST00000375812, ENST00000578570, ENST00000579031, ENST00000579147, ENST00000579708, ENST00000580063, ENST00000580265, ENST00000580864, ENST00000581764, ENST00000581842, ENST00000581882, ENST00000582130, ENST00000582420, ENST00000583283, ENST00000584320, ENST00000584536, ENST00000584657, ENST00000584880, ENST00000585123, ENST00000585242, ENST00000703608, ENST00000703609, ENST00000703610, ENST00000703611, ENST00000852530, ENST00000935073, ENST00000935074, ENST00000935075, ENST00000935076, ENST00000935077, ENST00000935078, ENST00000935079, ENST00000961597, ENST00000961598, ENST00000961599

RefSeq mRNA: 2 — MANE Select: NM_002805 NM_001199163, NM_002805

CCDS: CCDS11645, CCDS56043

Canonical transcript exons

ENST00000310144 — 12 exons

Exon	Start	End
ENSE00002689090	63827431	63827514
ENSE00003463206	63830133	63830189
ENSE00003476819	63829494	63829563
ENSE00003483112	63831036	63831226
ENSE00003494747	63830809	63830935
ENSE00003512163	63831506	63831616
ENSE00003538771	63829852	63829949
ENSE00003582062	63831724	63831810
ENSE00003606068	63831327	63831425
ENSE00003619858	63830271	63830501
ENSE00003672743	63831916	63832019
ENSE00003758613	63828138	63828209

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 98.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 130.5455 / max 975.0310, expressed in 1827 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162226	120.4484	1827
162227	4.9105	1610
162228	4.5719	1571
162229	0.5773	323
162231	0.0279	3
162230	0.0096	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.83	gold quality
endometrium epithelium	UBERON:0004811	98.66	gold quality
cerebellar cortex	UBERON:0002129	98.62	gold quality
cerebellar hemisphere	UBERON:0002245	98.62	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.61	gold quality
right testis	UBERON:0004534	98.54	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.54	gold quality
lower esophagus	UBERON:0013473	98.53	gold quality
gastrocnemius	UBERON:0001388	98.52	gold quality
left testis	UBERON:0004533	98.50	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.50	gold quality
mucosa of stomach	UBERON:0001199	98.47	gold quality
adenohypophysis	UBERON:0002196	98.47	gold quality
islet of Langerhans	UBERON:0000006	98.46	gold quality
cerebellum	UBERON:0002037	98.46	gold quality
right frontal lobe	UBERON:0002810	98.45	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.40	gold quality
metanephros cortex	UBERON:0010533	98.39	gold quality
cingulate cortex	UBERON:0003027	98.37	gold quality
skin of leg	UBERON:0001511	98.36	gold quality
skin of abdomen	UBERON:0001416	98.35	gold quality
anterior cingulate cortex	UBERON:0009835	98.35	gold quality
pituitary gland	UBERON:0000007	98.30	gold quality
prefrontal cortex	UBERON:0000451	98.28	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.27	gold quality
right lobe of thyroid gland	UBERON:0001119	98.26	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.26	gold quality
apex of heart	UBERON:0002098	98.25	gold quality
amygdala	UBERON:0001876	98.24	gold quality
right adrenal gland	UBERON:0001233	98.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-53	no	1092.84
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CIITA, CREBBP

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 19)

• SUG1 has a role in ubiquitin/proteasome-mediated degradation of estrogen receptors (PMID:14702340)
• Proteasome dysfunction by a proteasome inhibitor or siRNA-mediated knock-down of Sug1 caused the up-regulation of MYO18B protein and MYO18B was polyubiquitinated in vivo. (PMID:16499872)
• p45 plays an important role in regulating ataxin-3 degradation by the proteasome. (PMID:17302910)
• cyclic AMP-dependent protein kinase regulates proteasome function through phosphorylation of Rpt6 (PMID:17565987)
• These data demonstrate that both 19S and 20S subunits of the 26S proteasome play specific and critical roles in regulating CIITA activity and MHC class II transcription. (PMID:18215421)
• The current study strongly implicates the 19S ATPase Sug1 in modifying histones to initiate major histocompatibility complex class II transcription and provides novel insights into the role of the proteasome in the regulation of mammalian transcription. (PMID:18662994)
• SUG-1 has a unique role in linking the transcription and degradation processes via its ability to interact with SRC-3. (PMID:19144644)
• Findings show that Sug1 is crucial for regulating histone H3K4me3 and H3R17me2 at the cytokine inducible MHC-II and CIITA promoters. (PMID:19660582)
• Caspase-3 cleaves specific 19 S proteasome subunits in skeletal muscle stimulating proteasome activity (PMID:20424172)
• Sug1 plays a critical role in transcription of MHC class I, and the MHC class II-like molecules, HLA-DM and HLA-DO. (PMID:22771340)
• Rpt6 interacts directly with CKIP-1 and promotes the turnover of Smurf1. (PMID:23032291)
• gamma-aminobutyric acidB receptor proteasomal degradation is mediated by the interaction of the GABAB2 C terminus with the proteasomal ATPase Rtp6 and regulated by neuronal activity (PMID:24482233)
• TRIP-1 regulates fibroblast acquisition of phenotype and function associated with myofibroblasts. (PMID:24528651)
• XopJ has protease activity to specifically degrade RPT6. (PMID:25739698)
• results demonstrate that PSMC5 is a new and important player involved in regulating ERK1/2 signal transmission through the remodeling of Shoc2 scaffold complex in a spatially-defined manner. (PMID:26519477)
• Our data suggest that PSMC5 facilitates the damaging effects of radiation in radiation-responsive H460 cancer cells and therefore may serve as a prognostic indicator for radiotherapy and molecular targeted therapy in lung cancer patients. (PMID:26592665)
• autoinflammation-associated H443P nlrc4 mutant is altered in interaction with SUG1 and ubiquitinated proteins, triggering constitutive caspase-8-mediated cell death dependent on FADD but independent of Ser(533) phosphorylation. (PMID:27974463)
• Hypoxia-induced increase in Sug1 leads to poor post-transplantation survival of allogeneic mesenchymal stem cells. (PMID:32770803)
• Identification of a quality-control factor that monitors failures during proteasome assembly. (PMID:34446601)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmc5	ENSDARG00000015315
mus_musculus	Psmc5	ENSMUSG00000020708
rattus_norvegicus	Psmc5	ENSRNOG00000010038
drosophila_melanogaster	Rpt6	FBGN0020369
drosophila_melanogaster	Rpt6R	FBGN0039788
caenorhabditis_elegans		WBGENE00004506
caenorhabditis_elegans		WBGENE00018991

Paralogs (5): PSMC4 (ENSG00000013275), PSMC6 (ENSG00000100519), PSMC1 (ENSG00000100764), PSMC2 (ENSG00000161057), PSMC3 (ENSG00000165916)

Protein

Protein identifiers

26S proteasome regulatory subunit 8 — P62195 (reviewed: P62195)

Alternative names: 26S proteasome AAA-ATPase subunit RPT6, Proteasome 26S subunit ATPase 5, Proteasome subunit p45, Thyroid hormone receptor-interacting protein 1, p45/SUG

All UniProt accessions (13): P62195, A0A140VJS3, A0A994J3X6, A0A994J6H0, A0A994J6V8, J3KRP2, J3KTQ9, J3QLH6, J3QQM1, J3QRR3, J3QRW1, J3QSA9, J3QSE0

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. PSMC5 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.

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, a base containing 6 ATPases including PSMC5 and few additional components. Component of a complex with USP49 and RUVBL1. Interacts with PRPF19. Interacts with TRIM5. Interacts with NDC80. Interacts with PAAF1. Interacts, in vitro, with the thyroid hormone receptor (in a thyroid hormone T3-dependent manner) and with retinoid X receptor (RXR). Interacts with ERCC6.

Subcellular location. Cytoplasm. Nucleus.

Similarity. Belongs to the AAA ATPase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P62195-1	1	yes
P62195-2	2

RefSeq proteins (2): NP_001186092, NP_002796* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR003959	ATPase_AAA_core	Domain
IPR003960	ATPase_AAA_CS	Conserved_site
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032501	Prot_ATP_ID_OB_2nd	Domain
IPR041569	AAA_lid_3	Domain
IPR050221	26S_Proteasome_ATPase	Family

Pfam: PF00004, PF16450, PF17862

UniProt features (51 total): helix 14, strand 14, turn 7, sequence conflict 5, modified residue 4, sequence variant 2, initiator methionine 1, chain 1, region of interest 1, binding site 1, splice variant 1

Structure

Experimental structures (PDB)

131 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3KW6	X-RAY DIFFRACTION	2.1
9K53	ELECTRON MICROSCOPY	2.5
8USB	ELECTRON MICROSCOPY	2.73
9MBP	ELECTRON MICROSCOPY	2.75
9PDL	ELECTRON MICROSCOPY	2.76
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
9PDI	ELECTRON MICROSCOPY	2.98
6MSB	ELECTRON MICROSCOPY	3
7W37	ELECTRON MICROSCOPY	3
8CVT	ELECTRON MICROSCOPY	3
9E8G	ELECTRON MICROSCOPY	3.01
9PDN	ELECTRON MICROSCOPY	3.04
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
9U7R	ELECTRON MICROSCOPY	3.17
6MSD	ELECTRON MICROSCOPY	3.2
6MSK	ELECTRON MICROSCOPY	3.2
7W39	ELECTRON MICROSCOPY	3.2
7W3G	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62195-F1	82.47	0.29

Functional residue map

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

Ligand- & substrate-binding residues (1): 190–197

Post-translational modifications (4): 2, 120, 1, 222

Function

Pathways and Gene Ontology

Reactome pathways

67 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: 348 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, 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, REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GOBP_MACROMOLECULE_CATABOLIC_PROCESS

GO Biological Process (7): regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of programmed cell death (GO:0043069), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of inclusion body assembly (GO:0090261), positive regulation of proteasomal protein catabolic process (GO:1901800)

GO Molecular Function (11): ATP binding (GO:0005524), transcription factor binding (GO:0008134), ATP hydrolysis activity (GO:0016887), TBP-class protein binding (GO:0017025), thyrotropin-releasing hormone receptor binding (GO:0031531), proteasome-activating activity (GO:0036402), general transcription initiation factor binding (GO:0140296), DNA-binding transcription factor binding (GO:0140297), nucleotide binding (GO:0000166), signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (15): proteasome complex (GO:0000502), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), proteasome regulatory particle, base subcomplex (GO:0008540), membrane (GO:0016020), inclusion body (GO:0016234), proteasome accessory complex (GO:0022624), cytoplasmic vesicle (GO:0031410), nuclear proteasome complex (GO:0031595), cytosolic proteasome complex (GO:0031597), extracellular exosome (GO:0070062), blood microparticle (GO:0072562), 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	5
regulation of DNA-templated transcription	3
proteasomal protein catabolic process	3
intracellular anatomical structure	3
protein-containing complex	3
proteasome complex	3
DNA-templated transcription	2
protein binding	2
ATP-dependent activity	2
transcription factor binding	2
nuclear lumen	2
cytoplasm	2
transcription by RNA polymerase II	1
programmed cell death	1
regulation of programmed cell death	1
negative regulation of cellular process	1
ubiquitin-dependent protein catabolic process	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
inclusion body assembly	1
regulation of inclusion body assembly	1
positive regulation of protein catabolic process	1
regulation of proteasomal protein catabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
general transcription initiation factor binding	1
G protein-coupled receptor binding	1
peptide hormone receptor binding	1
polypeptide conformation or assembly isomerase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular protein-containing complex	1
endopeptidase complex	1
intracellular membrane-bounded organelle	1
proteasome regulatory particle	1
intracellular vesicle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

410 interactions, top by confidence:

A	B	Type	Score
PSMD10	PSMC4	psi-mi:“MI:0914”(association)	0.970
PSMC6	PSMC3	psi-mi:“MI:0915”(physical association)	0.950
PSMC4	PSMC5	psi-mi:“MI:0915”(physical association)	0.940
PSMC4	PSMC5	psi-mi:“MI:0407”(direct interaction)	0.940
PSMC5	PSMC6	psi-mi:“MI:0915”(physical association)	0.940
PSMC5	PDCL	psi-mi:“MI:0915”(physical association)	0.920
PDCL	PSMC5	psi-mi:“MI:0915”(physical association)	0.920
PSMC5	PSMC2	psi-mi:“MI:0914”(association)	0.860
PSMC5	PSMD10	psi-mi:“MI:0914”(association)	0.850
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
PSMC5	SKA1	psi-mi:“MI:0915”(physical association)	0.800
ERCC3	GTF2H1	psi-mi:“MI:0914”(association)	0.790
PAAF1	PSMC5	psi-mi:“MI:0407”(direct interaction)	0.790
PSMC5	PSMC3	psi-mi:“MI:0914”(association)	0.760
KRT40	PSMC5	psi-mi:“MI:0915”(physical association)	0.740
PSMC5	KRT40	psi-mi:“MI:0915”(physical association)	0.740

BioGRID (1040): PSMC5 (Two-hybrid), PSMC5 (Affinity Capture-MS), PSMC5 (Affinity Capture-Western), CIITA (Co-localization), PSMC5 (Two-hybrid), PSMC5 (Two-hybrid), KRT38 (Two-hybrid), KRT40 (Two-hybrid), PSMC5 (Affinity Capture-MS), PSMC5 (Affinity Capture-MS), PSMC5 (Affinity Capture-MS), PSMC5 (Affinity Capture-MS), PSMC5 (Affinity Capture-MS), PSMC5 (Affinity Capture-MS), PSMC5 (Affinity Capture-MS)

ESM2 similar proteins: A3CV35, A4G0S4, A6UQT3, A6VHR1, A7I8B8, A9A916, B8GGN4, O17071, O18413, O26824, O74445, O74894, P34124, P41836, P42811, P43686, P46502, P46507, P53549, P54775, P54778, P54814, P62194, P62195, P62196, P62197, P62198, P62333, P62334, P62335, Q01939, Q0W257, Q25544, Q2FQ56, Q2KIW6, Q3T030, Q4R7L3, Q54PJ1, Q63570, Q6LWR0

Diamond homologs: A0A061IR73, A0A7N9VSG0, A4G0S4, A6UQT3, A6VHR1, A7YSY2, A9A916, C4QXI8, C4R6C2, D1CDT8, D4A2B7, G1X4S3, G1X7C7, G3GXG9, O05209, O13764, O14325, O15381, O18413, O26824, O28303, O28972, O43933, O60058, O74941, P03974, P23787, P24004, P25694, P32794, P33289, P33760, P34124, P36966, P41836, P46462, P46463, P46468, P54609, P54774

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PSMC5	“form complex”	“26S Proteasome”	binding
HERC1	“down-regulates quantity”	PSMC5	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 128 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	16	49.0×	9e-22
Vpu mediated degradation of CD4	16	46.7×	1e-21
Autodegradation of the E3 ubiquitin ligase COP1	16	46.7×	1e-21
Ubiquitin-dependent degradation of Cyclin D	16	46.7×	1e-21
Proteasome assembly	20	44.8×	5e-26
Regulation of ornithine decarboxylase (ODC)	15	44.8×	2e-20
Cross-presentation of soluble exogenous antigens (endosomes)	16	44.6×	2e-21
Vif-mediated degradation of APOBEC3G	16	44.6×	2e-21

GO biological processes:

GO term	Partners	Fold	FDR
morphogenesis of an epithelium	5	16.4×	2e-03
intermediate filament organization	6	13.8×	2e-03
positive regulation of protein ubiquitination	6	12.2×	2e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	21	10.4×	6e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	33
Likely benign	0
Benign	4

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3939663	NM_002805.6(PSMC5):c.973C>T (p.Arg325Trp)	Pathogenic
4820285	NM_002805.6(PSMC5):c.754G>A (p.Asp252Asn)	Pathogenic
4573301	NM_002805.6(PSMC5):c.1103T>C (p.Met368Thr)	Likely pathogenic

SpliceAI

1615 predictions. Top by Δscore:

Variant	Effect	Δscore
17:63827400:T:TA	donor_gain	1.0000
17:63827434:T:TA	donor_gain	1.0000
17:63829482:T:TA	acceptor_gain	1.0000
17:63829486:T:TA	acceptor_gain	1.0000
17:63829489:CACA:C	acceptor_loss	1.0000
17:63829491:C:G	acceptor_gain	1.0000
17:63829492:A:AG	acceptor_gain	1.0000
17:63829492:AGCT:A	acceptor_gain	1.0000
17:63829493:G:A	acceptor_loss	1.0000
17:63829493:G:GT	acceptor_gain	1.0000
17:63829493:GC:G	acceptor_gain	1.0000
17:63829493:GCT:G	acceptor_gain	1.0000
17:63829493:GCTG:G	acceptor_gain	1.0000
17:63829493:GCTGA:G	acceptor_gain	1.0000
17:63829562:AG:A	donor_gain	1.0000
17:63829563:GG:G	donor_gain	1.0000
17:63829563:GGT:G	donor_gain	1.0000
17:63829564:G:C	donor_loss	1.0000
17:63829564:G:GG	donor_gain	1.0000
17:63829564:GTG:G	donor_gain	1.0000
17:63829565:T:A	donor_loss	1.0000
17:63829565:T:TC	donor_gain	1.0000
17:63829848:CTAG:C	acceptor_loss	1.0000
17:63829849:TAGT:T	acceptor_loss	1.0000
17:63829850:A:AG	acceptor_gain	1.0000
17:63829850:AGTT:A	acceptor_loss	1.0000
17:63829851:G:GC	acceptor_gain	1.0000
17:63829851:GT:G	acceptor_gain	1.0000
17:63829851:GTT:G	acceptor_gain	1.0000
17:63829851:GTTC:G	acceptor_gain	1.0000

AlphaMissense

2660 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:63829536:G:C	A47P	1.000
17:63829905:G:T	G74W	1.000
17:63829906:G:A	G74E	1.000
17:63829945:T:A	V87D	1.000
17:63830296:T:C	L116P	1.000
17:63830404:G:A	G152D	1.000
17:63830449:T:C	L167P	1.000
17:63830472:T:C	F175L	1.000
17:63830474:C:A	F175L	1.000
17:63830474:C:G	F175L	1.000
17:63830809:G:A	G185R	1.000
17:63830809:G:C	G185R	1.000
17:63830810:G:A	G185E	1.000
17:63830816:T:C	L187P	1.000
17:63830819:T:C	L188P	1.000
17:63830824:G:A	G190R	1.000
17:63830824:G:C	G190R	1.000
17:63830825:G:A	G190E	1.000
17:63830825:G:T	G190V	1.000
17:63830833:G:C	G193R	1.000
17:63830834:G:A	G193D	1.000
17:63830839:G:A	G195R	1.000
17:63830839:G:C	G195R	1.000
17:63830839:G:T	G195W	1.000
17:63830840:G:A	G195E	1.000
17:63830840:G:T	G195V	1.000
17:63830846:C:T	T197I	1.000
17:63830849:T:C	L198P	1.000
17:63830855:C:A	A200D	1.000
17:63830858:G:C	R201P	1.000

dbSNP variants (sampled 300 via entrez): RS1000521662 (17:63830262 T>G), RS1000576455 (17:63828367 T>C), RS1000628655 (17:63827929 C>A,G,T), RS1001589878 (17:63827193 T>A,C), RS1001802503 (17:63828974 G>A), RS1002123382 (17:63827608 G>A,C), RS1002191329 (17:63829224 A>G,T), RS1002429741 (17:63831989 A>C,G), RS1002475762 (17:63827984 G>A), RS1002529051 (17:63825831 A>C,G), RS1002537783 (17:63827455 G>A,C), RS1003436011 (17:63830013 A>AGC), RS1003915899 (17:63831254 C>A), RS1004036967 (17:63825616 T>C,G), RS1004315003 (17:63831556 G>A)

Disease associations

OMIM: gene MIM:601681 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

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), CHEMBL3831208 (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
7.54	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
6.35	Kd	443.3	nM	CHEMBL5653589
6.35	ED50	443.3	nM	CHEMBL5653589
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
(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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149119: Binding affinity to human PSMC5 incubated for 45 mins by Kinobead based pull down assay	kd	0.4433	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	2149119: Binding affinity to human PSMC5 incubated for 45 mins by Kinobead based pull down assay	kd	7.3978	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
bisphenol F	increases expression	1
2,4,6-tribromophenol	decreases expression	1
tetrabromobisphenol A	decreases expression	1
quinoline	increases expression	1
arsenic trichloride	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol B	increases expression	1
quinocetone	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases expression, affects cotreatment	1
Cadmium	increases abundance, increases expression	1
Clozapine	increases expression	1
Dinitrochlorobenzene	affects binding	1
Doxorubicin	increases expression	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Rotenone	decreases expression	1
Smoke	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)

202 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
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
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice