PSMC1

Summary

PSMC1 (proteasome 26S subunit, ATPase 1, HGNC:9547) is a protein-coding gene on chromosome 14q32.11, encoding 26S proteasome regulatory subunit 4 (P62191). 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 96.4% 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. This subunit and a 20S core alpha subunit interact specifically with the hepatitis B virus X protein, a protein critical to viral replication. This subunit also interacts with the adenovirus E1A protein and this interaction alters the activity of the proteasome. Finally, this subunit interacts with ataxin-7, suggesting a role for the proteasome in the development of spinocerebellar ataxia type 7, a progressive neurodegenerative disorder.

Source: NCBI Gene 5700 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 13 total
• Phenotypes (HPO): 23
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 96.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_002802

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9547
Approved symbol	PSMC1
Name	proteasome 26S subunit, ATPase 1
Location	14q32.11
Locus type	gene with protein product
Status	Approved
Aliases	S4, p56, RPT2
Ensembl gene	ENSG00000100764
Ensembl biotype	protein_coding
OMIM	602706
Entrez	5700

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 4 retained_intron

ENST00000261303, ENST00000543772, ENST00000553835, ENST00000554624, ENST00000555679, ENST00000555787, ENST00000557357, ENST00000906983, ENST00000906984, ENST00000906985, ENST00000906986, ENST00000928147, ENST00000928148, ENST00000943594

RefSeq mRNA: 2 — MANE Select: NM_002802 NM_001330212, NM_002802

CCDS: CCDS32139, CCDS81837

Canonical transcript exons

ENST00000261303 — 11 exons

Exon	Start	End
ENSE00000659644	90263662	90263847
ENSE00000659647	90265070	90265166
ENSE00000659648	90268224	90268413
ENSE00000659649	90269397	90269548
ENSE00000659650	90270198	90270352
ENSE00001093948	90272273	90275429
ENSE00002459256	90256553	90256600
ENSE00003498838	90259160	90259213
ENSE00003589928	90260115	90260211
ENSE00003600697	90263318	90263442
ENSE00003604482	90264041	90264169

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 99.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 60.5381 / max 2947.2528, expressed in 1818 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141005	57.8989	1816
141004	2.6392	1378

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.11	gold quality
gastrocnemius	UBERON:0001388	98.87	gold quality
muscle of leg	UBERON:0001383	98.84	gold quality
skeletal muscle organ	UBERON:0014892	98.82	gold quality
islet of Langerhans	UBERON:0000006	98.62	gold quality
skeletal muscle tissue	UBERON:0001134	98.48	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.48	gold quality
placenta	UBERON:0001987	98.36	gold quality
smooth muscle tissue	UBERON:0001135	98.25	gold quality
adrenal tissue	UBERON:0018303	98.18	gold quality
left testis	UBERON:0004533	98.11	gold quality
endometrium	UBERON:0001295	98.06	gold quality
muscle tissue	UBERON:0002385	98.05	gold quality
right testis	UBERON:0004534	98.03	gold quality
mucosa of stomach	UBERON:0001199	97.97	gold quality
descending thoracic aorta	UBERON:0002345	97.97	gold quality
popliteal artery	UBERON:0002250	97.96	gold quality
superior frontal gyrus	UBERON:0002661	97.96	gold quality
tibial artery	UBERON:0007610	97.96	gold quality
rectum	UBERON:0001052	97.88	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.84	gold quality
aorta	UBERON:0000947	97.80	gold quality
left coronary artery	UBERON:0001626	97.72	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.68	gold quality
ganglionic eminence	UBERON:0004023	97.67	gold quality
lower esophagus	UBERON:0013473	97.67	gold quality
heart left ventricle	UBERON:0002084	97.66	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.66	gold quality
ventricular zone	UBERON:0003053	97.64	gold quality
heart	UBERON:0000948	97.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.79
E-MTAB-5061	yes	5.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting PSMC1, 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-548C-3P	99.99	74.01	7587
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-3145-5P	98.57	67.83	900
HSA-MIR-194-3P	97.36	65.96	1027
HSA-MIR-12128	96.67	66.98	1471

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 8)

• Hepatocytes dying because of inhibition of proteasome function produce massive quantities of the proinflammatory chemokine IL-8, possibly resulting in neutrophil infiltration, increased inflammation, and liver injury. (PMID:14578856)
• Psmc1 conditional knock-out mice demonstrate that 26S proteasomal dysfunction is sufficient to trigger neurodegenerative disease. (PMID:18701681)
• Caspase-3 cleaves specific 19 S proteasome subunits in skeletal muscle stimulating proteasome activity (PMID:20424172)
• Our results suggest that there is no association between variations or haplotypes in the PSMC1 gene and Parkinson’s disease (PMID:22948515)
• P26s4 Associates with the C-Terminal Region of TOPORS. (PMID:26872363)
• 14q32.11 microdeletion including CALM1, TTC7B, PSMC1, and RPS6KA5: A new potential cause of developmental and language delay in three unrelated patients. (PMID:33634591)
• Low expression of TCP1 (T-Complex 1) and PSMC1 (Proteasome 26S subunit, ATPase 1) in heterotopic ossification during ankylosing spondylitis. (PMID:34612770)
• PSMC1 variant causes a novel neurological syndrome. (PMID:35861243)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmc1a	ENSDARG00000030537
danio_rerio	psmc1b	ENSDARG00000043561
mus_musculus	Psmc1	ENSMUSG00000021178
rattus_norvegicus	Psmc1	ENSRNOG00000003951
drosophila_melanogaster	Rpt2	FBGN0015282
caenorhabditis_elegans		WBGENE00004502

Paralogs (5): PSMC4 (ENSG00000013275), PSMC5 (ENSG00000087191), PSMC6 (ENSG00000100519), PSMC2 (ENSG00000161057), PSMC3 (ENSG00000165916)

Protein

Protein identifiers

26S proteasome regulatory subunit 4 — P62191 (reviewed: P62191)

Alternative names: 26S proteasome AAA-ATPase subunit RPT2, Proteasome 26S subunit ATPase 1

All UniProt accessions (3): P62191, G3V4X1, Q53XL8

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. PSMC1 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 PSMC1 and few additional components. Interacts with SCA7. Interacts with NGLY1. Interacts with PAAF1.

Subcellular location. Cytoplasm. Nucleus. Membrane.

Disease relevance. Birk-Aharoni syndrome (BKAH) [MIM:620071] An autosomal recessive disorder characterized by failure to thrive, severe developmental delay, intellectual disability, spastic tetraplegia with central hypotonia, chorea, hearing loss, micropenis and undescended testes, as well as mild elevation of liver enzymes. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the AAA ATPase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P62191-1	1	yes
P62191-2	2

RefSeq proteins (2): NP_001317141, NP_002793* (*=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 (54 total): helix 14, strand 13, turn 7, modified residue 5, sequence conflict 3, compositionally biased region 3, region of interest 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, cross-link 1, splice variant 1, sequence variant 1, binding site 1

Structure

Experimental structures (PDB)

131 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9K53	ELECTRON MICROSCOPY	2.5
8USD	ELECTRON MICROSCOPY	2.7
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
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
9U7R	ELECTRON MICROSCOPY	3.17
6MSD	ELECTRON MICROSCOPY	3.2
6MSK	ELECTRON MICROSCOPY	3.2
7W39	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62191-F1	78.19	0.13

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): 226–233

Post-translational modifications (7): 258, 434, 439, 2, 237, 4, 53

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-532668	N-glycan trimming in the ER and Calnexin/Calreticulin cycle
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

MSigDB gene sets: 384 (showing top): 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, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, MORF_MBD4, MORF_RAB5A, 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, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN

GO Biological Process (2): proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), positive regulation of proteasomal protein catabolic process (GO:1901800)

GO Molecular Function (6): RNA binding (GO:0003723), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), proteasome-activating activity (GO:0036402), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (9): proteasome complex (GO:0000502), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), proteasome regulatory particle, base subcomplex (GO:0008540), membrane (GO:0016020), proteasome accessory complex (GO:0022624), cytoplasm (GO:0005737), 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
proteasomal protein catabolic process	3
protein-containing complex	3
ATP-dependent activity	2
intracellular anatomical structure	2
ubiquitin-dependent protein catabolic process	1
positive regulation of protein catabolic process	1
regulation of proteasomal protein catabolic process	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	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
nuclear lumen	1
cytoplasm	1
proteasome regulatory particle	1
proteasome complex	1
proteasome accessory complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

327 interactions, top by confidence:

A	B	Type	Score
PSMC1	PSMD2	psi-mi:“MI:0915”(physical association)	0.960
PSMD2	PSMC1	psi-mi:“MI:0915”(physical association)	0.960
PSMD5	PSMC2	psi-mi:“MI:0914”(association)	0.960
PSMD2	PSMC1	psi-mi:“MI:0407”(direct interaction)	0.960
PSMC6	PSMC3	psi-mi:“MI:0915”(physical association)	0.950
PSMC6	PSMC3	psi-mi:“MI:0914”(association)	0.950
PSMC1	PSMD5	psi-mi:“MI:0915”(physical association)	0.940
PSMD5	PSMC1	psi-mi:“MI:0915”(physical association)	0.940
PSMC1	PSMC6	psi-mi:“MI:0915”(physical association)	0.900
PSMC1	PSMC2	psi-mi:“MI:0407”(direct interaction)	0.890
PSMC4	PSMC1	psi-mi:“MI:0915”(physical association)	0.860
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	PSMC3	psi-mi:“MI:0914”(association)	0.760

BioGRID (790): PSMC1 (Affinity Capture-MS), PSMC1 (Two-hybrid), PSMD2 (Two-hybrid), PSMD5 (Two-hybrid), ZBTB8A (Two-hybrid), PSMC1 (Affinity Capture-MS), PSMC1 (Affinity Capture-MS), PSMC1 (Affinity Capture-MS), PSMC1 (Affinity Capture-MS), PSMC1 (Affinity Capture-MS), PSMC1 (Affinity Capture-MS), PSMC1 (Affinity Capture-MS), PSMC6 (Affinity Capture-MS), PSMC3 (Affinity Capture-MS), PSMC5 (Affinity Capture-MS)

ESM2 similar proteins: A0JMA9, A8QFF6, A9RA82, B2RYN7, B3EX35, B4USW8, B5X3X5, B7NZ88, O04019, O14126, O16368, O17071, O23894, O42931, O61577, O75449, O76371, P34808, P35998, P36612, P46465, P46466, P46470, P46471, P46472, P48601, P54776, P62191, P62192, P62193, Q0IIR9, Q1HGK7, Q4R407, Q4R4R0, Q55BV5, Q5E9F9, Q5RII9, Q5U3S1, Q5XIK7, Q63347

Diamond homologs: A3CV35, A4G0S4, A6UQT3, A6VHR1, A7I8B8, A9A916, B6YXR2, B8GGN4, C3MRF1, C3MY47, C3MZI6, C3N7K8, C3NFW6, C4KIR6, C5A6P8, D4GUJ7, O04019, O16368, O17071, O18413, O23894, O26824, O28303, O42586, O42587, O57940, O74445, O76371, O88685, P17980, P33297, P34123, P34124, P36612, P40327, P41836, P43686, P46465, P46466, P46470

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PSMC1	“form complex”	“26S Proteasome”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 137 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	24	70.4×	6e-39
Regulation of ornithine decarboxylase (ODC)	24	68.7×	1e-38
AUF1 (hnRNP D0) binds and destabilizes mRNA	26	68.0×	3e-41
Vpu mediated degradation of CD4	24	67.1×	1e-38
Autodegradation of the E3 ubiquitin ligase COP1	24	67.1×	1e-38
Ubiquitin-dependent degradation of Cyclin D	24	67.1×	1e-38
Cross-presentation of soluble exogenous antigens (endosomes)	25	66.8×	1e-39
Vif-mediated degradation of APOBEC3G	24	64.1×	6e-38

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	30	13.8×	4e-23
ubiquitin-dependent protein catabolic process	10	6.6×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1624 predictions. Top by Δscore:

Variant	Effect	Δscore
14:90256597:GATG:G	donor_gain	1.0000
14:90256601:G:GG	donor_gain	1.0000
14:90256602:T:A	donor_loss	1.0000
14:90259155:TCCAG:T	acceptor_loss	1.0000
14:90259157:CAG:C	acceptor_loss	1.0000
14:90259158:A:AG	acceptor_gain	1.0000
14:90259158:A:AT	acceptor_loss	1.0000
14:90259158:AG:A	acceptor_gain	1.0000
14:90259159:G:GG	acceptor_gain	1.0000
14:90259159:GG:G	acceptor_gain	1.0000
14:90259211:AAGG:A	donor_loss	1.0000
14:90259212:AGG:A	donor_loss	1.0000
14:90259213:GGTA:G	donor_loss	1.0000
14:90259214:G:A	donor_loss	1.0000
14:90259215:T:A	donor_loss	1.0000
14:90260095:T:TA	acceptor_gain	1.0000
14:90260099:A:AG	acceptor_gain	1.0000
14:90260100:T:G	acceptor_gain	1.0000
14:90260104:A:AG	acceptor_gain	1.0000
14:90260105:A:G	acceptor_gain	1.0000
14:90260107:A:AG	acceptor_gain	1.0000
14:90260108:A:G	acceptor_gain	1.0000
14:90263313:TTCAG:T	acceptor_loss	1.0000
14:90263314:TCA:T	acceptor_loss	1.0000
14:90263316:A:AG	acceptor_gain	1.0000
14:90263316:AGT:A	acceptor_gain	1.0000
14:90263317:G:GA	acceptor_gain	1.0000
14:90263317:G:T	acceptor_loss	1.0000
14:90263317:GT:G	acceptor_gain	1.0000
14:90263317:GTG:G	acceptor_gain	1.0000

AlphaMissense

2891 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:90263378:T:C	L72P	1.000
14:90263710:G:A	G110R	1.000
14:90263710:G:C	G110R	1.000
14:90263711:G:A	G110E	1.000
14:90263744:C:A	A121D	1.000
14:90263750:T:A	V123E	1.000
14:90263831:T:A	V150D	1.000
14:90264056:G:T	G161W	1.000
14:90264137:G:A	G188R	1.000
14:90264137:G:C	G188R	1.000
14:90264137:G:T	G188W	1.000
14:90264138:G:A	G188E	1.000
14:90264138:G:T	G188V	1.000
14:90264140:G:A	G189R	1.000
14:90264140:G:C	G189R	1.000
14:90264140:G:T	G189W	1.000
14:90264141:G:A	G189E	1.000
14:90264141:G:T	G189V	1.000
14:90265070:G:A	E199K	1.000
14:90265073:T:C	S200P	1.000
14:90265077:T:A	V201E	1.000
14:90265083:T:C	L203P	1.000
14:90265086:C:A	P204H	1.000
14:90265086:C:G	P204R	1.000
14:90265089:T:A	L205H	1.000
14:90265089:T:C	L205P	1.000
14:90265122:T:A	I216K	1.000
14:90265122:T:G	I216R	1.000
14:90265131:C:A	P219H	1.000
14:90265136:G:A	G221R	1.000

dbSNP variants (sampled 300 via entrez): RS1000042076 (14:90275683 G>A,C), RS1000082175 (14:90256022 G>A), RS1000110869 (14:90268708 G>A,T), RS1000133252 (14:90255663 C>A,T), RS1000187243 (14:90260508 G>A), RS1000219803 (14:90260417 A>G), RS1000714150 (14:90273418 C>T), RS1000956895 (14:90263190 A>G), RS1001060449 (14:90256660 T>G), RS1001133627 (14:90256908 G>A), RS1001183632 (14:90269812 T>A), RS1001266847 (14:90275281 G>A,T), RS1001291670 (14:90268868 T>C), RS1001294872 (14:90266972 G>A), RS1001393804 (14:90261022 T>C)

Disease associations

OMIM: gene MIM:602706 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss	Limited	Autosomal recessive
neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (3): prostate cancer (MONDO:0008315), neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss (MONDO:0859296), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

23 total (23 of 23 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000081	Duplicated collecting system
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000574	Thick eyebrow
HP:0001344	Absent speech
HP:0001508	Failure to thrive
HP:0001972	Macrocytic anemia
HP:0002072	Chorea
HP:0002510	Spastic tetraplegia
HP:0002540	Inability to walk
HP:0003593	Infantile onset
HP:0006844	Absent patellar reflexes
HP:0008936	Axial hypotonia
HP:0010864	Severe intellectual disability
HP:0011623	Muscular ventricular septal defect
HP:0011800	Midface retrusion
HP:0033142	Long nasal bridge
HP:0033454	Tube feeding

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001591_14	Response to citalopram treatment	9.000000e-07
GCST004097_2	Response to platinum-based neoadjuvant chemotherapy in cervical cancer	7.000000e-06
GCST007102_6	Seasonality and depression	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007943	response to platinum-based neoadjuvant chemotherapy
EFO:0006876	seasonality measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3831204 (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

64 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
8.32	Kd	4.772	nM	CHEMBL5653589
8.32	ED50	4.772	nM	CHEMBL5653589
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
6.30	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

61 with measured affinity, of 137 total; 33 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149115: Binding affinity to human PSMC1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0048	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-(4-phenylmethoxybutyl)butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0048	uM
(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
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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases methylation	2
sodium arsenite	increases expression, affects cotreatment, increases abundance	2
beta-Naphthoflavone	increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
cupric chloride	increases expression	1
quinoline	increases expression	1
flavone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
ICG 001	increases expression	1
elesclomol	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
Sunitinib	decreases expression	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Benztropine	decreases expression	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1
Diacetyl	increases expression	1
Doxorubicin	affects expression	1
Furaldehyde	affects cotreatment, affects localization, increases expression	1
Ivermectin	decreases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Naled	affects 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)

502 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,
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery