PSMD12

Summary

PSMD12 (proteasome 26S subunit, non-ATPase 12, HGNC:9557) is a protein-coding gene on chromosome 17q24.2, encoding 26S proteasome non-ATPase regulatory subunit 12 (O00232). 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 99.6% 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 a non-ATPase subunit of the 19S regulator. A pseudogene has been identified on chromosome 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5718 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Stankiewicz-Isidor syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 162 total — 21 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 125
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_002816

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9557
Approved symbol	PSMD12
Name	proteasome 26S subunit, non-ATPase 12
Location	17q24.2
Locus type	gene with protein product
Status	Approved
Aliases	p55, Rpn5
Ensembl gene	ENSG00000197170
Ensembl biotype	protein_coding
OMIM	604450
Entrez	5718

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 12 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000356126, ENST00000357146, ENST00000577724, ENST00000578015, ENST00000579365, ENST00000581618, ENST00000584008, ENST00000584289, ENST00000875728, ENST00000875729, ENST00000875730, ENST00000875731, ENST00000875732, ENST00000956699, ENST00000956700, ENST00000956701, ENST00000956702, ENST00000956703

RefSeq mRNA: 3 — MANE Select: NM_002816 NM_001316341, NM_002816, NM_174871

CCDS: CCDS11669, CCDS11670

Canonical transcript exons

ENST00000356126 — 11 exons

Exon	Start	End
ENSE00001828257	67337916	67341052
ENSE00002721815	67366412	67366577
ENSE00003487601	67357519	67357578
ENSE00003511043	67347116	67347250
ENSE00003520686	67344606	67344780
ENSE00003523955	67350229	67350336
ENSE00003606001	67347336	67347485
ENSE00003629002	67357303	67357431
ENSE00003641707	67348550	67348654
ENSE00003668268	67342186	67342263
ENSE00003683062	67345745	67345857

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 95.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.3557 / max 576.1547, expressed in 1819 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167689	43.8515	1818
167688	2.5042	1226

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.98	gold quality
biceps brachii	UBERON:0001507	95.05	gold quality
islet of Langerhans	UBERON:0000006	95.02	gold quality
adrenal tissue	UBERON:0018303	94.91	gold quality
tibialis anterior	UBERON:0001385	94.79	gold quality
gastrocnemius	UBERON:0001388	94.72	gold quality
heart right ventricle	UBERON:0002080	94.60	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.43	gold quality
muscle of leg	UBERON:0001383	94.31	gold quality
deltoid	UBERON:0001476	94.26	gold quality
paraflocculus	UBERON:0005351	94.11	gold quality
cerebellar vermis	UBERON:0004720	93.89	gold quality
frontal pole	UBERON:0002795	93.88	gold quality
muscle organ	UBERON:0001630	93.83	gold quality
cartilage tissue	UBERON:0002418	93.69	gold quality
pons	UBERON:0000988	93.55	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.02	gold quality
skeletal muscle tissue	UBERON:0001134	92.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.76	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.73	gold quality
substantia nigra pars compacta	UBERON:0001965	92.62	gold quality
Brodmann (1909) area 10	UBERON:0013541	92.46	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.41	gold quality
esophagus squamous epithelium	UBERON:0006920	92.37	gold quality
quadriceps femoris	UBERON:0001377	92.16	gold quality
muscle tissue	UBERON:0002385	92.11	gold quality
sperm	CL:0000019	92.10	gold quality
monocyte	CL:0000576	92.08	gold quality
bone marrow	UBERON:0002371	92.03	gold quality
mononuclear cell	CL:0000842	91.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7606	no	352.45
E-MTAB-7303	no	166.70
E-GEOD-93593	no	7.08
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

120 targeting PSMD12, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-664B-3P	99.84	71.65	3590

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 7)

• we identified six de novo genomic deletions and four de novo point mutations in unrelated individuals with intellectual disability, congenital malformations, ophthalmologic anomalies, feeding difficulties, deafness, and subtle dysmorphic facial features (PMID:28132691)
• We performed WES on six affected siblings from a multiplex family with ID and autistic features. We identified an inherited heterozygous nonsense mutation in PSMD12 (NM_002816: c.367C>T: p.R123X) in the multiplex family and a de novo nonsense mutation in the same gene (NM_002816: c.601C>T: p.R201X) in the simplex family. (PMID:30421579)
• PSMD12 promotes breast cancer growth via inhibiting the expression of pro-apoptotic genes. (PMID:32222279)
• Haploinsufficiency of PSMD12 Causes Proteasome Dysfunction and Subclinical Autoinflammation. (PMID:35080150)
• PSMD12 promotes the activation of the MEK-ERK pathway by upregulating KIF15 to promote the malignant progression of liver cancer. (PMID:36137220)
• PSMD12 interacts with CDKN3 and facilitates pancreatic cancer progression. (PMID:37037907)
• PSMD12 promotes non-small cell lung cancer progression through activating the Nrf2/TrxR1 pathway. (PMID:38243044)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmd12	ENSDARG00000052377
mus_musculus	Psmd12	ENSMUSG00000020720
rattus_norvegicus	Psmd12	ENSRNOG00000003117
drosophila_melanogaster	Rpn5	FBGN0028690
caenorhabditis_elegans		WBGENE00004461

Paralogs (1): COPS4 (ENSG00000138663)

Protein

Protein identifiers

26S proteasome non-ATPase regulatory subunit 12 — O00232 (reviewed: O00232)

Alternative names: 26S proteasome regulatory subunit RPN5, 26S proteasome regulatory subunit p55

All UniProt accessions (4): A0A0S2Z489, O00232, J3KSK1, J3KTJ5

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD12, a base containing 6 ATPases and few additional components. Interacts with ERCC6.

Disease relevance. Stankiewicz-Isidor syndrome (STISS) [MIM:617516] A neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, behavioral disorders, mild dysmorphism, ophthalmologic anomalies, feeding difficulties, deafness, and variable congenital malformations of the cardiac and/or urogenital systems. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the proteasome subunit p55 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00232-1	1	yes
O00232-2	2

RefSeq proteins (3): NP_001303270, NP_002807, NP_777360 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR040134	PSMD12/CSN4	Family
IPR040896	RPN5_C	Domain
IPR054559	PSMD12-CSN4-like_N	Domain

Pfam: PF01399, PF18098, PF22241

UniProt features (41 total): helix 23, turn 3, strand 3, modified residue 3, sequence conflict 2, cross-link 2, initiator methionine 1, chain 1, domain 1, splice variant 1, sequence 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-O00232-F1	79.27	0.06

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 (5): 2, 221, 368, 92, 92

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: 567 (showing top): REACTOME_DNA_REPLICATION, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, REACTOME_SIGNALING_BY_NOTCH, AP1_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, 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

GO Biological Process (1): proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (12): proteasome complex (GO:0000502), extracellular region (GO:0005576), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), proteasome regulatory particle (GO:0005838), proteasome regulatory particle, lid subcomplex (GO:0008541), membrane (GO:0016020), proteasome accessory complex (GO:0022624), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813)

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
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
binding	1
intracellular protein-containing complex	1
endopeptidase complex	1
nuclear lumen	1
cytoplasm	1
proteasome accessory complex	1
proteasome regulatory particle	1
proteasome complex	1
secretory granule	1
cytoplasmic vesicle lumen	1
extracellular vesicle	1
intracellular organelle lumen	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

2808 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMD12	PSMD3	O43242	998
PSMD12	PSMD8	P48556	997
PSMD12	PSMD7	P51665	997
PSMD12	PSMD11	O00231	997
PSMD12	PSMD14	O00487	997
PSMD12	PSMD6	Q15008	997
PSMD12	PSMD13	Q9UNM6	997
PSMD12	SEM1	Q6ZVN7	978
PSMD12	EIF3E	P60228	920
PSMD12	PSMD4	P55036	920
PSMD12	ADRM1	Q16186	900
PSMD12	PSMC4	P43686	883
PSMD12	PSMD2	Q13200	818
PSMD12	PSMC2	P35998	813
PSMD12	PSMD1	Q99460	812

IntAct

230 interactions, top by confidence:

A	B	Type	Score
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
UCHL5	PSMD12	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
PSMD7	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMC1	PSMD12	psi-mi:“MI:0914”(association)	0.730
PSMD11	PSMD12	psi-mi:“MI:0915”(physical association)	0.730
PSMB2	PSMD11	psi-mi:“MI:0914”(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:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710

BioGRID (688): PSMD12 (Affinity Capture-MS), FUS (Affinity Capture-Western), PSMD12 (Affinity Capture-MS), PSMD12 (Affinity Capture-MS), PSMD12 (Affinity Capture-MS), PSMD12 (Affinity Capture-MS), PSMD12 (Affinity Capture-MS), PSMD12 (Affinity Capture-MS), PSMD12 (Affinity Capture-MS), PSMD12 (Affinity Capture-MS), PSMD12 (Affinity Capture-MS), PSMD12 (Affinity Capture-MS), PSMD12 (Affinity Capture-MS), PSMD12 (Affinity Capture-MS), EIF3E (Co-fractionation)

ESM2 similar proteins: A0JN39, A8WGF4, B5DGH9, D2SW95, O00232, O60763, O95782, P17426, P23514, P41541, P53618, P91926, P93768, Q05AY2, Q0JNK5, Q1LUA8, Q29N38, Q2KJ25, Q3B8M3, Q3UGF1, Q4R4I8, Q53PC7, Q5R4J9, Q5R664, Q5R922, Q5RBI3, Q5VQ78, Q5XI83, Q5ZIA5, Q5ZLA5, Q66HV4, Q6DRI1, Q6H8D5, Q6H8D6, Q6N069, Q6NWV3, Q6P7L9, Q7QG73, Q80UM3, Q8BWQ6

Diamond homologs: O00232, P0CU17, P0CU18, Q12250, Q2KJ25, Q54UJ0, Q5RBI3, Q8VWK0, Q9D8W5, Q9FIB6, Q54B82

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PSMD12	“form complex”	“26S Proteasome”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 145 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	28	78.0×	8e-48
Regulation of ornithine decarboxylase (ODC)	28	76.1×	2e-47
Vpu mediated degradation of CD4	28	74.4×	3e-47
Autodegradation of the E3 ubiquitin ligase COP1	28	74.4×	3e-47
Ubiquitin-dependent degradation of Cyclin D	28	74.4×	3e-47
Cross-presentation of soluble exogenous antigens (endosomes)	29	73.6×	4e-48
Proteasome assembly	35	71.4×	7e-58
Vif-mediated degradation of APOBEC3G	28	71.1×	2e-46

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	6	53.5×	3e-07
translational initiation	6	17.1×	2e-04
proteasome-mediated ubiquitin-dependent protein catabolic process	37	15.3×	6e-31
ubiquitin-dependent protein catabolic process	9	5.3×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	11
Uncertain significance	96
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1679244	NM_002816.5(PSMD12):c.1078G>T (p.Glu360Ter)	Pathogenic
3250362	NM_002816.5(PSMD12):c.686T>G (p.Leu229Ter)	Pathogenic
3310984	NM_002816.5(PSMD12):c.415G>T (p.Glu139Ter)	Pathogenic
4056338	NM_002816.5(PSMD12):c.319C>T (p.Gln107Ter)	Pathogenic
427779	NM_002816.5(PSMD12):c.367C>T (p.Arg123Ter)	Pathogenic
427780	NM_002816.5(PSMD12):c.1274T>G (p.Leu425Ter)	Pathogenic
427781	NM_002816.5(PSMD12):c.601C>T (p.Arg201Ter)	Pathogenic
427782	NM_002816.5(PSMD12):c.909-2A>G	Pathogenic
4526987	NM_002816.5(PSMD12):c.1246del (p.Gln416fs)	Pathogenic
4530839	NM_002816.5(PSMD12):c.685_689del (p.Leu229fs)	Pathogenic
4531675	NM_002816.5(PSMD12):c.937del (p.Glu313fs)	Pathogenic
4628564	NM_002816.5(PSMD12):c.865C>T (p.Arg289Ter)	Pathogenic
4823452	NM_002816.5(PSMD12):c.286C>T (p.Gln96Ter)	Pathogenic
620300	NM_002816.5(PSMD12):c.544C>T (p.Arg182Ter)	Pathogenic
620497	NM_002816.5(PSMD12):c.316C>T (p.Gln106Ter)	Pathogenic
638584	NM_002816.5(PSMD12):c.1033G>T (p.Glu345Ter)	Pathogenic
807474	NM_002816.5(PSMD12):c.148_149del (p.Leu50fs)	Pathogenic
817952	NM_002816.5(PSMD12):c.356del (p.Pro119fs)	Pathogenic
818024	NM_002816.5(PSMD12):c.526del (p.Ser176fs)	Pathogenic
916097	NM_002816.5(PSMD12):c.1162-1G>A	Pathogenic
984994	NM_002816.5(PSMD12):c.1071_1072del (p.Arg357fs)	Pathogenic
1992320	NM_002816.5(PSMD12):c.1084-1G>A	Likely pathogenic
2577965	NM_002816.5(PSMD12):c.906C>A (p.Tyr302Ter)	Likely pathogenic
2635486	NM_002816.5(PSMD12):c.435_438del (p.Thr146fs)	Likely pathogenic
2691850	NM_002816.5(PSMD12):c.333T>A (p.Tyr111Ter)	Likely pathogenic
3337337	NM_002816.5(PSMD12):c.539_542del (p.Lys180fs)	Likely pathogenic
3899968	NM_002816.5(PSMD12):c.1301C>A (p.Ser434Ter)	Likely pathogenic
4072149	NM_002816.5(PSMD12):c.1284G>A (p.Trp428Ter)	Likely pathogenic
4814154	NM_002816.5(PSMD12):c.565C>T (p.Gln189Ter)	Likely pathogenic
4820155	NM_002816.5(PSMD12):c.818_819del (p.Tyr273fs)	Likely pathogenic

SpliceAI

1788 predictions. Top by Δscore:

Variant	Effect	Δscore
17:67341050:CTC:C	acceptor_gain	1.0000
17:67342178:CTA:C	donor_gain	1.0000
17:67342181:CTT:C	donor_loss	1.0000
17:67342182:TTA:T	donor_loss	1.0000
17:67342183:TAC:T	donor_loss	1.0000
17:67342184:A:AC	donor_gain	1.0000
17:67342184:ACAT:A	donor_gain	1.0000
17:67342184:ACATC:A	donor_loss	1.0000
17:67342185:C:CA	donor_gain	1.0000
17:67342185:CA:C	donor_gain	1.0000
17:67342185:CAT:C	donor_gain	1.0000
17:67342185:CATC:C	donor_gain	1.0000
17:67342185:CATCA:C	donor_gain	1.0000
17:67342260:TATT:T	acceptor_gain	1.0000
17:67342261:ATT:A	acceptor_gain	1.0000
17:67342262:TT:T	acceptor_gain	1.0000
17:67342264:C:CC	acceptor_gain	1.0000
17:67342275:A:AC	acceptor_gain	1.0000
17:67342275:A:C	acceptor_gain	1.0000
17:67342283:C:CT	acceptor_gain	1.0000
17:67344600:TCTTA:T	donor_loss	1.0000
17:67344601:CTTA:C	donor_loss	1.0000
17:67344602:TTACA:T	donor_loss	1.0000
17:67344603:TA:T	donor_loss	1.0000
17:67344604:A:AC	donor_gain	1.0000
17:67344605:C:CC	donor_gain	1.0000
17:67344605:CAT:C	donor_gain	1.0000
17:67344605:CATG:C	donor_gain	1.0000
17:67345740:CTTA:C	donor_gain	1.0000
17:67345741:TTA:T	donor_loss	1.0000

AlphaMissense

3006 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:67340880:A:G	L445P	1.000
17:67340932:A:G	W428R	1.000
17:67340932:A:T	W428R	1.000
17:67341003:G:T	A404D	1.000
17:67342248:C:G	A367P	1.000
17:67340970:A:G	F415S	0.999
17:67340990:T:A	R408S	0.999
17:67340990:T:G	R408S	0.999
17:67340991:C:G	R408T	0.999
17:67341027:A:G	L396P	0.999
17:67341036:A:G	L393P	0.999
17:67342196:A:G	L384P	0.999
17:67342205:A:G	L381P	0.999
17:67342261:A:C	N362K	0.999
17:67342261:A:T	N362K	0.999
17:67344607:T:G	H361P	0.999
17:67344740:A:G	W317R	0.999
17:67344740:A:T	W317R	0.999
17:67345853:A:G	L267P	0.999
17:67347421:A:G	L192P	0.999
17:67347472:C:T	G175E	0.999
17:67347482:C:T	E172K	0.999
17:67348612:C:G	A150P	0.999
17:67348626:A:G	L145P	0.999
17:67348629:C:G	R144P	0.999
17:67348635:C:G	R142P	0.999
17:67348647:A:T	V138D	0.999
17:67350251:A:G	L128P	0.999
17:67357321:C:A	R93S	0.999
17:67357321:C:G	R93S	0.999

dbSNP variants (sampled 300 via entrez): RS1000003213 (17:67354360 T>A,C), RS1000133585 (17:67359352 C>G), RS1000205906 (17:67341594 T>G), RS1000291437 (17:67365156 C>T), RS1000339331 (17:67364921 C>A), RS1000568830 (17:67349343 G>T), RS1000571874 (17:67349125 T>G), RS1000763015 (17:67366481 G>A,T), RS1000811001 (17:67342905 C>A,T), RS1000831543 (17:67361589 A>G), RS1000882202 (17:67361246 T>A,C), RS1001106827 (17:67355622 T>A), RS1001119838 (17:67347581 A>G), RS1001158499 (17:67343213 C>G,T), RS1001257681 (17:67338511 A>T)

Disease associations

OMIM: gene MIM:604450 | disease phenotypes: MIM:617516, MIM:123100

GenCC curated gene-disease

Disease	Classification	Inheritance
Stankiewicz-Isidor syndrome	Strong	Autosomal dominant
syndromic intellectual disability	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Stankiewicz-Isidor syndrome	Definitive	AD

Mondo (5): Stankiewicz-Isidor syndrome (MONDO:0054591), neurodevelopmental disorder (MONDO:0700092), craniosynostosis (MONDO:0015469), intellectual disability (MONDO:0001071), syndromic intellectual disability (MONDO:0000508)

Orphanet (2): Craniosynostosis (Orphanet:1531), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

125 total (30 of 125 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000041	Chordee
HP:0000047	Hypospadias
HP:0000049	Shawl scrotum
HP:0000054	Micropenis
HP:0000073	Ureteral duplication
HP:0000076	Vesicoureteral reflux
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000189	Narrow palate
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000248	Brachycephaly
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000324	Facial asymmetry
HP:0000325	Triangular face
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000362	Otosclerosis
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000403	Recurrent otitis media
HP:0000431	Wide nasal bridge
HP:0000448	Prominent nose
HP:0000470	Short neck
HP:0000475	Broad neck

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90020025_1486	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST90020027_436	Waist-hip index	8.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3831211 (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
7.30	Kd	50.36	nM	CHEMBL5653589
7.30	ED50	50.36	nM	CHEMBL5653589
7.27	IC50	54	nM	CHEMBL3237872
7.12	IC50	75	nM	CHEMBL3237865
7.12	IC50	76	nM	CHEMBL3237866
6.96	IC50	110	nM	CHEMBL3262766
6.92	IC50	120	nM	CHEMBL3237864
6.92	IC50	120	nM	BORTEZOMIB
6.89	IC50	130	nM	CHEMBL3237869
6.85	IC50	140	nM	CHEMBL3237862
6.82	IC50	150	nM	CHEMBL3237863
6.77	IC50	170	nM	CHEMBL3237873
6.77	IC50	170	nM	CHEMBL3262765
6.72	IC50	190	nM	CHEMBL3262758
6.68	IC50	210	nM	CHEMBL3237870
6.66	IC50	220	nM	CHEMBL3262756
6.60	IC50	250	nM	CHEMBL3237868
6.47	IC50	340	nM	CHEMBL3262752
6.47	IC50	340	nM	CHEMBL3262755
6.44	IC50	360	nM	CHEMBL3262757
6.42	IC50	380	nM	CHEMBL3262754
6.36	IC50	440	nM	CHEMBL3262753
6.30	IC50	500	nM	CHEMBL3237872
6.20	IC50	630	nM	CHEMBL3262762
6.02	IC50	950	nM	CHEMBL3262761
6.00	IC50	1000	nM	CHEMBL3237871
5.96	IC50	1100	nM	CHEMBL3237862
5.85	IC50	1400	nM	BELACTOSIN A
5.84	IC50	1440	nM	BELACTOSIN A

PubChem BioAssay actives

62 with measured affinity, of 137 total; 34 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Bortezomib	1985684: Inhibition of 26S proteasome (unknown origin)	ic50	0.0024	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0027	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[3-phenylmethoxy-2-(phenylmethoxymethyl)propyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0039	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[5-phenylmethoxy-4-(phenylmethoxymethyl)pentyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0041	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[5-phenylmethoxy-4-(phenylmethoxymethyl)pentyl]pentanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0041	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-(4-phenylmethoxybutyl)butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0048	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[3-phenylmethoxy-2-(phenylmethoxymethyl)propyl]pentanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0051	uM
(2S)-2-acetamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]pentanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0057	uM
benzyl N-[(2S)-1-[[(2R)-1-[(1R,2S)-2-[[(2R,3S)-3-[(2S)-butan-2-yl]-4-oxooxetane-2-carbonyl]amino]cyclopropyl]-4-phenylbutan-2-yl]amino]-1-oxopropan-2-yl]carbamate	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0057	uM
(2S)-2-[(2,5-dichlorobenzoyl)amino]-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0059	uM
(2S)-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]-2-(pyrazine-2-carbonylamino)butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0071	uM
(2S)-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]-2-[(6-phenylpyridine-2-carbonyl)amino]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0075	uM
[(1R)-1-[[(2S)-2-acetamido-4-oxo-4-[[3-phenylmethoxy-2-(phenylmethoxymethyl)propyl]amino]butanoyl]amino]-3-methylbutyl]boronic acid	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0077	uM
(2S)-2-benzamido-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-N’-[4-phenylmethoxy-3-(phenylmethoxymethyl)butyl]butanediamide	1128229: Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-LLVY-AMC as substrate	ic50	0.0078	uM
Carfilzomib	1141825: Inhibition of chymotrypsin-like enzyme activity of purified human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate by fluorescence method	ic50	0.0086	uM
(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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149123: Binding affinity to human PSMD12 incubated for 45 mins by Kinobead based pull down assay	kd	0.0504	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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149123: Binding affinity to human PSMD12 incubated for 45 mins by Kinobead based pull down assay	kd	3.1956	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

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects expression, affects reaction, decreases expression, affects cotreatment	4
bisphenol A	affects expression, decreases expression	3
sodium arsenite	affects expression, affects cotreatment, increases abundance, increases expression	3
Tobacco Smoke Pollution	increases expression	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	3
cobaltous chloride	increases expression	2
Air Pollutants	decreases expression, affects expression, increases abundance	2
Hydrogen Peroxide	affects expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
methylparaben	decreases expression	1
nickel chloride	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
CGP 52608	increases reaction, affects binding	1
chloropicrin	increases expression	1
bisphenol B	increases expression	1
elesclomol	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
jinfukang	affects cotreatment, decreases expression	1
picoxystrobin	increases expression	1
bisphenol AF	increases expression	1
Bortezomib	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Decitabine	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)

299 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,
NCT00722436	PHASE4	TERMINATED	Tranexamic Acid for Craniofacial Surgery
NCT02188576	PHASE4	COMPLETED	The Efficacy and Population Pharmacokinetics of Tranexamic Acid for Craniosynostosis Surgery
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
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
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
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
NCT02229968	PHASE2	ACTIVE_NOT_RECRUITING	Efficacy of Amicar for Children Having Craniofacial Surgery
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
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
NCT00912119	PHASE1	COMPLETED	Amicar Pharmacokinetics of Children Having Craniofacial Surgery
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
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