PSMD13

Summary

PSMD13 (proteasome 26S subunit, non-ATPase 13, HGNC:9558) is a protein-coding gene on chromosome 11p15.5, encoding 26S proteasome non-ATPase regulatory subunit 13 (Q9UNM6). 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 99.4% 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 a non-ATPase subunit of the 19S regulator. Two transcripts encoding different isoforms have been described.

Source: NCBI Gene 5719 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 63 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_002817

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9558
Approved symbol	PSMD13
Name	proteasome 26S subunit, non-ATPase 13
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	p40.5, Rpn9
Ensembl gene	ENSG00000185627
Ensembl biotype	protein_coding
OMIM	603481
Entrez	5719

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 20 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000352303, ENST00000382671, ENST00000431206, ENST00000525665, ENST00000526783, ENST00000527047, ENST00000527982, ENST00000528906, ENST00000529372, ENST00000529679, ENST00000532025, ENST00000532097, ENST00000533717, ENST00000534590, ENST00000873099, ENST00000873100, ENST00000873101, ENST00000932008, ENST00000932009, ENST00000932010, ENST00000932011, ENST00000932012, ENST00000963573, ENST00000963574, ENST00000963575, ENST00000963576, ENST00000963577, ENST00000963578, ENST00000963579

RefSeq mRNA: 2 — MANE Select: NM_002817 NM_002817, NM_175932

CCDS: CCDS44504, CCDS7692

Canonical transcript exons

ENST00000532097 — 13 exons

Exon	Start	End
ENSE00001683656	236976	237144
ENSE00002161781	252505	252984
ENSE00003512300	244161	244216
ENSE00003547447	248932	249057
ENSE00003583776	250803	250865
ENSE00003612990	238998	239076
ENSE00003636408	244426	244469
ENSE00003659685	247277	247448
ENSE00003665552	251546	251626
ENSE00003666213	251820	251936
ENSE00003674213	244041	244075
ENSE00003685852	248776	248855
ENSE00003694671	244675	244761

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 97.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 91.8218 / max 377.8983, expressed in 1827 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112152	87.2676	1827
112153	3.4169	1504
112149	0.5191	53
112150	0.3670	118
112151	0.2513	80

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.61	gold quality
gastrocnemius	UBERON:0001388	97.57	gold quality
mucosa of transverse colon	UBERON:0004991	97.51	gold quality
skin of leg	UBERON:0001511	97.49	gold quality
apex of heart	UBERON:0002098	97.44	gold quality
skin of abdomen	UBERON:0001416	97.35	gold quality
adenohypophysis	UBERON:0002196	97.30	gold quality
muscle of leg	UBERON:0001383	97.29	gold quality
ganglionic eminence	UBERON:0004023	97.17	gold quality
lower esophagus mucosa	UBERON:0035834	97.16	gold quality
rectum	UBERON:0001052	97.12	gold quality
cortical plate	UBERON:0005343	97.07	gold quality
body of uterus	UBERON:0009853	97.07	gold quality
upper lobe of left lung	UBERON:0008952	97.06	gold quality
islet of Langerhans	UBERON:0000006	97.02	gold quality
lower esophagus	UBERON:0013473	96.99	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.99	gold quality
ectocervix	UBERON:0012249	96.98	gold quality
right lung	UBERON:0002167	96.97	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.91	gold quality
endocervix	UBERON:0000458	96.88	gold quality
monocyte	CL:0000576	96.87	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.87	gold quality
metanephros cortex	UBERON:0010533	96.87	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.87	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.86	gold quality
tibial nerve	UBERON:0001323	96.84	gold quality
spleen	UBERON:0002106	96.83	gold quality
left uterine tube	UBERON:0001303	96.77	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.76	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-29	no	725.06
E-MTAB-6386	no	671.90
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting PSMD13, 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-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-7114-3P	98.42	66.53	569
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-1180-5P	98.16	65.32	460
HSA-MIR-193B-5P	97.91	65.88	837
HSA-MIR-647	97.73	67.79	927
HSA-MIR-10398-5P	97.12	64.94	1051
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-552-3P	96.68	64.12	1026
HSA-MIR-3678-5P	96.64	74.02	93
HSA-MIR-6738-5P	96.33	63.61	815
HSA-MIR-1914-3P	95.07	63.37	762

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 4)

• The SIRT3 5’ flanking region encompasses the PSMD13 gene encoding the p40.5 regulator subunit of the 26S proteasome. (PMID:17059877)
• Studies have found significant associations of the treatment response with the 26S proteasome non-ATPase subunit 9 (PSMD9), proteasome alpha type 7 subunit (PSMA7) and PSMD13 genes. (PMID:26624926)
• Data show that UBLCP1 selectively binds to the 26S proteasome non-ATPase regulatory subunit 13 (19S regulatory particle) in regulating proteasome assembly. (PMID:28539385)
• Alternative splicing of PSMD13 mediated by genetic variants is significantly associated with endometrial cancer risk. (PMID:36731897)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmd13	ENSDARG00000016239
mus_musculus	Psmd13	ENSMUSG00000025487
rattus_norvegicus	Psmd13	ENSRNOG00000014109
drosophila_melanogaster	Rpn9	FBGN0028691
caenorhabditis_elegans		WBGENE00004465

Protein

Protein identifiers

26S proteasome non-ATPase regulatory subunit 13 — Q9UNM6 (reviewed: Q9UNM6)

Alternative names: 26S proteasome regulatory subunit RPN9, 26S proteasome regulatory subunit S11, 26S proteasome regulatory subunit p40.5

All UniProt accessions (7): E9PL38, E9PPD2, E9PQG3, Q9UNM6, F8W8J6, H0YD73, J3KNQ3

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 PSMD13, a base containing 6 ATPases and few additional components.

Similarity. Belongs to the proteasome subunit S11 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UNM6-1	1	yes
Q9UNM6-2	2

RefSeq proteins (2): NP_002808, NP_787128 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR035298	PSMD13	Family
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR054179	PSD13_N	Domain

Pfam: PF01399, PF22037

UniProt features (40 total): helix 23, turn 4, strand 4, sequence variant 4, chain 1, domain 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

118 structures, top 30 by resolution.

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

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UNM6-F1	70.94	0.00

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 (1): 298

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: 314 (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, 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, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS

GO Biological Process (3): ubiquitin-dependent protein catabolic process (GO:0006511), meiosis I (GO:0007127), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

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

GO Cellular Component (12): proteasome complex (GO:0000502), extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), proteasome regulatory particle (GO:0005838), proteasome regulatory particle, lid subcomplex (GO:0008541), membrane (GO:0016020), proteasome accessory complex (GO:0022624), secretory granule lumen (GO:0034774), ficolin-1-rich granule lumen (GO:1904813), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-18 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein-containing complex	3
protein ubiquitination	1
modification-dependent protein catabolic process	1
meiotic telophase I	1
meiosis I cell cycle process	1
meiotic nuclear division	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
molecular_function	1
binding	1
intracellular protein-containing complex	1
endopeptidase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
proteasome accessory complex	1
proteasome regulatory particle	1
proteasome complex	1
intracellular anatomical structure	1
secretory granule	1
cytoplasmic vesicle lumen	1
intracellular organelle lumen	1
ficolin-1-rich granule	1
cellular_component	1

Protein interactions and networks

STRING

2148 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMD13	PSMD8	P48556	997
PSMD13	PSMD3	O43242	997
PSMD13	PSMD12	O00232	997
PSMD13	PSMD7	P51665	996
PSMD13	PSMD11	O00231	996
PSMD13	PSMD14	O00487	996
PSMD13	PSMD6	Q15008	996
PSMD13	PSMC1	P49014	968
PSMD13	SEM1	Q6ZVN7	966
PSMD13	PSMD10	O75832	956
PSMD13	PSMD4	P55036	955
PSMD13	PSMC4	P43686	852
PSMD13	ADRM1	Q16186	852
PSMD13	PSMD2	Q13200	789
PSMD13	PSMC3	P17980	787

IntAct

220 interactions, top by confidence:

A	B	Type	Score
STK24	STRN	psi-mi:“MI:0914”(association)	0.870
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
PSMD13	PSMD11	psi-mi:“MI:0914”(association)	0.750
PSMD11	PSMD12	psi-mi:“MI:0915”(physical association)	0.730
PSMB2	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMD7	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMD2	PSMD11	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PSMD14	PSMD11	psi-mi:“MI:0914”(association)	0.650
PSMD5	PSMD12	psi-mi:“MI:0914”(association)	0.640
PSMB3	PSMD11	psi-mi:“MI:0914”(association)	0.640
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
USP14	PSMD11	psi-mi:“MI:0914”(association)	0.530
PSMC6	PSMD11	psi-mi:“MI:0915”(physical association)	0.530

BioGRID (605): PSMD13 (Affinity Capture-MS), PSMD13 (Affinity Capture-MS), PSMD13 (Affinity Capture-MS), PSMD13 (Affinity Capture-MS), PSMD13 (Affinity Capture-MS), PSMD13 (Affinity Capture-MS), PSMD13 (Affinity Capture-MS), PSMD13 (Affinity Capture-MS), PSMD13 (Affinity Capture-MS), PSMD13 (Affinity Capture-MS), PSMD13 (Affinity Capture-MS), PSMB8 (Co-fractionation), PSMC5 (Co-fractionation), PSMD13 (Co-fractionation), PSMD13 (Co-fractionation)

ESM2 similar proteins: A6QNX3, B2GV77, P09851, P20936, P50904, P61970, P61971, P61972, Q1JP79, Q29425, Q2KI42, Q2KIW0, Q2TBL9, Q32KP9, Q3UNA4, Q4R4K5, Q4R5H6, Q5E9J4, Q5F415, Q5FVJ7, Q5R8G4, Q5R8I6, Q5RB36, Q5RES2, Q5RKN4, Q5ZLH0, Q6PC62, Q8BG32, Q8BUH1, Q8IUI8, Q8K0F1, Q8MJJ1, Q92747, Q93034, Q99PD4, Q9CQC8, Q9CZQ9, Q9D5V5, Q9DAI2, Q9ES56

Diamond homologs: B0BN93, B3NRC6, B4P6M6, P84169, Q04062, Q54NQ0, Q5E964, Q8GYA6, Q8RWF0, Q9UNM6, Q9US13, Q9WVJ2, A7SPX9, B0WTN3, B3MCZ5, B4GDM5, B4HR14, B4JW83, B4KT65, B4LJT9, B4MY75, B4QFD2, Q17D30, Q292F0, Q3T148, Q5DHT6, Q5R8C4, Q5ZJ64, Q6DK91, Q7JVI3, Q7L2H7, Q7Q068, Q7SEK1, Q7T3B0, Q7ZYU8, Q99JX4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PSMD13	“form complex”	“26S Proteasome”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 154 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	30	78.8×	1e-51
Antigen processing: Ub, ATP-independent proteasomal degradation	14	75.4×	5e-24
Regulation of ornithine decarboxylase (ODC)	29	74.4×	6e-49
Vpu mediated degradation of CD4	29	72.7×	1e-48
Autodegradation of the E3 ubiquitin ligase COP1	29	72.7×	1e-48
Ubiquitin-dependent degradation of Cyclin D	29	72.7×	1e-48
Cross-presentation of soluble exogenous antigens (endosomes)	30	71.8×	7e-50
Vif-mediated degradation of APOBEC3G	29	69.4×	7e-48

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	36	13.7×	5e-28

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1636 predictions. Top by Δscore:

Variant	Effect	Δscore
11:237142:G:GT	donor_gain	1.0000
11:237142:GAA:G	donor_gain	1.0000
11:237145:G:GG	donor_gain	1.0000
11:244664:T:A	acceptor_gain	1.0000
11:244670:CTTAG:C	acceptor_loss	1.0000
11:244672:TAG:T	acceptor_loss	1.0000
11:244673:A:AG	acceptor_gain	1.0000
11:244673:A:G	acceptor_loss	1.0000
11:244674:G:A	acceptor_loss	1.0000
11:244674:G:GG	acceptor_gain	1.0000
11:244674:GGT:G	acceptor_gain	1.0000
11:244757:CAAAG:C	donor_loss	1.0000
11:244758:AAAG:A	donor_loss	1.0000
11:244761:GGT:G	donor_loss	1.0000
11:244762:G:GA	donor_loss	1.0000
11:244763:T:A	donor_loss	1.0000
11:247272:TATAG:T	acceptor_loss	1.0000
11:247275:A:AC	acceptor_loss	1.0000
11:247275:A:AG	acceptor_gain	1.0000
11:247276:G:GG	acceptor_gain	1.0000
11:247444:ACCAG:A	donor_loss	1.0000
11:247445:CCAG:C	donor_loss	1.0000
11:247446:CAGG:C	donor_loss	1.0000
11:247447:AGGTA:A	donor_loss	1.0000
11:247448:GG:G	donor_loss	1.0000
11:247450:T:A	donor_loss	1.0000
11:248926:TCACA:T	acceptor_loss	1.0000
11:248927:CACA:C	acceptor_loss	1.0000
11:248928:ACAG:A	acceptor_loss	1.0000
11:248929:CAGCT:C	acceptor_loss	1.0000

AlphaMissense

2493 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:239012:T:C	L37P	1.000
11:247410:T:C	L177P	1.000
11:248848:G:A	G214E	1.000
11:248977:T:A	W232R	1.000
11:248977:T:C	W232R	1.000
11:251865:G:C	G322R	1.000
11:239002:T:A	W34R	0.999
11:239002:T:C	W34R	0.999
11:239004:G:C	W34C	0.999
11:239004:G:T	W34C	0.999
11:239005:C:G	H35D	0.999
11:244178:T:C	L76P	0.999
11:244703:T:C	L113P	0.999
11:247332:T:A	V151D	0.999
11:247353:T:C	L158P	0.999
11:247406:G:C	A176P	0.999
11:247413:G:C	R178P	0.999
11:247421:G:C	G181R	0.999
11:248797:C:A	A197D	0.999
11:248806:T:C	L200P	0.999
11:248808:G:A	G201R	0.999
11:248808:G:C	G201R	0.999
11:248808:G:T	G201W	0.999
11:248809:G:A	G201E	0.999
11:248815:C:A	A203E	0.999
11:248818:G:A	G204E	0.999
11:248821:T:C	L205P	0.999
11:248843:C:A	N212K	0.999
11:248843:C:G	N212K	0.999
11:248847:G:A	G214R	0.999

dbSNP variants (sampled 300 via entrez): RS1000284075 (11:247263 CT>C), RS1000510473 (11:252308 T>C), RS1000529982 (11:247871 T>A), RS1000756257 (11:236526 G>A), RS1001129383 (11:252777 A>T), RS1001190808 (11:240393 G>A), RS1001202621 (11:238697 G>A,T), RS1001350533 (11:247611 C>G,T), RS1001433169 (11:252918 C>T), RS1001898883 (11:243670 C>G,T), RS1001972738 (11:248424 G>A), RS1002041617 (11:244979 T>C), RS1002067954 (11:249217 G>A), RS1002083963 (11:237982 C>T), RS1002564499 (11:241224 C>T)

Disease associations

OMIM: gene MIM:603481 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001335_19	Mean platelet volume	2.000000e-15
GCST001337_31	Platelet count	7.000000e-25
GCST002186_8	Platelet count	5.000000e-12
GCST005348_77	Total body bone mineral density	8.000000e-16
GCST009066_21	Mosaic loss of chromosome Y (Y chromosome dosage)	1.000000e-08
GCST010231_5	Mean platelet volume	1.000000e-08
GCST90002399_57	Neutrophil percentage of white cells	3.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3831215 (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

62 potent at pChembl≥5 of 65 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
6.30	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
5.70	IC50	2000	nM	BORTEZOMIB
5.66	IC50	2170	nM	CHEMBL3237873

PubChem BioAssay actives

60 with measured affinity, of 135 total; 32 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
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

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	3
sodium arsenite	affects methylation, increases expression	2
Arsenic	decreases expression, increases abundance	2
Valproic Acid	decreases methylation, increases expression	2
beta-Naphthoflavone	increases expression	2
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
cobaltous chloride	increases expression	1
cupric chloride	increases expression	1
arsenic trichloride	increases abundance, decreases expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol B	increases expression	1
Bortezomib	increases expression	1
Arsenic Trioxide	affects cotreatment, increases expression	1
Arbutin	decreases expression	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Furaldehyde	affects localization, increases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Ketoconazole	decreases expression	1
Lead	affects splicing	1
Naled	affects expression	1
Smoke	decreases expression	1
Sodium Chloride	affects cotreatment, affects localization, increases expression	1
Thiram	increases expression	1
Tretinoin	affects cotreatment, increases expression	1

ChEMBL screening assays

27 unique, capped per target: 27 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3222879	Binding	Inhibition of human 20S proteasome using Suc-LLVY-AMC as substrate preincubated for 30 mins followed by substrate addition measured after 90 mins by fluorescence assay	Oxathiazole-2-one derivative of bortezomib: Synthesis, stability and proteasome inhibition activity — Medchemcomm

Clinical trials (associated diseases)

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