PSMD6

Summary

PSMD6 (proteasome 26S subunit, non-ATPase 6, HGNC:9564) is a protein-coding gene on chromosome 3p14.1, encoding 26S proteasome non-ATPase regulatory subunit 6 (Q15008). Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

This gene encodes a member of the protease subunit S10 family. The encoded protein is a subunit of the 26S proteasome which colocalizes with DNA damage foci and is involved in the ATP-dependent degradation of ubiquinated proteins. Alternative splicing results in multiple transcript variants

Source: NCBI Gene 9861 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 60 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_014814

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9564
Approved symbol	PSMD6
Name	proteasome 26S subunit, non-ATPase 6
Location	3p14.1
Locus type	gene with protein product
Status	Approved
Aliases	S10, p44S10, KIAA0107, Rpn7
Ensembl gene	ENSG00000163636
Ensembl biotype	protein_coding
OMIM	617857
Entrez	9861

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 5 retained_intron

ENST00000295901, ENST00000394431, ENST00000463139, ENST00000467853, ENST00000475036, ENST00000476464, ENST00000478185, ENST00000480205, ENST00000482510, ENST00000492933, ENST00000497315, ENST00000497323, ENST00000916270, ENST00000916271, ENST00000916272, ENST00000957764, ENST00000957765

RefSeq mRNA: 4 — MANE Select: NM_014814 NM_001271779, NM_001271780, NM_001271781, NM_014814

CCDS: CCDS2901, CCDS63677, CCDS63678, CCDS63679

Canonical transcript exons

ENST00000295901 — 8 exons

Exon	Start	End
ENSE00001878538	64010551	64010764
ENSE00001958661	64023275	64023494
ENSE00003484890	64018599	64018707
ENSE00003510660	64022318	64022523
ENSE00003581959	64013439	64013607
ENSE00003651428	64018818	64019037
ENSE00003654044	64019296	64019441
ENSE00003681198	64010878	64010955

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 133.5082 / max 1600.9458, expressed in 1826 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42843	132.5672	1826
42841	0.4288	144
42842	0.2853	126
42839	0.2129	96
42844	0.0141	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	99.45	gold quality
body of pancreas	UBERON:0001150	99.22	gold quality
sperm	CL:0000019	98.67	gold quality
right testis	UBERON:0004534	98.48	gold quality
left testis	UBERON:0004533	98.47	gold quality
male germ cell	CL:0000015	98.19	gold quality
pancreas	UBERON:0001264	98.15	gold quality
tibialis anterior	UBERON:0001385	98.13	gold quality
testis	UBERON:0000473	97.94	gold quality
gastrocnemius	UBERON:0001388	97.78	gold quality
muscle of leg	UBERON:0001383	97.64	gold quality
adrenal tissue	UBERON:0018303	97.58	gold quality
islet of Langerhans	UBERON:0000006	97.49	gold quality
adult organism	UBERON:0007023	97.45	gold quality
deltoid	UBERON:0001476	97.39	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.35	gold quality
muscle organ	UBERON:0001630	97.29	gold quality
calcaneal tendon	UBERON:0003701	97.23	gold quality
gluteal muscle	UBERON:0002000	97.21	gold quality
upper leg skin	UBERON:0004262	97.08	gold quality
right adrenal gland	UBERON:0001233	97.06	gold quality
triceps brachii	UBERON:0001509	97.02	gold quality
right adrenal gland cortex	UBERON:0035827	97.00	gold quality
left adrenal gland	UBERON:0001234	96.92	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.84	gold quality
heart right ventricle	UBERON:0002080	96.82	gold quality
oral cavity	UBERON:0000167	96.80	gold quality
trabecular bone tissue	UBERON:0002483	96.76	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.76	gold quality
left adrenal gland cortex	UBERON:0035825	96.75	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	27.59
E-MTAB-6524	no	247.90
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BRCA2

miRNA regulators (miRDB)

9 targeting PSMD6, 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-196A-1-3P	99.99	72.15	2772
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-4289	98.26	66.90	810

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 4)

• interaction of Rpn7 with DNA damage response foci in situ mediates the protection of DNA damage foci from premature resolution. (PMID:22473755)
• Suggest AK124742 and PSMD6 as a new lncRNA-messenger RNA gene pair in human cumulus cells that may be considered as potential biomarkers to aid embryo selection. (PMID:25670720)
• we observed that the PSMD6 variant rs831571 might be associated with the therapeutic efficacy of rosiglitazone and repaglinide in Chinese patients with type 2 diabetes. (PMID:26024304)
• Prognostic Value and Molecular Mechanisms of Proteasome 26S Subunit, Non-ATPase Family Genes for Pancreatic Ductal Adenocarcinoma Patients after Pancreaticoduodenectomy. (PMID:33525943)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psmd6	ENSDARG00000070674
mus_musculus	Psmd6	ENSMUSG00000021737
rattus_norvegicus	Psmd6	ENSRNOG00000006751
drosophila_melanogaster	Rpn7	FBGN0028688
caenorhabditis_elegans		WBGENE00004463

Paralogs (1): GPS1 (ENSG00000169727)

Protein

Protein identifiers

26S proteasome non-ATPase regulatory subunit 6 — Q15008 (reviewed: Q15008)

Alternative names: 26S proteasome regulatory subunit RPN7, 26S proteasome regulatory subunit S10, Breast cancer-associated protein SGA-113M, Phosphonoformate immuno-associated protein 4, Proteasome regulatory particle subunit p44S10, p42A

All UniProt accessions (4): C9J0E9, C9J7B7, Q15008, H7C531

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 PSMD6, a base containing 6 ATPases and few additional components.

Similarity. Belongs to the proteasome subunit S10 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q15008-1	1	yes
Q15008-2	2
Q15008-3	3
Q15008-4	4

RefSeq proteins (4): NP_001258708, NP_001258709, NP_001258710, NP_055629* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019585	Rpn7/CSN1	Family
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR045135	Rpn7_N	Domain
IPR049549	RPN7_PSMD6_C	Domain

Pfam: PF01399, PF10602, PF21154

UniProt features (32 total): helix 19, strand 4, turn 3, splice variant 3, initiator methionine 1, chain 1, domain 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
9BV3	ELECTRON MICROSCOPY	2.9
9NKF	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-Q15008-F1	82.49	0.22

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: 297 (showing top): REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_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, PAL_PRMT5_TARGETS_UP, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOCC_SECRETORY_GRANULE, MODULE_151, 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 (9): proteasome complex (GO:0000502), extracellular region (GO:0005576), nucleoplasm (GO:0005654), cytosol (GO:0005829), proteasome regulatory particle (GO:0005838), 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	3
protein-containing complex	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 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

2504 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSMD6	PSMD3	O43242	997
PSMD6	PSMD12	O00232	997
PSMD6	PSMD8	P48556	996
PSMD6	PSMD11	O00231	996
PSMD6	PSMD13	Q9UNM6	996
PSMD6	PSMD7	P51665	995
PSMD6	PSMD14	O00487	991
PSMD6	SEM1	Q6ZVN7	940
PSMD6	PSMD4	P55036	914
PSMD6	ADRM1	Q16186	891
PSMD6	PSMD1	Q99460	862
PSMD6	PSMC4	P43686	861
PSMD6	PSMC1	P49014	813
PSMD6	PSMD2	Q13200	811
PSMD6	PSMC6	P49719	797

IntAct

291 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
MED23	MED19	psi-mi:“MI:2364”(proximity)	0.770
PSMD7	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMD11	PSMD12	psi-mi:“MI:0915”(physical association)	0.730
PSMB2	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
PSMB3	PSMD11	psi-mi:“MI:0914”(association)	0.640
PSMD5	PSMD12	psi-mi:“MI:0914”(association)	0.640
UBQLN1	PSMD6	psi-mi:“MI:0915”(physical association)	0.560
PSMD6	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
PSMD6	BET2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (625): PSMD6 (Affinity Capture-MS), UBQLN1 (Two-hybrid), PSMD6 (Affinity Capture-MS), PSMD6 (Affinity Capture-MS), PSMD6 (Affinity Capture-MS), PSMD6 (Affinity Capture-MS), PSMD6 (Affinity Capture-MS), PSMD6 (Affinity Capture-MS), PSMD6 (Affinity Capture-MS), PSMD6 (Affinity Capture-MS), PSMD6 (Affinity Capture-MS), PSMD6 (Affinity Capture-MS), PSMD6 (Affinity Capture-MS), PSMD6 (Affinity Capture-MS), PSMD6 (Affinity Capture-MS)

ESM2 similar proteins: A1CKN7, A1D6T6, A2R7S7, A4R796, A5AAA4, A6S1A3, A6SM77, A7E5J5, A7F3L0, A8NY27, B0WAM5, B0XXL3, B3M4D9, B3NDH5, B4H5N1, B4HK67, B4IXG1, B4KT65, B4KY00, B4LG58, B4MY75, B4MYA1, B4N3B0, B4PK98, B4QMY7, O61820, O77410, P0CN50, P0CN51, Q0CNR3, Q0U0X1, Q15008, Q1E170, Q1HQY6, Q29EX2, Q2F5R8, Q2HBQ2, Q2UKS9, Q3T0B2, Q4WY08

Diamond homologs: Q06103, Q10335, Q15008, Q20585, Q3T0B2, Q55C75, Q8W425, Q93Y35, Q99JI4, Q9V3G7, Q6K1U0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PSMD6	“form complex”	“26S Proteasome”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 157 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
Antigen processing: Ub, ATP-independent proteasomal degradation	17	77.0×	2e-30
Regulation of activated PAK-2p34 by proteasome mediated degradation	32	70.7×	2e-54
Proteasome assembly	43	69.6×	2e-73
Cross-presentation of soluble exogenous antigens (endosomes)	34	68.5×	7e-57
Vpu mediated degradation of CD4	32	67.5×	2e-53
Autodegradation of the E3 ubiquitin ligase COP1	32	67.5×	2e-53
Ubiquitin-dependent degradation of Cyclin D	32	67.5×	2e-53
AUF1 (hnRNP D0) binds and destabilizes mRNA	34	67.0×	2e-56

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of proteasomal protein catabolic process	5	34.9×	5e-05
regulation of proteasomal protein catabolic process	6	32.4×	6e-06
proteasome-mediated ubiquitin-dependent protein catabolic process	38	14.0×	5e-30
ubiquitin-dependent protein catabolic process	11	5.8×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1263 predictions. Top by Δscore:

Variant	Effect	Δscore
3:64013437:A:AC	donor_gain	1.0000
3:64013438:C:CT	donor_gain	1.0000
3:64013438:CTG:C	donor_gain	1.0000
3:64013438:CTGAT:C	donor_gain	1.0000
3:64022312:ACT:A	donor_loss	1.0000
3:64022313:CTCA:C	donor_gain	1.0000
3:64022314:TCA:T	donor_loss	1.0000
3:64022315:CA:C	donor_loss	1.0000
3:64022316:A:AC	donor_gain	1.0000
3:64022316:ACT:A	donor_loss	1.0000
3:64022317:C:CA	donor_gain	1.0000
3:64022317:CT:C	donor_gain	1.0000
3:64022317:CTT:C	donor_gain	1.0000
3:64022317:CTTT:C	donor_gain	1.0000
3:64022328:AT:A	donor_gain	1.0000
3:64022329:T:C	donor_gain	1.0000
3:64022519:CATGT:C	acceptor_gain	1.0000
3:64022520:ATGT:A	acceptor_gain	1.0000
3:64022521:TGT:T	acceptor_gain	1.0000
3:64022522:GT:G	acceptor_gain	1.0000
3:64022522:GTCT:G	acceptor_loss	1.0000
3:64022523:TC:T	acceptor_loss	1.0000
3:64022524:C:CC	acceptor_gain	1.0000
3:64022524:CTAA:C	acceptor_loss	1.0000
3:64022528:CA:C	acceptor_gain	1.0000
3:64022529:A:AC	acceptor_gain	1.0000
3:64022529:A:C	acceptor_gain	1.0000
3:64023273:A:AC	donor_gain	1.0000
3:64023274:C:CC	donor_gain	1.0000
3:64010765:C:CC	acceptor_gain	0.9900

AlphaMissense

2561 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:64010721:C:G	G373R	1.000
3:64010721:C:T	G373R	1.000
3:64018911:A:C	F208L	1.000
3:64018911:A:T	F208L	1.000
3:64018912:A:G	F208S	1.000
3:64018913:A:G	F208L	1.000
3:64018981:C:T	G185D	1.000
3:64018982:C:G	G185R	1.000
3:64018996:A:G	L180P	1.000
3:64018999:C:G	R179P	1.000
3:64019000:G:T	R179S	1.000
3:64019001:G:C	N178K	1.000
3:64019001:G:T	N178K	1.000
3:64019003:T:C	N178D	1.000
3:64019004:T:A	R177S	1.000
3:64019004:T:G	R177S	1.000
3:64019005:C:G	R177T	1.000
3:64019007:C:A	R176S	1.000
3:64019007:C:G	R176S	1.000
3:64019008:C:A	R176M	1.000
3:64019008:C:G	R176T	1.000
3:64019012:C:G	D175H	1.000
3:64019013:C:A	W174C	1.000
3:64019013:C:G	W174C	1.000
3:64019014:C:A	W174L	1.000
3:64019014:C:G	W174S	1.000
3:64019015:A:G	W174R	1.000
3:64019015:A:T	W174R	1.000
3:64019016:G:C	D173E	1.000
3:64019016:G:T	D173E	1.000

dbSNP variants (sampled 300 via entrez): RS1000193419 (3:64011646 AG>A,AGG), RS1000526085 (3:64012644 C>CAACT), RS1000593505 (3:64011844 AAAG>A), RS1000616884 (3:64016397 T>C), RS1000726944 (3:64011340 A>G), RS1000732511 (3:64017336 C>A), RS1000793693 (3:64022717 G>A,C), RS1000863267 (3:64011703 A>G), RS1001039705 (3:64017591 G>A,T), RS1001071760 (3:64016604 G>A,C,T), RS1001792781 (3:64016673 A>T), RS1001849503 (3:64023467 G>A,C,T), RS1001941063 (3:64011752 C>A,T), RS1002076985 (3:64011948 T>C,G), RS1002195696 (3:64013827 A>C)

Disease associations

OMIM: gene MIM:617857 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001351_7	Type 2 diabetes	8.000000e-11
GCST002120_1	Metabolite levels (Dihydroxy docosatrienoic acid)	8.000000e-06
GCST002539_49	Schizophrenia	1.000000e-08
GCST002875_5	Diisocyanate-induced asthma	1.000000e-06
GCST003400_32	Type 2 diabetes	1.000000e-07
GCST006803_106	Schizophrenia	1.000000e-10
GCST007847_3	Type 2 diabetes	3.000000e-15
GCST008059_35	Estimated glomerular filtration rate	2.000000e-14
GCST009379_252	Type 2 diabetes	2.000000e-13
GCST009379_253	Type 2 diabetes	7.000000e-06
GCST010118_22	Type 2 diabetes	9.000000e-32
GCST010698_66	Subcortical volume (min-P)	1.000000e-16
GCST010699_21	Brain morphology (min-P)	9.000000e-10
GCST010701_75	Cortical surface area (MOSTest)	4.000000e-09
GCST010702_127	Subcortical volume (MOSTest)	4.000000e-09
GCST010703_71	Brain morphology (MOSTest)	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005275	dihydroxy docosatrienoic acid measurement
EFO:0006995	response to diisocyanate
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2364701 (PROTEIN COMPLEX), CHEMBL3831213 (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 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
7.32	Kd	48.35	nM	CHEMBL5653589
7.32	ED50	48.35	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

61 with measured affinity, of 135 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
(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	2149129: Binding affinity to human PSMD6 incubated for 45 mins by Kinobead based pull down assay	kd	0.0483	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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	2
cobaltous chloride	increases expression	2
Valproic Acid	affects expression, increases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, affects localization	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
arsenite	affects binding, increases reaction	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
afimoxifene	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	decreases expression	1
Vorinostat	decreases expression	1
Arsenic	increases abundance, increases expression	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1
Dinitrochlorobenzene	affects binding	1
Estradiol	increases expression	1
Furaldehyde	affects cotreatment, affects localization, increases expression	1
Ivermectin	decreases expression	1
Mustard Gas	increases expression	1
Nickel	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Selenium	increases expression	1
Sodium Chloride	affects cotreatment, affects localization, 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.