PSME4

Summary

PSME4 (proteasome activator subunit 4, HGNC:20635) is a protein-coding gene on chromosome 2p16.2, encoding Proteasome activator complex subunit 4 (Q14997). Associated component of the proteasome that specifically recognizes acetylated histones and promotes ATP- and ubiquitin-independent degradation of core histones during spermatogenesis and DNA damage response.

Predicted to enable lysine-acetylated histone binding activity; peptidase activator activity; and proteasome binding activity. Predicted to be involved in DNA repair; proteasomal ubiquitin-independent protein catabolic process; and sperm DNA condensation. Located in nucleoplasm.

Source: NCBI Gene 23198 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 246 total
• Druggable target: yes
• MANE Select transcript: NM_014614

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20635
Approved symbol	PSME4
Name	proteasome activator subunit 4
Location	2p16.2
Locus type	gene with protein product
Status	Approved
Aliases	PA200, KIAA0077
Ensembl gene	ENSG00000068878
Ensembl biotype	protein_coding
OMIM	607705
Entrez	23198

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 6 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000389993, ENST00000404125, ENST00000461810, ENST00000466539, ENST00000475694, ENST00000476586, ENST00000478731, ENST00000481518, ENST00000488687, ENST00000878865, ENST00000933258, ENST00000933259, ENST00000933260, ENST00000967911

RefSeq mRNA: 1 — MANE Select: NM_014614 NM_014614

CCDS: CCDS33197

Canonical transcript exons

ENST00000404125 — 47 exons

Exon	Start	End
ENSE00000752841	53925539	53925689
ENSE00000752842	53925959	53926023
ENSE00000752843	53927394	53927483
ENSE00000752844	53928117	53928303
ENSE00000752845	53931835	53932100
ENSE00000752847	53932668	53932760
ENSE00000752848	53934605	53934727
ENSE00000752849	53936087	53936161
ENSE00001558467	53864069	53865573
ENSE00003459173	53920193	53920350
ENSE00003466396	53869376	53869538
ENSE00003468560	53899881	53900017
ENSE00003472184	53906598	53906693
ENSE00003484033	53948421	53948537
ENSE00003497963	53895583	53895736
ENSE00003502439	53908784	53908840
ENSE00003502725	53922517	53922584
ENSE00003507940	53896804	53896885
ENSE00003511455	53892808	53892960
ENSE00003511543	53890104	53890208
ENSE00003547423	53919151	53919246
ENSE00003552144	53898301	53898354
ENSE00003553295	53906806	53906868
ENSE00003556411	53866085	53866223
ENSE00003564324	53908320	53908418
ENSE00003568315	53923321	53923419
ENSE00003579925	53910075	53910130
ENSE00003582663	53936764	53936827
ENSE00003588166	53888721	53888812
ENSE00003599624	53920889	53921104
ENSE00003607832	53901350	53901559
ENSE00003611045	53887858	53887989
ENSE00003620651	53939956	53940000
ENSE00003621579	53904025	53904156
ENSE00003630714	53897870	53897999
ENSE00003642056	53866747	53866880
ENSE00003642311	53887259	53887467
ENSE00003642757	53908510	53908565
ENSE00003669882	53937391	53937540
ENSE00003672444	53949143	53949283
ENSE00003673288	53885690	53885775
ENSE00003678780	53923049	53923118
ENSE00003678819	53893674	53893799
ENSE00003683180	53895007	53895076
ENSE00003687928	53874339	53874494
ENSE00003692816	53875627	53875755
ENSE00003850625	53970543	53970993

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.2199 / max 105.4209, expressed in 1785 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
28370	4.7216	1622
28369	3.6533	1520
28368	1.3675	996
28367	0.3853	146
28364	0.0468	16
28372	0.0315	7
28363	0.0083	2
28371	0.0056	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.36	gold quality
male germ cell	CL:0000015	97.38	gold quality
gluteal muscle	UBERON:0002000	97.19	gold quality
gastrocnemius	UBERON:0001388	97.07	gold quality
left testis	UBERON:0004533	96.85	gold quality
biceps brachii	UBERON:0001507	96.66	gold quality
right testis	UBERON:0004534	96.63	gold quality
muscle of leg	UBERON:0001383	96.44	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.18	gold quality
muscle organ	UBERON:0001630	96.08	gold quality
deltoid	UBERON:0001476	96.03	gold quality
testis	UBERON:0000473	95.66	gold quality
triceps brachii	UBERON:0001509	95.55	gold quality
vastus lateralis	UBERON:0001379	95.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.16	gold quality
tibialis anterior	UBERON:0001385	95.13	gold quality
skeletal muscle tissue	UBERON:0001134	95.09	gold quality
quadriceps femoris	UBERON:0001377	94.99	gold quality
minor salivary gland	UBERON:0001830	94.88	gold quality
body of tongue	UBERON:0011876	94.03	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.02	gold quality
heart left ventricle	UBERON:0002084	93.97	gold quality
muscle tissue	UBERON:0002385	93.92	gold quality
cardiac ventricle	UBERON:0002082	93.91	gold quality
right atrium auricular region	UBERON:0006631	93.85	gold quality
mouth mucosa	UBERON:0003729	93.65	gold quality
choroid plexus epithelium	UBERON:0003911	93.60	gold quality
cartilage tissue	UBERON:0002418	93.49	gold quality
cardiac atrium	UBERON:0002081	93.31	gold quality
stromal cell of endometrium	CL:0002255	93.29	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

135 targeting PSME4, 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-5692A	100.00	74.40	6850
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4425	100.00	67.59	1049
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-1184	99.99	68.19	1458
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-4789-5P	99.98	70.76	2721
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972

Literature-anchored findings (GeneRIF, showing 8)

• identified a novel 200 kDa nuclear protein that activates the proteasome; findings implicate PA200 in DNA repair, possibly by recruiting proteasomes to double strand breaks (PMID:12093752)
• this degradation of acetylated histones is independent of ubiquitylation but requires the PA200-proteasome activator, a complex that specifically targets acetylated histones for degradation (PMID:30104204)
• Its 3.0 A resolution cryo-EM structure reveals the PA200 unique architecture; the details of its intricate interactions with the proteasome, resulting in unparalleled proteasome alpha ring rearrangements; and the molecular basis for PA200 allosteric modulation of the proteasome active sites. (PMID:31473102)
• Proteasome activator PA200 regulates myofibroblast differentiation. (PMID:31645612)
• The proteasome activator PA200 regulates expression of genes involved in cell survival upon selective mitochondrial inhibition in neuroblastoma cells. (PMID:32368861)
• The Proteasome Activators Blm10/PA200 Enhance the Proteasomal Degradation of N-Terminal Huntingtin. (PMID:33233776)
• Cells Lacking PA200 Adapt to Mitochondrial Dysfunction by Enhancing Glycolysis via Distinct Opa1 Processing. (PMID:33562813)
• The proteasome regulator PSME4 modulates proteasome activity and antigen diversity to abrogate antitumor immunity in NSCLC. (PMID:37217651)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psme4b	ENSDARG00000018742
danio_rerio	psme4a	ENSDARG00000087911
mus_musculus	Psme4	ENSMUSG00000040850
rattus_norvegicus	Psme4	ENSRNOG00000060340
caenorhabditis_elegans		WBGENE00007588

Protein

Protein identifiers

Proteasome activator complex subunit 4 — Q14997 (reviewed: Q14997)

Alternative names: Proteasome activator PA200, Protein BLM10 homolog

All UniProt accessions (2): Q14997, F8WBH5

UniProt curated annotations — full annotation on UniProt →

Function. Associated component of the proteasome that specifically recognizes acetylated histones and promotes ATP- and ubiquitin-independent degradation of core histones during spermatogenesis and DNA damage response. Recognizes and binds acetylated histones via its bromodomain-like (BRDL) region and activates the proteasome by opening the gated channel for substrate entry. Binds to the core proteasome via its C-terminus, which occupies the same binding sites as the proteasomal ATPases, opening the closed structure of the proteasome via an active gating mechanism. Component of the spermatoproteasome, a form of the proteasome specifically found in testis: binds to acetylated histones and promotes degradation of histones, thereby participating actively to the exchange of histones during spermatogenesis. Also involved in DNA damage response in somatic cells, by promoting degradation of histones following DNA double-strand breaks.

Subunit / interactions. Homodimer. Interacts with the 20S and 26S proteasomes. Component of the spermatoproteasome, a form of the proteasome specifically found in testis.

Subcellular location. Cytoplasm. Cytosol. Nucleus. Nucleus speckle.

Domain organisation. The bromodomain-like (BRDL) region specifically recognizes and binds acetylated histones.

Similarity. Belongs to the BLM10 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q14997-1	1	yes
Q14997-2	2
Q14997-3	3
Q14997-4	4

RefSeq proteins (1): NP_055429* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR021843	PSME4_C	Domain
IPR032430	Blm10_mid	Domain
IPR035309	PSME4	Family
IPR055455	HEAT_PSME4	Domain

Pfam: PF11919, PF16507, PF23096

UniProt features (196 total): helix 101, strand 39, turn 30, repeat 6, splice variant 4, sequence conflict 4, modified residue 3, sequence variant 3, compositionally biased region 2, region of interest 2, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6KWY	ELECTRON MICROSCOPY	2.72
6REY	ELECTRON MICROSCOPY	3
8CVS	ELECTRON MICROSCOPY	3.1
7NAQ	ELECTRON MICROSCOPY	3.2
6KWX	ELECTRON MICROSCOPY	3.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14997-F1	90.29	0.72

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 (3): 1121, 1614, 1746

Mutagenesis-validated functional residues (1):

Position	Phenotype
1716–1717	abolishes binding to acetylated histones.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9907900	Proteasome assembly

MSigDB gene sets: 248 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, KEGG_PROTEASOME, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_511, GOBP_MALE_GAMETE_GENERATION, NAGASHIMA_NRG1_SIGNALING_UP, AATGGAG_MIR136, MARTINEZ_RB1_TARGETS_UP, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, AP1_Q4_01, CATTTCA_MIR203, ONKEN_UVEAL_MELANOMA_UP, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_NUCLEUS_ORGANIZATION

GO Biological Process (6): DNA repair (GO:0006281), DNA damage response (GO:0006974), proteasomal ubiquitin-independent protein catabolic process (GO:0010499), sperm DNA condensation (GO:0035092), spermatogenesis (GO:0007283), cell differentiation (GO:0030154)

GO Molecular Function (4): peptidase activator activity (GO:0016504), proteasome binding (GO:0070628), protein binding (GO:0005515), obsolete lysine-acetylated histone binding (GO:0070577)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear speck (GO:0016607), spermatoproteasome complex (GO:1990111), proteasome complex (GO:0000502), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
proteasomal protein catabolic process	1
chromatin organization	1
spermatid nucleus differentiation	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
enzyme activator activity	1
peptidase activity	1
peptidase regulator activity	1
protein-containing complex binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
proteasome complex	1
intracellular protein-containing complex	1
endopeptidase complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1470 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSME4	PSME3	P61289	870
PSME4	PSMF1	Q92530	819
PSME4	USP14	P54578	752
PSME4	ECPAS	Q5VYK3	736
PSME4	ADRM1	Q16186	736
PSME4	PSMD4	P55036	728
PSME4	POMP	Q9Y244	722
PSME4	PSMD11	O00231	718
PSME4	PSME1	Q06323	716
PSME4	PSMD7	P51665	710
PSME4	PSMD12	O00232	710
PSME4	PRKDC	P78527	700
PSME4	PSMD14	O00487	692
PSME4	PSMD13	Q9UNM6	689
PSME4	PSMA8	Q8TAA3	688

IntAct

126 interactions, top by confidence:

A	B	Type	Score
ATG14	BECN1	psi-mi:“MI:0914”(association)	0.980
PSMA1	PSMA7	psi-mi:“MI:0915”(physical association)	0.950
PSMA1	PSMA7	psi-mi:“MI:0914”(association)	0.950
PSMA2	PSMA7	psi-mi:“MI:0914”(association)	0.850
PSMA5	PSMA7	psi-mi:“MI:0914”(association)	0.800
PSMB7	PSMA7	psi-mi:“MI:0914”(association)	0.790
PSMB2	PSMA7	psi-mi:“MI:0914”(association)	0.790
PSMB3	PSMA7	psi-mi:“MI:0914”(association)	0.770
PSMB2	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMB4	PSMA7	psi-mi:“MI:0914”(association)	0.730
POMP	PSMA7	psi-mi:“MI:0915”(physical association)	0.720
PSMB3	PSMD11	psi-mi:“MI:0914”(association)	0.640
PSMB7	PSMD11	psi-mi:“MI:0914”(association)	0.640
PSMB1	PSMA7	psi-mi:“MI:0914”(association)	0.640
CALCOCO2	PSME4	psi-mi:“MI:0915”(physical association)	0.560
NUTM1	PSME4	psi-mi:“MI:0915”(physical association)	0.560
PSME4	CALCOCO2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (187): PSME4 (Two-hybrid), NUTM1 (Two-hybrid), PSME4 (Affinity Capture-MS), PSME4 (Affinity Capture-MS), PSME4 (Affinity Capture-MS), PSME4 (Affinity Capture-MS), PSME4 (Affinity Capture-MS), DDX3X (Co-fractionation), PSMA1 (Co-fractionation), PSMA3 (Co-fractionation), PSMA5 (Co-fractionation), PSMB6 (Co-fractionation), PSMD3 (Co-fractionation), PSME4 (Affinity Capture-MS), PSME4 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4ITC5, A1L1F4, A4L9P7, E9Q8I9, F1MKX4, F1QFR9, F1R2X6, F8VPU6, O94915, P21359, P42345, P42346, P51593, P97526, Q04690, Q14997, Q29RF7, Q2HJG5, Q498H0, Q4KLU7, Q4QXM3, Q4VA53, Q5F3U9, Q5F3V3, Q5R6J0, Q5SSW2, Q5TBA9, Q5U241, Q5VYK3, Q6A026, Q6DDM4, Q6GP04, Q6NRP2, Q6P4S8, Q6PDI5, Q6TRW4, Q7PX35, Q7TMY8, Q7Z3U7, Q7Z6Z7

Diamond homologs: F1MKX4, F1QFR9, F1R2X6, Q14997, Q5SSW2, Q6NRP2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 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	16	125.2×	6e-32
Regulation of activated PAK-2p34 by proteasome mediated degradation	29	110.7×	4e-55
Vpu mediated degradation of CD4	29	105.5×	2e-54
Autodegradation of the E3 ubiquitin ligase COP1	29	105.5×	2e-54
Ubiquitin-dependent degradation of Cyclin D	29	105.5×	2e-54
Cross-presentation of soluble exogenous antigens (endosomes)	30	104.3×	1e-55
Regulation of ornithine decarboxylase (ODC)	28	104.3×	2e-52
AUF1 (hnRNP D0) binds and destabilizes mRNA	30	102.0×	3e-55

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	33	20.0×	6e-32

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	188
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

7042 predictions. Top by Δscore:

Variant	Effect	Δscore
2:53866221:CAT:C	acceptor_gain	1.0000
2:53866741:CTGTA:C	donor_loss	1.0000
2:53866743:GTA:G	donor_loss	1.0000
2:53866744:TA:T	donor_loss	1.0000
2:53866745:A:AG	donor_loss	1.0000
2:53866879:CT:C	acceptor_gain	1.0000
2:53866881:C:CC	acceptor_gain	1.0000
2:53869537:ACCT:A	acceptor_loss	1.0000
2:53869538:CCTG:C	acceptor_loss	1.0000
2:53869539:CTGTA:C	acceptor_loss	1.0000
2:53869540:T:G	acceptor_loss	1.0000
2:53875625:A:AC	donor_gain	1.0000
2:53875626:C:CC	donor_gain	1.0000
2:53875701:A:C	donor_gain	1.0000
2:53885684:CCTTA:C	donor_loss	1.0000
2:53885685:CTTA:C	donor_loss	1.0000
2:53885686:TTA:T	donor_loss	1.0000
2:53885687:TACC:T	donor_loss	1.0000
2:53885688:A:AG	donor_loss	1.0000
2:53885689:C:A	donor_loss	1.0000
2:53885771:CAATA:C	acceptor_gain	1.0000
2:53885772:AATA:A	acceptor_gain	1.0000
2:53885774:TA:T	acceptor_gain	1.0000
2:53885774:TACTA:T	acceptor_loss	1.0000
2:53885775:AC:A	acceptor_loss	1.0000
2:53885776:C:CC	acceptor_gain	1.0000
2:53885777:T:C	acceptor_loss	1.0000
2:53885781:T:C	acceptor_gain	1.0000
2:53885781:T:TC	acceptor_gain	1.0000
2:53887255:TCA:T	donor_loss	1.0000

AlphaMissense

12118 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:53866150:A:G	F1824S	1.000
2:53866184:G:C	H1813D	1.000
2:53866195:A:G	F1809S	1.000
2:53874476:A:G	W1655R	1.000
2:53874476:A:T	W1655R	1.000
2:53885767:A:G	W1580R	1.000
2:53885767:A:T	W1580R	1.000
2:53887944:T:A	R1478S	1.000
2:53887944:T:G	R1478S	1.000
2:53887949:A:G	W1477R	1.000
2:53887949:A:T	W1477R	1.000
2:53890130:A:G	W1424R	1.000
2:53890130:A:T	W1424R	1.000
2:53906689:C:G	R951P	1.000
2:53920308:A:G	W769R	1.000
2:53920308:A:T	W769R	1.000
2:53920347:A:G	W756R	1.000
2:53920347:A:T	W756R	1.000
2:53922533:A:G	L677P	1.000
2:53925591:A:G	L586P	1.000
2:53928123:T:A	K499N	1.000
2:53928123:T:G	K499N	1.000
2:53928124:T:A	K499I	1.000
2:53928125:T:C	K499E	1.000
2:53928262:A:G	L453P	1.000
2:53936107:A:G	W272R	1.000
2:53936107:A:T	W272R	1.000
2:53936772:A:G	W251R	1.000
2:53936772:A:T	W251R	1.000
2:53937500:A:G	W196R	1.000

dbSNP variants (sampled 300 via entrez): RS1000055224 (2:53909152 C>G), RS1000064849 (2:53947909 G>A,T), RS1000128702 (2:53865881 T>C,G), RS1000133169 (2:53926784 C>A), RS1000137677 (2:53937074 CTTAT>C), RS1000140190 (2:53961198 G>C), RS1000184993 (2:53905398 C>A,T), RS1000187342 (2:53866574 T>C), RS1000236947 (2:53910890 TC>T), RS1000265010 (2:53947741 C>T), RS1000297203 (2:53971043 A>G,T), RS1000310652 (2:53932436 G>T), RS1000312459 (2:53937564 T>A,C), RS1000317943 (2:53947933 T>A,C), RS1000357318 (2:53966123 A>T)

Disease associations

OMIM: gene MIM:607705 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003837_13	Chronotype	4.000000e-08
GCST003838_12	Morning vs. evening chronotype	4.000000e-08
GCST004904_224	Body mass index	5.000000e-12
GCST005830_64	Hand grip strength	2.000000e-08
GCST007576_117	Chronotype	6.000000e-09
GCST010002_365	Refractive error	3.000000e-34

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0006941	grip strength measurement
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067095 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	3
Estradiol	increases expression	3
Valproic Acid	decreases expression, increases expression	3
Arsenic Trioxide	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
geldanamycin	increases expression	1
beauvericin	affects cotreatment, decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
trichostatin A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
afimoxifene	decreases expression	1
decamethrin	decreases expression	1
nickel chloride	decreases expression	1
1-nitropyrene	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression	1
enniatins	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
elesclomol	decreases reaction, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652178	Binding	Binding affinity to human PSME4 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2CI	Abcam HeLa PSME4 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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