USP46

Summary

USP46 (ubiquitin specific peptidase 46, HGNC:20075) is a protein-coding gene on chromosome 4q12, encoding Ubiquitin carboxyl-terminal hydrolase 46 (P62068). Deubiquitinating enzyme that plays a role in behavior, possibly by regulating GABA action.

Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP46 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes (Quesada et al., 2004 [PubMed 14715245]).

Source: NCBI Gene 64854 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 33 total
• Druggable target: yes
• MANE Select transcript: NM_022832

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20075
Approved symbol	USP46
Name	ubiquitin specific peptidase 46
Location	4q12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12552
Ensembl gene	ENSG00000109189
Ensembl biotype	protein_coding
OMIM	612849
Entrez	64854

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000441222, ENST00000451218, ENST00000502443, ENST00000503060, ENST00000504078, ENST00000506707, ENST00000508499, ENST00000512656, ENST00000514536, ENST00000903415, ENST00000903416

RefSeq mRNA: 4 — MANE Select: NM_022832 NM_001134223, NM_001286767, NM_001286768, NM_022832

CCDS: CCDS47053, CCDS47054

Canonical transcript exons

ENST00000441222 — 9 exons

Exon	Start	End
ENSE00001743558	52659115	52659301
ENSE00002050243	52590960	52597741
ENSE00003477735	52627950	52628163
ENSE00003540832	52604501	52604584
ENSE00003553582	52598628	52598706
ENSE00003567807	52631064	52631144
ENSE00003663058	52601857	52602054
ENSE00003668651	52626018	52626247
ENSE00003687683	52610541	52610617

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 96.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3294 / max 129.1825, expressed in 1758 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52110	12.8846	1754
52109	0.2316	73
52108	0.1959	73
52107	0.0173	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
choroid plexus epithelium	UBERON:0003911	96.06	gold quality
endothelial cell	CL:0000115	96.01	gold quality
esophagus squamous epithelium	UBERON:0006920	94.58	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.54	gold quality
medial globus pallidus	UBERON:0002477	94.26	gold quality
CA1 field of hippocampus	UBERON:0003881	94.25	gold quality
globus pallidus	UBERON:0001875	93.61	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.28	gold quality
renal glomerulus	UBERON:0000074	93.15	gold quality
entorhinal cortex	UBERON:0002728	93.13	gold quality
metanephric glomerulus	UBERON:0004736	92.79	gold quality
temporal lobe	UBERON:0001871	92.45	gold quality
amygdala	UBERON:0001876	92.45	gold quality
superior frontal gyrus	UBERON:0002661	92.11	gold quality
palpebral conjunctiva	UBERON:0001812	92.10	gold quality
postcentral gyrus	UBERON:0002581	91.97	gold quality
substantia nigra pars compacta	UBERON:0001965	91.83	gold quality
subthalamic nucleus	UBERON:0001906	91.81	gold quality
orbitofrontal cortex	UBERON:0004167	91.80	gold quality
prefrontal cortex	UBERON:0000451	91.78	gold quality
Ammon’s horn	UBERON:0001954	91.62	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.47	gold quality
primary visual cortex	UBERON:0002436	91.40	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.19	gold quality
caudate nucleus	UBERON:0001873	91.18	gold quality
epithelium of esophagus	UBERON:0001976	91.11	gold quality
parietal lobe	UBERON:0001872	90.96	gold quality
lateral globus pallidus	UBERON:0002476	90.95	gold quality
cerebral cortex	UBERON:0000956	90.84	gold quality
telencephalon	UBERON:0001893	90.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	13.10
E-ANND-3	yes	4.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

314 targeting USP46, 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-513A-5P	100.00	69.77	2465
HSA-MIR-1277-5P	100.00	73.95	5056
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-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939

Literature-anchored findings (GeneRIF, showing 13)

• two novel multisubunit deubiquitinating enzyme complexes containing USP12 and USP46, respectively. Both complexes contain the UAF1 protein as a bona fide subunit. Interestingly, UAF1 (PMID:19075014)
• These data argue against the presence of any strong genetic susceptibility factors for bipolar disorder or schizophrenia in the region USP46. (PMID:20111060)
• results suggest that the USP46 gene might play a role in the pathophysiology of major depressive disorder in the Japanese population. (PMID:21663972)
• USP46-mediated stabilization of PHLPP and the subsequent inhibition of Akt. (PMID:22391563)
• Results suggest role for USP46/USP12 in Epstein-Barr virus induced growth transformation. (PMID:25855980)
• The deubiquitinase USP46 is essential for proliferation and tumor growth of HPV-transformed cancers. (PMID:30415951)
• Data indicate a mechanism of USP46 regulation in renal cell carcinoma (RCC), and that USP46 is a tumor suppressor in RCC via proto-oncogene protein Akt (AKT) signaling pathway inactivation. (PMID:31542232)
• USP46 Inhibits Cell Proliferation in Lung Cancer through PHLPP1/AKT Pathway. (PMID:33029497)
• Deubiquitinating enzyme USP46 suppresses the progression of hepatocellular carcinoma by stabilizing MST1. (PMID:34029571)
• MiR-27a-3p targets USP46 to inhibit the cell proliferation of hepatocellular carcinoma. (PMID:35637630)
• Ubiquitin specific protease 46 potentiates triple negative breast cancer development by stabilizing PGAM1-mediated glycolysis. (PMID:36335636)
• The USP46 complex deubiquitylates LRP6 to promote Wnt/beta-catenin signaling. (PMID:37798301)
• WDR20 prevents hepatocellular carcinoma senescence by orchestrating the simultaneous USP12/46-mediated deubiquitination of c-Myc. (PMID:39432777)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	usp46	ENSDARG00000045343
mus_musculus	Usp46	ENSMUSG00000054814
rattus_norvegicus	Usp46	ENSRNOG00000002106
drosophila_melanogaster	Usp12-46	FBGN0039025
caenorhabditis_elegans		WBGENE00011216

Paralogs (2): USP12 (ENSG00000152484), USP39 (ENSG00000168883)

Protein

Protein identifiers

Ubiquitin carboxyl-terminal hydrolase 46 — P62068 (reviewed: P62068)

Alternative names: Deubiquitinating enzyme 46, Ubiquitin thioesterase 46, Ubiquitin-specific-processing protease 46

All UniProt accessions (3): P62068, D6R9Z4, H7BZK6

UniProt curated annotations — full annotation on UniProt →

Function. Deubiquitinating enzyme that plays a role in behavior, possibly by regulating GABA action. May act by mediating the deubiquitination of GAD1/GAD67. Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity. Not involved in deubiquitination of monoubiquitinated FANCD2.

Subunit / interactions. Interacts with WDR48. Interacts with WDR20. Interacts with DMWD. Component of the USP46/WDR20/WDR48 deubiquitinating complex.

Subcellular location. Cytoplasm.

Tissue specificity. Broadly expressed.

Activity regulation. Activated by interaction with WDR48.

Similarity. Belongs to the peptidase C19 family. USP12/USP46 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
P62068-1	1	yes
P62068-2	2
P62068-3	3
P62068-4	4

RefSeq proteins (4): NP_001127695, NP_001273696, NP_001273697, NP_073743* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR018200	USP_CS	Conserved_site
IPR028889	USP	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050164	Peptidase_C19	Family

Pfam: PF00443

UniProt features (52 total): strand 22, helix 10, splice variant 4, binding site 4, sequence conflict 3, turn 3, active site 2, chain 1, domain 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
5L8H	X-RAY DIFFRACTION	1.85
5CVM	X-RAY DIFFRACTION	1.9
6JLQ	X-RAY DIFFRACTION	3.1
5CVN	X-RAY DIFFRACTION	3.36
5CVO	X-RAY DIFFRACTION	3.88

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62068-F1	89.99	0.77

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 44 (nucleophile); 313 (proton acceptor)

Ligand- & substrate-binding residues (4): 182; 185; 229; 232

Mutagenesis-validated functional residues (1):

Position	Phenotype
44	abolishes enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 247 (showing top): GCM_MAP4K4, GOBP_RESPONSE_TO_ETHANOL, GOBP_BEHAVIOR, MORF_MSH3, GOBP_ADULT_BEHAVIOR, AREB6_03, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, WONG_PROTEASOME_GENE_MODULE, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOBP_REFLEX, MORF_RAD51L3, GOBP_MULTICELLULAR_ORGANISMAL_RESPONSE_TO_STRESS

GO Biological Process (10): behavioral fear response (GO:0001662), proteolysis (GO:0006508), adult feeding behavior (GO:0008343), protein deubiquitination (GO:0016579), regulation of protein stability (GO:0031647), regulation of synaptic transmission, GABAergic (GO:0032228), behavioral response to ethanol (GO:0048149), righting reflex (GO:0060013), regulation of postsynaptic neurotransmitter receptor internalization (GO:0099149), regulation of macromolecule metabolic process (GO:0060255)

GO Molecular Function (7): cysteine-type deubiquitinase activity (GO:0004843), metal ion binding (GO:0046872), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787), deubiquitinase activity (GO:0101005)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), glutamatergic synapse (GO:0098978), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
adult behavior	2
regulation of biological quality	2
cellular anatomical structure	2
behavioral defense response	1
fear response	1
protein metabolic process	1
feeding behavior	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
modulation of chemical synaptic transmission	1
synaptic transmission, GABAergic	1
response to ethanol	1
reflex	1
regulation of receptor internalization	1
postsynaptic neurotransmitter receptor internalization	1
regulation of metabolic process	1
macromolecule metabolic process	1
cysteine-type peptidase activity	1
deubiquitinase activity	1
cation binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
ubiquitin-like protein peptidase activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
synapse	1
cell junction	1

Protein interactions and networks

STRING

1010 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP46	WDR48	Q8TAF3	985
USP46	WDR20	Q8TBZ3	863
USP46	USP5	P45974	736
USP46	GABRA1	P14867	713
USP46	GAD1	Q99259	681
USP46	DMWD	Q09019	649
USP46	ZUP1	Q96AP4	648
USP46	PHLPP2	Q6ZVD8	646
USP46	USP14	P54578	629
USP46	USP13	Q92995	599
USP46	USP28	Q96RU2	590
USP46	PHLPP1	O60346	568
USP46	USP39	Q53GS9	565
USP46	USP30	Q70CQ3	550
USP46	ERVMER34-1	Q9H9K5	543

IntAct

54 interactions, top by confidence:

A	B	Type	Score
USP46	WDR20	psi-mi:“MI:0915”(physical association)	0.800
WDR20	USP12	psi-mi:“MI:0914”(association)	0.800
PHLPP2	NHERF1	psi-mi:“MI:0914”(association)	0.760
USP46	PHLPP1	psi-mi:“MI:0914”(association)	0.740
VSX1	USP12	psi-mi:“MI:0914”(association)	0.730
WDR20	PHLPP1	psi-mi:“MI:0914”(association)	0.670
TSPYL6	USP12	psi-mi:“MI:0914”(association)	0.640
PHLPP1	USP12	psi-mi:“MI:0914”(association)	0.570
ATXN1	USP46	psi-mi:“MI:0915”(physical association)	0.560
WDR48	USP12	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
RNF19B	PIK3R2	psi-mi:“MI:0914”(association)	0.530
CHRM3	PLD2	psi-mi:“MI:0914”(association)	0.530
IFI30	PRC1	psi-mi:“MI:0914”(association)	0.530
RAD51AP1	USP12	psi-mi:“MI:0914”(association)	0.530
GORASP1	PPP6R2	psi-mi:“MI:0914”(association)	0.530
SGO1	USP12	psi-mi:“MI:0914”(association)	0.530
USP46	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
USP46	MAPK8IP2	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
USH1C	USP46	psi-mi:“MI:0914”(association)	0.350
USP46	PJA2	psi-mi:“MI:0914”(association)	0.350
DMWD	P4HA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (139): USP46 (Affinity Capture-MS), USP46 (Affinity Capture-Western), PHLPP1 (Biochemical Activity), UBA52 (Biochemical Activity), USP46 (Affinity Capture-MS), PHLPP1 (Affinity Capture-MS), WDR20 (Affinity Capture-MS), DMWD (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), ACTB (Affinity Capture-MS), WDR48 (Affinity Capture-MS), SNX6 (Affinity Capture-MS), SNX2 (Affinity Capture-MS), PHLPP2 (Affinity Capture-MS), USP46 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JTR4, A4FUN7, A5D9H7, A5WWB0, A6H8I0, A6NNY8, A6QNS3, C0HB46, D0RB01, E1C1R4, F1M625, O24454, O75317, P09851, P0C8Z3, P20936, P50904, P62068, P62069, Q09LZ8, Q12979, Q16288, Q3TIX9, Q52KZ6, Q53GS9, Q5DU02, Q5F415, Q5F450, Q5IFJ9, Q5IS37, Q5IS82, Q5M981, Q5R573, Q5R761, Q5R8I6, Q5RBQ4, Q5RDP3, Q5SSL4, Q60969, Q6DCJ1

Diamond homologs: A0A0R4IB93, A1CIL1, A1CW53, A2Q9N1, A4FUN7, A5D9H7, A5PJS6, A5WWB0, A6QR55, B0Y4P5, B2GUZ1, B3LGK1, B8NSV5, C0HB46, D0RB01, E2RK09, E7F6T8, E9Q9U0, F1M625, F1N5V1, G5E8G2, G5E8I7, O22207, O24454, O57429, O60079, O75317, O94966, P34547, P35123, P35125, P38187, P39967, P40818, P50102, P51784, P52479, P62068, P62069, Q01988

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 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
G2/M DNA damage checkpoint	5	15.8×	5e-04
Cell Cycle Checkpoints	5	11.7×	2e-03
RHO GTPase Effectors	5	8.9×	3e-03
Signaling by Rho GTPases	6	5.4×	8e-03
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	6	5.3×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1869 predictions. Top by Δscore:

Variant	Effect	Δscore
4:52598704:CCA:C	acceptor_gain	1.0000
4:52598705:CAC:C	acceptor_gain	1.0000
4:52598707:C:CC	acceptor_gain	1.0000
4:52602050:TCATC:T	acceptor_gain	1.0000
4:52602051:CATC:C	acceptor_gain	1.0000
4:52602051:CATCC:C	acceptor_gain	1.0000
4:52602052:ATC:A	acceptor_gain	1.0000
4:52602053:TC:T	acceptor_gain	1.0000
4:52602054:CC:C	acceptor_gain	1.0000
4:52602055:C:CC	acceptor_gain	1.0000
4:52602055:C:CG	acceptor_loss	1.0000
4:52602055:C:T	acceptor_gain	1.0000
4:52602064:C:CT	acceptor_gain	1.0000
4:52602065:A:T	acceptor_gain	1.0000
4:52610536:TATAC:T	donor_loss	1.0000
4:52610537:ATACC:A	donor_loss	1.0000
4:52610538:TA:T	donor_loss	1.0000
4:52610539:A:T	donor_loss	1.0000
4:52610540:C:CA	donor_loss	1.0000
4:52610613:CTAAC:C	acceptor_gain	1.0000
4:52610614:TAAC:T	acceptor_gain	1.0000
4:52610615:AACC:A	acceptor_loss	1.0000
4:52610618:CTGA:C	acceptor_loss	1.0000
4:52610619:T:C	acceptor_loss	1.0000
4:52626012:ACTT:A	donor_loss	1.0000
4:52626013:CT:C	donor_loss	1.0000
4:52626014:TT:T	donor_loss	1.0000
4:52626015:T:TG	donor_loss	1.0000
4:52626016:A:AC	donor_gain	1.0000
4:52626016:A:AG	donor_loss	1.0000

AlphaMissense

2452 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:52597657:A:C	Y362D	1.000
4:52597669:A:G	Y358H	1.000
4:52597671:C:T	G357E	1.000
4:52598640:A:C	D329E	1.000
4:52598640:A:T	D329E	1.000
4:52598641:T:A	D329V	1.000
4:52598641:T:C	D329G	1.000
4:52598641:T:G	D329A	1.000
4:52598642:C:A	D329Y	1.000
4:52598642:C:G	D329H	1.000
4:52598644:T:A	D328V	1.000
4:52598657:A:G	W324R	1.000
4:52598657:A:T	W324R	1.000
4:52598687:A:G	Y314H	1.000
4:52598688:A:C	H313Q	1.000
4:52598688:A:T	H313Q	1.000
4:52598690:G:C	H313D	1.000
4:52598692:C:A	G312V	1.000
4:52598692:C:T	G312E	1.000
4:52598693:C:A	G312W	1.000
4:52598693:C:G	G312R	1.000
4:52598693:C:T	G312R	1.000
4:52601867:G:C	H304D	1.000
4:52601879:C:G	A300P	1.000
4:52601884:A:C	L298W	1.000
4:52601938:A:G	L280P	1.000
4:52601970:C:A	K269N	1.000
4:52601970:C:G	K269N	1.000
4:52602003:G:C	F258L	1.000
4:52602003:G:T	F258L	1.000

dbSNP variants (sampled 300 via entrez): RS1000025493 (4:52629408 TTC>T), RS10000311 (4:52641778 T>C), RS1000092592 (4:52622400 T>A,C), RS10001370 (4:52597564 G>A), RS10001387 (4:52627743 G>A), RS1000163490 (4:52623911 T>C), RS1000210170 (4:52649885 G>A), RS1000224397 (4:52622336 A>T), RS10002261 (4:52622695 G>A,T), RS1000293904 (4:52629572 C>T), RS1000400392 (4:52615678 C>T), RS1000443652 (4:52591058 T>G), RS1000445047 (4:52636259 T>C), RS10004461 (4:52628630 G>C), RS1000527274 (4:52603682 CTTTTTCT>C,CTTTTTCTTTTTTCT)

Disease associations

OMIM: gene MIM:612849 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000328_13	Biochemical measures	2.000000e-06
GCST005991_9	Platelet count	2.000000e-14
GCST008839_51	Height	2.000000e-08
GCST009379_259	Type 2 diabetes	4.000000e-08
GCST009379_260	Type 2 diabetes	8.000000e-06
GCST010699_75	Brain morphology (min-P)	3.000000e-18
GCST010701_71	Cortical surface area (MOSTest)	2.000000e-09
GCST010702_63	Subcortical volume (MOSTest)	8.000000e-12
GCST010703_102	Brain morphology (MOSTest)	6.000000e-21

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004309	platelet count
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5291970 (PROTEIN COMPLEX), CHEMBL6067588 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression, decreases expression	5
Aflatoxin B1	decreases methylation, increases methylation	2
GSK-J4	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases abundance, increases expression	1
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	decreases expression	1
Carbamazepine	affects expression	1
Methyl Methanesulfonate	increases expression	1
Phthalic Acids	increases methylation	1
Piroxicam	decreases expression	1
Quercetin	decreases expression	1
Rotenone	increases expression	1
Testosterone	decreases expression	1
Tretinoin	decreases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5251168	Binding	Inhibition of USP46/UAF1/WDR20 (unknown origin) using ubiquitin rhodamine 110 as substrate at 1 to 10 uM by DUBprofiler fluorometric assay	Discovery and Characterization of BAY-805, a Potent and Selective Inhibitor of Ubiquitin-Specific Protease USP21. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TX01	HAP1 USP46 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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