DUSP3

Summary

DUSP3 (dual specificity phosphatase 3, HGNC:3069) is a protein-coding gene on chromosome 17q21.31, encoding Dual specificity protein phosphatase 3 (P51452). Shows activity both for tyrosine-protein phosphate and serine-protein phosphate, but displays a strong preference toward phosphotyrosines.

The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene maps in a region that contains the BRCA1 locus which confers susceptibility to breast and ovarian cancer. Although DUSP3 is expressed in both breast and ovarian tissues, mutation screening in breast cancer pedigrees and in sporadic tumors was negative, leading to the conclusion that this gene is not BRCA1.

Source: NCBI Gene 1845 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 24 total
• Druggable target: yes
• MANE Select transcript: NM_004090

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3069
Approved symbol	DUSP3
Name	dual specificity phosphatase 3
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000108861
Ensembl biotype	protein_coding
OMIM	600183
Entrez	1845

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000226004, ENST00000590342, ENST00000590753, ENST00000590935, ENST00000591618, ENST00000861136, ENST00000949183

RefSeq mRNA: 1 — MANE Select: NM_004090 NM_004090

CCDS: CCDS11469

Canonical transcript exons

ENST00000226004 — 3 exons

Exon	Start	End
ENSE00000854206	43778800	43778977
ENSE00001292277	43766125	43769814
ENSE00003568193	43774712	43774938

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 98.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.1384 / max 297.3607, expressed in 1813 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166277	44.6308	1812
166276	1.7228	1012
166272	0.4248	205
166273	0.3600	174

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.72	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.62	gold quality
biceps brachii	UBERON:0001507	98.34	gold quality
saphenous vein	UBERON:0007318	98.28	gold quality
vastus lateralis	UBERON:0001379	98.22	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.22	gold quality
skeletal muscle tissue	UBERON:0001134	98.20	gold quality
left ventricle myocardium	UBERON:0006566	98.20	gold quality
quadriceps femoris	UBERON:0001377	98.10	gold quality
cardiac ventricle	UBERON:0002082	98.08	gold quality
heart left ventricle	UBERON:0002084	98.08	gold quality
diaphragm	UBERON:0001103	97.97	gold quality
gastrocnemius	UBERON:0001388	97.86	gold quality
heart right ventricle	UBERON:0002080	97.83	gold quality
muscle tissue	UBERON:0002385	97.79	gold quality
muscle organ	UBERON:0001630	97.71	gold quality
skeletal muscle organ	UBERON:0014892	97.71	gold quality
apex of heart	UBERON:0002098	97.70	gold quality
myocardium	UBERON:0002349	97.70	gold quality
gluteal muscle	UBERON:0002000	97.66	gold quality
body of tongue	UBERON:0011876	97.60	gold quality
muscle of leg	UBERON:0001383	97.53	gold quality
heart	UBERON:0000948	97.37	gold quality
triceps brachii	UBERON:0001509	97.22	gold quality
deltoid	UBERON:0001476	97.17	gold quality
right coronary artery	UBERON:0001625	97.04	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.93	gold quality
cauda epididymis	UBERON:0004360	96.82	gold quality
cardiac atrium	UBERON:0002081	96.77	gold quality
right atrium auricular region	UBERON:0006631	96.72	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)

167 targeting DUSP3, 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-4668-3P	100.00	68.74	2635
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057

Literature-anchored findings (GeneRIF, showing 27)

• VHR, a Vaccinia virus VH1-related dual-specific protein phosphatase, is phosphorylated at Y138 by ZAP-70. (PMID:12447358)
• VHR is required for cell-cycle progression as it modulates MAP kinase activation in a cell-cycle phase-dependent manner. (PMID:16604064)
• deregulated expression of BRCA1-IRIS is likely to reduce dependence on normal physiological growth stimuli (PMID:17278098)
• Small dual-specificity phosphatase VHR selectively dephosphorylates tyrosine-phosphorylated interferon-alpha- and beta-activated transcription factor STAT5, leading to the subsequent inhibition of STAT5 function. (PMID:17785772)
• Results highlight the importance of a high intracellular Zn(2+) content and the VHR/ZAP-70/ERK1,2-associated pathways in the modulation of LNCaP prostate cancer cell growth. (PMID:18311544)
• VHR can be considered as a new marker for cancer progression in cervix carcinoma and potential new target for anticancer therapy (PMID:18505570)
• VHR has a direct role in the inhibition of JNK-dependent apoptosis in LNCaP cells and may therefore have a role in prostate cancer progression. (PMID:19010898)
• VHR expression enhances the signaling of ErbB receptors and may be involved in NSCLC pathogenesis. (PMID:21262974)
• Enteric commensal bacteria induce extracellular signal-regulated kinase pathway signaling via formyl peptide receptor-dependent redox modulation of dual specific phosphatase 3 (PMID:21921027)
• Proteins containing the class II motifs are efficient VHR substrates in vitro, suggesting that VHR may act on a novel class of yet unidentified Tyr(P) proteins in vivo. (PMID:23322772)
• we report the first successful site-specific incorporation of sulfotyrisine into VHR through the use of expanding genetic code (PMID:23918168)
• DUSP3 interacting partners are nucleolar proteins involved in processes related to DNA repair and senescence. (PMID:24245651)
• VHR can dimerize inside cells, and that VHR catalytic activity is reduced upon dimerization. (PMID:24798147)
• DUSP3 is a pro-angiogenic atypical dual-specificity phosphatase. (PMID:24886454)
• Data suggest levels of gene expression of both DUSP3 (dual specificity phosphatase 3) and PSME3 (proteasome activator subunit 3) are associated with susceptibility to Staphylococcus aureus infection/sepsis in humans and in mouse disease model. (PMID:24901344)
• Our results demonstrate that DUSP3 plays a key and nonredundant role as a regulator of innate immune responses (PMID:25876765)
• In the phosphatase-silenced cells, the normal bipolar spindle structure was restored by chemical inhibition of Erk1/2 and ectopic overexpression of Dusp3. We propose that at M phase Dusp3 keeps Erk1/2 activity in check to facilitate normal mitosis. (PMID:27423135)
• Nuclear HSP70 leads to enhancement of vaccinia H1-related phosphatase (VHR) activity via protein-protein interaction rather than its molecular chaperone activity, thereby suppressing excessive ERK activation. Downregulation of either VRK3 or HSP70 rendered cells vulnerable to glutamate-induced apoptosis. (PMID:27941812)
• The loss of DUSP3 activity markedly increases gamma radiation-induced DNA strand breaks, suggesting a potential novel role for DUSP3 in DNA repair. (PMID:28389334)
• In PTP1B and VHR, two new allosteric clusters were identified in each enzyme. (PMID:28625849)
• Data indicated that regulating non-receptor tyrosine kinase FAK and cell migration is a newly revealed function of VHR/DUSP3. (PMID:28759036)
• Study demonstrated that miR-1915-3p might promote the proliferation and metastasis of breast cancer by repression of DUSP3 and serum miR-1915-3p and miR-455-3p could serve as diagnostic and predictive biomarkers for breast cancer. (PMID:30048472)
• Allosteric Impact of the Variable Insert Loop in Vaccinia H1-Related (VHR) Phosphatase. (PMID:32348128)
• DUSP3 maintains genomic stability and cell proliferation by modulating NER pathway and cell cycle regulatory proteins. (PMID:32380926)
• Regulation of signal transducer and activator of transcription 3 activation by dual-specificity phosphatase 3. (PMID:32475380)
• The role of dual-specificity phosphatase 3 in melanocytic oncogenesis. (PMID:35899430)
• DUSP3 modulates IRES-dependent translation of mRNAs through dephosphorylation of the HNRNPC protein in cells under genotoxic stimulus. (PMID:38538536)

Cross-species orthologs

0 orthologs

Paralogs (31): DUSP13B (ENSG00000079393), DUSP12 (ENSG00000081721), SSH1 (ENSG00000084112), PTPMT1 (ENSG00000110536), DUSP16 (ENSG00000111266), EPM2A (ENSG00000112425), DUSP22 (ENSG00000112679), DUSP1 (ENSG00000120129), DUSP4 (ENSG00000120875), STYXL1 (ENSG00000127952), DUSP9 (ENSG00000130829), DUSP26 (ENSG00000133878), DUSP5 (ENSG00000138166), DUSP6 (ENSG00000139318), SSH2 (ENSG00000141298), DUSP10 (ENSG00000143507), DUSP15 (ENSG00000149599), DUSP2 (ENSG00000158050), KASH5 (ENSG00000161609), DUSP19 (ENSG00000162999), DUSP7 (ENSG00000164086), DUSP18 (ENSG00000167065), SSH3 (ENSG00000172830), DUSP8 (ENSG00000184545), DUSP28 (ENSG00000188542), DUSP29 (ENSG00000188716), DUSP21 (ENSG00000189037), STYX (ENSG00000198252), STYXL2 (ENSG00000198842), DUSP14 (ENSG00000276023), DUSP13A (ENSG00000293543)

Protein

Protein identifiers

Dual specificity protein phosphatase 3 — P51452 (reviewed: P51452)

Alternative names: Dual specificity protein phosphatase VHR, Vaccinia H1-related phosphatase

All UniProt accessions (4): P51452, K7ELG5, K7EPK5, K7ES89

UniProt curated annotations — full annotation on UniProt →

Function. Shows activity both for tyrosine-protein phosphate and serine-protein phosphate, but displays a strong preference toward phosphotyrosines. Specifically dephosphorylates and inactivates ERK1 and ERK2.

Subunit / interactions. Microtubule inner protein component of sperm flagellar doublet microtubules. Interacts with VRK3; this interaction activates DUSP3 phosphatase activity.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Flagellum axoneme.

Similarity. Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P51452-1	1	yes
P51452-2	2

RefSeq proteins (1): NP_004081* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000340	Dual-sp_phosphatase_cat-dom	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR016130	Tyr_Pase_AS	Active_site
IPR020405	Atypical_DUSP_subfamA	Family
IPR020422	TYR_PHOSPHATASE_DUAL_dom	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily

Pfam: PF00782

Enzyme classification (BRENDA):

• EC 3.1.3.16 — protein-serine/threonine phosphatase (BRENDA: 92 organisms, 641 substrates, 468 inhibitors, 127 Km, 67 kcat entries)
• EC 3.1.3.48 — protein-tyrosine-phosphatase (BRENDA: 59 organisms, 501 substrates, 1326 inhibitors, 270 Km, 165 kcat entries)

Substrate kinetics (BRENDA)

129 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-NITROPHENYL PHOSPHATE	0.0008–148	84
6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE	0.0039–0.862	27
6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE	0.023–0.862	22
P-NITROPHENYL PHOSPHATE	0.0024–10	20
4-NITROPHENYL PHOSPHATE	0.0028–12.7	13
DADEPYLIPQQG	0.0003–0.1	12
P-NITROPHENYL PHOSPHATE	3–200	11
PHOSPHOTYROSINE	0.012–30	11
LYSOZYME	0.0003–0.012	5
MYELIN BASIC PROTEIN	0.0001–0.022	5
RRAPTVA	0.058–1.954	4
ACETYL-DADEPY-NH2	0.0228–0.219	4
ACETYL-DADEPYL-NH2	1.1–97.5	4
PHOSPHOCASEIN	0.0001–0.002	3
PHOSPHOHISTONE	0.0023–0.0723	3

Catalyzed reactions (Rhea), 3 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)
• O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
• O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)

UniProt features (23 total): helix 9, strand 8, turn 2, chain 1, domain 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
8TK6	X-RAY DIFFRACTION	1.65
8TK2	X-RAY DIFFRACTION	1.7
8TK4	X-RAY DIFFRACTION	1.8
3F81	X-RAY DIFFRACTION	1.9
8TK5	X-RAY DIFFRACTION	1.9
9DJ9	X-RAY DIFFRACTION	1.92
8TK3	X-RAY DIFFRACTION	2
1VHR	X-RAY DIFFRACTION	2.1
1J4X	X-RAY DIFFRACTION	2.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51452-F1	96.10	0.93

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 (1): 124 (phosphocysteine intermediate)

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-202670	ERKs are inactivated

MSigDB gene sets: 344 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_FOCAL_ADHESION_ASSEMBLY, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP

GO Biological Process (16): dephosphorylation (GO:0016311), negative regulation of cell migration (GO:0030336), peptidyl-tyrosine dephosphorylation (GO:0035335), negative regulation of epidermal growth factor receptor signaling pathway (GO:0042059), negative regulation of MAPK cascade (GO:0043409), positive regulation of mitotic cell cycle (GO:0045931), negative regulation of JNK cascade (GO:0046329), negative regulation of T cell receptor signaling pathway (GO:0050860), negative regulation of T cell activation (GO:0050868), negative regulation of chemotaxis (GO:0050922), regulation of focal adhesion assembly (GO:0051893), negative regulation of ERK1 and ERK2 cascade (GO:0070373), cellular response to epidermal growth factor stimulus (GO:0071364), positive regulation of focal adhesion disassembly (GO:0120183), protein dephosphorylation (GO:0006470), negative regulation of signal transduction (GO:0009968)

GO Molecular Function (13): protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine phosphatase activity (GO:0004725), cytoskeletal protein binding (GO:0008092), protein tyrosine/serine/threonine phosphatase activity (GO:0008138), phosphatase activity (GO:0016791), protein kinase binding (GO:0019901), receptor signaling protein tyrosine kinase inhibitor activity (GO:0030294), receptor tyrosine kinase binding (GO:0030971), MAP kinase phosphatase activity (GO:0033549), protein tyrosine kinase binding (GO:1990782), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (9): immunological synapse (GO:0001772), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
ERK/MAPK targets	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
phosphoprotein phosphatase activity	4
negative regulation of MAPK cascade	2
phosphate-containing compound metabolic process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
protein dephosphorylation	1
epidermal growth factor receptor signaling pathway	1
regulation of epidermal growth factor receptor signaling pathway	1
negative regulation of ERBB signaling pathway	1
MAPK cascade	1
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
mitotic cell cycle	1
regulation of mitotic cell cycle	1
positive regulation of cell cycle	1
JNK cascade	1
regulation of JNK cascade	1
T cell receptor signaling pathway	1
regulation of T cell receptor signaling pathway	1
negative regulation of antigen receptor-mediated signaling pathway	1
T cell activation	1
regulation of T cell activation	1
negative regulation of lymphocyte activation	1
negative regulation of leukocyte cell-cell adhesion	1
chemotaxis	1
negative regulation of response to external stimulus	1
negative regulation of locomotion	1
regulation of chemotaxis	1
regulation of cell-matrix adhesion	1
focal adhesion assembly	1
regulation of cell-substrate junction assembly	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
response to epidermal growth factor	1
cellular response to growth factor stimulus	1
focal adhesion disassembly	1
regulation of focal adhesion disassembly	1
positive regulation of cell-substrate junction organization	1

Protein interactions and networks

STRING

1746 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUSP3	VRK3	Q8IV63	795
DUSP3	PTS	Q03393	712
DUSP3	PTPN1	P18031	676
DUSP3	DUSP23	Q9BVJ7	671
DUSP3	EPM2A	O95278	647
DUSP3	PTPN7	P35236	640
DUSP3	PTPRA	P18433	616
DUSP3	PTPN2	P17706	583
DUSP3	ZAP70	P43403	574
DUSP3	VRK2	Q86Y07	561
DUSP3	GBP5	Q96PP8	544
DUSP3	ACP1	P24666	543
DUSP3	CDC14A	Q9UNH5	512
DUSP3	MAPK1	P28482	502
DUSP3	STAT5B	P51692	501

IntAct

47 interactions, top by confidence:

A	B	Type	Score
ERLIN2	ERLIN1	psi-mi:“MI:0914”(association)	0.740
MEOX1	DUSP3	psi-mi:“MI:0915”(physical association)	0.560
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
DNAAF8	CCDC85C	psi-mi:“MI:0914”(association)	0.530
ARL6IP6	YKT6	psi-mi:“MI:0914”(association)	0.530
ERLIN1	DUSP3	psi-mi:“MI:0914”(association)	0.530
DUSP3	ERLIN1	psi-mi:“MI:0914”(association)	0.530
ARF5	ARF4	psi-mi:“MI:0914”(association)	0.530
DUSP3	MAPK3	psi-mi:“MI:0203”(dephosphorylation reaction)	0.440
DUSP3	MAPK1	psi-mi:“MI:0203”(dephosphorylation reaction)	0.440
DUSP3	TUFM	psi-mi:“MI:0915”(physical association)	0.400
DUSP3	BNIP3L	psi-mi:“MI:0915”(physical association)	0.370
DUSP3	NEUROD1	psi-mi:“MI:0915”(physical association)	0.370
CASK	DUSP3	psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
GTF2E2	UBA6	psi-mi:“MI:0914”(association)	0.350
FGB	NME2	psi-mi:“MI:0914”(association)	0.350
DUSP3	Ptpn6	psi-mi:“MI:0914”(association)	0.350
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
SPANXN4	UBA6	psi-mi:“MI:0914”(association)	0.350
RPL35A	SMCHD1	psi-mi:“MI:0914”(association)	0.350
CARTPT	MEIS1	psi-mi:“MI:0914”(association)	0.350
GSX1	YKT6	psi-mi:“MI:0914”(association)	0.350
POLR2J2	POLR2D	psi-mi:“MI:0914”(association)	0.350
CRYGN	ALOX12B	psi-mi:“MI:0914”(association)	0.350

BioGRID (87): DUSP3 (Affinity Capture-MS), DUSP3 (Affinity Capture-MS), DUSP3 (Affinity Capture-MS), DUSP3 (Affinity Capture-MS), DUSP3 (Affinity Capture-MS), DUSP3 (Affinity Capture-MS), DUSP3 (Affinity Capture-MS), CLEC1B (Affinity Capture-MS), NT5C2 (Affinity Capture-MS), DOCK11 (Affinity Capture-MS), HOOK3 (Affinity Capture-MS), RPIA (Affinity Capture-MS), UGT8 (Affinity Capture-MS), DUSP3 (Affinity Capture-MS), DUSP3 (Affinity Capture-MS)

ESM2 similar proteins: A4D256, A4IHU7, O14830, O35239, O35385, O95147, P0C591, P0C592, P0C593, P0C594, P0C595, P0C596, P0C597, P0C598, P0C599, P0C5A0, P0C5A1, P0C5A2, P43378, P51452, Q16828, Q17QM8, Q29RA3, Q2KJ36, Q4KL92, Q4RQD3, Q566R7, Q5RD73, Q5XHB2, Q641Z2, Q64346, Q68J44, Q6AXW7, Q6GQJ8, Q86BN8, Q8BK84, Q8K4T5, Q8WTR2, Q8WUK0, Q90W58

Diamond homologs: A0A7H0DN78, P07239, P0C597, P0C598, P0C5A0, P0C5A1, P0DOQ5, P0DOQ6, P20495, P28191, P28562, P28563, P29074, P51452, P80994, Q05923, Q13115, Q16690, Q16828, Q2KJ36, Q4RQD3, Q54R42, Q54T76, Q5RD73, Q62767, Q64346, Q64623, Q6B8I0, Q6B8I1, Q84JU4, Q85297, Q8BFV3, Q90W58, Q91790, Q99956, Q9D0T2, Q9DBB1, Q9J592, Q9M8K7, Q9PW71

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
DUSP3	“down-regulates activity”	MAPK3	dephosphorylation
TYK2	up-regulates	DUSP3	phosphorylation
DUSP3	“down-regulates activity”	EGFR	dephosphorylation
DUSP3	“down-regulates activity”	ERBB2	dephosphorylation
DUSP3	“down-regulates activity”	NPM1	dephosphorylation
DUSP3	“down-regulates activity”	PTK2	dephosphorylation
DUSP3	“down-regulates activity”	STAT3	dephosphorylation
ZAP70	up-regulates	DUSP3	phosphorylation
DUSP3	“down-regulates activity”	MAPK1	dephosphorylation
DUSP3	“down-regulates activity”	Gbeta	dephosphorylation
DUSP3	“down-regulates activity”	ERK1/2	dephosphorylation
VRK3	“up-regulates activity”	DUSP3	binding
SYK	“up-regulates activity”	DUSP3	phosphorylation
ZAP70	“up-regulates activity”	DUSP3	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

497 predictions. Top by Δscore:

Variant	Effect	Δscore
17:43769623:T:TA	donor_gain	1.0000
17:43769624:C:A	donor_gain	1.0000
17:43769628:T:TA	donor_gain	1.0000
17:43774706:CCTTA:C	donor_loss	1.0000
17:43774707:CTTAC:C	donor_loss	1.0000
17:43774708:TTA:T	donor_loss	1.0000
17:43774709:TA:T	donor_loss	1.0000
17:43774711:C:A	donor_loss	1.0000
17:43774711:CCATT:C	donor_gain	1.0000
17:43774937:ACC:A	acceptor_loss	1.0000
17:43774938:CCT:C	acceptor_loss	1.0000
17:43774939:C:CA	acceptor_loss	1.0000
17:43778798:A:AC	donor_gain	1.0000
17:43778799:C:CC	donor_gain	1.0000
17:43778799:CG:C	donor_gain	1.0000
17:43778799:CGCG:C	donor_gain	1.0000
17:43769694:CGGTT:C	donor_gain	0.9900
17:43769810:CCGGC:C	acceptor_gain	0.9900
17:43769811:CGGC:C	acceptor_gain	0.9900
17:43769811:CGGCC:C	acceptor_gain	0.9900
17:43769812:GGCCT:G	acceptor_loss	0.9900
17:43769813:GCCTG:G	acceptor_loss	0.9900
17:43769815:C:CC	acceptor_gain	0.9900
17:43769816:T:A	acceptor_loss	0.9900
17:43774710:A:AC	donor_gain	0.9900
17:43774711:C:CC	donor_gain	0.9900
17:43774781:C:CA	donor_gain	0.9900
17:43774934:CAGAC:C	acceptor_gain	0.9900
17:43778793:GACT:G	donor_loss	0.9900
17:43778794:ACTC:A	donor_loss	0.9900

AlphaMissense

1224 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:43774789:T:A	D92V	1.000
17:43769669:G:C	F166L	0.999
17:43769669:G:T	F166L	0.999
17:43769671:A:G	F166L	0.999
17:43769695:G:T	R158S	0.999
17:43774788:G:C	D92E	0.999
17:43774788:G:T	D92E	0.999
17:43774789:T:C	D92G	0.999
17:43774789:T:G	D92A	0.999
17:43774790:C:G	D92H	0.999
17:43769670:A:G	F166S	0.998
17:43769779:G:T	R130S	0.998
17:43769788:C:G	G127R	0.998
17:43769682:G:T	P162H	0.997
17:43769694:C:G	R158P	0.997
17:43769779:G:C	R130G	0.997
17:43769780:G:C	S129R	0.997
17:43769780:G:T	S129R	0.997
17:43769782:T:G	S129R	0.997
17:43769787:C:A	G127V	0.997
17:43769788:C:A	G127C	0.997
17:43769797:A:G	C124R	0.997
17:43769802:A:T	V122D	0.997
17:43774776:G:C	F96L	0.997
17:43774776:G:T	F96L	0.997
17:43774778:A:G	F96L	0.997
17:43774790:C:A	D92Y	0.997
17:43774881:G:C	N61K	0.997
17:43774881:G:T	N61K	0.997
17:43778807:C:G	G40R	0.997

dbSNP variants (sampled 300 via entrez): RS1000405652 (17:43770940 T>G), RS1000566559 (17:43776038 G>C), RS1000602014 (17:43778777 C>A,T), RS1000737382 (17:43772895 C>CA), RS1000887209 (17:43767059 G>A,T), RS1000948518 (17:43770141 G>C), RS1000972813 (17:43778936 G>A,T), RS1001088813 (17:43779011 G>A,C,T), RS1001118554 (17:43776226 A>T), RS1001236686 (17:43778873 C>T), RS1001423211 (17:43775263 C>T), RS1001463316 (17:43769983 A>T), RS1001508577 (17:43766833 C>A), RS1001683019 (17:43772473 C>G), RS1001790932 (17:43779344 C>T)

Disease associations

OMIM: gene MIM:600183 | 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
GCST002897_7	Triglycerides	8.000000e-13
GCST002899_38	HDL cholesterol	1.000000e-14
GCST003660_18	HDL cholesterol	1.000000e-11
GCST006423_13	Fracture	3.000000e-25
GCST009391_1766	Metabolite levels	8.000000e-06
GCST011348_50	High density lipoprotein cholesterol levels	2.000000e-41

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0010370	lysophosphatidylethanolamine 20:4 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2635 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

295 measured of 382 human assays (391 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
5-(tosylmethyl)-2-furoic acid	IC50	23 nM
4-chloranyl-N-(3,4-dihydro-2H-thiochromen-4-yl)-3-sulfamoyl-benzamide	IC50	121 nM
N-[3-[(2-methoxyphenyl)sulfamoyl]-4-(1-pyrrolidinyl)phenyl]-3-methyl-2-thiophenecarboxamide	IC50	163 nM
4-amino-3-(4-methylphenyl)-5-[(4-methyl-1-piperazinyl)carbonyl]-1,3-thiazole-2(3H)-thione	IC50	250 nM
1-(2,6-dichlorophenyl)-3-(2-phenylethyl)thiourea	IC50	342 nM
cid_3578672	IC50	342 nM
1-[[1-(1-phenylethyl)-3-pyrrolidinyl]methyl]-3-(2,4,6-trimethylphenyl)thiourea	IC50	343 nM
cid_67062	IC50	485 nM
1-[2,3-bis(2-furanyl)-6-quinoxalinyl]-3-(2-methoxyethyl)urea	IC50	492 nM
MLS000409155	IC50	498 nM
SMR000311544	IC50	500 nM
cid_2162931	IC50	567 nM
MLS-0437609.0002	IC50	682 nM
MLS000584539	IC50	696 nM
MLS000050448	IC50	716 nM
(4-bromophenyl)-[4-(phenylmethyl)-1-piperazinyl]methanethione	IC50	719 nM
1-(3-chloro-4-methoxyphenyl)-3-[2-(4-methyl-1-piperidinyl)ethyl]thiourea	IC50	720 nM
MLS-0109562.0001	IC50	727 nM
cid_6161440	IC50	730 nM
MLS000621546	IC50	740 nM
N’-(5-chloro-2-methoxyphenyl)-N-[(1-methyl-1H-indol-3-yl)methyl]-N-(3-morpholin-4-ylpropyl)thiourea	IC50	754 nM
SMR000624920	IC50	804 nM
SMR000143195	IC50	810 nM
SMR001268769	IC50	927 nM
MLS000679877	IC50	937 nM
SMR000198085	IC50	942 nM
(5-methyl-2-thiophenyl)-[4-(phenylmethyl)-1-piperazinyl]methanethione	IC50	997 nM
MLS001008494	IC50	1030 nM
N’-(4-chloro-2-methoxyphenyl)-N-[(1-methyl-1H-indol-3-yl)methyl]-N-(3-morpholin-4-ylpropyl)thiourea	IC50	1030 nM
MLS001196239	IC50	1030 nM
1-(3-propan-2-yloxypropyl)-3-(4-sulfamoylphenyl)thiourea	IC50	1080 nM
1-(3-chloro-4-methoxyphenyl)-3-[3-(1-pyrrolidinyl)propyl]thiourea	IC50	1120 nM
1-[(4-bromophenyl)carbonothioyl]-4-methylpiperazine	IC50	1140 nM
2-[2-chloranyl-6-methoxy-4-[(Z)-[3-[2-[(4-methylphenyl)amino]-2-oxidanylidene-ethyl]-2,4-bis(oxidanylidene)-1,3-thiazolidin-5-ylidene]methyl]phenoxy]ethanoic acid	IC50	1180 nM
1-[(E)-(1,3-dimethylpyrazol-4-yl)methylideneamino]-3-phenyl-thiourea	IC50	1220 nM
(7Z)-3-bromanyl-7-(furan-2-ylmethylidene)-[1,3]thiazolo[4,5]imidazo[1,2-b]pyridin-8-one	IC50	1230 nM
3-(2-{(E)-[1-(4-chlorophenyl)-2,5-dioxoimidazolidin-4-ylidene]methyl}-1H-pyrrol-1-yl)benzoic acid	IC50	1230 nM
2,3,4,5-tetrahydroxy-6-benzo[7]annulenone	IC50	1230 nM
(5E)-1-(4-fluorophenyl)-5-(2-furanylmethylidene)-2-sulfanylidene-1,3-diazinane-4,6-dione	IC50	1230 nM
(5E)-5-(2-furanylmethylidene)-1-(2-methylphenyl)-2-sulfanylidene-1,3-diazinane-4,6-dione	IC50	1230 nM
3-[(5E)-5-[1-(2-chlorobenzyl)-2-keto-indolin-3-ylidene]-4-keto-2-thioxo-thiazolidin-3-yl]propionic acid	IC50	1230 nM
(5E)-1-(2,5-dimethoxyphenyl)-5-(2-furanylmethylidene)-2-sulfanylidene-1,3-diazinane-4,6-dione	IC50	1230 nM
MLS000516376	IC50	1230 nM
MLS000737363	IC50	1240 nM
2-[5-[(Z)-(3-bromanyl-8-oxidanylidene-[1,3]thiazolo[4,5]imidazo[1,2-b]pyridin-7-ylidene)methyl]furan-2-yl]benzoic acid	IC50	1250 nM
3-(3-chloranyl-4-methoxy-phenyl)-1-(3-methylbutyl)-1-(1-propan-2-ylpiperidin-4-yl)thiourea	IC50	1260 nM
(3E)-5-hydroxy-6-methyl-3-(2,3,5-trihydroxy-4-methyl-6-oxo-1-cyclohexa-2,4-dienylidene)cyclohex-5-ene-1,2,4-trione	IC50	1270 nM
SMR000549393	IC50	1290 nM
2-[4-[[[4-[2-(4-chloroanilino)-1,3-thiazol-4-yl]benzoyl]hydrazinylidene]methyl]phenoxy]acetic acid	IC50	1300 nM
MLS000577024	IC50	1300 nM

ChEMBL bioactivities

458 potent at pChembl≥5 of 686 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.75	IC50	18	nM	CHEMBL565795
7.19	IC50	65	nM	CHEMBL1460470
7.15	IC50	71	nM	CHEMBL567069
7.13	IC50	74	nM	CHEMBL584481
7.11	IC50	78	nM	CHEMBL565810
7.08	IC50	82.8	nM	CHEMBL1460470
6.92	IC50	121	nM	CHEMBL1460470
6.90	IC50	127	nM	CHEMBL1608642
6.84	IC50	143	nM	CHEMBL1322542
6.79	IC50	163	nM	CHEMBL1463248
6.74	IC50	181	nM	CHEMBL1448629
6.67	IC50	216	nM	CHEMBL1385949
6.66	IC50	220	nM	CHEMBL1705741
6.66	IC50	218	nM	CHEMBL1445488
6.65	IC50	226	nM	CHEMBL1393151
6.60	IC50	250	nM	CHEMBL1605172
6.58	IC50	260	nM	CHEMBL1304193
6.57	IC50	271	nM	CHEMBL1385949
6.57	IC50	270	nM	CHEMBL565371
6.51	IC50	312	nM	CHEMBL1421970
6.51	IC50	308	nM	CHEMBL1371869
6.48	IC50	331	nM	CHEMBL1608642
6.47	IC50	341	nM	CHEMBL1410244
6.47	IC50	339	nM	CHEMBL1426299
6.47	IC50	342	nM	CHEMBL1331149
6.47	IC50	342	nM	CHEMBL1408579
6.46	IC50	343	nM	CHEMBL1381413
6.46	IC50	343	nM	CHEMBL1353918
6.46	IC50	345	nM	CHEMBL1603381
6.46	IC50	347	nM	CHEMBL1408579
6.45	IC50	353	nM	CHEMBL1370165
6.44	IC50	366	nM	CHEMBL1608642
6.43	IC50	370	nM	CHEMBL1608642
6.42	IC50	382	nM	CHEMBL1445488
6.41	IC50	386	nM	CHEMBL1504939
6.40	IC50	402	nM	CHEMBL1605172
6.39	IC50	408	nM	CHEMBL1727679
6.32	IC50	480	nM	CHEMBL1536896
6.32	IC50	480	nM	CHEMBL1732016
6.31	IC50	485	nM	CHEMBL1271266
6.31	IC50	492	nM	CHEMBL1501132
6.30	IC50	500	nM	CHEMBL1540065
6.30	IC50	498	nM	CHEMBL1421470
6.29	IC50	509	nM	CHEMBL1461216
6.28	IC50	530	nM	CHEMBL1304193
6.26	IC50	549	nM	CHEMBL1445488
6.26	IC50	544	nM	CHEMBL1724282
6.25	IC50	567	nM	CHEMBL1540317
6.24	IC50	570	nM	CHEMBL1569991
6.17	IC50	680	nM	CHEMBL1608654

PubChem BioAssay actives

88 with measured affinity, of 474 total; 50 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
2-[(5Z)-5-[[3-[4-[(4-chlorophenyl)methoxy]phenyl]-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid	443928: Inhibition of recombinant vaccina H1-related phosphatase	ic50	0.0180	uM
2-[(5Z)-5-[[3-[4-[(2-chlorophenyl)methoxy]phenyl]-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid	443928: Inhibition of recombinant vaccina H1-related phosphatase	ic50	0.0710	uM
2-[(5Z)-5-[[3-[4-[(2-fluorophenyl)methoxy]phenyl]-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid	443928: Inhibition of recombinant vaccina H1-related phosphatase	ic50	0.0740	uM
2-[(5Z)-4-oxo-5-[[1-phenyl-3-(4-phenylmethoxyphenyl)pyrazol-4-yl]methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid	443928: Inhibition of recombinant vaccina H1-related phosphatase	ic50	0.0780	uM
2-[(5Z)-4-oxo-5-[[1-phenyl-3-(4-piperidin-1-ylsulfonylphenyl)pyrazol-4-yl]methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid	443928: Inhibition of recombinant vaccina H1-related phosphatase	ic50	0.2700	uM
(4-hydroxy-3-methoxyphenyl)-piperidin-1-ylmethanethione	1206872: Inhibition of recombinant VHR (unknown origin) using OMFP as substrate after 1 hr by fluorescence assay	ic50	0.3700	uM
6-hydroxy-3-[2-(4-phenoxyphenyl)ethynyl]-2-phenyl-1-benzofuran-5-carboxylic acid	725032: Inhibition of VHR (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	0.8000	uM
2-[(5Z)-5-[(E)-3-phenylprop-2-enylidene]-2-sulfanylidene-1,3,4-thiadiazolidin-3-yl]ethanesulfonic acid	443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies	ki	0.8090	uM
6-chloro-7-(2-morpholin-4-ylethylamino)phthalazine-5,8-dione	217196: Inhibitory Activity against Recombinant Human VHR	ic50	1.1000	uM
4-[N-[(3-chlorophenyl)methyl]-C-pentadecylcarbonimidoyl]-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one	673781: Inhibition of VHR	ic50	1.4300	uM
3-hydroxy-2-(hydroxymethyl)-4-[N-[(3-methylphenyl)methyl]-C-pentadecylcarbonimidoyl]-2H-furan-5-one	1139714: Inhibition of Vaccinia H1-related phosphatase (unknown origin) by fluorescence emission assay	ic50	1.6000	uM
(E)-N-[4-(1,3-benzoxazol-2-yl)phenyl]-3-[5-(2-nitrophenyl)furan-2-yl]prop-2-enamide	443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies	ki	1.7600	uM
2-[(3S)-1-[[(2R)-4-hexadecanoyl-3-hydroxy-5-oxo-2H-furan-2-yl]methoxy]-2-methyl-1-oxopentan-3-yl]oxyethyl (2R)-3-hydroxy-2-(hydroxymethyl)-5-oxo-2H-furan-4-carboxylate	593417: Inhibition of VHR	ic50	1.8000	uM
2-[(5Z)-5-[[3-(4-chlorophenyl)-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid	443928: Inhibition of recombinant vaccina H1-related phosphatase	ic50	1.8000	uM
2-[(5Z)-5-[[3-(4-methoxyphenyl)-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid	443928: Inhibition of recombinant vaccina H1-related phosphatase	ic50	1.8000	uM
(5Z)-5-[[5-(4-nitrophenyl)furan-2-yl]methylidene]-4-sulfanylidene-1,3-thiazolidin-2-one	443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies	ki	1.8600	uM
6-hydroxy-2-phenyl-3-[2-[3-(trifluoromethyl)phenyl]ethynyl]-1-benzofuran-5-carboxylic acid	725032: Inhibition of VHR (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	1.9000	uM
2-[(5Z)-4-oxo-5-[(E)-3-phenylprop-2-enylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid	443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies	ki	2.0100	uM
2-[4-(2,5-dimethylpyrrol-1-yl)phenyl]sulfanylacetic acid	443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies	ki	2.0900	uM
6-hydroxy-2-phenyl-3-[2-[4-(trifluoromethoxy)phenyl]ethynyl]-1-benzofuran-5-carboxylic acid	725032: Inhibition of VHR (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	2.1000	uM
2-[(5Z)-5-[[3-(4-morpholin-4-ylsulfonylphenyl)-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid	443928: Inhibition of recombinant vaccina H1-related phosphatase	ic50	2.4000	uM
ethyl 5-(4-bromophenyl)-4,6-dioxo-2H-pyrrolo[3,4-c]pyrazole-3-carboxylate	443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies	ki	2.6400	uM
3-hydroxy-2-(hydroxymethyl)-4-[N-[(4-methylphenyl)methyl]-C-pentadecylcarbonimidoyl]-2H-furan-5-one	673781: Inhibition of VHR	ic50	2.6800	uM
N-(4-methoxy-1,3-benzothiazol-2-yl)-5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-amine	1206872: Inhibition of recombinant VHR (unknown origin) using OMFP as substrate after 1 hr by fluorescence assay	ic50	2.6800	uM
1-dibenzofuran-3-yl-3-naphthalen-1-ylthiourea	443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies	ki	2.9400	uM
1,4-dimethoxyanthracene-9,10-dione	443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies	ki	3.0700	uM
2-[(5Z)-5-[[3-(4-methylphenyl)-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid	443928: Inhibition of recombinant vaccina H1-related phosphatase	ic50	3.1000	uM
2-[(5Z)-5-[[5-(3-chlorophenyl)furan-2-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid	443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies	ki	3.1300	uM
(5Z)-5-[[5-(2-bromo-4,5-dimethylphenyl)furan-2-yl]methylidene]-2-sulfanylideneimidazolidin-4-one	443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies	ki	3.1900	uM
6-hydroxy-3-iodo-1-methyl-2-[3-[[2-oxo-2-(4-thiophen-3-ylanilino)acetyl]amino]phenyl]indole-5-carboxylic acid	1182551: Inhibition of VHR (unknown origin)	ic50	3.2000	uM
1-(3-chlorophenyl)-6-hydroxy-5-[(E)-pyrrol-2-ylidenemethyl]-2-sulfanylidenepyrimidin-4-one	443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies	ki	3.4900	uM
4-[N-[(4-chlorophenyl)methyl]-C-pentadecylcarbonimidoyl]-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one	673781: Inhibition of VHR	ic50	3.6300	uM
N-(4-fluoro-1,3-benzothiazol-2-yl)-5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-amine	1206872: Inhibition of recombinant VHR (unknown origin) using OMFP as substrate after 1 hr by fluorescence assay	ic50	3.7000	uM
4-[5-[(E)-(2-amino-3,7-dicyano-4,6-dimethylcyclopenta[b]pyridin-5-ylidene)methyl]furan-2-yl]-2-chlorobenzoic acid	443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies	ki	3.8700	uM
3-[2-(2,4-difluorophenyl)ethynyl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid	725032: Inhibition of VHR (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	3.9000	uM
6-chloro-7-(2-morpholin-4-ylethylamino)quinoline-5,8-dione	217196: Inhibitory Activity against Recombinant Human VHR	ic50	4.0000	uM
[3-[3-[(3S)-3-(methylcarbamoyl)-7-(sulfoamino)-3,4-dihydro-1H-isoquinolin-2-yl]-3-oxopropyl]phenyl]sulfamic acid	262288: Inhibition of VHR	ic50	4.0000	uM
(3-benzoylphenyl) 2-[(2R)-4-hexadecanoyl-3-hydroxy-5-oxo-2H-furan-2-yl]acetate	217197: Inhibitory activity against vaccinia VH1-related phosphatase (VHR)	ic50	4.0000	uM
3-[2-(3-fluorophenyl)ethynyl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid	725032: Inhibition of VHR (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	4.1000	uM
2-[4-[(Z)-[5-(4-chlorophenyl)-6-ethoxycarbonyl-7-methyl-3-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidin-2-ylidene]methyl]phenoxy]acetic acid	569642: Inhibition of recombinant VHR expressed in Escherichia coli	ic50	4.2000	uM
(5E)-5-[(5-iodofuran-2-yl)methylidene]-1-(4-methoxyphenyl)-2-sulfanylidene-1,3-diazinane-4,6-dione	443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies	ki	4.4400	uM
4-[C-[4-[4-[(4-chlorophenyl)methoxy]phenyl]butyl]-N-[(3-methylphenyl)methyl]carbonimidoyl]-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one	1139709: Inhibition of Vaccinia H1-related phosphatase (unknown origin) by fluorescence emission assay in presence of 0.001% NP-40	ic50	4.6000	uM
(4-benzoylphenyl) 2-[(2R)-4-hexadecanoyl-3-hydroxy-5-oxo-2H-furan-2-yl]acetate	217197: Inhibitory activity against vaccinia VH1-related phosphatase (VHR)	ic50	4.6000	uM
4-[N-[(3-fluorophenyl)methyl]-C-pentadecylcarbonimidoyl]-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one	673781: Inhibition of VHR	ic50	4.6900	uM
[4-[3-(trifluoromethyl)diazirin-3-yl]phenyl] 2-[(2R)-4-hexadecanoyl-3-hydroxy-5-oxo-2H-furan-2-yl]acetate	217197: Inhibitory activity against vaccinia VH1-related phosphatase (VHR)	ic50	4.7000	uM
(2Z)-2-[1-[5-(1H-pyrrol-2-yl)furan-2-yl]ethylidene]pyrrole	1799614: Phosphatase Inhibition Assay from Article 10.1002/cbic.200400135: “The core structures of roseophilin and the prodigiosin alkaloids define a new class of protein tyrosine phosphatase inhibitors.”	ic50	4.9000	uM
6-hydroxy-2-phenyl-3-(2-phenylethynyl)-1-benzofuran-5-carboxylic acid	725032: Inhibition of VHR (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	5.0000	uM
methyl 5-amino-6-(7-amino-6-methoxy-5,8-dioxoquinolin-2-yl)-4-(2-hydroxy-3,4-dimethoxyphenyl)-3-methylpyridine-2-carboxylate	217196: Inhibitory Activity against Recombinant Human VHR	ic50	5.1000	uM
4-[N-[[3-(dimethylamino)phenyl]methyl]-C-pentadecylcarbonimidoyl]-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one	673781: Inhibition of VHR	ic50	5.1300	uM
4-[N-[[2-(dimethylamino)phenyl]methyl]-C-pentadecylcarbonimidoyl]-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one	673781: Inhibition of VHR	ic50	5.1900	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	6
Benzo(a)pyrene	affects methylation, increases expression	3
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression, increases abundance	2
methylmercuric chloride	increases expression	1
bisphenol A	increases expression	1
sodium arsenite	increases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
nutlin 3	increases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression	1
bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV)	increases expression	1
Gefitinib	affects response to substance	1
Sorafenib	affects cotreatment, increases expression	1
Resveratrol	decreases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	increases methylation	1
Cadmium	increases expression	1
Chelating Agents	increases expression, affects binding	1
Cisplatin	affects expression	1
Coal	decreases expression, increases abundance	1
Copper	affects binding, increases expression	1

ChEMBL screening assays

101 unique, capped per target: 95 binding, 5 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1034380	Binding	Inhibition of VHR expressed in Escherichia coli BL21(DE9)	Bitungolides A-F, new polyketides from the Indonesian sponge Theonella cf. swinhoei. — J Nat Prod
CHEMBL1738089	Functional	PUBCHEM_BIOASSAY: SAR VHR1 Fluorescent Assay for In Vitro dose response studies. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID1654, AID1661, AID1878, AID1992, AID2004, AID2070, AID2085]	PubChem BioAssay data set
CHEMBL4626312	ADMET	Inhibition of VHR (unknown origin) expressed in Escherichia coli BL21 using p-nitrophenyl phosphate as substrate measured after 30 mins by UV-vis spectrophotometric method	Highly Potent and Selective N-Aryl Oxamic Acid-Based Inhibitors for Mycobacterium tuberculosis Protein Tyrosine Phosphatase B. — J Med Chem

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7P2	Ubigene A-549 DUSP3 KO	Cancer cell line	Male
CVCL_D8KH	Ubigene HCT 116 DUSP3 KO	Cancer cell line	Male
CVCL_D9DT	Ubigene HEK293 DUSP3 KO	Transformed cell line	Female
CVCL_E0C4	Ubigene HeLa DUSP3 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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