DUSP22

Summary

DUSP22 (dual specificity phosphatase 22, HGNC:16077) is a protein-coding gene on chromosome 6p25.3, encoding Dual specificity protein phosphatase 22 (Q9NRW4). Dual specificity phosphatase; can dephosphorylate both phosphotyrosine and phosphoserine or phosphothreonine residues.

Enables phosphoprotein phosphatase activity; protein tyrosine kinase binding activity; and protein tyrosine kinase inhibitor activity. Involved in several processes, including cellular response to epidermal growth factor stimulus; negative regulation of T cell receptor signaling pathway; and negative regulation of focal adhesion assembly. Acts upstream of or within negative regulation of transcription by RNA polymerase II. Located in cytoplasm; leading edge of lamellipodium; and plasma membrane. Part of filamentous actin.

Source: NCBI Gene 56940 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 179 total — 8 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001286555

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16077
Approved symbol	DUSP22
Name	dual specificity phosphatase 22
Location	6p25.3
Locus type	gene with protein product
Status	Approved
Aliases	MKPX, JSP1, JKAP, VHX
Ensembl gene	ENSG00000112679
Ensembl biotype	protein_coding
OMIM	616778
Entrez	56940

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 protein_coding, 5 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000344450, ENST00000419235, ENST00000603005, ENST00000603290, ENST00000603296, ENST00000603453, ENST00000603726, ENST00000603795, ENST00000603881, ENST00000604914, ENST00000604971, ENST00000604988, ENST00000605035, ENST00000605315, ENST00000605391, ENST00000605863

RefSeq mRNA: 7 — MANE Select: NM_001286555 NM_001286555, NM_001422034, NM_001422035, NM_001422040, NM_001422041, NM_001422043, NM_020185

CCDS: CCDS4468, CCDS69035

Canonical transcript exons

ENST00000419235 — 7 exons

Exon	Start	End
ENSE00003480795	335114	335163
ENSE00003525221	304628	304661
ENSE00003537204	348103	348274
ENSE00003568725	311880	311962
ENSE00003686131	345854	345928
ENSE00003917749	292487	292560
ENSE00003918570	348769	351355

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.2001 / max 166.9609, expressed in 1812 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65387	9.9256	1749
65385	8.4446	1687
65386	4.9453	1647
65388	0.3648	156
65384	0.2818	90
65391	0.1367	60
65392	0.1014	56

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.32	gold quality
cervix squamous epithelium	UBERON:0006922	97.92	gold quality
gingival epithelium	UBERON:0001949	97.72	gold quality
squamous epithelium	UBERON:0006914	97.63	gold quality
esophagus squamous epithelium	UBERON:0006920	97.53	gold quality
tongue squamous epithelium	UBERON:0006919	97.19	gold quality
epithelium of esophagus	UBERON:0001976	97.14	gold quality
hair follicle	UBERON:0002073	96.95	gold quality
gingiva	UBERON:0001828	96.88	gold quality
visceral pleura	UBERON:0002401	96.41	gold quality
monocyte	CL:0000576	96.40	gold quality
mononuclear cell	CL:0000842	96.26	gold quality
oocyte	CL:0000023	96.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.09	gold quality
leukocyte	CL:0000738	96.01	gold quality
parietal pleura	UBERON:0002400	95.94	gold quality
pleura	UBERON:0000977	95.83	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.66	gold quality
tibia	UBERON:0000979	95.64	gold quality
endothelial cell	CL:0000115	95.26	gold quality
epithelium of nasopharynx	UBERON:0001951	94.87	gold quality
skin of hip	UBERON:0001554	94.82	gold quality
middle temporal gyrus	UBERON:0002771	94.76	gold quality
palpebral conjunctiva	UBERON:0001812	94.75	gold quality
oral cavity	UBERON:0000167	94.62	gold quality
adult organism	UBERON:0007023	94.46	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.32	gold quality
esophagus mucosa	UBERON:0002469	94.29	gold quality
lower esophagus	UBERON:0013473	94.22	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.86
E-GEOD-99795	no	34.46
E-HCAD-13	no	2.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting DUSP22, 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-205-3P	99.92	69.92	3165
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-34B-3P	98.70	67.40	1171
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-1243	97.07	65.44	719
HSA-MIR-134-3P	96.83	66.22	1001
HSA-MIR-3189-3P	96.80	66.34	896
HSA-MIR-381-5P	91.91	65.03	65

Literature-anchored findings (GeneRIF, showing 40)

• The crystal structre showed 1 domain with 6 alpha helices & 5 beta strans, a PTP-loop at the active site binding MES, and an Ala instead of a Trp at the substrate-stacking loop. (PMID:17068812)
• DUSP22 acts as a negative regulator of the estrogen receptor alpha-mediated signaling pathway in breast cancer cells. (PMID:17384676)
• a new role for JKAP in the modulation of FAK phosphorylation and cell motility. (PMID:20018849)
• Data show that t(6;7)(p25.3;q32.3) was associated with down-regulation of DUSP22 and up-regulation of MIR29 microRNAs on 7q32.3. (PMID:21030553)
• Firefighters had a higher prevalence of dual specificity phosphatase 22-promoter hypomethylation in blood DNA (P = 0.03) and the extent of hypomethylation correlated with duration of firefighting service (P = 0.04) but not with age. (PMID:22796920)
• Biallelic rearrangements of DUSP22 is found in CD30-positive T-cell lymphoproliferative disorders. (PMID:23337887)
• study identified presence of promoter hypermethylation of the DUSP22 gene in Alzheimer’s disease(AD); DUSP22 is a likely candidate gene for involvement in the pathogenesis of AD since it inhibits PKA activity and thereby determines TAU phosphorylation status and CREB signaling (PMID:24436131)
• findings suggest that CCR8 expression in ALCL is more closely related to the presence of DUSP22 rearrangements than to cutaneous involvement and that the function of CCR8 may extend beyond its skin-homing properties in this disease (PMID:25390351)
• The structure illuminates the molecular basis for substrate binding and may also facilitate the structure-assisted development of DUSP22 inhibitors. (PMID:25664796)
• Reduced DUSP22 expression was found in colorectal cancer specimens. Low expression level of DUSP22 in stage IV patients had a poor survival outcome (PMID:26032091)
• Studies suggest that the presence of dual specificity phosphatase 22 (DUSP22) and p63 tumor suppressor protein (TP63) rearrangements might be useful to support a diagnosis of anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL). (PMID:26223379)
• Report morphologic features of ALK-negative anaplastic large cell lymphomas with DUSP22 gene rearrangements. (PMID:26379151)
• JKAP/DUSP22 is downregulated in T cells of systemic lupus erythematosus nephritis (PMID:27557500)
• Data show that dual specificity phosphatase 22 (DUSP22) functions as a tumor suppressor gene in peripheral T-cell lymphomas (PTCL). (PMID:27626696)
• findings connect NOTCH1, DUSP22, and CCL19-driven chemotaxis within a single functional network, suggesting that modulation of the homing process may provide a relevant contribution to the unfavorable prognosis associated with NOTCH1 mutations in CLL. (PMID:28017968)
• These findings indicate that DUSP22 rearrangements define a molecularly distinct subgroup of Anaplastic large cell lymphomas, and that immunogenic cues related to antigenicity, costimulatory molecule expression, and inactivity of the PD-1/PD-L1 immune checkpoint likely contribute to their favorable prognosis. (PMID:30093402)
• DUSP22-rearranged anaplastic lymphomas are characterized by specific morphological features and a lack of cytotoxic and JAK/STAT surrogate markers. (PMID:30361415)
• Authors confirm that DUSP22- rearranged ALK-negative ALCL have unique pathological features. (PMID:30873584)
• JNK pathway-associated phosphatase is of good value in predicting lower sepsis risk. (PMID:31206807)
• Loss of DUSP22 in prostate cancer cells leads to aberrant activation of both EGFR-ERKs and AR signaling and cancer progression. (PMID:31693867)
• Striking Association of Lymphoid Enhancing Factor (LEF1) Overexpression and DUSP22 Rearrangements in Anaplastic Large Cell Lymphoma. (PMID:33165091)
• JNK Pathway-Associated Phosphatase as a Serum Marker for Disease Activity and Treatment Outcome of Juvenile Idiopathic Arthritis. (PMID:33441511)
• JNK pathway-associated phosphatase associates with rheumatoid arthritis risk, disease activity, and its longitudinal elevation relates to etanercept treatment response. (PMID:33547838)
• JKAP relates to disease risk, severity, and Th1 and Th17 differentiation in Parkinson’s disease. (PMID:34289265)
• JKAP, Th1 cells, and Th17 cells are dysregulated and inter-correlated, among them JKAP and Th17 cells relate to cognitive impairment progression in Alzheimer’s disease patients. (PMID:34595688)
• Measurement of synovium and serum dual specificity phosphatase 22 level: Their inter-correlation and potency as biomarkers in rheumatoid arthritis. (PMID:34811816)
• Clinical value of serum JKAP in acute ischemic stroke patients. (PMID:35274367)
• Hepatocyte phosphatase DUSP22 mitigates NASH-HCC progression by targeting FAK. (PMID:36209205)
• The longitudinal changes of serum JKAP and IL-17A, and their linkage with anxiety, depression, and cognitive impairment in acute ischemic stroke patients. (PMID:36397283)
• DUSP22 rearrangement is associated with a distinctive immunophenotype but not outcome in patients with systemic ALK-negative anaplastic large cell lymphoma. (PMID:36453104)
• ALK-negative anaplastic large cell lymphoma with DUSP22 rearrangement has distinctive disease characteristics with better progression-free survival: a LYSA study. (PMID:36453105)
• DUSP22-rearranged ALK-negative anaplastic large cell lymphoma is a pathogenetically distinct disease but can have variable clinical outcome. (PMID:36453106)
• Dual-specificity phosphatases 22-deficient T cells contribute to the pathogenesis of ankylosing spondylitis. (PMID:36765305)
• DUSP22 suppresses tumor progression by directly dephosphorylating AKT in non-small cell lung cancer. (PMID:37937915)
• Serum JKAP reflects Th2 and Th17 cell levels, and diabetic nephropathy risk and severity in diabetes mellitus patients. (PMID:38179996)
• The phosphatase DUSP22 inhibits UBR2-mediated K63-ubiquitination and activation of Lck downstream of TCR signalling. (PMID:38225265)
• DUSP22 Ameliorates Endothelial-to-Mesenchymal Transition in HUVECs through Smad2/3 and MAPK Signaling Pathways. (PMID:38495810)
• JNK Pathway-Associated Phosphatase Deficiency Facilitates Atherosclerotic Progression by Inducing T-Helper 1 and 17 Polarization and Inflammation in an ERK- and NF-kappaB Pathway-Dependent Manner. (PMID:38797677)
• Exosomal miR-1228-5p down-regulates DUSP22 to promotes cell proliferation and migration in small cell lung cancer. (PMID:38851418)
• DUSP22-rearranged primary cutaneous CD30-positive T-cell lymphoproliferative disorders and adult T-cell leukemia/lymphoma frequently share the LEF1+/TIA1- immunophenotype. (PMID:38971328)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dusp22b	ENSDARG00000039850
mus_musculus	Dusp22	ENSMUSG00000069255
rattus_norvegicus	Dusp22	ENSRNOG00000056376

Paralogs (31): DUSP13B (ENSG00000079393), DUSP12 (ENSG00000081721), SSH1 (ENSG00000084112), DUSP3 (ENSG00000108861), PTPMT1 (ENSG00000110536), DUSP16 (ENSG00000111266), EPM2A (ENSG00000112425), 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 22 — Q9NRW4 (reviewed: Q9NRW4)

Alternative names: JNK pathway associated phosphatase, JNK-stimulatory phosphatase-1, Low molecular weight dual specificity phosphatase 2, Mitogen-activated protein kinase phosphatase x

All UniProt accessions (7): A0A384NLC8, Q9NRW4, S4R378, S4R3A4, S4R3K1, S4R3M1, S4R459

UniProt curated annotations — full annotation on UniProt →

Function. Dual specificity phosphatase; can dephosphorylate both phosphotyrosine and phosphoserine or phosphothreonine residues. Activates the JNK signaling pathway. Inhibits T-cell receptor signaling and T-cell mediated immune responses, acting, at least in part, by inducing degradation of E3 ubiquitin ligase UBR2. Dephosphorylates and thereby induces ‘Lys-48’-linked ubiquitination of UBR2, leading to proteasomal degradation of UBR2. Dephosphorylates and thereby inactivates tyrosine kinase LCK. Inhibits UBR2-mediated ‘Lys-63’-linked ubiquitination of LCK. May play a role in B-cell receptor (BCR) signaling and B-cell function.

Subunit / interactions. Monomer. Interacts with LCK; the interaction is direct. Interacts with UBR2; the interaction is direct.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitous. Highest expression seen in heart, placenta, lung, liver, kidney and pancreas.

Post-translational modifications. Myristoylation regulates subcellular location, and is necessary for activation of JNK.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NRW4-1	1	yes
Q9NRW4-2	2

RefSeq proteins (11): NP_001273484, NP_001408961, NP_001408963, NP_001408964, NP_001408967, NP_001408968, NP_001408969, NP_001408970, NP_001408971, NP_001408972, NP_064570 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000340	Dual-sp_phosphatase_cat-dom	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR020422	TYR_PHOSPHATASE_DUAL_dom	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily

Pfam: PF00782

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 (31 total): helix 8, strand 6, binding site 5, mutagenesis site 4, initiator methionine 1, chain 1, lipid moiety-binding region 1, splice variant 1, sequence variant 1, domain 1, active site 1, modified residue 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
7C8S	X-RAY DIFFRACTION	1.31
4WOH	X-RAY DIFFRACTION	1.34
6L1S	X-RAY DIFFRACTION	1.36
6LVQ	X-RAY DIFFRACTION	1.38
1WRM	X-RAY DIFFRACTION	1.5
6LMY	X-RAY DIFFRACTION	1.5
6LOU	X-RAY DIFFRACTION	1.53
6LOT	X-RAY DIFFRACTION	1.69

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRW4-F1	93.64	0.90

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): 88 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (5): 89; 90; 92; 93; 94

Post-translational modifications (2): 2, 58

Mutagenesis-validated functional residues (4):

Position	Phenotype
57	over 40-fold decrease in catalytic efficiency for p-nitrophenyl phosphate.
88	does not dephosphorylate ubr2.
93	over 150-fold decrease in catalytic efficiency for p-nitrophenyl phosphate.
128	over 100-fold decrease in catalytic efficiency for p-nitrophenyl phosphate.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 272 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_FOCAL_ADHESION_ASSEMBLY, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_CELL_JUNCTION_ASSEMBLY

GO Biological Process (21): negative regulation of transcription by RNA polymerase II (GO:0000122), immune system process (GO:0002376), negative regulation of T cell mediated immunity (GO:0002710), transforming growth factor beta receptor signaling pathway (GO:0007179), negative regulation of cell migration (GO:0030336), intracellular signal transduction (GO:0035556), regulation of cell population proliferation (GO:0042127), positive regulation of JNK cascade (GO:0046330), negative regulation of T cell receptor signaling pathway (GO:0050860), negative regulation of T cell activation (GO:0050868), negative regulation of focal adhesion assembly (GO:0051895), cellular response to epidermal growth factor stimulus (GO:0071364), protein dephosphorylation (GO:0006470), negative regulation of cell adhesion (GO:0007162), signal transduction (GO:0007165), dephosphorylation (GO:0016311), T cell receptor signaling pathway (GO:0050852), positive regulation of T cell receptor signaling pathway (GO:0050862), protein K63-linked ubiquitination (GO:0070534), protein K48-linked ubiquitination (GO:0070936), cellular response to growth factor stimulus (GO:0071363)

GO Molecular Function (8): protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine phosphatase activity (GO:0004725), non-membrane spanning protein tyrosine phosphatase activity (GO:0004726), protein tyrosine/serine/threonine phosphatase activity (GO:0008138), protein tyrosine kinase inhibitor activity (GO:0030292), protein tyrosine kinase binding (GO:1990782), phosphoprotein phosphatase activity (GO:0004721), hydrolase activity (GO:0016787)

GO Cellular Component (5): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), filamentous actin (GO:0031941), leading edge of lamellipodium (GO:0061851)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphoprotein phosphatase activity	3
intracellular anatomical structure	2
regulation of cellular process	2
T cell receptor signaling pathway	2
regulation of T cell receptor signaling pathway	2
protein polyubiquitination	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
biological_process	1
T cell mediated immunity	1
negative regulation of lymphocyte mediated immunity	1
regulation of T cell mediated immunity	1
negative regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
signal transduction	1
cell population proliferation	1
JNK cascade	1
positive regulation of MAPK cascade	1
regulation of JNK cascade	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
negative regulation of cell-matrix adhesion	1
focal adhesion assembly	1
regulation of focal adhesion assembly	1
negative regulation of cell-substrate junction organization	1
negative regulation of cell junction assembly	1
response to epidermal growth factor	1
cellular response to growth factor stimulus	1
dephosphorylation	1
protein modification process	1
cell adhesion	1

Protein interactions and networks

STRING

1640 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUSP22	TP63	Q9H3D4	616
DUSP22	IRF4	Q15306	598
DUSP22	STAT3	P40763	587
DUSP22	ALK	Q9UM73	587
DUSP22	DUSP23	Q9BVJ7	584
DUSP22	TNFRSF8	P28908	576
DUSP22	EXOC2	Q96KP1	568
DUSP22	PTP4A2	Q12974	509
DUSP22	NAIP	Q13075	493
DUSP22	TCAF1	Q9Y4C2	475
DUSP22	NPY4R2	P0DQD5	469
DUSP22	ACTMAP	Q5BKX5	450
DUSP22	ARHGEF35	A5YM69	443
DUSP22	ZNF169	Q14929	441
DUSP22	DUSP11	O75319	438
DUSP22	GPRIN2	O60269	438

IntAct

13 interactions, top by confidence:

A	B	Type	Score
DUSP22	MBP	psi-mi:“MI:0915”(physical association)	0.400
DUSP22	HOXA1	psi-mi:“MI:0915”(physical association)	0.370
DUSP22	ACACB	psi-mi:“MI:0914”(association)	0.350
DUSP22	POTEF	psi-mi:“MI:0914”(association)	0.350
CALML3	MYO1C	psi-mi:“MI:0914”(association)	0.350
DIABLO	GFER	psi-mi:“MI:0914”(association)	0.350
CALM1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
COMMD2		psi-mi:“MI:0914”(association)	0.350
DUSP22	RAP2A	psi-mi:“MI:0914”(association)	0.350
FUNDC2	RAP2A	psi-mi:“MI:0914”(association)	0.350
MND1		psi-mi:“MI:0914”(association)	0.350
TMED2		psi-mi:“MI:0914”(association)	0.350

BioGRID (160): HSD17B4 (Proximity Label-MS), RPL27A (Proximity Label-MS), DUSP22 (Affinity Capture-MS), ARF5 (Affinity Capture-MS), TAGLN2 (Affinity Capture-MS), DUSP23 (Affinity Capture-MS), VTI1B (Affinity Capture-MS), SVIP (Affinity Capture-MS), PGRMC1 (Affinity Capture-MS), PGRMC2 (Affinity Capture-MS), RAB14 (Affinity Capture-MS), DUSP28 (Affinity Capture-MS), TMEM11 (Affinity Capture-MS), HMOX2 (Affinity Capture-MS), NME1 (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: A4IHU7, F1QWM2, O09112, O13632, O55737, O95147, P0C591, P0C592, P0C593, P0C594, P0C595, P0C596, P0C597, P0C598, P0C599, P0C5A0, P0C5A1, P0C5A2, P28562, P28563, P51452, Q05922, Q13115, Q13202, Q148W8, Q16828, Q16829, Q17QJ3, Q17QM8, Q1LWL2, Q29RA3, Q2KJ36, Q39491, Q4KL92, Q4RQD3, Q4V7N3, Q54T76, Q54Y32, Q556Y8, Q55BI8

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
DUSP22	“down-regulates activity”	ESR1	dephosphorylation
DUSP22	“down-regulates activity”	LCK	dephosphorylation
DUSP22	“down-regulates activity”	STAT3	dephosphorylation
FUS	“down-regulates quantity by repression”	DUSP22	“post transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	1
Uncertain significance	39
Likely benign	21
Benign	89

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
146312	GRCh38/hg38 6p25.3(chr6:163083-2029531)x3	Pathogenic
253658	GRCh37/hg19 6p25.3(chr6:180959-2180143)x1	Pathogenic
2685192	GRCh37/hg19 6p25.3(chr6:156975-2072578)x1	Pathogenic
4076015	GRCh37/hg19 6p25.3(chr6:156975-2132685)x1	Pathogenic
441555	GRCh37/hg19 6p25.3(chr6:156974-2030623)x1	Pathogenic
442601	GRCh37/hg19 6p25.3(chr6:195229-2117379)x1	Pathogenic
57019	GRCh38/hg38 6p25.3(chr6:163083-1951351)x3	Pathogenic
58408	GRCh38/hg38 6p25.3-25.2(chr6:163083-2724611)x1	Pathogenic
3391822	GRCh37/hg19 6p25.3-25.2(chr6:156975-2836366)x3	Likely pathogenic

SpliceAI

1582 predictions. Top by Δscore:

Variant	Effect	Δscore
6:292557:CAAGG:C	donor_loss	1.0000
6:292558:AAGGT:A	donor_loss	1.0000
6:292559:AGG:A	donor_loss	1.0000
6:292562:T:A	donor_loss	1.0000
6:304661:GGT:G	donor_loss	1.0000
6:304662:G:GC	donor_loss	1.0000
6:335164:G:GG	donor_gain	1.0000
6:345927:TGGTA:T	donor_loss	1.0000
6:345929:G:GA	donor_loss	1.0000
6:345930:T:A	donor_loss	1.0000
6:348101:A:AG	acceptor_gain	1.0000
6:348101:AGCCT:A	acceptor_gain	1.0000
6:348102:G:GG	acceptor_gain	1.0000
6:348102:GCCTG:G	acceptor_gain	1.0000
6:348767:A:AG	acceptor_gain	1.0000
6:348768:G:GG	acceptor_gain	1.0000
6:293995:G:GA	donor_gain	0.9900
6:304622:TCCTA:T	acceptor_loss	0.9900
6:304623:CCTAG:C	acceptor_loss	0.9900
6:304624:CTAG:C	acceptor_loss	0.9900
6:304625:TAG:T	acceptor_loss	0.9900
6:304626:A:AC	acceptor_loss	0.9900
6:304626:A:AG	acceptor_gain	0.9900
6:304627:G:GG	acceptor_gain	0.9900
6:304627:G:T	acceptor_loss	0.9900
6:304662:G:GG	donor_gain	0.9900
6:311878:A:AG	acceptor_gain	0.9900
6:311879:G:GG	acceptor_gain	0.9900
6:335159:AACCT:A	donor_gain	0.9900
6:335161:CCT:C	donor_gain	0.9900

AlphaMissense

1353 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:348230:T:C	F131L	1.000
6:348232:C:A	F131L	1.000
6:348232:C:G	F131L	1.000
6:335144:G:C	D57H	0.999
6:348110:G:T	G91W	0.999
6:348111:G:A	G91E	0.999
6:348120:G:T	R94M	0.999
6:348205:A:C	R122S	0.999
6:348205:A:T	R122S	0.999
6:348231:T:C	F131S	0.999
6:348243:T:C	L135P	0.999
6:304650:G:A	G15D	0.998
6:304650:G:T	G15V	0.998
6:335145:A:G	D57G	0.998
6:335145:A:T	D57V	0.998
6:335146:T:A	D57E	0.998
6:335146:T:G	D57E	0.998
6:345882:T:C	F73L	0.998
6:345884:C:A	F73L	0.998
6:345884:C:G	F73L	0.998
6:345917:C:G	C84W	0.998
6:345919:T:C	L85P	0.998
6:348110:G:A	G91R	0.998
6:348110:G:C	G91R	0.998
6:348111:G:T	G91V	0.998
6:348120:G:C	R94T	0.998
6:348121:G:C	R94S	0.998
6:348121:G:T	R94S	0.998
6:348122:A:C	S95R	0.998
6:348124:C:A	S95R	0.998

dbSNP variants (sampled 300 via entrez): RS1000062330 (6:312302 A>G), RS1000103756 (6:316298 C>T), RS1000104604 (6:329925 T>G), RS1000133317 (6:340918 G>A), RS1000139367 (6:308912 G>A,T), RS1000163486 (6:299236 C>A), RS1000191986 (6:308712 C>T), RS1000223381 (6:333351 T>A,C,G), RS1000237911 (6:337234 T>A), RS1000334968 (6:319806 C>A,G), RS1000362493 (6:305255 G>A,C), RS1000375363 (6:329929 T>C,G), RS1000447038 (6:296251 T>C), RS1000475689 (6:350065 C>G), RS1000478786 (6:293555 G>C)

Disease associations

OMIM: gene MIM:616778 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary amenorrhea (MONDO:1060208)

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST003043_171	Inflammatory bowel disease	6.000000e-09
GCST003044_106	Crohn’s disease	1.000000e-09
GCST004866_25	Alopecia areata	9.000000e-07
GCST005987_38	Albumin-globulin ratio	4.000000e-12
GCST005989_15	Serum total protein levels	3.000000e-17
GCST005990_54	Non-albumin protein levels	2.000000e-19
GCST006661_206	Male-pattern baldness	1.000000e-08
GCST006984_2	Takayasu arteritis	3.000000e-09
GCST007995_48	Asthma (childhood onset)	7.000000e-11
GCST011100_8	Aging traits (healthspan, parental lifespan or longevity) (multivariate analysis)	8.000000e-26
GCST90002381_408	Eosinophil count	2.000000e-14
GCST90011866_13	Systemic lupus erythematosus	3.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005128	albumin:globulin ratio measurement
EFO:0007796	parental longevity
EFO:0009762	healthspan
EFO:0004842	eosinophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3924 (SINGLE PROTEIN)

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

ChEMBL bioactivities

20 potent at pChembl≥5 of 33 total, top 20 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.89	IC50	1300	nM	CHEMBL365871
5.85	IC50	1400	nM	CHEMBL2316902
5.72	IC50	1900	nM	CHEMBL2316907
5.68	IC50	2100	nM	CHEMBL4750435
5.65	IC50	2250	nM	CHEMBL230941
5.63	IC50	2350	nM	CHEMBL230472
5.60	IC50	2500	nM	CHEMBL230576
5.58	IC50	2600	nM	CHEMBL435096
5.55	IC50	2790	nM	CHEMBL396800
5.54	IC50	2900	nM	CHEMBL2316906
5.52	IC50	3020	nM	CHEMBL230843
5.38	IC50	4200	nM	CHEMBL185401
5.26	IC50	5550	nM	CHEMBL230471
5.18	IC50	6600	nM	CHEMBL183967
5.16	IC50	7000	nM	CHEMBL183967
5.14	IC50	7300	nM	CHEMBL360332
5.09	IC50	8050	nM	CHEMBL425838
5.08	IC50	8360	nM	CHEMBL230681
5.08	IC50	8390	nM	CHEMBL446453
5.00	IC50	1e+04	nM	CHEMBL181535

PubChem BioAssay actives

20 with measured affinity, of 75 total; 19 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
3-[(5Z)-5-[(4-fluorophenyl)methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]benzoic acid	241216: Inhibition of JNK-stimulating phosphatase-1 (JSP-1)	ic50	1.3000	uM
6-hydroxy-2-phenyl-3-[2-[3-(trifluoromethyl)phenyl]ethynyl]-1-benzofuran-5-carboxylic acid	725028: Inhibition of VHX (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	1.4000	uM
6-hydroxy-2-phenyl-3-[2-[4-(trifluoromethoxy)phenyl]ethynyl]-1-benzofuran-5-carboxylic acid	725028: Inhibition of VHX (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	1.9000	uM
4-[1-(4-methoxyphenyl)-3-(2-oxochromen-7-yl)pyrrolo[2,3-b]pyridin-5-yl]benzoic acid	1706921: Inhibition of DUSP22 (unknown origin) pre-incubated for 20 mins followed by fluorescence substrate addition and measured after 120 mins by DiFMUP assay	ic50	2.1000	uM
1-N-[2,3-bis(furan-2-yl)quinoxalin-6-yl]-3-N-cyclohexylpiperidine-1,3-dicarboxamide	290337: Inhibition of GST-tagged human recombinant JSP1	ic50	2.2500	uM
1-N-[2,3-bis(furan-2-yl)quinoxalin-6-yl]-3-N-butyl-3-N-ethylpiperidine-1,3-dicarboxamide	290337: Inhibition of GST-tagged human recombinant JSP1	ic50	2.3500	uM
1-N-[2,3-bis(furan-2-yl)quinoxalin-6-yl]-3-N,3-N-dipropylpiperidine-1,3-dicarboxamide	290337: Inhibition of GST-tagged human recombinant JSP1	ic50	2.5000	uM
3-[(5Z)-5-[(4-nitrophenyl)methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]benzoic acid	241216: Inhibition of JNK-stimulating phosphatase-1 (JSP-1)	ic50	2.6000	uM
1-N-[2,3-bis(furan-2-yl)quinoxalin-6-yl]-3-N-butylpiperidine-1,3-dicarboxamide	290337: Inhibition of GST-tagged human recombinant JSP1	ic50	2.7900	uM
3-[2-(3,5-difluorophenyl)ethynyl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid	725028: Inhibition of VHX (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	2.9000	uM
1-N-[2,3-bis(furan-2-yl)quinoxalin-6-yl]-3-N-cyclopentylpiperidine-1,3-dicarboxamide	290337: Inhibition of GST-tagged human recombinant JSP1	ic50	3.0200	uM
4-[(5Z)-5-[(4-fluorophenyl)methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]benzoic acid	241216: Inhibition of JNK-stimulating phosphatase-1 (JSP-1)	ic50	4.2000	uM
1-N-[2,3-bis(furan-2-yl)quinoxalin-6-yl]-3-N-butyl-3-N-methylpiperidine-1,3-dicarboxamide	290337: Inhibition of GST-tagged human recombinant JSP1	ic50	5.5500	uM
3-[(5Z)-5-benzylidene-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]benzoic acid	241216: Inhibition of JNK-stimulating phosphatase-1 (JSP-1)	ic50	6.6000	uM
3-[(5Z)-5-(cyclohexylmethylidene)-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]benzoic acid	241216: Inhibition of JNK-stimulating phosphatase-1 (JSP-1)	ic50	7.3000	uM
1-N-[2,3-bis(furan-2-yl)quinoxalin-6-yl]-3-N-tert-butylpiperidine-1,3-dicarboxamide	290337: Inhibition of GST-tagged human recombinant JSP1	ic50	8.0500	uM
1-N-[2,3-bis(furan-2-yl)quinoxalin-6-yl]-3-N-(2-methylpropyl)piperidine-1,3-dicarboxamide	290337: Inhibition of GST-tagged human recombinant JSP1	ic50	8.3600	uM
N-[2,3-bis(furan-2-yl)quinoxalin-6-yl]-3-(piperidine-1-carbonyl)piperidine-1-carboxamide	290337: Inhibition of GST-tagged human recombinant JSP1	ic50	8.3900	uM
[4-[(5Z)-5-benzylidene-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]phenyl]methylphosphonic acid	241216: Inhibition of JNK-stimulating phosphatase-1 (JSP-1)	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects expression, affects cotreatment, increases expression	3
Benzo(a)pyrene	increases expression, affects methylation, decreases methylation	2
chloroacetaldehyde	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects cotreatment, decreases methylation	1
benzo(e)pyrene	affects methylation	1
nickel sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
thifluzamide	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Cidofovir	increases expression	1
Coumestrol	decreases expression	1
Clodronic Acid	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Ibuprofen	increases expression	1
Ifosfamide	increases expression	1
Methapyrilene	affects methylation	1
Methyl Methanesulfonate	decreases expression	1
Oxygen	decreases expression	1
Progesterone	increases expression	1
Valproic Acid	decreases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Crocidolite	affects expression	1

ChEMBL screening assays

19 unique, capped per target: 19 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1767974	Binding	Inhibition of human DUSP22	Utilization of nitrophenylphosphates and oxime-based ligation for the development of nanomolar affinity inhibitors of the Yersinia pestis outer protein H (YopH) phosphatase. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07164248	Not specified	COMPLETED	Evaluation of Bone Mineral Density Indications and Outcomes in Female Adolescents: Implications for Early Detection of Osteopenia/Osteoporosis and Gynecologic Practice