DUSP5

Summary

DUSP5 (dual specificity phosphatase 5, HGNC:3071) is a protein-coding gene on chromosome 10q25.2, encoding Dual specificity protein phosphatase 5 (Q16690). Dual specificity protein phosphatase; active with phosphotyrosine, phosphoserine and phosphothreonine residues.

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 product inactivates ERK1, is expressed in a variety of tissues with the highest levels in pancreas and brain, and is localized in the nucleus.

Source: NCBI Gene 1847 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 74 total
• Druggable target: yes
• MANE Select transcript: NM_004419

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3071
Approved symbol	DUSP5
Name	dual specificity phosphatase 5
Location	10q25.2
Locus type	gene with protein product
Status	Approved
Aliases	HVH3
Ensembl gene	ENSG00000138166
Ensembl biotype	protein_coding
OMIM	603069
Entrez	1847

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000369583, ENST00000468749, ENST00000895745, ENST00000925260

RefSeq mRNA: 1 — MANE Select: NM_004419 NM_004419

CCDS: CCDS7566

Canonical transcript exons

ENST00000369583 — 4 exons

Exon	Start	End
ENSE00001450392	110510020	110511533
ENSE00001450398	110497907	110498500
ENSE00003317820	110502721	110502869
ENSE00003597252	110506935	110507154

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 98.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.1634 / max 1233.3961, expressed in 1756 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106969	26.5593	1729
106968	4.4501	1191
106967	0.6252	228
106972	0.3078	159
106970	0.1276	51
106971	0.0933	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	98.67	gold quality
mucosa of urinary bladder	UBERON:0001259	97.60	gold quality
pharyngeal mucosa	UBERON:0000355	95.88	gold quality
gall bladder	UBERON:0002110	94.24	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.37	gold quality
epithelium of esophagus	UBERON:0001976	93.25	gold quality
esophagus squamous epithelium	UBERON:0006920	93.16	gold quality
esophagus mucosa	UBERON:0002469	92.86	gold quality
islet of Langerhans	UBERON:0000006	92.56	gold quality
adrenal tissue	UBERON:0018303	92.16	gold quality
secondary oocyte	CL:0000655	92.14	gold quality
cartilage tissue	UBERON:0002418	92.07	gold quality
vena cava	UBERON:0004087	92.00	gold quality
palpebral conjunctiva	UBERON:0001812	91.53	gold quality
oral cavity	UBERON:0000167	91.38	gold quality
cerebellar cortex	UBERON:0002129	90.77	gold quality
cerebellar hemisphere	UBERON:0002245	90.72	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.45	gold quality
rectum	UBERON:0001052	90.33	gold quality
cerebellum	UBERON:0002037	89.90	gold quality
omental fat pad	UBERON:0010414	89.68	gold quality
oocyte	CL:0000023	89.65	gold quality
peritoneum	UBERON:0002358	89.59	gold quality
placenta	UBERON:0001987	89.56	gold quality
trachea	UBERON:0003126	88.79	gold quality
amniotic fluid	UBERON:0000173	88.20	gold quality
stromal cell of endometrium	CL:0002255	87.82	gold quality
ileal mucosa	UBERON:0000331	87.61	gold quality
adipose tissue of abdominal region	UBERON:0007808	87.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.06	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	269.78
E-CURD-88	yes	203.65
E-MTAB-9467	yes	51.79
E-MTAB-10287	yes	31.99
E-MTAB-8142	yes	27.45
E-HCAD-11	yes	17.81
E-CURD-46	yes	13.63
E-GEOD-84465	yes	6.87
E-MTAB-7381	no	558.81
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, FOXO3, TP53

miRNA regulators (miRDB)

82 targeting DUSP5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-196A-1-3P	99.99	72.15	2772
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-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
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
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-3912-5P	99.95	66.11	925
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1297	99.91	73.41	3162

Literature-anchored findings (GeneRIF, showing 36)

• DUSP5 is a direct target of p53. (PMID:12944906)
• DUSP5 inactivates ERK2 and causes both nuclear translocation and sequestration of inactive ERK2. (PMID:15713638)
• the crystal structure of the catalytic domain of DUSP5 in an active conformation. (PMID:17078075)
• These results suggest the existence of an ERK1/2-driven negative feed-back regulation of ERK5 signaling in epidermal growth factor-stimulated HK-2 cells, which is mediated by MKP-3, DUSP5 and/or MKP-1. (PMID:17131384)
• proper regulation of DUSP5 activity is critical for normal immune system development, IL-2 actions, and tolerance (PMID:18430737)
• mutations in dusp-5 and snrk-1 have been identified in affected tissues of patients with vascular anomalies, implicating the Snrk-1-Dusp-5 signaling pathway in human disease. (PMID:18927432)
• In FD-Fms cells, overexpression of human DUSP5 increased M-CSF-dependent proliferation & decreased differentiation. Overexpression in multipotent EGER-Fms cells increased M-CSF-induced proliferation & caused granulocytic, not macrophage, differentiation. (PMID:19801501)
• the differential up-regulation of MKP3 by Ets2 and of DUSP5 by c-Jun may converge in similar functional roles for these MAP kinase phosphatases in the growth arrest versus proliferation decisions of breast cancer cells (PMID:20554528)
• DUSP5 and DUSP6 selectively control ERK pathway activity and proliferation. (PMID:20806045)
• Studies indicate that dual-specificity MAP kinase phosphatases (MKPs) DUSP6/MKP-3 and DUSP5 are localized in the cytoplasm and nuclear compartments. (PMID:22812510)
• DUSP5 methylation may serve as a prognostic marker for gastric cancer (GC), but this requires validation in a larger set of GC samples. (PMID:23402999)
• DUSP1, DUSP4, and DUSP5 differentially modulate endothelial MAPK signaling pathways downstream of Tie-2 receptors. (PMID:24308939)
• Data indicate that cells from Burkitt’s lymphoma, leukemia, neuroblastoma and Ewing sarcoma showed a higher dual-specificity phosphatase 5 pseudogene 1 (DUSP5P1)/dual specificity phosphatase 5 (DUSP5 ratio than normal cells. (PMID:24651368)
• The DUSP5 S147P protein is hypoactive compared to the DUSP5 wild-type protein. (PMID:25519881)
• Findings indicate that zinc-finger protein X-linked (ZFX) promotes colorectal cancer (CRC) progression by suppressing dual specificity phosphatase 5 (DUSP5) expression and suggest that ZFX is a prognostic biomarker and potentially useful therapeutic target in stage II/III CRC patients. (PMID:26967242)
• role of the secondary binding site in assembling the DUSP5-pERK pre-reactive complex was further demonstrated by molecular dynamics simulations that showed that the remote C197-C219 disulfide linkage controls the structure of the secondary binding pocket based on its redox state (i.e., disulfide/dithiol) and, in turn, the enzymatic activity of DUSP5 (PMID:27739308)
• Results show that DUSP5 and DUSP6 mRNA are overexpressed in human PTCs, especially in BRAFV600E mutated papillary thyroid carcinomas (PTCs), and positively control cell migration and invasion. (PMID:28910386)
• DUSP5 expression in skeletal muscle was ninefold higher immediately after exercise and returned to pre-exercise level within 2 h. (PMID:28989118)
• DUSP5 functions in the feedback inhibition of ERK1/2 signaling in response to TNFalpha, which resulted in increased inflammatory gene expression. (PMID:29018280)
• Methylation the DUSP5 gene promoter can serve as an additional means of identifying CIMP-high colorectal cancers. (PMID:29379130)
• Data show that dual specificity phosphatase 5 (DUSP5) is a downstream target of p68 RNA helicase (p68). (PMID:30387548)
• Conserved Histidine and Serine in the HCXXXXXRS Motif of Human Dual-Specificity Phosphatase 5 (PMID:30835471)
• Dual-specificity phosphatase (DUSP) genetic variants predict pulmonary hypertension in patients with bronchopulmonary dysplasia. (PMID:31330530)
• DUSP5 expression is elevated in hepatocytes by ER stress through the PERK-CHOP pathway, contributing to hepatocyte death possibly through ERK inhibition. (PMID:31491992)
• Integrated analysis identifies DUSP5 as a novel prognostic indicator for thyroid follicular carcinoma. (PMID:31821724)
• Distinct intra-mitochondrial localizations of pro-survival kinases and regulation of their functions by DUSP5 and PHLPP-1. (PMID:32480039)
• The long noncoding RNA H19 attenuates force-driven cartilage degeneration via miR-483-5p/Dusp5. (PMID:32703413)
• Long non-coding RNA ARAP1-AS1 promotes the proliferation and migration in cervical cancer through epigenetic regulation of DUSP5. (PMID:32985327)
• DUSP5 suppresses interleukin-1beta-induced chondrocyte inflammation and ameliorates osteoarthritis in rats. (PMID:33361528)
• DUSP5-mediated inhibition of smooth muscle cell proliferation suppresses pulmonary hypertension and right ventricular hypertrophy. (PMID:34142888)
• Silencing of AFAP1-AS1 lncRNA impairs cell proliferation and migration by epigenetically promoting DUSP5 expression in pre-eclampsia. (PMID:34192359)
• METTL3-mediated N6-methyladenosine modification of DUSP5 mRNA promotes gallbladder-cancer progression. (PMID:34799724)
• miR-203 suppresses pancreatic cancer cell proliferation and migration by modulating DUSP5 expression. (PMID:36183924)
• BAF53A drives colorectal cancer development by regulating DUSP5-mediated ERK phosphorylation. (PMID:36526622)
• Targeting DUSP5 suppresses malignant phenotypes of BRAF-mutant thyroid cancer cells and improves their response to sorafenib. (PMID:38564084)
• Epithelial cells derived exosomal miR-203a-3p facilitates stromal inflammation of type IIIA chronic prostatitis/chronic pelvic pain syndrome by targeting DUSP5 and increasing MCP-1 generation. (PMID:38724995)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dusp5	ENSDARG00000019307
mus_musculus	Dusp5	ENSMUSG00000034765
rattus_norvegicus	Dusp5	ENSRNOG00000014061

Paralogs (31): DUSP13B (ENSG00000079393), DUSP12 (ENSG00000081721), SSH1 (ENSG00000084112), DUSP3 (ENSG00000108861), PTPMT1 (ENSG00000110536), DUSP16 (ENSG00000111266), EPM2A (ENSG00000112425), DUSP22 (ENSG00000112679), DUSP1 (ENSG00000120129), DUSP4 (ENSG00000120875), STYXL1 (ENSG00000127952), DUSP9 (ENSG00000130829), DUSP26 (ENSG00000133878), 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 5 — Q16690 (reviewed: Q16690)

Alternative names: Dual specificity protein phosphatase hVH3

All UniProt accessions (1): Q16690

UniProt curated annotations — full annotation on UniProt →

Function. Dual specificity protein phosphatase; active with phosphotyrosine, phosphoserine and phosphothreonine residues. The highest relative activity is toward ERK1.

Subcellular location. Nucleus.

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

RefSeq proteins (1): NP_004410* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000340	Dual-sp_phosphatase_cat-dom	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR001763	Rhodanese-like_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR008343	MKP	Family
IPR016130	Tyr_Pase_AS	Active_site
IPR020422	TYR_PHOSPHATASE_DUAL_dom	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR036873	Rhodanese-like_dom_sf	Homologous_superfamily

Pfam: PF00581, 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 (26 total): helix 7, sequence conflict 5, strand 5, sequence variant 4, domain 2, chain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2G6Z	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16690-F1	78.76	0.52

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): 263 (phosphocysteine intermediate)

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-112409	RAF-independent MAPK1/3 activation
R-HSA-5675221	Negative regulation of MAPK pathway

MSigDB gene sets: 483 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE45365_NK_CELL_VS_CD11B_DC_DN, AGGAAGC_MIR5163P, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, ZHAN_LATE_DIFFERENTIATION_GENES_UP, WWTAAGGC_UNKNOWN, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, ENK_UV_RESPONSE_KERATINOCYTE_UP, KEGG_MAPK_SIGNALING_PATHWAY, SHEPARD_CRASH_AND_BURN_MUTANT_UP, MODULE_64, AAGCCAT_MIR135A_MIR135B, DITTMER_PTHLH_TARGETS_UP, NAGASHIMA_NRG1_SIGNALING_UP

GO Biological Process (9): MAPK cascade (GO:0000165), endoderm formation (GO:0001706), protein dephosphorylation (GO:0006470), signal transduction (GO:0007165), dephosphorylation (GO:0016311), peptidyl-tyrosine dephosphorylation (GO:0035335), peptidyl-threonine dephosphorylation (GO:0035970), negative regulation of MAPK cascade (GO:0043409), ERK1 and ERK2 cascade (GO:0070371)

GO Molecular Function (8): phosphoprotein phosphatase activity (GO:0004721), protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine phosphatase activity (GO:0004725), protein tyrosine/serine/threonine phosphatase activity (GO:0008138), phosphatase activity (GO:0016791), MAP kinase tyrosine/serine/threonine phosphatase activity (GO:0017017), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
MAPK1/MAPK3 signaling	1
RAF/MAP kinase cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphoprotein phosphatase activity	3
protein dephosphorylation	2
MAPK cascade	2
cellular anatomical structure	2
intracellular signaling cassette	1
formation of primary germ layer	1
endoderm development	1
dephosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
phosphate-containing compound metabolic process	1
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
phosphatase activity	1
catalytic activity, acting on a protein	1
phosphoric ester hydrolase activity	1
protein tyrosine/serine/threonine phosphatase activity	1
MAP kinase phosphatase activity	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2440 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUSP5	DUSP11	O75319	894
DUSP5	ITIH4	Q14624	890
DUSP5	SNRK	Q9NRH2	837
DUSP5	MAPK3	P27361	722
DUSP5	FOS	P01100	721
DUSP5	IGHV4-38-2	P0DP08	669
DUSP5	CDR2	Q01850	665
DUSP5	MAPK8	P45983	640
DUSP5	SPRY2	O43597	635
DUSP5	TJP1	Q07157	619
DUSP5	LIMA1	Q9UHB6	614
DUSP5	EIF2AK3	Q9NZJ5	584
DUSP5	HEY2	Q9UBP5	566
DUSP5	ANTXR1	Q9H6X2	557
DUSP5	SPRED2	Q7Z698	555

IntAct

130 interactions, top by confidence:

A	B	Type	Score
MAPK1	DUSP5	psi-mi:“MI:0915”(physical association)	0.540
DUSP5	MAPK1	psi-mi:“MI:0915”(physical association)	0.540
DUSP5	MAPK1	psi-mi:“MI:0403”(colocalization)	0.540
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
DUSP5	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
DLG3	DUSP5	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
PICK1	DUSP5	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	LIN7A	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	PDLIM1	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	PTPN13	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	FRMPD4	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	GRIP2	psi-mi:“MI:0407”(direct interaction)	0.440
IL16	DUSP5	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	AHNAK	psi-mi:“MI:0407”(direct interaction)	0.440
DUSP5	DVL3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (58): IPO7 (Proximity Label-MS), TEX10 (Proximity Label-MS), COIL (Proximity Label-MS), DUSP5 (Affinity Capture-MS), RPL32 (Affinity Capture-MS), LZTS2 (Affinity Capture-MS), RPS15 (Affinity Capture-MS), FBXO11 (Affinity Capture-MS), MRPS35 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), DENR (Affinity Capture-MS), RPL5 (Affinity Capture-MS), RPL36 (Affinity Capture-MS), AP3S1 (Affinity Capture-MS), DUSP5 (Two-hybrid)

ESM2 similar proteins: O43304, O54838, O75038, O95382, P0C591, P0C592, P0C594, P0C595, P0C596, P28562, P28563, Q05922, Q05923, Q13115, Q14451, Q16690, Q16828, Q16829, Q17QJ3, Q2KJ36, Q4RQD3, Q561R2, Q5FVI9, Q5R6H6, Q60806, Q61152, Q62767, Q63340, Q64346, Q64623, Q68J44, Q6B8I0, Q6PAT0, Q8BFV3, Q8BK84, Q90W58, Q91790, Q91Z46, Q99952, Q99956

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

6 interactions.

A	Effect	B	Mechanism
DUSP5	down-regulates	MAPK1	dephosphorylation
DUSP5	down-regulates	MAPK14	dephosphorylation
DUSP5	down-regulates	Gbeta	dephosphorylation
DUSP5	down-regulates	ERK1/2	dephosphorylation
DUSP5	down-regulates	MAPK3	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 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
Ras activation upon Ca2+ influx through NMDA receptor	5	51.9×	3e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	49.4×	3e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	49.4×	3e-06
Long-term potentiation	5	43.3×	5e-06
Assembly and cell surface presentation of NMDA receptors	9	41.5×	2e-10
Neurexins and neuroligins	9	32.2×	1e-09
Protein-protein interactions at synapses	5	24.1×	8e-05
RHOB GTPase cycle	6	16.8×	7e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	77.0×	4e-16
receptor clustering	7	52.6×	1e-08
protein localization to synapse	5	46.1×	5e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	7	41.8×	5e-08
cell-cell adhesion	10	12.2×	9e-07
protein-containing complex assembly	8	11.0×	4e-05
regulation of small GTPase mediated signal transduction	6	10.4×	8e-04
chemical synaptic transmission	8	7.5×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

761 predictions. Top by Δscore:

Variant	Effect	Δscore
10:110502710:T:TA	acceptor_gain	1.0000
10:110502716:T:A	acceptor_gain	1.0000
10:110502718:TAGG:T	acceptor_loss	1.0000
10:110502719:A:AG	acceptor_gain	1.0000
10:110502719:A:G	acceptor_loss	1.0000
10:110502719:AG:A	acceptor_gain	1.0000
10:110502719:AGG:A	acceptor_gain	1.0000
10:110502719:AGGG:A	acceptor_gain	1.0000
10:110502719:AGGGG:A	acceptor_gain	1.0000
10:110502720:G:GA	acceptor_gain	1.0000
10:110502720:GG:G	acceptor_gain	1.0000
10:110502720:GGG:G	acceptor_gain	1.0000
10:110502720:GGGG:G	acceptor_gain	1.0000
10:110502720:GGGGG:G	acceptor_gain	1.0000
10:110502834:GTG:G	donor_gain	1.0000
10:110502869:GG:G	donor_loss	1.0000
10:110502870:G:A	donor_loss	1.0000
10:110502871:T:G	donor_loss	1.0000
10:110506932:CAG:C	acceptor_loss	1.0000
10:110506933:AG:A	acceptor_gain	1.0000
10:110506934:GG:G	acceptor_gain	1.0000
10:110507136:G:GT	donor_gain	1.0000
10:110507153:TGGTA:T	donor_loss	1.0000
10:110507155:G:GG	donor_gain	1.0000
10:110507156:T:A	donor_loss	1.0000
10:110510015:TCCA:T	acceptor_loss	1.0000
10:110510016:CCA:C	acceptor_loss	1.0000
10:110510017:CAGA:C	acceptor_loss	1.0000
10:110510018:A:AG	acceptor_gain	1.0000
10:110510018:A:G	acceptor_loss	1.0000

AlphaMissense

2461 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:110507100:G:C	D232H	1.000
10:110510053:T:A	V261D	1.000
10:110510100:T:G	Y277D	1.000
10:110510187:T:C	F306L	1.000
10:110510188:T:C	F306S	1.000
10:110510189:C:A	F306L	1.000
10:110510189:C:G	F306L	1.000
10:110510200:T:C	L310P	1.000
10:110498206:C:T	R29W	0.999
10:110498492:T:C	F124S	0.999
10:110498495:T:A	L125H	0.999
10:110502724:G:A	G128E	0.999
10:110502736:T:C	F132S	0.999
10:110506963:T:C	L186P	0.999
10:110506972:G:A	G189E	0.999
10:110506974:A:C	S190R	0.999
10:110506976:T:A	S190R	0.999
10:110506976:T:G	S190R	0.999
10:110507032:T:C	L209P	0.999
10:110507038:T:A	V211D	0.999
10:110507089:T:C	I228T	0.999
10:110507101:A:C	D232A	0.999
10:110507101:A:T	D232V	0.999
10:110507131:T:C	F242S	0.999
10:110507148:T:C	F248L	0.999
10:110507149:T:C	F248S	0.999
10:110507150:C:A	F248L	0.999
10:110507150:C:G	F248L	0.999
10:110507152:T:A	I249N	0.999
10:110510047:T:A	V259D	0.999

dbSNP variants (sampled 300 via entrez): RS1000119986 (10:110498032 T>C,G), RS1000153585 (10:110508176 A>G), RS1000292537 (10:110511760 G>A), RS1000300345 (10:110502950 TC>T), RS1000402448 (10:110506014 T>C), RS1000422236 (10:110508436 T>G), RS1000463064 (10:110503165 T>C), RS1000611970 (10:110501669 T>C), RS1000677170 (10:110500396 G>C,T), RS1000736939 (10:110507240 C>A,T), RS1000768378 (10:110506914 G>A), RS1001030988 (10:110498736 G>A,C), RS1001615511 (10:110505612 A>G), RS1001646653 (10:110505314 A>G), RS1001706133 (10:110511022 G>C)

Disease associations

OMIM: gene MIM:603069 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002094_7	Crohn’s disease	2.000000e-10
GCST005348_125	Total body bone mineral density	3.000000e-08
GCST005990_33	Non-albumin protein levels	1.000000e-08
GCST006979_605	Heel bone mineral density	1.000000e-19
GCST007015_3	Lumbar spine bone mineral density (integral)	7.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0007620	volumetric bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1250380 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

1 measured of 6 human assays (6 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
5,5’,5’’-[1,3,6-naphthalenetriyltris(sulfonylimino)]tris[1,3-benzenesulfonate analogue	KI	25 nM

ChEMBL bioactivities

2 potent at pChembl≥5 of 8 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.10	IC50	8	nM	SODIUM ORTHOVANAD
6.79	IC50	161	nM	CHEMBL590572

PubChem BioAssay actives

6 with measured affinity, of 25 total; 3 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
8-[[4-methyl-3-[[3-[[3-[[2-methyl-5-[(4,6,8-trisulfonaphthalen-1-yl)carbamoyl]phenyl]carbamoyl]phenyl]carbamoylamino]benzoyl]amino]benzoyl]amino]naphthalene-1,3,5-trisulfonic acid	1802735: p-NPP Assay from Article 10.1186/s12858-015-0048-3: “Identification of inhibitors that target dual-specificity phosphatase 5 provide new insights into the binding requirements for the two phosphate pockets.”	ki	0.0250	uM
8-amino-4-hydroxynaphthalene-2-sulfonic acid	1802897: pERK Assay from Article 10.1186/s12858-017-0083-3: “Serendipitous discovery of light-induced (In Situ) formation of an Azo-bridged dimeric sulfonated naphthol as a potent PTP1B inhibitor.”	ic50	1.7000	uM
4-hydroxy-8-[(5-hydroxy-7-sulfonaphthalen-1-yl)diazenyl]naphthalene-2-sulfonic acid	1802897: pERK Assay from Article 10.1186/s12858-017-0083-3: “Serendipitous discovery of light-induced (In Situ) formation of an Azo-bridged dimeric sulfonated naphthol as a potent PTP1B inhibitor.”	ic50	4.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, increases methylation, affects cotreatment	9
Estradiol	decreases expression, increases expression, affects expression, affects cotreatment	7
Benzo(a)pyrene	increases expression, affects methylation	6
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, decreases reaction	5
Cyclosporine	increases expression	5
Aflatoxin B1	affects expression, increases expression	5
trichostatin A	increases expression, affects expression, affects cotreatment	4
sodium arsenite	decreases expression, decreases reaction, increases expression	4
Cisplatin	affects expression, increases expression	4
Particulate Matter	increases abundance, increases expression, affects cotreatment, decreases expression	4
Copper	decreases expression, affects binding, increases expression	3
Ethinyl Estradiol	affects expression, increases expression	3
Silicon Dioxide	increases expression	3
Tobacco Smoke Pollution	increases expression	3
bisphenol A	affects cotreatment, decreases expression, affects expression	2
cobaltous chloride	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Zoledronic Acid	decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	increases expression, increases abundance	2
Cadmium	increases expression	2
Calcitriol	increases expression, affects cotreatment	2
Oxygen	affects cotreatment, decreases expression, decreases reaction, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silver	increases expression	2
Tamoxifen	affects cotreatment, increases expression	2
Tretinoin	increases expression	2
Zinc	affects cotreatment, increases expression	2
Asbestos, Crocidolite	affects expression, increases expression	2

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1244672	Binding	Inhibition of Dusp5	Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages. — Nat Chem Biol

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7P4	Ubigene A-549 DUSP5 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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