DUSP26

Summary

DUSP26 (dual specificity phosphatase 26, HGNC:28161) is a protein-coding gene on chromosome 8p12, encoding Dual specificity protein phosphatase 26 (Q9BV47). Inactivates MAPK1 and MAPK3 which leads to dephosphorylation of heat shock factor protein 4 and a reduction in its DNA-binding activity.

This gene encodes a member of the tyrosine phosphatase family of proteins and exhibits dual specificity by dephosphorylating tyrosine as well as serine and threonine residues. This gene has been described as both a tumor suppressor and an oncogene depending on the cellular context. This protein may regulate neuronal proliferation and has been implicated in the progression of glioblastoma through its ability to dephosphorylate the p53 tumor suppressor. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 78986 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 31 total — 2 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_024025

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28161
Approved symbol	DUSP26
Name	dual specificity phosphatase 26
Location	8p12
Locus type	gene with protein product
Status	Approved
Aliases	MGC1136, DUSP24, NEAP
Ensembl gene	ENSG00000133878
Ensembl biotype	protein_coding
OMIM	618368
Entrez	78986

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000256261, ENST00000522982, ENST00000523956, ENST00000854271, ENST00000854272, ENST00000854273, ENST00000854274, ENST00000854275, ENST00000854276, ENST00000854277, ENST00000963993, ENST00000963994

RefSeq mRNA: 3 — MANE Select: NM_024025 NM_001305115, NM_001305116, NM_024025

CCDS: CCDS6092

Canonical transcript exons

ENST00000256261 — 4 exons

Exon	Start	End
ENSE00000911629	33593533	33593747
ENSE00000911631	33597295	33597591
ENSE00000980064	33591330	33592212
ENSE00002123562	33599665	33600023

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 98.63.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6994 / max 237.7157, expressed in 337 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92675	1.6725	256
92673	1.4716	172
92674	0.2588	122
92671	0.2242	102
92672	0.0442	15
92670	0.0281	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	98.63	gold quality
gluteal muscle	UBERON:0002000	98.44	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.36	gold quality
gastrocnemius	UBERON:0001388	98.11	gold quality
quadriceps femoris	UBERON:0001377	97.52	gold quality
vastus lateralis	UBERON:0001379	97.50	gold quality
triceps brachii	UBERON:0001509	97.49	gold quality
skeletal muscle tissue	UBERON:0001134	97.06	gold quality
body of tongue	UBERON:0011876	96.49	gold quality
muscle organ	UBERON:0001630	96.43	gold quality
skeletal muscle organ	UBERON:0014892	96.43	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.18	gold quality
muscle of leg	UBERON:0001383	96.13	gold quality
tibialis anterior	UBERON:0001385	96.12	gold quality
biceps brachii	UBERON:0001507	96.11	gold quality
deltoid	UBERON:0001476	95.92	gold quality
apex of heart	UBERON:0002098	95.59	gold quality
cerebellar hemisphere	UBERON:0002245	95.09	gold quality
cerebellar cortex	UBERON:0002129	95.08	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.73	gold quality
cerebellar vermis	UBERON:0004720	94.54	gold quality
cerebellum	UBERON:0002037	94.36	gold quality
right frontal lobe	UBERON:0002810	94.27	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.12	gold quality
heart left ventricle	UBERON:0002084	94.08	gold quality
cardiac ventricle	UBERON:0002082	93.90	gold quality
prefrontal cortex	UBERON:0000451	93.85	gold quality
muscle tissue	UBERON:0002385	93.75	gold quality
diaphragm	UBERON:0001103	93.70	silver quality
pituitary gland	UBERON:0000007	93.68	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-9154	yes	306.35
E-ANND-3	no	3.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting DUSP26, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-1914-5P	97.83	66.21	807
HSA-MIR-7855-5P	97.39	67.18	925
HSA-MIR-4732-3P	97.15	65.45	881
HSA-MIR-3194-5P	96.80	64.90	1027
HSA-MIR-1236-5P	96.62	66.38	856
HSA-MIR-635	96.00	65.54	687
HSA-MIR-6774-5P	95.94	65.18	722
HSA-MIR-6851-3P	95.73	65.11	688
HSA-MIR-328-3P	92.82	64.37	521

Literature-anchored findings (GeneRIF, showing 14)

• DUSP26 effectively dephosphorylates p38 and has a little effect on extracellular signal-regulated kinase in anaplastic thyroid cancer. (PMID:16924234)
• Downregulation of Dusp26 may contribute to malignant phenotypes of glioma. (PMID:19043453)
• DUSP26 may function as a tumour suppressor in particular cancers. (PMID:20347885)
• DUSP26 functions as a p53 phosphatase (PMID:20562916)
• The study reports the 1.68 A crystal structure of a catalytically inactive mutant (Cys152Ser) of DUSP26 lacking the first 60 N-terminal residues (DeltaN60-C/S-DUSP26). (PMID:23298255)
• results suggest that AK2 is an associated activator of DUSP26 and suppresses cell proliferation by FADD dephosphorylation, postulating AK2 as a negative regulator of tumour growth. (PMID:24548998)
• Enhanced expression of DUSP26 was observed in the hippocampus of Alzheimer’s disease patients. (PMID:26924229)
• overexpression in liver cell line attenuated lipid deposition and inflammation induced by palmitate (PMID:30582764)
• DUSP26 might be a promising therapeutic target for developing effective treatments against Diabetic nephropathy progression. (PMID:31155289)
• A Review of DUSP26: Structure, Regulation and Relevance in Human Disease. (PMID:33466673)
• DUSP26 induces aortic valve calcification by antagonizing MDM2-mediated ubiquitination of DPP4 in human valvular interstitial cells. (PMID:34179958)
• Falnidamol and cisplatin combinational treatment inhibits non-small cell lung cancer (NSCLC) by targeting DUSP26-mediated signal pathways. (PMID:35278641)
• Dusp26 phosphatase regulates mitochondrial respiration and oxidative stress and protects neuronal cell death. (PMID:35313355)
• Upregulation of dual-specificity phosphatase-26 is required for transforming growth factor beta1(TGFbeta1)-induced Epithelial-mesenchymal transition in A549 and PANC1 cells. (PMID:36053282)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	DUSP26	ENSDARG00000103752
mus_musculus	Dusp26	ENSMUSG00000039661
rattus_norvegicus	Dusp26	ENSRNOG00000011518

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), 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 26 — Q9BV47 (reviewed: Q9BV47)

Alternative names: Dual specificity phosphatase SKRP3, Low-molecular-mass dual-specificity phosphatase 4, Mitogen-activated protein kinase phosphatase 8, Novel amplified gene in thyroid anaplastic cancer

All UniProt accessions (2): E5RHD0, Q9BV47

UniProt curated annotations — full annotation on UniProt →

Function. Inactivates MAPK1 and MAPK3 which leads to dephosphorylation of heat shock factor protein 4 and a reduction in its DNA-binding activity. Inhibits MAP kinase p38 by dephosphorylating it and inhibits p38-mediated apoptosis in anaplastic thyroid cancer cells. Can also induce activation of MAP kinase p38 and c-Jun N-terminal kinase (JNK).

Subunit / interactions. Interacts with HSF4.

Subcellular location. Cytoplasm. Nucleus. Golgi apparatus.

Tissue specificity. Brain. In the brain it is expressed ubiquitously except in the hippocampus. Expressed in embryonal cancers (retinoblastoma, neuroepithilioma and neuroblastoma) and in anaplatic thyroid cancer.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BV47-1	1	yes
Q9BV47-2	2

RefSeq proteins (3): NP_001292044, NP_001292045, NP_076930* (*=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)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE	0.023–0.862	22
4-NITROPHENYL PHOSPHATE	0.0028–12.7	13
P-NITROPHENYL PHOSPHATE	3–200	11
RRAPTVA	0.058–1.954	4
PHOSPHOCASEIN	0.0001–0.002	3
PHOSPHOHISTONE	0.0023–0.0723	3
PHOSPHORYLATED MYOSIN LIGHT CHAIN PEPTIDE	0.01–0.11	3
PHOSPHOSERINE-MYELIN BASIC PROTEIN	0.0004–0.022	3
DLDVPIPGRFDRRVSVAAE	0.0006–0.0138	2
DLDVPIPGRFDRRVY(P)VAAE	0.0025–0.023	2
PHOSPHORYLASE A	0.004–0.021	2
RRA(PT)VA	0.0536–0.308	2
80S-RIBOSOME	0.0027	1
AAAPTVA	0.206	1
AGPALSPVPPV	0.357	1

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 (20 total): helix 8, strand 6, chain 1, domain 1, turn 1, active site 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2E0T	X-RAY DIFFRACTION	1.67
4HRF	X-RAY DIFFRACTION	1.68
5GTJ	X-RAY DIFFRACTION	2
4B04	X-RAY DIFFRACTION	2.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BV47-F1	84.35	0.68

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): 152 (phosphocysteine intermediate)

Mutagenesis-validated functional residues (1):

Position	Phenotype
152	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 105 (showing top): GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, ZHAN_MULTIPLE_MYELOMA_PR_DN, CAGCTG_AP4_Q5, YY1_Q6, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, HEN1_01, GOBP_DEPHOSPHORYLATION, GOBP_PROTEIN_DEPHOSPHORYLATION, chr8p12, DOUGLAS_BMI1_TARGETS_UP, GCM_CALM1, GCM_MAP1B, GOBP_ERK1_AND_ERK2_CASCADE

GO Biological Process (6): negative regulation of transcription by RNA polymerase II (GO:0000122), protein dephosphorylation (GO:0006470), negative regulation of MAPK cascade (GO:0043409), positive regulation of cell adhesion (GO:0045785), negative regulation of ERK1 and ERK2 cascade (GO:0070373), dephosphorylation (GO:0016311)

GO Molecular Function (10): p53 binding (GO:0002039), 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), MAP kinase phosphatase activity (GO:0033549), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), protein binding (GO:0005515), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphoprotein phosphatase activity	4
intracellular membrane-bounded organelle	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
dephosphorylation	1
protein modification process	1
MAPK cascade	1
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
cell adhesion	1
regulation of cell adhesion	1
positive regulation of cellular process	1
negative regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
phosphate-containing compound metabolic process	1
protein binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
DNA-binding transcription factor binding	1
binding	1
catalytic activity	1
phosphoric ester hydrolase activity	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
endomembrane system	1
extracellular vesicle	1

Protein interactions and networks

STRING

2120 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUSP26	AK2	P54819	699
DUSP26	HSF4	Q9ULV5	501
DUSP26	PMPCA	Q10713	446
DUSP26	PTS	Q03393	421
DUSP26	AFG3L2	Q9Y4W6	420
DUSP26	PTPN3	P26045	411
DUSP26	GAB2	Q9UQC2	402
DUSP26	ANXA1	P04083	386
DUSP26	DUSP23	Q9BVJ7	386
DUSP26	EPM2A	O95278	385
DUSP26	ATXN1	P54253	384
DUSP26	RNF122	Q9H9V4	383
DUSP26	EPS8L2	Q9H6S3	365
DUSP26	DEF8	Q6ZN54	357
DUSP26	VSIR	Q9H7M9	355

IntAct

33 interactions, top by confidence:

A	B	Type	Score
TP53	DUSP26	psi-mi:“MI:0915”(physical association)	0.650
TP53	DUSP26	psi-mi:“MI:0407”(direct interaction)	0.650
DUSP26	TP53	psi-mi:“MI:0915”(physical association)	0.650
DUSP26	TP53	psi-mi:“MI:0203”(dephosphorylation reaction)	0.650
DUSP26	CALCOCO2	psi-mi:“MI:0915”(physical association)	0.560
CALCOCO2	DUSP26	psi-mi:“MI:0915”(physical association)	0.560
GRIPAP1	DUSP26	psi-mi:“MI:0915”(physical association)	0.560
KRT27	DUSP26	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	DUSP26	psi-mi:“MI:0915”(physical association)	0.560
DUSP26	CARD10	psi-mi:“MI:0915”(physical association)	0.560
	DUSP26	psi-mi:“MI:0915”(physical association)	0.460
DUSP26		psi-mi:“MI:0403”(colocalization)	0.460
DUSP26	RET	psi-mi:“MI:0915”(physical association)	0.370
DUSP26	IGF1R	psi-mi:“MI:0915”(physical association)	0.370
DUSP26	PTK7	psi-mi:“MI:0915”(physical association)	0.370
DUSP26	EPHA7	psi-mi:“MI:0915”(physical association)	0.370
DUSP26	EPHA2	psi-mi:“MI:0915”(physical association)	0.370
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
DUSP26	GRIPAP1	psi-mi:“MI:0915”(physical association)	0.000
DUSP26	KRT27	psi-mi:“MI:0915”(physical association)	0.000
DUSP26	GOLGA6L9	psi-mi:“MI:0915”(physical association)	0.000
DUSP26	CARD10	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (63): DUSP26 (Two-hybrid), DUSP26 (Two-hybrid), NEURL4 (Proximity Label-MS), HERC2 (Proximity Label-MS), PTPRG (Proximity Label-MS), DUSP26 (Affinity Capture-MS), ABTB2 (Affinity Capture-MS), TRMT10C (Affinity Capture-MS), DCTPP1 (Affinity Capture-MS), DUSP23 (Affinity Capture-MS), UBR2 (Affinity Capture-MS), GID8 (Affinity Capture-MS), DOCK7 (Affinity Capture-MS), WDR45 (Affinity Capture-MS), ATG2B (Affinity Capture-MS)

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: 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

8 interactions.

A	Effect	B	Mechanism
DUSP26	down-regulates	TP53	dephosphorylation
DUSP26	“down-regulates activity”	FADD	dephosphorylation
DUSP26	“down-regulates activity”	TP53	dephosphorylation
DUSP26	“down-regulates activity”	FGFR1	dephosphorylation
DUSP26	“down-regulates activity”	NTRK1	dephosphorylation
“8-Hydroxy-7-(6-sulfo-naphthalen-2-ylazo)-quinoline-5-sulfonic acid”	“down-regulates activity”	DUSP26	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	25
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
148997	GRCh38/hg38 8p23.1-12(chr8:12698495-35476082)x3	Pathogenic
563535	GRCh37/hg19 8p12(chr8:30335124-33770070)x1	Pathogenic

SpliceAI

710 predictions. Top by Δscore:

Variant	Effect	Δscore
8:33592208:CTTCC:C	acceptor_gain	1.0000
8:33592209:TTCC:T	acceptor_gain	1.0000
8:33592210:TCC:T	acceptor_gain	1.0000
8:33592211:CC:C	acceptor_gain	1.0000
8:33592211:CCC:C	acceptor_gain	1.0000
8:33592212:CC:C	acceptor_gain	1.0000
8:33592213:C:CC	acceptor_gain	1.0000
8:33592213:C:T	acceptor_gain	1.0000
8:33593528:CCTA:C	donor_loss	1.0000
8:33593530:TA:T	donor_loss	1.0000
8:33593531:ACCT:A	donor_gain	1.0000
8:33593532:C:CA	donor_loss	1.0000
8:33593532:CCTC:C	donor_gain	1.0000
8:33593534:T:TA	donor_gain	1.0000
8:33593743:TGTCC:T	acceptor_gain	1.0000
8:33593744:GTCC:G	acceptor_gain	1.0000
8:33593745:TCC:T	acceptor_gain	1.0000
8:33593746:CCC:C	acceptor_gain	1.0000
8:33593748:C:CC	acceptor_gain	1.0000
8:33597293:A:AC	donor_gain	1.0000
8:33597294:C:CA	donor_gain	1.0000
8:33597294:CTGGT:C	donor_gain	1.0000
8:33593744:GTCCC:G	acceptor_loss	0.9900
8:33593745:TCCC:T	acceptor_loss	0.9900
8:33593746:CC:C	acceptor_gain	0.9900
8:33593746:CCCT:C	acceptor_loss	0.9900
8:33593747:CC:C	acceptor_gain	0.9900
8:33593747:CCT:C	acceptor_loss	0.9900
8:33593748:C:CG	acceptor_loss	0.9900
8:33593749:T:A	acceptor_loss	0.9900

AlphaMissense

1360 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:33592067:G:C	F194L	1.000
8:33592067:G:T	F194L	1.000
8:33592068:A:G	F194S	1.000
8:33592069:A:G	F194L	1.000
8:33592080:G:T	P190H	1.000
8:33593610:T:A	D120V	1.000
8:33593610:T:C	D120G	1.000
8:33593610:T:G	D120A	1.000
8:33592056:A:G	L198P	0.999
8:33592068:A:C	F194C	0.999
8:33592069:A:C	F194V	0.999
8:33592069:A:T	F194I	0.999
8:33592081:G:A	P190S	0.999
8:33592117:C:G	A178P	0.999
8:33592173:G:A	S159F	0.999
8:33592177:G:C	R158G	0.999
8:33592178:G:C	S157R	0.999
8:33592178:G:T	S157R	0.999
8:33592179:C:A	S157I	0.999
8:33592179:C:T	S157N	0.999
8:33592180:T:G	S157R	0.999
8:33592185:C:A	G155V	0.999
8:33592185:C:T	G155D	0.999
8:33592186:C:A	G155C	0.999
8:33592186:C:G	G155R	0.999
8:33592193:A:C	C152W	0.999
8:33592194:C:T	C152Y	0.999
8:33592195:A:G	C152R	0.999
8:33593580:A:G	F130S	0.999
8:33593597:A:C	F124L	0.999

dbSNP variants (sampled 300 via entrez): RS1000179301 (8:33592883 A>G), RS1000508202 (8:33599361 T>A), RS1000585245 (8:33599138 A>G), RS1000739511 (8:33593299 A>C), RS1000964617 (8:33598988 T>G), RS1001027968 (8:33596890 A>G,T), RS1001218272 (8:33591532 T>A), RS1001913685 (8:33601673 A>G), RS1002030457 (8:33595732 C>T), RS1002262971 (8:33601492 C>A,G,T), RS1002633461 (8:33595527 CCCA>C), RS1002863071 (8:33599934 C>T), RS1002958313 (8:33594358 C>T), RS1003031833 (8:33594546 C>T), RS1003324458 (8:33600351 C>T)

Disease associations

OMIM: gene MIM:618368 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST002783_458	Body mass index	6.000000e-06
GCST002783_493	Body mass index	4.000000e-06
GCST004904_40	Body mass index	8.000000e-09
GCST006810_14	Self-reported risk-taking behaviour	6.000000e-09
GCST007325_235	General risk tolerance (MTAG)	5.000000e-09
GCST007565_10	Morning person	4.000000e-19
GCST007565_172	Morning person	2.000000e-16
GCST007565_182	Morning person	2.000000e-16
GCST007565_8	Morning person	5.000000e-20
GCST007576_34	Chronotype	5.000000e-20
GCST009391_475	Metabolite levels	8.000000e-06
GCST009897_5	Reading disability	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008579	risk-taking behaviour
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2295562 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 12 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.05	IC50	8900	nM	CHEMBL2299386

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	6
Tunicamycin	increases expression	2
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
butyraldehyde	increases expression	1
aflatoxin B2	increases methylation	1
pentanal	increases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	affects methylation	1
Hydrogen Peroxide	affects expression	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Tretinoin	decreases expression	1
Triclosan	decreases expression	1
Cadmium Chloride	decreases expression	1
Thapsigargin	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3068773	Binding	Inhibition of DUSP26 (unknown origin)-mediated p38 dephosphorylation	Virtual screening and biochemical evaluation of the inhibitors of dual-specificity phosphatase 26 — Med Chem Res

Clinical trials (associated diseases)

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