PTPN5

Summary

PTPN5 (protein tyrosine phosphatase non-receptor type 5, HGNC:9657) is a protein-coding gene on chromosome 11p15.1, encoding Tyrosine-protein phosphatase non-receptor type 5 (P54829). May regulate the activity of several effector molecules involved in synaptic plasticity and neuronal cell survival, including MAPKs, Src family kinases and NMDA receptors.

Enables phosphotyrosine residue binding activity. Predicted to be involved in signal transduction. Predicted to act upstream of or within protein dephosphorylation. Predicted to be located in membrane and nucleoplasm. Predicted to be active in cell junction; cytosol; and plasma membrane. Biomarker of Alzheimer’s disease.

Source: NCBI Gene 84867 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 51 total
• Druggable target: yes
• MANE Select transcript: NM_006906

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9657
Approved symbol	PTPN5
Name	protein tyrosine phosphatase non-receptor type 5
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	STEP, PTPSTEP, STEP61
Ensembl gene	ENSG00000110786
Ensembl biotype	protein_coding
OMIM	176879
Entrez	84867

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000358540, ENST00000396166, ENST00000396168, ENST00000396170, ENST00000477854, ENST00000496201, ENST00000856224, ENST00000856225, ENST00000856226, ENST00000935333, ENST00000957010, ENST00000957011, ENST00000957012, ENST00000957013

RefSeq mRNA: 6 — MANE Select: NM_006906 NM_001039970, NM_001278236, NM_001278238, NM_001278239, NM_006906, NM_032781

CCDS: CCDS41626, CCDS60746, CCDS7845

Canonical transcript exons

ENST00000358540 — 15 exons

Exon	Start	End
ENSE00000706728	18740603	18740792
ENSE00000706730	18737880	18737964
ENSE00000706732	18733556	18733635
ENSE00000706737	18733235	18733372
ENSE00001129124	18744006	18744199
ENSE00001150696	18729453	18729566
ENSE00001150704	18729658	18729818
ENSE00001150710	18732592	18732702
ENSE00001333579	18791525	18791798
ENSE00001399458	18771939	18772071
ENSE00001819428	18727928	18729027
ENSE00003474655	18743322	18743429
ENSE00003604468	18742262	18742503
ENSE00003621024	18742992	18743075
ENSE00003674559	18765807	18765883

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 99.73.

FANTOM5 (CAGE): breadth broad, TPM avg 6.4248 / max 641.6208, expressed in 301 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118965	1.8492	118
118970	1.7629	266
118964	1.0541	34
118960	0.5410	26
118971	0.4855	162
118966	0.3141	85
118969	0.1528	76
118963	0.0888	21
118968	0.0797	55
118967	0.0528	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.73	gold quality
middle temporal gyrus	UBERON:0002771	99.46	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.66	gold quality
nucleus accumbens	UBERON:0001882	98.61	gold quality
putamen	UBERON:0001874	98.52	gold quality
caudate nucleus	UBERON:0001873	98.12	gold quality
primary visual cortex	UBERON:0002436	98.12	gold quality
occipital lobe	UBERON:0002021	96.94	gold quality
lateral globus pallidus	UBERON:0002476	96.92	gold quality
superior frontal gyrus	UBERON:0002661	96.58	gold quality
postcentral gyrus	UBERON:0002581	95.94	gold quality
parietal lobe	UBERON:0001872	95.78	gold quality
entorhinal cortex	UBERON:0002728	95.00	gold quality
cortical plate	UBERON:0005343	94.97	gold quality
frontal cortex	UBERON:0001870	94.76	gold quality
prefrontal cortex	UBERON:0000451	94.58	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.53	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.52	gold quality
right frontal lobe	UBERON:0002810	94.44	gold quality
neocortex	UBERON:0001950	94.12	gold quality
cerebral cortex	UBERON:0000956	93.34	gold quality
anterior cingulate cortex	UBERON:0009835	92.94	gold quality
pons	UBERON:0000988	92.31	gold quality
temporal lobe	UBERON:0001871	92.24	gold quality
hypothalamus	UBERON:0001898	91.28	gold quality
forebrain	UBERON:0001890	90.87	gold quality
amygdala	UBERON:0001876	90.32	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.04	gold quality
Ammon’s horn	UBERON:0001954	89.31	gold quality
secondary oocyte	CL:0000655	88.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.16

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZNF143

miRNA regulators (miRDB)

68 targeting PTPN5, 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-340-5P	100.00	72.50	4437
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-137-3P	99.87	74.74	2401
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6885-3P	99.75	70.36	3187

Literature-anchored findings (GeneRIF, showing 21)

• determined high-resolution structures of all of the human family members of Mitogen-Activated Protein Kinase-specific protein tyrosine phosphatases (PMID:16441242)
• in colorectal tumors, microsatellite repeats mutation rates are higher than the mean mutation frequency (PMID:19000305)
• findings show that STEP(61) levels are progressively increased in the prefrontal cortex of Alzheimer disease brains (PMID:20427654)
• STEP contributes to aspects of the pathophysiology in Alzheimer’s disease; loss of GluN1/GluN2B subunits from neuronal membranes and Abeta-mediated NMDAR internalization are discussed (PMID:20699650)
• STEP(61kDa) is required for Abeta transgene-mediated internalization of GluA1/GluA2 glutamate receptors in a transgenic mousemodel. (PMID:21883219)
• The results imply a model in which PTPN5 may play a role in normal cognitive functioning and contribute to aspects of the neuropathology of schizophrenia. (PMID:22555153)
• This study identified a novel role for PTPN5 in mediating the development of stress-related cognitive and morphological changes. (PMID:22649233)
• This experiments demonstrated that deletion of STEP can enhance experience-induced neuroplasticity and memory formation (PMID:22885232)
• Decreased STEP protein activation in corpus striatum contributes to early enhanced apoptotic signaling in YAC model transgenic mice. (PMID:24588402)
• Article focuses on the most recent findings on STEP, discuss how STEP expression and activity are maintained during normal cognitive function, and how disruptions in STEP activity contribute to a number of illnesses. [Review] (PMID:25218562)
• STEP levels are unchanged in pre-frontal cortex and associative striatum in post-mortem human brain samples from subjects with schizophrenia, bipolar disorder and major depressive disorder (PMID:25786133)
• A rare missense variant in the PTPN5 gene (rs56234898; minor allele frequency 1.5%) was significantly associated with decreased severity of Post-Burn Hypertrophic Scarring(P = 1.3x10-6). (PMID:26872063)
• a dual role for PSD-95 in stabilizing synaptic NMDARs by binding directly to GluN2B but also by promoting synaptic exclusion and degradation of the negative regulator STEP61. (PMID:27457929)
• This current study demonstrated that spinal STEP61 regulated LTP of C fiber-evoked field potentials, one of the extensively studied cellular models of central sensitization. (PMID:28389375)
• Data suggest that PP5/PTPN5 is overexpressed in liver samples from patients with hepatocellular carcinoma (HCC); overexpression of PP5/PTPN5 appears to correlate with tumor burden/stage. Inhibition of PP5/PTPN5 suppresses proliferation and promotes apoptosis of HCC cells; inhibition of PP5/PTPN5 involves activation of AMPK. (PMID:28528695)
• validated the functional importance of an identified interaction network by characterizing a distinct novel interaction between PTPN5 and Mob1a. (PMID:28675297)
• STEP is involved in the mechanism of depressive disorders and it is a promising molecular target for atypical antidepressant drugs of new generation. (Review) (PMID:28699511)
• that STEP61 is the molecular brake that is lost following KCC2-dependent disinhibition and that the decrease in STEP61 activity drives the potentiation of excitatory GluN2B NMDAR responses in rodent and human models of pathological pain (PMID:31135041)
• Inhibition of striatal-enriched protein tyrosine phosphatase (STEP) activity reverses behavioral deficits in a rodent model of autism. (PMID:32461127)
• PTPN5 promotes follicle-stimulating hormone secretion through regulating intracellular calcium homeostasis. (PMID:34270805)
• Tyrosine phosphatase STEP61 in human dementia and in animal models with amyloid and tau pathology. (PMID:36639708)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptpn5	ENSDARG00000074866
mus_musculus	Ptpn5	ENSMUSG00000030854
rattus_norvegicus	Ptpn5	ENSRNOG00000013981

Paralogs (35): PTPRN (ENSG00000054356), PTPRU (ENSG00000060656), PTPN3 (ENSG00000070159), PTPN21 (ENSG00000070778), PTPN18 (ENSG00000072135), PTPN23 (ENSG00000076201), PTPRH (ENSG00000080031), PTPRC (ENSG00000081237), PTPN4 (ENSG00000088179), PTPRS (ENSG00000105426), PTPRZ1 (ENSG00000106278), PTPN6 (ENSG00000111679), PTPRB (ENSG00000127329), PTPN12 (ENSG00000127947), PTPRE (ENSG00000132334), PTPRA (ENSG00000132670), PTPN22 (ENSG00000134242), PTPRF (ENSG00000142949), PTPN7 (ENSG00000143851), PTPRG (ENSG00000144724), PTPRJ (ENSG00000149177), PTPRO (ENSG00000151490), PTPN14 (ENSG00000152104), PTPRK (ENSG00000152894), PTPRR (ENSG00000153233), PTPRD (ENSG00000153707), PTPRN2 (ENSG00000155093), PTPN13 (ENSG00000163629), PTPN9 (ENSG00000169410), PTPRM (ENSG00000173482), PTPN2 (ENSG00000175354), PTPN11 (ENSG00000179295), PTPRT (ENSG00000196090), PTPN1 (ENSG00000196396), PTPN20 (ENSG00000204179)

Protein

Protein identifiers

Tyrosine-protein phosphatase non-receptor type 5 — P54829 (reviewed: P54829)

Alternative names: Neural-specific protein-tyrosine phosphatase, Striatum-enriched protein-tyrosine phosphatase

All UniProt accessions (3): P54829, A8MXF1, E9PLZ4

UniProt curated annotations — full annotation on UniProt →

Function. May regulate the activity of several effector molecules involved in synaptic plasticity and neuronal cell survival, including MAPKs, Src family kinases and NMDA receptors.

Subcellular location. Endoplasmic reticulum membrane.

Post-translational modifications. Phosphorylation at Ser-245 by PKA deactivates PTPN5. Phosphorylation at Thr-255 and Ser-268 by MAPKs stabilizes the phosphatase, dephosphorylation of these sites results in ubiquitin-mediated degradation of the active phosphatase.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P54829-1	1, STEP61	yes
P54829-2	2
P54829-3	3

RefSeq proteins (6): NP_001035059, NP_001265165, NP_001265167, NP_001265168, NP_008837, NP_116170 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000242	PTP_cat	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR008356	Tyr_Pase_KIM-con	Family
IPR016130	Tyr_Pase_AS	Active_site
IPR016334	Tyr_Pase_rcpt_R/non-rcpt_5	Family
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily

Pfam: PF00102

Enzyme classification (BRENDA):

• EC 3.1.3.48 — protein-tyrosine-phosphatase (BRENDA: 59 organisms, 501 substrates, 1326 inhibitors, 270 Km, 165 kcat entries)

Substrate kinetics (BRENDA)

70 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
P-NITROPHENYL PHOSPHATE	0.0024–10	20
DADEPYLIPQQG	0.0003–0.1	12
PHOSPHOTYROSINE	0.012–30	11
LYSOZYME	0.0003–0.012	5
MYELIN BASIC PROTEIN	0.0001–0.022	5
ACETYL-DADEPY-NH2	0.0228–0.219	4
ACETYL-DADEPYL-NH2	1.1–97.5	4
4,6,8-TRIMETHYL-2-OXO-2H-CHROMEN-7-YL DIHYDROGEN	0.02–0.156	3
SASASPYSASA	0.53–2.3	3
1-NAPHTHYL PHOSPHATE	1.19–1.88	2
3,6-FLUORESCEIN DIPHOSPHATE	15–19	2
4-METHYLUMBELLIFERYL PHOSPHATE	0.953–2.41	2
BOVINE SERUM ALBUMIN	0.0001–0.0003	2

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (55 total): helix 14, sequence conflict 11, strand 9, binding site 3, modified residue 3, transmembrane region 2, splice variant 2, sequence variant 2, turn 2, region of interest 2, compositionally biased region 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
9EEX	X-RAY DIFFRACTION	1.27
9EEZ	X-RAY DIFFRACTION	1.6
6H8R	X-RAY DIFFRACTION	1.66
2CJZ	X-RAY DIFFRACTION	1.7
8SLS	X-RAY DIFFRACTION	1.71
9EEY	X-RAY DIFFRACTION	1.75
2BV5	X-RAY DIFFRACTION	1.8
8SLU	X-RAY DIFFRACTION	1.84
8SLT	X-RAY DIFFRACTION	1.96
2BIJ	X-RAY DIFFRACTION	2.05
5OW1	X-RAY DIFFRACTION	2.05
5OVX	X-RAY DIFFRACTION	2.1
5OVR	X-RAY DIFFRACTION	2.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54829-F1	72.67	0.47

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): 496 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (3): 496–502; 540; 461

Post-translational modifications (3): 245, 255, 268

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9008059	Interleukin-37 signaling

MSigDB gene sets: 117 (showing top): REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, KEGG_MAPK_SIGNALING_PATHWAY, MAZ_Q6, GCM_RING1, GCM_FCGR2B, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, GOBP_DEPHOSPHORYLATION, GOBP_PROTEIN_DEPHOSPHORYLATION, DOUGLAS_BMI1_TARGETS_UP, MCCLUNG_COCAINE_REWARD_5D, GCM_LTK, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_PHOSPHOPROTEIN_BINDING, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_UP

GO Biological Process (3): protein dephosphorylation (GO:0006470), signal transduction (GO:0007165), dephosphorylation (GO:0016311)

GO Molecular Function (6): phosphotyrosine residue binding (GO:0001784), protein tyrosine phosphatase activity (GO:0004725), protein kinase binding (GO:0019901), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (7): nucleoplasm (GO:0005654), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), cell junction (GO:0030054), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interleukin-1 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	2
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
protein phosphorylated amino acid binding	1
phosphoprotein phosphatase activity	1
kinase binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
nuclear lumen	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1924 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPN5	PTS	Q03393	881
PTPN5	GRIN2B	Q13224	708
PTPN5	FYN	P06241	621
PTPN5	GRIA2	P42262	507
PTPN5	PTK2B	Q14289	507
PTPN5	PPP1R1B	Q9UD71	505
PTPN5	GRIN2A	Q12879	495
PTPN5	DLG4	P78352	479
PTPN5	GRIA1	P42261	478
PTPN5	GRM5	P41594	446
PTPN5	MAPK3	P27361	441
PTPN5	MAPK14	Q16539	434
PTPN5	FMR1	Q06787	419
PTPN5	MAP6	Q96JE9	413
PTPN5	PRKACA	P17612	391

IntAct

53 interactions, top by confidence:

A	B	Type	Score
VTI1B	PTPN5	psi-mi:“MI:0915”(physical association)	0.670
PTPN5	VTI1B	psi-mi:“MI:0915”(physical association)	0.670
PTPN5	CXCL9	psi-mi:“MI:0915”(physical association)	0.560
TMEM51	PTPN5	psi-mi:“MI:0915”(physical association)	0.560
PTPN5	TMEM51	psi-mi:“MI:0915”(physical association)	0.560
CXCL9	PTPN5	psi-mi:“MI:0915”(physical association)	0.560
ENTPD3	PTPN5	psi-mi:“MI:0915”(physical association)	0.560
PTPN5	CLEC4G	psi-mi:“MI:0915”(physical association)	0.560
PTPN5	SLC35B1	psi-mi:“MI:0915”(physical association)	0.560
PTPN5	TMEM201	psi-mi:“MI:0915”(physical association)	0.560
PTPN5	MARCHF5	psi-mi:“MI:0915”(physical association)	0.560
CYB561D2	PTPN5	psi-mi:“MI:0915”(physical association)	0.560
PTPN5	TERF1	psi-mi:“MI:0915”(physical association)	0.510
CUL5	PTPN5	psi-mi:“MI:0915”(physical association)	0.370
SNX4	PTPN5	psi-mi:“MI:0915”(physical association)	0.370
PTPN5	ZBTB5	psi-mi:“MI:0915”(physical association)	0.370
CCNQ	PTPN5	psi-mi:“MI:0915”(physical association)	0.370
APOA1	CNMD	psi-mi:“MI:0914”(association)	0.350
PTPN5	PGRMC1	psi-mi:“MI:0914”(association)	0.350
CDKN3	STMN1	psi-mi:“MI:0914”(association)	0.350
DUSP15	PSMD3	psi-mi:“MI:0914”(association)	0.350

BioGRID (109): PTPN5 (Two-hybrid), PTPN5 (Two-hybrid), PTPN5 (Two-hybrid), Park2 (Reconstituted Complex), Mapk1 (Reconstituted Complex), PARK2 (Affinity Capture-Western), PTPN5 (Affinity Capture-Western), PTPN5 (Biochemical Activity), PTPN5 (Affinity Capture-Western), DLG4 (Affinity Capture-Western), ATP5H (Affinity Capture-MS), DCAKD (Affinity Capture-MS), HLA-A (Affinity Capture-MS), MAPK1 (Affinity Capture-MS), MAPK3 (Affinity Capture-MS)

ESM2 similar proteins: B4F7B7, D3YWQ0, D4A615, F1MAB7, O08560, O35787, O43896, O75912, O88831, P29473, P29474, P29597, P54829, P54830, P70313, P97270, Q13574, Q39491, Q499Z3, Q4R3B7, Q5R7G9, Q5U464, Q5XHB2, Q5XIS1, Q62137, Q62600, Q63272, Q66HE5, Q6AXX1, Q6GQJ8, Q6NZL6, Q80TF6, Q80UP3, Q8BHW9, Q8BUI3, Q8C078, Q8K330, Q8K4T5, Q8R4V2, Q8TDY4

Diamond homologs: A0A6I8TCE0, A1L1L3, A2ALK8, A4IFW2, B0V2N1, B0X4T2, B1AUH1, B2GV87, B2RU80, B3DK56, B9EKR1, E9Q0N2, E9Q612, F1NWE3, G5EC24, G5EGJ9, H2KZM6, O02695, O08617, O13016, O35239, O55082, P06800, P16620, P17706, P18031, P18052, P18433, P20417, P23467, P23468, P23469, P23470, P23471, P26045, P28191, P29074, P29350, P29351, P29352

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
PTPN5	up-regulates	MAPK14	binding
PTPN5	“up-regulates activity”	BAK1	dephosphorylation
PTPN5	“down-regulates activity”	GRIN2B	dephosphorylation
PTPN5	“down-regulates activity”	GRIA2	dephosphorylation
PTPN5	“up-regulates activity”	MOB1B	dephosphorylation
PTPN5	“down-regulates activity”	GRIN2A	dephosphorylation
PTPN5	down-regulates	FYN	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3263 predictions. Top by Δscore:

Variant	Effect	Δscore
11:18732586:CCTCA:C	donor_loss	1.0000
11:18732587:CTCA:C	donor_loss	1.0000
11:18732588:TCA:T	donor_loss	1.0000
11:18732589:CA:C	donor_loss	1.0000
11:18732590:A:T	donor_loss	1.0000
11:18732776:A:T	acceptor_gain	1.0000
11:18733229:CCCTA:C	donor_loss	1.0000
11:18733230:CCTA:C	donor_loss	1.0000
11:18733231:CTA:C	donor_loss	1.0000
11:18733232:TAC:T	donor_loss	1.0000
11:18733234:C:CT	donor_loss	1.0000
11:18737875:CTCA:C	donor_gain	1.0000
11:18737878:A:AC	donor_gain	1.0000
11:18737879:C:CC	donor_gain	1.0000
11:18737879:CTGGG:C	donor_gain	1.0000
11:18737961:TTTC:T	acceptor_gain	1.0000
11:18737962:TTC:T	acceptor_gain	1.0000
11:18737962:TTCC:T	acceptor_loss	1.0000
11:18737963:TC:T	acceptor_gain	1.0000
11:18737963:TCCT:T	acceptor_loss	1.0000
11:18737964:CC:C	acceptor_gain	1.0000
11:18737965:C:CC	acceptor_gain	1.0000
11:18737965:CTGT:C	acceptor_loss	1.0000
11:18737966:T:C	acceptor_loss	1.0000
11:18740601:A:AC	donor_gain	1.0000
11:18740602:C:CC	donor_gain	1.0000
11:18740788:CCCTC:C	acceptor_gain	1.0000
11:18740789:CCTCC:C	acceptor_gain	1.0000
11:18740790:CTC:C	acceptor_gain	1.0000
11:18742265:T:A	donor_gain	1.0000

AlphaMissense

3693 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:18729012:C:A	Q540H	1.000
11:18729012:C:G	Q540H	1.000
11:18729027:C:A	R535S	1.000
11:18729027:C:G	R535S	1.000
11:18729453:C:A	R535M	1.000
11:18729453:C:G	R535T	1.000
11:18729463:G:T	R532S	1.000
11:18729465:A:G	L531P	1.000
11:18729546:C:T	G504D	1.000
11:18729551:C:A	R502S	1.000
11:18729551:C:G	R502S	1.000
11:18729552:C:A	R502M	1.000
11:18729552:C:G	R502T	1.000
11:18729553:T:A	R502W	1.000
11:18729553:T:C	R502G	1.000
11:18729555:C:A	G501V	1.000
11:18729555:C:T	G501E	1.000
11:18729556:C:A	G501W	1.000
11:18729556:C:G	G501R	1.000
11:18729556:C:T	G501R	1.000
11:18729561:C:A	G499V	1.000
11:18729561:C:T	G499E	1.000
11:18729562:C:A	G499W	1.000
11:18729562:C:G	G499R	1.000
11:18729562:C:T	G499R	1.000
11:18729660:G:C	C496W	1.000
11:18729662:A:G	C496R	1.000
11:18729667:A:T	V494D	1.000
11:18729754:G:T	P465Q	1.000
11:18729767:C:G	D461H	1.000

dbSNP variants (sampled 300 via entrez): RS1000106312 (11:18748840 G>A), RS1000151859 (11:18778009 A>G), RS1000158001 (11:18787004 G>A), RS1000227536 (11:18761930 G>A), RS1000258701 (11:18770665 G>A,T), RS1000345631 (11:18770398 T>C), RS1000390735 (11:18742771 C>T), RS1000396132 (11:18736635 C>A,G), RS1000408429 (11:18776014 C>T), RS1000408518 (11:18767074 T>A), RS1000427266 (11:18736430 C>G), RS1000454534 (11:18755257 C>G), RS1000508951 (11:18787196 C>A), RS1000514856 (11:18781291 T>C), RS1000562307 (11:18781131 A>T)

Disease associations

OMIM: gene MIM:176879 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002007_2	Adverse response to chemotherapy (neutropenia/leucopenia) (cisplatin)	4.000000e-06
GCST003997_11	Myopia	1.000000e-12
GCST010002_232	Refractive error	2.000000e-27

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2007628 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

154 measured of 160 human assays (168 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
N-[3-[(2-methoxyphenyl)sulfamoyl]-4-(1-pyrrolidinyl)phenyl]-3-methyl-2-thiophenecarboxamide	IC50	163 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
MLS000409155	IC50	498 nM
SMR000311544	IC50	500 nM
cid_2162931	IC50	567 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
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
1-[(E)-(1,3-dimethylpyrazol-4-yl)methylideneamino]-3-phenyl-thiourea	IC50	1220 nM
MLS000516376	IC50	1230 nM
MLS000737363	IC50	1240 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
MLS000577024	IC50	1300 nM
N-[4-(aminosulfonyl)phenyl]-4-methyl-1-piperazinecarbothioamide	IC50	1320 nM
2-(2,3-dihydro-1H-inden-5-yl)-N-[2-[(2-methoxyphenyl)amino]-2-oxidanylidene-ethyl]-N-propyl-ethanamide	IC50	1320 nM
cid_3390606	IC50	1360 nM
N-(3-chloranyl-4-methoxy-phenyl)-4-[methyl(oxolan-2-ylmethyl)amino]piperidine-1-carbothioamide	IC50	1370 nM
(4-ethoxyphenyl)-(4-methyl-1-piperazinyl)methanethione	IC50	1420 nM
MLS002638664	IC50	1480 nM
sodium;phenylsulfonylazanide	IC50	1500 nM
cid_7693352	IC50	1510 nM
(5Z)-2-azanylidene-3-(4-fluorophenyl)-5-[(4-hydroxyphenyl)methylidene]-1,3-thiazolidin-4-one	IC50	1550 nM
ethyl 5-(diethylcarbamoyl)-2-(methoxycarbonylamino)-4-methylthiophene-3-carboxylate	IC50	1560 nM
N-(1,3-benzothiazol-2-yl)-2-(3-methoxyphenyl)-4-quinolinecarboxamide	IC50	1620 nM
5-chloro-2-thiophenecarboxylic acid [4-[(E)-2-(1H-benzimidazol-2-yl)-2-cyanoethenyl]phenyl] ester	IC50	1770 nM
MLS001216500	IC50	1850 nM
2-[4-(4-ethylpiperazin-1-yl)carbothioylphenoxy]-N-(phenylmethyl)ethanamide	IC50	1920 nM
(2Z)-2-[[(2-hydroxyphenyl)-oxomethyl]hydrazinylidene]-1-benzopyran-3-carboxamide	IC50	1930 nM

ChEMBL bioactivities

139 potent at pChembl≥5 of 449 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.00	IC50	10	nM	CHEMBL3398243
7.62	IC50	24	nM	CHEMBL3398246
7.61	IC50	24.6	nM	CHEMBL3398242
7.60	IC50	25	nM	CHEMBL3398244
7.50	IC50	32	nM	CHEMBL3398245
7.48	IC50	33	nM	CHEMBL3398250
7.31	IC50	49	nM	CHEMBL3398247
7.23	IC50	59	nM	CHEMBL3398248
7.11	IC50	78	nM	CHEMBL3398249
6.96	Ki	109	nM	CHEMBL3398243
6.96	Ki	110	nM	CHEMBL4077342
6.94	Ki	115	nM	CHEMBL3398242
6.94	Ki	116	nM	CHEMBL3398244
6.91	Ki	123	nM	CHEMBL3398247
6.91	Ki	124	nM	CHEMBL3398250
6.84	IC50	145	nM	CHEMBL3398251
6.76	Ki	175	nM	CHEMBL3398249
6.74	Ki	183	nM	CHEMBL3398245
6.68	Ki	210	nM	CHEMBL3398251
6.64	Ki	230	nM	CHEMBL3398248
6.64	Kd	230	nM	CHEMBL5077745
6.63	Ki	235	nM	CHEMBL3398246
6.40	Ki	400	nM	CHEMBL5077745
6.40	Kd	400	nM	CHEMBL5077972
6.37	Ki	430	nM	CHEMBL4076072
6.35	Kd	450	nM	CHEMBL5090224
6.27	Ki	540	nM	CHEMBL4092589
6.17	Kd	670	nM	CHEMBL5083288
6.15	IC50	710	nM	SODIUM ORTHOVANAD
6.04	Ki	920	nM	CHEMBL5083897
6.00	Ki	1000	nM	CHEMBL4070970
5.96	Ki	1090	nM	CHEMBL5072214
5.82	Ki	1500	nM	CHEMBL4103050
5.77	Ki	1700	nM	CHEMBL4102693
5.74	Ki	1820	nM	CHEMBL5085890
5.70	IC50	1980	nM	CHEMBL1461216
5.68	Ki	2070	nM	CHEMBL5071305
5.67	Ki	2120	nM	CHEMBL5080018
5.66	IC50	2180	nM	CHEMBL1445488
5.66	Ki	2200	nM	CHEMBL4792956
5.65	IC50	2260	nM	CHEMBL1370165
5.64	Ki	2300	nM	CHEMBL4780469
5.62	Ki	2400	nM	CHEMBL4069436
5.62	Ki	2400	nM	CHEMBL4084768
5.62	Ki	2420	nM	CHEMBL5074161
5.61	Ki	2460	nM	CHEMBL5083791
5.59	Ki	2590	nM	CHEMBL5078422
5.58	Ki	2600	nM	CHEMBL4088863
5.57	Ki	2700	nM	CHEMBL4105477
5.56	IC50	2730	nM	CHEMBL1463248

PubChem BioAssay actives

90 with measured affinity, of 390 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
7-(trifluoromethyl)-1,2,3,4,5-benzopentathiepine	1191870: Inhibition of STEP (unknown origin) pre-incubated for 10 mins before addition of p-nitrophenyl phosphate substrate in absence of GSH	ic50	0.0100	uM
2,2,2-trifluoro-N-[8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-yl]acetamide	1191870: Inhibition of STEP (unknown origin) pre-incubated for 10 mins before addition of p-nitrophenyl phosphate substrate in absence of GSH	ic50	0.0240	uM
8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine;hydrochloride	1191870: Inhibition of STEP (unknown origin) pre-incubated for 10 mins before addition of p-nitrophenyl phosphate substrate in absence of GSH	ic50	0.0246	uM
8-methyl-1,2,3,4,5-benzopentathiepin-6-amine;hydrochloride	1191870: Inhibition of STEP (unknown origin) pre-incubated for 10 mins before addition of p-nitrophenyl phosphate substrate in absence of GSH	ic50	0.0250	uM
1,2,3,4,5-benzopentathiepin-6-amine;hydrochloride	1191870: Inhibition of STEP (unknown origin) pre-incubated for 10 mins before addition of p-nitrophenyl phosphate substrate in absence of GSH	ic50	0.0320	uM
8,17-bis(trifluoromethyl)-2,3,4,11,12,13-hexathiatricyclo[12.4.0.05,10]octadeca-1(18),5,7,9,14,16-hexaene-6,15-diamine;dihydrochloride	1191870: Inhibition of STEP (unknown origin) pre-incubated for 10 mins before addition of p-nitrophenyl phosphate substrate in absence of GSH	ic50	0.0330	uM
N-[8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-yl]acetamide	1191870: Inhibition of STEP (unknown origin) pre-incubated for 10 mins before addition of p-nitrophenyl phosphate substrate in absence of GSH	ic50	0.0490	uM
N-ethyl-8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine	1191870: Inhibition of STEP (unknown origin) pre-incubated for 10 mins before addition of p-nitrophenyl phosphate substrate in absence of GSH	ic50	0.0590	uM
N-benzyl-8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine	1191870: Inhibition of STEP (unknown origin) pre-incubated for 10 mins before addition of p-nitrophenyl phosphate substrate in absence of GSH	ic50	0.0780	uM
[fluoro-[4-[2-fluoro-3-[(2,4,5-trichlorophenyl)methyl]phenyl]phenyl]-morpholin-4-ylsulfonylmethyl]phosphonic acid	1477071: Inhibition of STEP (unknown origin) using pNPP as substrate preincubated for 5 mins followed by substrate addition measured for 20 mins by spectrophotometric analysis	ki	0.1100	uM
4-nitro-6-(trifluoromethyl)-1,2,3-benzotrithiole	1191870: Inhibition of STEP (unknown origin) pre-incubated for 10 mins before addition of p-nitrophenyl phosphate substrate in absence of GSH	ic50	0.1450	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[2-[[(2S)-2-amino-4-carboxybutanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-oxobutanoyl]amino]-3-methylbutanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]pentanedioic acid	1818842: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) by SPR analysis	kd	0.2300	uM
(4S)-4-[[(2S)-6-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-aminopropanoyl]amino]-3-hydroxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]-5-[[2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-(carboxymethylamino)-3-[4-[difluoro(phosphono)methyl]phenyl]-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid	1818842: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) by SPR analysis	kd	0.4000	uM
[[4-[2-fluoro-3-[(2,4,5-trichlorophenyl)methyl]phenyl]phenyl]-morpholin-4-ylsulfonylmethyl]phosphonic acid	1477071: Inhibition of STEP (unknown origin) using pNPP as substrate preincubated for 5 mins followed by substrate addition measured for 20 mins by spectrophotometric analysis	ki	0.4300	uM
(4S)-4-amino-5-[[2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(1S)-1-carboxy-2-[4-[difluoro(phosphono)methyl]phenyl]ethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid	1818842: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) by SPR analysis	kd	0.4500	uM
[1-fluoro-1-[4-[2-fluoro-3-[(2,4,5-trichlorophenyl)methyl]phenyl]phenyl]-2-oxo-2-phenylethyl]phosphonic acid	1477071: Inhibition of STEP (unknown origin) using pNPP as substrate preincubated for 5 mins followed by substrate addition measured for 20 mins by spectrophotometric analysis	ki	0.5400	uM
(4S)-4-[[(2S)-6-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-aminopropanoyl]amino]-3-hydroxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]-5-[[2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-(carboxymethylamino)-1-oxo-3-(4-phosphonooxyphenyl)propan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid	1818842: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) by SPR analysis	kd	0.6700	uM
(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[2-[[(2S)-2-amino-4-carboxybutanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-oxobutanoyl]amino]-3-methylbutanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]acetyl]amino]butanedioic acid	1818841: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) measured for 30 mins by fluorescence polarization method	ki	0.9200	uM
[2-cyclohexyl-1-fluoro-1-[4-[2-fluoro-3-[(2,4,5-trichlorophenyl)methyl]phenyl]phenyl]-2-oxoethyl]phosphonic acid	1477071: Inhibition of STEP (unknown origin) using pNPP as substrate preincubated for 5 mins followed by substrate addition measured for 20 mins by spectrophotometric analysis	ki	1.0000	uM
(4S)-5-[[2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(1S)-1-carboxy-2-(4-phosphonooxyphenyl)ethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-4-[[2-[2-(2-aminoethoxy)ethoxy]acetyl]amino]-5-oxopentanoic acid	1818841: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) measured for 30 mins by fluorescence polarization method	ki	1.0900	uM
[fluoro-[4-[2-fluoro-3-[(2,4,5-trichlorophenyl)methyl]phenyl]phenyl]methyl]phosphonic acid	1477071: Inhibition of STEP (unknown origin) using pNPP as substrate preincubated for 5 mins followed by substrate addition measured for 20 mins by spectrophotometric analysis	ki	1.5000	uM
[1-[4-[2-fluoro-3-[(2,4,5-trichlorophenyl)methyl]phenyl]phenyl]-2-morpholin-4-yl-2-oxoethyl]phosphonic acid	1477071: Inhibition of STEP (unknown origin) using pNPP as substrate preincubated for 5 mins followed by substrate addition measured for 20 mins by spectrophotometric analysis	ki	1.7000	uM
(4S)-4-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]-5-[[2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-(carboxymethylamino)-1-oxo-3-(4-phosphonooxyphenyl)propan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid	1818841: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) measured for 30 mins by fluorescence polarization method	ki	1.8200	uM
(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-oxobutanoyl]amino]-3-methylbutanoyl]amino]-3-(4-phosphonooxyphenyl)propanoic acid	1818841: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) measured for 30 mins by fluorescence polarization method	ki	2.0700	uM
(3S)-3-amino-4-[[2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(1S)-1-carboxy-2-(4-phosphonooxyphenyl)ethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-4-oxobutanoic acid	1818841: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) measured for 30 mins by fluorescence polarization method	ki	2.1200	uM
4-[5-[(1,3-dioxoinden-2-ylidene)methyl]furan-2-yl]-3-methylbenzoic acid	1736795: Competitive inhibition of N-terminal His-tagged striatal-enriched protein tyrosine phosphatase (unknown origin) assessed as inhibition of p-nitrophenyl phosphate substrate hydrolysis at 3 to 9 uM measured by Lineweaver-Burk plot	ki	2.2000	uM
1-chloro-4-(4-fluorophenyl)-2-(2-nitrophenyl)sulfanyl-2,3,3a,4,5,9b-hexahydro-1H-cyclopenta[c]quinoline-6-carboxylic acid	1736793: Competitive inhibition of N-terminal His-tagged striatal-enriched protein tyrosine phosphatase (unknown origin) assessed as inhibition of p-nitrophenyl phosphate substrate hydrolysis at 2 to 8 uM measured by Lineweaver-Burk plot	ki	2.3000	uM
[difluoro-[4-[2-fluoro-3-[(2,4,5-trichlorophenyl)methyl]phenyl]phenyl]methyl]phosphonic acid	1477071: Inhibition of STEP (unknown origin) using pNPP as substrate preincubated for 5 mins followed by substrate addition measured for 20 mins by spectrophotometric analysis	ki	2.4000	uM
[2-(dimethylamino)-1-[4-[2-fluoro-3-[(2,4,5-trichlorophenyl)methyl]phenyl]phenyl]-2-oxoethyl]phosphonic acid	1477071: Inhibition of STEP (unknown origin) using pNPP as substrate preincubated for 5 mins followed by substrate addition measured for 20 mins by spectrophotometric analysis	ki	2.4000	uM
(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[2-[[(2S)-2,4-diamino-4-oxobutanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-oxobutanoyl]amino]-3-methylbutanoyl]amino]-3-(4-phosphonooxyphenyl)propanoic acid	1818841: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) measured for 30 mins by fluorescence polarization method	ki	2.4200	uM
(4S)-4-[[(2S)-6-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-aminopropanoyl]amino]-3-hydroxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-(carboxymethylamino)-1-oxo-3-(4-phosphonooxyphenyl)propan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1818841: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) measured for 30 mins by fluorescence polarization method	ki	2.4600	uM
(4S)-5-[[2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-(carboxymethylamino)-1-oxo-3-(4-phosphonooxyphenyl)propan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-aminopropanoyl]amino]-3-hydroxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]-5-oxopentanoic acid	1818841: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) measured for 30 mins by fluorescence polarization method	ki	2.5900	uM
[(S)-[4-[2-fluoro-3-[(2,4,5-trichlorophenyl)methyl]phenyl]phenyl]-hydroxymethyl]phosphonic acid	1477071: Inhibition of STEP (unknown origin) using pNPP as substrate preincubated for 5 mins followed by substrate addition measured for 20 mins by spectrophotometric analysis	ki	2.6000	uM
[1-[4-[2-fluoro-3-[(2,4,5-trichlorophenyl)methyl]phenyl]phenyl]-2-oxo-2-piperidin-1-ylethyl]phosphonic acid	1477071: Inhibition of STEP (unknown origin) using pNPP as substrate preincubated for 5 mins followed by substrate addition measured for 20 mins by spectrophotometric analysis	ki	2.7000	uM
(4S)-4-[[(2S)-6-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-aminopropanoyl]amino]-3-hydroxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]-5-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-(carboxymethylamino)-1-oxo-3-(4-phosphonooxyphenyl)propan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid	1818841: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) measured for 30 mins by fluorescence polarization method	ki	2.7500	uM
[1-fluoro-1-[4-[2-fluoro-3-[(2,4,5-trichlorophenyl)methyl]phenyl]phenyl]-2-oxo-2-piperidin-1-ylethyl]phosphonic acid	1477071: Inhibition of STEP (unknown origin) using pNPP as substrate preincubated for 5 mins followed by substrate addition measured for 20 mins by spectrophotometric analysis	ki	3.0000	uM
(4S)-4-[[(2S)-6-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-aminopropanoyl]amino]-3-hydroxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]-5-[[2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxyethyl]amino]-1-oxo-3-(4-phosphonooxyphenyl)propan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid	1818841: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) measured for 30 mins by fluorescence polarization method	ki	3.0600	uM
[[4-[3-[(2-bromo-4,5-dichlorophenyl)methyl]phenyl]phenyl]-difluoromethyl]phosphonic acid	1477071: Inhibition of STEP (unknown origin) using pNPP as substrate preincubated for 5 mins followed by substrate addition measured for 20 mins by spectrophotometric analysis	ki	3.7000	uM
2-hydroxy-5-[5-[(Z)-(3-oxo-1-benzothiophen-2-ylidene)methyl]furan-2-yl]benzoic acid	1736794: Competitive inhibition of N-terminal His-tagged striatal-enriched protein tyrosine phosphatase (unknown origin) assessed as inhibition of p-nitrophenyl phosphate substrate hydrolysis at 5 to 15 uM measured by Lineweaver-Burk plot	ki	3.7000	uM
6-hydroxy-3-iodo-1-methyl-2-[3-[[2-oxo-2-(4-thiophen-3-ylanilino)acetyl]amino]phenyl]indole-5-carboxylic acid	1182553: Inhibition of STEP (unknown origin)	ic50	4.0000	uM
2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-aminopropanoyl]amino]-3-hydroxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]propanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-oxobutanoyl]amino]-3-methylbutanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]acetic acid	1818841: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) measured for 30 mins by fluorescence polarization method	ki	4.6000	uM
[difluoro-[4-[3-[(2,4,5-trichlorophenyl)methyl]phenyl]phenyl]methyl]phosphonic acid	1477071: Inhibition of STEP (unknown origin) using pNPP as substrate preincubated for 5 mins followed by substrate addition measured for 20 mins by spectrophotometric analysis	ki	4.7000	uM
(4S)-4-[[(2S)-6-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-aminopropanoyl]amino]-3-hydroxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]-5-[[2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-(carboxymethylamino)-1-oxo-3-(4-phosphonooxyphenyl)propan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid	1818841: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) measured for 30 mins by fluorescence polarization method	ki	4.8700	uM
N-[4-[5-(naphthalen-1-ylsulfonylamino)-1,3-benzoxazol-2-yl]phenyl]naphthalene-1-sulfonamide	1589997: Inhibition of human PTPN5 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method	ic50	4.9000	uM
2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[2-(2-aminoethoxy)ethoxy]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]acetic acid	1818841: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) measured for 30 mins by fluorescence polarization method	ki	5.0100	uM
5-chloro-N-[4-[5-(naphthalen-1-ylsulfonylamino)-1,3-benzoxazol-2-yl]phenyl]thiophene-2-sulfonamide	1589997: Inhibition of human PTPN5 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method	ic50	5.1000	uM
(4S)-4-[[(2S)-6-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-aminopropanoyl]amino]-3-hydroxybutanoyl]amino]propanoyl]amino]hexanoyl]amino]-5-[[2-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-(carboxymethylamino)-1-oxo-3-(4-phosphonooxyphenyl)propan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid	1818841: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) measured for 30 mins by fluorescence polarization method	ki	5.3500	uM
4-(3-bromophenyl)-1-chloro-2-(2-nitrophenyl)sulfanyl-2,3,3a,4,5,9b-hexahydro-1H-cyclopenta[c]quinoline-6-carboxylic acid	1736793: Competitive inhibition of N-terminal His-tagged striatal-enriched protein tyrosine phosphatase (unknown origin) assessed as inhibition of p-nitrophenyl phosphate substrate hydrolysis at 2 to 8 uM measured by Lineweaver-Burk plot	ki	5.4000	uM
2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[2-[2-(2-aminoethoxy)ethoxy]acetyl]amino]-4-oxobutanoyl]amino]-3-methylbutanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]acetic acid	1818841: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) measured for 30 mins by fluorescence polarization method	ki	5.5100	uM
[[4-[3-[(4,5-dichloro-2-fluorophenyl)methyl]phenyl]phenyl]-difluoromethyl]phosphonic acid	1477071: Inhibition of STEP (unknown origin) using pNPP as substrate preincubated for 5 mins followed by substrate addition measured for 20 mins by spectrophotometric analysis	ki	5.6000	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	4
trichostatin A	affects cotreatment, decreases expression	3
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
sodium arsenite	decreases expression	1
ferrous chloride	decreases expression	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
belinostat	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation	1
Vorinostat	affects cotreatment, decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Arsenates	affects cotreatment, increases expression	1
Atrazine	affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Aflatoxin B1	decreases methylation	1
Acrylamide	decreases expression	1
Particulate Matter	increases expression, increases abundance	1

ChEMBL screening assays

46 unique, capped per target: 44 binding, 1 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1963968	Functional	PUBCHEM_BIOASSAY: Dose response confirmation of uHTS small molecule inhibitors of Striatal-Enriched Phosphatase via a fluorescence intensity assay. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL2432851	Binding	Inhibition of human STEP using pNPP as substrate after 5 mins by spectrophotometric plate reader analysis	Substrate-based fragment identification for the development of selective, nonpeptidic inhibitors of striatal-enriched protein tyrosine phosphatase. — J Med Chem
CHEMBL4626311	ADMET	Inhibition of STEP (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

Clinical trials (associated diseases)

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