PTPN9

Summary

PTPN9 (protein tyrosine phosphatase non-receptor type 9, HGNC:9661) is a protein-coding gene on chromosome 15q24.2, encoding Tyrosine-protein phosphatase non-receptor type 9 (P43378). Protein-tyrosine phosphatase that could participate in the transfer of hydrophobic ligands or in functions of the Golgi apparatus.

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains an N-terminal domain that shares a significant similarity with yeast SEC14, which is a protein that has phosphatidylinositol transfer activity and is required for protein secretion through the Golgi complex in yeast. This PTP was found to be activated by polyphosphoinositide, and is thought to be involved in signaling events regulating phagocytosis.

Source: NCBI Gene 5780 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 82 total
• Druggable target: yes
• MANE Select transcript: NM_002833

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9661
Approved symbol	PTPN9
Name	protein tyrosine phosphatase non-receptor type 9
Location	15q24.2
Locus type	gene with protein product
Status	Approved
Aliases	MEG2
Ensembl gene	ENSG00000169410
Ensembl biotype	protein_coding
OMIM	600768
Entrez	5780

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000561731, ENST00000563835, ENST00000564970, ENST00000568108, ENST00000618819, ENST00000893934, ENST00000893935, ENST00000893936, ENST00000893937, ENST00000893938, ENST00000936113, ENST00000936114, ENST00000936115, ENST00000944252, ENST00000944253

RefSeq mRNA: 1 — MANE Select: NM_002833 NM_002833

CCDS: CCDS10280

Canonical transcript exons

ENST00000618819 — 13 exons

Exon	Start	End
ENSE00001162407	75470680	75470830
ENSE00001162432	75479848	75479914
ENSE00001208491	75505675	75506003
ENSE00001208494	75508917	75509027
ENSE00001208509	75517259	75517364
ENSE00001235366	75523121	75523245
ENSE00001235373	75524209	75524298
ENSE00001235380	75527118	75527261
ENSE00001235394	75578714	75579315
ENSE00003546423	75469792	75469999
ENSE00003573839	75473689	75473767
ENSE00003624657	75490208	75490301
ENSE00003746977	75463251	75468983

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 91.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.8509 / max 124.1254, expressed in 1804 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150984	8.4088	1733
150985	7.5114	1753
150983	0.9820	595
150982	0.7670	397
150986	0.1816	77

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	91.85	gold quality
cortical plate	UBERON:0005343	91.52	gold quality
ganglionic eminence	UBERON:0004023	91.50	gold quality
stromal cell of endometrium	CL:0002255	90.97	gold quality
right lobe of thyroid gland	UBERON:0001119	90.31	gold quality
left lobe of thyroid gland	UBERON:0001120	90.22	gold quality
thyroid gland	UBERON:0002046	89.63	gold quality
tibial nerve	UBERON:0001323	89.14	gold quality
olfactory bulb	UBERON:0002264	88.19	gold quality
monocyte	CL:0000576	87.97	gold quality
hair follicle	UBERON:0002073	87.84	silver quality
leukocyte	CL:0000738	87.81	gold quality
mononuclear cell	CL:0000842	87.79	gold quality
islet of Langerhans	UBERON:0000006	87.78	gold quality
rectum	UBERON:0001052	87.75	gold quality
smooth muscle tissue	UBERON:0001135	87.70	gold quality
type B pancreatic cell	CL:0000169	87.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.02	gold quality
lower esophagus	UBERON:0013473	86.99	gold quality
embryo	UBERON:0000922	86.90	gold quality
dorsal root ganglion	UBERON:0000044	86.48	gold quality
endocervix	UBERON:0000458	86.29	gold quality
tibial artery	UBERON:0007610	86.23	gold quality
popliteal artery	UBERON:0002250	86.22	gold quality
descending thoracic aorta	UBERON:0002345	86.17	gold quality
diaphragm	UBERON:0001103	86.13	gold quality
aorta	UBERON:0000947	85.87	gold quality
calcaneal tendon	UBERON:0003701	85.54	gold quality
colonic epithelium	UBERON:0000397	85.52	gold quality
thoracic aorta	UBERON:0001515	85.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

143 targeting PTPN9, 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-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548P	99.98	72.25	3784
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-4745-5P	99.98	65.95	1028
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-338-5P	99.92	72.34	2951

Literature-anchored findings (GeneRIF, showing 20)

• Purification and characterization of protein tyrosine phosphatase PTP-MEG2 (PMID:12112018)
• PTP-MEG2 has an important role in the development of erythroid cells. (PMID:12920026)
• PTPase-MEG2 through its Sec14p homology domain couples inositide phosphorylation to tyrosine dephosphorylation and the regulation of intracellular traffic of the secretory pathway in T cells. (PMID:14662869)
• PTP-MEG2 reduced the phosphotyrosine content of NSF and co-localized with NSF and syntaxin 6 in intact cells, the first demonstrated role for a protein tyrosine phosphatase in the regulated secretory pathway (PMID:15322554)
• role in the negative regulation of hepatic insulin signaling (PMID:16679294)
• the N terminus of PTPMEG2 is necessary for the targeting of this phosphatase to the secretory vesicle compartment by association with other proteins involved in intracellular transport. (PMID:17387180)
• data suggest PTPN9 as a negative regulator of breast cancer cells by targeting ErbB2 and EGFR and inhibiting STAT activation (PMID:20335174)
• PTPMeg2 is an important phosphatase for the dephosphorylation of STAT3 and plays a critical role in breast cancer development. (PMID:22394684)
• This study indentified VEGFR2 as a PTPN9 substrate, and indicated that PTPN9 is a negative regulator of VEGFR2 signaling and function in endothelial cells. (PMID:22763125)
• Results from a study on gene expression variability markers in early-stage human embryos shows that PTPN9 is a putative expression variability marker for the 3-day, 8-cell embryo stage. (PMID:26288249)
• PTPN9 inhibited cell proliferation in HepG2 cells. (PMID:26715439)
• this study highlights an important role for miR-96 in the regulation of PTPN9 in breast cancer cells and may provide insight into the molecular mechanisms of breast carcinogenesis. (PMID:27857177)
• Expression of MEG2 is reversely correlated with that of miR-181a-5p in gastric cancer. (PMID:28747184)
• Low MEG2 expression is associated with metastasis of hepatocellular carcinoma. (PMID:30399427)
• PTPN9-mediated dephosphorylation of VTI1B promotes ATG16L1 precursor fusion and autophagosome formation. (PMID:33112705)
• The Critical Role of the miR-21-MEG2 Axis in Colorectal Cancer. (PMID:33463918)
• Effect of L3MBTL3/PTPN9 polymorphisms on risk to alcohol-induced ONFH in Chinese Han population. (PMID:34373992)
• CircMMD_007 promotes oncogenic effects in the progression of lung adenocarcinoma through microRNA-197-3p/protein tyrosine phosphatase non-receptor type 9 axis. (PMID:35156900)
• Signature of miR-21 and MEG-2 and their correlation with TGF-beta signaling in breast cancer. (PMID:36825546)
• The binding of PKCepsilon and MEG2 to STAT3 regulates IL-6-mediated microglial hyperalgesia during inflammatory pain. (PMID:38656553)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptpn9a	ENSDARG00000077495
mus_musculus	Ptpn9	ENSMUSG00000032290
rattus_norvegicus	Ptpn9	ENSRNOG00000017600

Paralogs (35): PTPRN (ENSG00000054356), PTPRU (ENSG00000060656), PTPN3 (ENSG00000070159), PTPN21 (ENSG00000070778), PTPN18 (ENSG00000072135), PTPN23 (ENSG00000076201), PTPRH (ENSG00000080031), PTPRC (ENSG00000081237), PTPN4 (ENSG00000088179), PTPRS (ENSG00000105426), PTPRZ1 (ENSG00000106278), PTPN5 (ENSG00000110786), 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), PTPRM (ENSG00000173482), PTPN2 (ENSG00000175354), PTPN11 (ENSG00000179295), PTPRT (ENSG00000196090), PTPN1 (ENSG00000196396), PTPN20 (ENSG00000204179)

Protein

Protein identifiers

Tyrosine-protein phosphatase non-receptor type 9 — P43378 (reviewed: P43378)

Alternative names: Protein-tyrosine phosphatase MEG2

All UniProt accessions (2): P43378, H3BQT6

UniProt curated annotations — full annotation on UniProt →

Function. Protein-tyrosine phosphatase that could participate in the transfer of hydrophobic ligands or in functions of the Golgi apparatus.

Subcellular location. Cytoplasm.

Similarity. Belongs to the protein-tyrosine phosphatase family. Non-receptor class 3 subfamily.

RefSeq proteins (1): NP_002824* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000242	PTP_cat	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR001251	CRAL-TRIO_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR011074	CRAL/TRIO_N_dom	Domain
IPR016130	Tyr_Pase_AS	Active_site
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR036273	CRAL/TRIO_N_dom_sf	Homologous_superfamily
IPR036865	CRAL-TRIO_dom_sf	Homologous_superfamily
IPR050348	Protein-Tyr_Phosphatase	Family

Pfam: PF00102, PF00650

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 (36 total): strand 14, helix 9, turn 4, binding site 3, domain 2, chain 1, region of interest 1, active site 1, modified residue 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
4GE6	X-RAY DIFFRACTION	1.4
2PA5	X-RAY DIFFRACTION	1.6
6KZQ	X-RAY DIFFRACTION	1.7
4GE2	X-RAY DIFFRACTION	1.8
4ICZ	X-RAY DIFFRACTION	1.9
4GE5	X-RAY DIFFRACTION	2
6L03	X-RAY DIFFRACTION	2.08

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43378-F1	87.72	0.64

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): 515 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (3): 470; 515–521; 559

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9008059	Interleukin-37 signaling

MSigDB gene sets: 210 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, MORF_RAGE, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MODULE_45, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_NEUROGENESIS, TACAATC_MIR508, MODULE_308, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GTGCCTT_MIR506, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_NEGATIVE_REGULATION_OF_CELL_PROJECTION_ORGANIZATION

GO Biological Process (6): protein dephosphorylation (GO:0006470), signal transduction (GO:0007165), negative regulation of neuron projection development (GO:0010977), peptidyl-tyrosine dephosphorylation (GO:0035335), positive regulation of protein localization to plasma membrane (GO:1903078), dephosphorylation (GO:0016311)

GO Molecular Function (5): protein tyrosine phosphatase activity (GO:0004725), non-membrane spanning protein tyrosine phosphatase activity (GO:0004726), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (3): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), neuron projection terminus (GO:0044306)

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	3
dephosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
protein dephosphorylation	1
protein localization to plasma membrane	1
regulation of protein localization to plasma membrane	1
positive regulation of protein localization to cell periphery	1
positive regulation of protein localization to membrane	1
phosphate-containing compound metabolic process	1
phosphoprotein phosphatase activity	1
protein tyrosine phosphatase activity	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
nuclear lumen	1
intracellular anatomical structure	1
neuron projection	1

Protein interactions and networks

STRING

1302 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPN9	SEC14L1	Q92503	892
PTPN9	PTS	Q03393	711
PTPN9	PPP4R1	Q8TF05	602
PTPN9	DUSP3	P51452	487
PTPN9	PTPRJ	Q12913	459
PTPN9	CDC14A	Q9UNH5	410
PTPN9	AP4B1	Q9Y6B7	393
PTPN9	EPM2A	O95278	374
PTPN9	ACP1	P24666	365
PTPN9	DUSP15	Q9H1R2	358
PTPN9	FAM53B	Q14153	358
PTPN9	OR52W1	Q6IF63	357
PTPN9	RLBP1	P12271	356
PTPN9	DUSP9	Q99956	346
PTPN9	STAT3	P40763	326

IntAct

164 interactions, top by confidence:

A	B	Type	Score
PTPN9	RTN3	psi-mi:“MI:0915”(physical association)	0.740
AGTRAP	PTPN9	psi-mi:“MI:0915”(physical association)	0.740
PTPN9	AGTRAP	psi-mi:“MI:0915”(physical association)	0.740
RTN3	PTPN9	psi-mi:“MI:0915”(physical association)	0.740
PTPN9	MAL2	psi-mi:“MI:0915”(physical association)	0.670
CMTM5	PTPN9	psi-mi:“MI:0915”(physical association)	0.670
MAL2	PTPN9	psi-mi:“MI:0915”(physical association)	0.670
PTPN9	GHR	psi-mi:“MI:0407”(direct interaction)	0.560
PTPN9	GHR	psi-mi:“MI:0203”(dephosphorylation reaction)	0.560
PTPN9	TMX2	psi-mi:“MI:0915”(physical association)	0.560
PTPN9	HSD17B13	psi-mi:“MI:0915”(physical association)	0.560
PTPN9	AQP6	psi-mi:“MI:0915”(physical association)	0.560
PTPN9	CMTM5	psi-mi:“MI:0915”(physical association)	0.560
PTPN9	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.560
PTPN9	REEP6	psi-mi:“MI:0915”(physical association)	0.560
RTN3	PTPN9	psi-mi:“MI:0915”(physical association)	0.560
PTPN9	SPAG4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (137): RTN3 (Two-hybrid), AGTRAP (Two-hybrid), REEP6 (Two-hybrid), MAL2 (Two-hybrid), CMTM5 (Two-hybrid), PTPN9 (Affinity Capture-RNA), PTPN9 (Affinity Capture-RNA), PTPN9 (Affinity Capture-RNA), RTN3 (Two-hybrid), PTPN9 (Affinity Capture-MS), PTPN9 (Two-hybrid), PTPN9 (Two-hybrid), PTPN9 (Two-hybrid), LZTR1 (Affinity Capture-MS), PC (Affinity Capture-MS)

ESM2 similar proteins: A2ALK8, A8XWC4, D3ZDI6, F1LYQ8, F1M386, F1MSG6, F1P065, F1PBJ0, F8VPU2, G5EDB9, O14936, O35239, O70589, O94887, P26045, P28191, P43378, P54936, P70600, P97874, Q05397, Q05AK5, Q14289, Q14644, Q15283, Q28013, Q3UYK3, Q4KWH5, Q4KWH8, Q58CU2, Q5RAB8, Q60790, Q62915, Q641Z2, Q6NVF0, Q6P7F1, Q6TEM9, Q8BM54, Q8CHG7, Q8TEU7

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

10 interactions.

A	Effect	B	Mechanism
PTPN9	down-regulates	GHR	dephosphorylation
PTPN9	down-regulates	NSF	dephosphorylation
PTPN9	down-regulates	INSR	dephosphorylation
PTPN9	“down-regulates activity”	STAT3	dephosphorylation
PTPN9	“down-regulates activity”	EGFR	dephosphorylation
PTPN9	“down-regulates activity”	ERBB2	dephosphorylation
PTPN9	“down-regulates activity”	GHR	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2443 predictions. Top by Δscore:

Variant	Effect	Δscore
15:75468771:A:AC	donor_gain	1.0000
15:75468772:C:CC	donor_gain	1.0000
15:75468775:A:AC	donor_gain	1.0000
15:75468776:C:CC	donor_gain	1.0000
15:75469847:C:A	donor_gain	1.0000
15:75470001:T:C	acceptor_gain	1.0000
15:75470001:T:TC	acceptor_gain	1.0000
15:75470675:TTTA:T	donor_loss	1.0000
15:75470676:TTA:T	donor_loss	1.0000
15:75470677:TACC:T	donor_loss	1.0000
15:75470678:A:AG	donor_loss	1.0000
15:75470679:CCT:C	donor_gain	1.0000
15:75470826:CAAAG:C	acceptor_gain	1.0000
15:75470828:AAG:A	acceptor_gain	1.0000
15:75470829:AG:A	acceptor_gain	1.0000
15:75470831:C:CC	acceptor_gain	1.0000
15:75470831:CTGAA:C	acceptor_loss	1.0000
15:75473685:TCA:T	donor_loss	1.0000
15:75473686:CACCG:C	donor_loss	1.0000
15:75473688:C:CA	donor_loss	1.0000
15:75473768:C:CC	acceptor_gain	1.0000
15:75473773:A:AC	acceptor_gain	1.0000
15:75505673:A:AC	donor_gain	1.0000
15:75505674:C:CC	donor_gain	1.0000
15:75508912:CTTA:C	donor_loss	1.0000
15:75508913:TTACC:T	donor_loss	1.0000
15:75508914:T:TG	donor_loss	1.0000
15:75508915:A:AC	donor_gain	1.0000
15:75508915:A:T	donor_loss	1.0000
15:75508915:AC:A	donor_gain	1.0000

AlphaMissense

3908 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:75468874:C:A	Q559H	1.000
15:75468874:C:G	Q559H	1.000
15:75468880:G:C	S557R	1.000
15:75468880:G:T	S557R	1.000
15:75468882:T:G	S557R	1.000
15:75468889:C:A	R554S	1.000
15:75468889:C:G	R554S	1.000
15:75468890:C:A	R554M	1.000
15:75468890:C:G	R554T	1.000
15:75468899:C:A	R551M	1.000
15:75468973:G:C	C526W	1.000
15:75468975:A:G	C526R	1.000
15:75468983:C:T	G523D	1.000
15:75469794:G:A	T522I	1.000
15:75469796:C:A	R521S	1.000
15:75469796:C:G	R521S	1.000
15:75469797:C:A	R521M	1.000
15:75469797:C:G	R521T	1.000
15:75469800:C:A	G520V	1.000
15:75469800:C:T	G520D	1.000
15:75469801:C:G	G520R	1.000
15:75469806:C:A	G518V	1.000
15:75469806:C:T	G518D	1.000
15:75469807:C:A	G518C	1.000
15:75469807:C:G	G518R	1.000
15:75469811:A:C	S516R	1.000
15:75469811:A:T	S516R	1.000
15:75469813:T:G	S516R	1.000
15:75469814:G:C	C515W	1.000
15:75469815:C:T	C515Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000017487 (15:75566393 C>T), RS1000021063 (15:75468031 T>C), RS1000038656 (15:75487004 C>A,T), RS1000043610 (15:75541347 C>CGCTGGGAT), RS1000096268 (15:75521908 T>C), RS1000136882 (15:75560158 T>G), RS1000147525 (15:75527341 T>C), RS1000198769 (15:75480434 C>G), RS1000205358 (15:75473193 G>A,C), RS1000224942 (15:75535163 T>A,C), RS1000227782 (15:75465945 C>G), RS1000257524 (15:75465514 T>C,G), RS1000258571 (15:75566151 G>C), RS1000283392 (15:75578446 A>G,T), RS1000292212 (15:75520297 G>A,T)

Disease associations

OMIM: gene MIM:600768 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000611_16	Height	8.000000e-08
GCST002702_15	Height	2.000000e-10
GCST007876_30	Estimated glomerular filtration rate	3.000000e-25
GCST008839_185	Height	4.000000e-38
GCST009379_207	Type 2 diabetes	6.000000e-10
GCST012227_515	Hip circumference adjusted for BMI	1.000000e-10
GCST90013466_14	Height	3.000000e-09
GCST90013466_35	Height	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4296101 (PROTEIN-PROTEIN INTERACTION), CHEMBL6117 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

2 measured of 4 human assays (4 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[[4-[3-[[1-amino-5-[(3-iodobenzoyl)amino]-1-oxopentan-2-yl]amino]-2-[(3-bromo-4-methylbenzoyl)amino]-3-oxopropyl]phenyl]-difluoromethyl]phosphonic acid	IC50	3400 nM	US-9340574: Inhibitors of protein tyrosine phosphatases
[[4-[2-acetamido-3-[[1-amino-5-[(3-iodobenzoyl)amino]-1-oxopentan-2-yl]amino]-3-oxopropyl]phenyl]-difluoromethyl]phosphonic acid	IC50	7800 nM	US-9340574: Inhibitors of protein tyrosine phosphatases

ChEMBL bioactivities

21 potent at pChembl≥5 of 35 total, top 21 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.47	Ki	34	nM	CHEMBL3978384
7.12	IC50	75	nM	CHEMBL3978384
6.57	IC50	270	nM	CHEMBL3949280
6.39	IC50	410	nM	CHEMBL4569405
6.23	IC50	590	nM	CHEMBL2396718
6.05	IC50	900	nM	CHEMBL3917014
5.97	IC50	1070	nM	CHEMBL2316908
5.64	IC50	2300	nM	CHEMBL2316906
5.62	IC50	2400	nM	CHEMBL4530344
5.52	IC50	3000	nM	CHEMBL2396719
5.40	IC50	4000	nM	CHEMBL2316907
5.40	IC50	4000	nM	CHEMBL2316905
5.37	IC50	4300	nM	CHEMBL2316902
5.32	IC50	4800	nM	CHEMBL2316910
5.23	IC50	5900	nM	CHEMBL4540813
5.11	IC50	7700	nM	CHEMBL2316896
5.10	IC50	8000	nM	CHEMBL4227292
5.08	IC50	8400	nM	CHEMBL2316895
5.07	IC50	8600	nM	CHEMBL2316894
5.05	IC50	9000	nM	CHEMBL2316904
5.04	IC50	9200	nM	CHEMBL2311593

PubChem BioAssay actives

17 with measured affinity, of 104 total; 17 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
phenyl-[[25,26,27,28-tetrahydroxy-11,17,23-tris[[hydroxy(phenyl)phosphoryl]methyl]-2,2,8,8,14,14,20,20-octaoxo-2lambda6,8lambda6,14lambda6,20lambda6-tetrathiapentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(24),3,5,7(28),9,11,13(27),15(26),16,18,21(25),22-dodecaen-5-yl]methyl]phosphinic acid	1624389: Inhibition of recombinant human N-terminal GST-tagged MEG2 catalytic domain (285 to 593 residues) expressed in Escherichia coli using p-nitrophenol as substrate preincubated with substrate for 5 mins followed by enzyme addition	ic50	0.4100	uM
3-[2-(3-chlorophenyl)ethynyl]-6-hydroxy-2-[4-[2-oxo-2-(propylamino)ethoxy]phenyl]-1-benzofuran-5-carboxylic acid	755775: Inhibition of recombinant PTP-MEG2 (unknown origin) using pNPP as substrate by spectrophotometric analysis	ic50	0.5900	uM
6-hydroxy-3-[2-(4-phenoxyphenyl)ethynyl]-2-phenyl-1-benzofuran-5-carboxylic acid	725034: Inhibition of PTPMEG2 (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	1.0700	uM
3-[2-(3,5-difluorophenyl)ethynyl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid	725034: Inhibition of PTPMEG2 (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	2.3000	uM
phenyl-[[25,26,27,28-tetrahydroxy-11,17,23-tris[[hydroxy(phenyl)phosphoryl]methyl]-5-pentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(24),3,5,7(28),9,11,13(27),15(26),16,18,21(25),22-dodecaenyl]methyl]phosphinic acid	1624389: Inhibition of recombinant human N-terminal GST-tagged MEG2 catalytic domain (285 to 593 residues) expressed in Escherichia coli using p-nitrophenol as substrate preincubated with substrate for 5 mins followed by enzyme addition	ic50	2.4000	uM
3-[2-(3-chlorophenyl)ethynyl]-2-[4-[2-(cyclopropylamino)-2-oxoethoxy]phenyl]-6-hydroxy-1-benzofuran-5-carboxylic acid	755775: Inhibition of recombinant PTP-MEG2 (unknown origin) using pNPP as substrate by spectrophotometric analysis	ic50	3.0000	uM
6-hydroxy-2-phenyl-3-[2-[4-(trifluoromethoxy)phenyl]ethynyl]-1-benzofuran-5-carboxylic acid	725034: Inhibition of PTPMEG2 (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	4.0000	uM
3-[2-(3-chlorophenyl)ethynyl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid	725034: Inhibition of PTPMEG2 (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	4.0000	uM
6-hydroxy-2-phenyl-3-[2-[3-(trifluoromethyl)phenyl]ethynyl]-1-benzofuran-5-carboxylic acid	725034: Inhibition of PTPMEG2 (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	4.3000	uM
3-[2-(2,4-difluorophenyl)ethynyl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid	725034: Inhibition of PTPMEG2 (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	4.8000	uM
phenyl-[[25,26,27,28-tetrahydroxy-11,17,23-tris[[hydroxy(phenyl)phosphoryl]methyl]-2,8,14,20-tetrathiapentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(24),3,5,7(28),9,11,13(27),15(26),16,18,21(25),22-dodecaen-5-yl]methyl]phosphinic acid	1624389: Inhibition of recombinant human N-terminal GST-tagged MEG2 catalytic domain (285 to 593 residues) expressed in Escherichia coli using p-nitrophenol as substrate preincubated with substrate for 5 mins followed by enzyme addition	ic50	5.9000	uM
6-hydroxy-3-[2-(4-phenoxyphenyl)ethyl]-2-phenyl-1-benzofuran-5-carboxylic acid	725034: Inhibition of PTPMEG2 (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	7.7000	uM
(2Z)-4-methoxy-2-[(E)-1-methoxy-3-phenylprop-2-enylidene]cyclopent-4-ene-1,3-dione	1389392: Modulation of MEG2 in human HCT116 cells harboring pSTAT3 (unknown origin)-TA-Luc assessed as inhibition of STAT3 transcriptional activity after 24 hrs by luciferase reporter gene assay	ic50	8.0000	uM
6-hydroxy-2-phenyl-3-[2-[4-(trifluoromethoxy)phenyl]ethyl]-1-benzofuran-5-carboxylic acid	725034: Inhibition of PTPMEG2 (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	8.4000	uM
6-hydroxy-2-phenyl-3-[2-[3-(trifluoromethyl)phenyl]ethyl]-1-benzofuran-5-carboxylic acid	725034: Inhibition of PTPMEG2 (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	8.6000	uM
3-[2-(3-fluorophenyl)ethynyl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid	725034: Inhibition of PTPMEG2 (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	9.0000	uM
3-[(Z)-2-(3,5-difluorophenyl)ethenyl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid	725034: Inhibition of PTPMEG2 (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	9.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression, affects expression, increases reaction	2
Arsenic	increases methylation, affects methylation	2
Valproic Acid	affects expression, decreases expression	2
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases methylation	1
anthranilic acid	affects binding, decreases activity	1
oxovanadium IV	affects binding, decreases activity	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
U 0126	affects expression, affects reaction	1
salicylideneaniline	decreases activity, affects binding	1
Erlotinib Hydrochloride	decreases response to substance, decreases expression	1
Decitabine	decreases expression, affects reaction	1
Sunitinib	increases expression	1
Panobinostat	affects expression, increases reaction	1
Atrazine	increases expression	1
Caffeine	increases phosphorylation	1
Doxorubicin	decreases expression	1
Folic Acid	decreases expression	1
Ivermectin	decreases expression	1
Maneb	affects activity	1
Pesticides	decreases methylation	1
Schiff Bases	affects binding, decreases activity	1
1-Methyl-4-phenylpyridinium	affects expression, affects reaction	1
Cyclosporine	increases expression	1

ChEMBL screening assays

29 unique, capped per target: 28 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4220955	Binding	Modulation of MEG2 in human HCT116 cells harboring pSTAT3 (unknown origin)-TA-Luc assessed as inhibition of STAT3 transcriptional activity after 24 hrs by luciferase reporter gene assay	Methyllucidone inhibits STAT3 activity by regulating the expression of the protein tyrosine phosphatase MEG2 in DU145 prostate carcinoma cells. — Bioorg Med Chem Lett
CHEMBL4626303	ADMET	Inhibition of PTP-MEG2 (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.