PTPRE

Summary

PTPRE (protein tyrosine phosphatase receptor type E, HGNC:9669) is a protein-coding gene on chromosome 10q26.2, encoding Receptor-type tyrosine-protein phosphatase epsilon (P23469). Isoform 1 plays a critical role in signaling transduction pathways and phosphoprotein network topology in red blood cells.

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. Several alternatively spliced transcript variants of this gene have been reported, at least two of which encode a receptor-type PTP that possesses a short extracellular domain, a single transmembrane region, and two tandem intracytoplasmic catalytic domains; another one encodes a PTP that contains a distinct hydrophilic N-terminus, and thus represents a nonreceptor-type isoform of this PTP. Studies of the similar gene in mice suggested the regulatory roles of this PTP in RAS related signal transduction pathways, cytokine-induced SATA signaling, as well as the activation of voltage-gated K+ channels.

Source: NCBI Gene 5791 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 111 total — 2 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_006504

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9669
Approved symbol	PTPRE
Name	protein tyrosine phosphatase receptor type E
Location	10q26.2
Locus type	gene with protein product
Status	Approved
Aliases	PTPE
Ensembl gene	ENSG00000132334
Ensembl biotype	protein_coding
OMIM	600926
Entrez	5791

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 20 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000254667, ENST00000306042, ENST00000442830, ENST00000455661, ENST00000463727, ENST00000467366, ENST00000471218, ENST00000479896, ENST00000487428, ENST00000492479, ENST00000495530, ENST00000870711, ENST00000870712, ENST00000870713, ENST00000870714, ENST00000968589, ENST00000968590, ENST00000968591, ENST00000968592, ENST00000968593, ENST00000968594, ENST00000968595, ENST00000968596, ENST00000968597, ENST00000968598

RefSeq mRNA: 8 — MANE Select: NM_006504 NM_001316676, NM_001316677, NM_001323354, NM_001323355, NM_001323356, NM_001323357, NM_006504, NM_130435

CCDS: CCDS7657, CCDS7658

Canonical transcript exons

ENST00000254667 — 21 exons

Exon	Start	End
ENSE00001190473	127982274	127982296
ENSE00001190478	127907103	127907309
ENSE00001764214	128070808	128070901
ENSE00003480338	128079560	128079695
ENSE00003493715	128066075	128066194
ENSE00003497089	128047390	128047489
ENSE00003506468	128069692	128069827
ENSE00003511026	128073337	128073471
ENSE00003561179	128060939	128061015
ENSE00003561185	128068123	128068286
ENSE00003583220	128063083	128063180
ENSE00003617670	128070301	128070450
ENSE00003619320	128082832	128085855
ENSE00003634815	128077617	128077783
ENSE00003635913	128040875	128040990
ENSE00003665553	128072138	128072214
ENSE00003671504	128056123	128056213
ENSE00003673996	128076603	128076728
ENSE00003684247	128047764	128047837
ENSE00003692645	128061679	128061715
ENSE00003786459	128049530	128049666

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 96.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.4930 / max 4424.3553, expressed in 1379 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107649	19.5882	688
107648	8.3824	648
107630	6.1254	1077
107650	2.0430	292
107640	1.1232	163
107631	1.0399	607
107647	0.8939	282
107643	0.1195	65
107641	0.0632	48
107628	0.0597	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	96.37	gold quality
mononuclear cell	CL:0000842	96.37	gold quality
leukocyte	CL:0000738	96.25	gold quality
blood	UBERON:0000178	95.70	gold quality
bone marrow cell	CL:0002092	95.47	gold quality
granulocyte	CL:0000094	94.55	gold quality
bone marrow	UBERON:0002371	94.09	gold quality
sural nerve	UBERON:0015488	93.16	gold quality
visceral pleura	UBERON:0002401	92.18	gold quality
bone element	UBERON:0001474	91.81	gold quality
trigeminal ganglion	UBERON:0001675	90.41	gold quality
right lung	UBERON:0002167	90.02	gold quality
vermiform appendix	UBERON:0001154	89.94	gold quality
pleura	UBERON:0000977	89.77	gold quality
upper lobe of left lung	UBERON:0008952	89.31	gold quality
decidua	UBERON:0002450	89.14	gold quality
upper lobe of lung	UBERON:0008948	89.14	gold quality
CA1 field of hippocampus	UBERON:0003881	88.89	gold quality
spleen	UBERON:0002106	88.45	gold quality
parietal pleura	UBERON:0002400	88.01	gold quality
caecum	UBERON:0001153	87.79	gold quality
right adrenal gland cortex	UBERON:0035827	87.79	gold quality
trabecular bone tissue	UBERON:0002483	87.73	gold quality
adrenal cortex	UBERON:0001235	87.59	gold quality
left adrenal gland cortex	UBERON:0035825	87.47	gold quality
left adrenal gland	UBERON:0001234	87.42	gold quality
lower lobe of lung	UBERON:0008949	87.41	gold quality
lung	UBERON:0002048	87.37	gold quality
middle temporal gyrus	UBERON:0002771	87.37	gold quality
right adrenal gland	UBERON:0001233	87.18	gold quality

Single-cell (SCXA)

Detected in 25 experiment(s), a significant marker in 25.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	1152.79
E-CURD-11	yes	524.05
E-CURD-122	yes	82.11
E-HCAD-4	yes	37.47
E-MTAB-8142	yes	35.10
E-MTAB-10553	yes	33.90
E-HCAD-6	yes	33.16
E-MTAB-10287	yes	23.67
E-HCAD-13	yes	22.66
E-HCAD-1	yes	21.16
E-MTAB-9221	yes	20.84
E-MTAB-6701	yes	18.18
E-MTAB-9467	yes	15.56
E-CURD-46	yes	14.59
E-CURD-112	yes	13.65

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SPI1

miRNA regulators (miRDB)

157 targeting PTPRE, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-5688	99.96	73.23	4504

Literature-anchored findings (GeneRIF, showing 12)

• Transfection of cells with different PTPepsilon constructs and activator protein-1 reporter gene indicates that the catalytic activity of PTPepsilon is involved in the regulation of the mitogen-activated protein kinase cascade. (PMID:12121439)
• Characterization, expression and functional aspects of an alternative spliced isoform of protein tyrosine phosphatase epsilon (PMID:12193229)
• interactions between RPTP-domain1s and RPTP-domain 2s are a common but specific mechanism that is likely to be regulated- domain2s and the wedge structures are crucial determinants of binding specificity, thus regulating cross-talk between RPTPs (PMID:12376545)
• Functions to prevent inappropriate activation and to terminate prolonged, rather than acute, activation of ERK in the cytosol. (PMID:12754301)
• cyt-PTP epsilon is dimerized and phosphorylated in the absence of direct interaction between the PTP and extracellular molecules (PMID:12861030)
• Transgenic mice overexpressing catalytically inactive transmembrane protein tyrosine phosphatase epsilon provide unexpected insight into the cell-cell interactions that occur between oligodendrocytes and the cells which they myelinate. (PMID:15390114)
• Protein-tyrosine phosphatase epsilon regulates Shc signaling in a kinase-specific manner: increasing coherence in tyrosine phosphatase signaling (PMID:18093973)
• Studies indicate that RAD50 and PTPRE of crude associations with asthma at a Bonferroni-corrected level of significance, while IL4R, CCL5 and TBXA2R of nominal significance. (PMID:21734400)
• Epidermal growth factor receptor (EGFR)-mediated positive feedback of protein-tyrosine phosphatase epsilon (PTPepsilon) on ERK1/2 and AKT protein pathways is required for survival of human breast cancer cells. (PMID:22117074)
• these data demonstrate that HCV infection reduces PTPRE expression in the liver and peripheral blood mononuclear cell sof infected humans (PMID:28235043)
• RPTPepsilon promotes M2-polarized macrophage migration through ROCK2 signaling and podosome formation. (PMID:31722979)
• Receptor Type Protein Tyrosine Phosphatase Epsilon (PTPRE) Plays an Oncogenic Role in Thyroid Carcinoma by Activating the AKT and ERK1/2 Signaling Pathway. (PMID:36654463)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptprea	ENSDARG00000015891
danio_rerio	ptpreb	ENSDARG00000021151
mus_musculus	Ptpre	ENSMUSG00000041836
rattus_norvegicus	Ptpre	ENSRNOG00000015717

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), 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

Receptor-type tyrosine-protein phosphatase epsilon — P23469 (reviewed: P23469)

All UniProt accessions (7): P23469, Q5VWH5, Q5VWH6, S4R2Y5, S4R3B0, S4R3X3, S4R448

UniProt curated annotations — full annotation on UniProt →

Function. Isoform 1 plays a critical role in signaling transduction pathways and phosphoprotein network topology in red blood cells. May play a role in osteoclast formation and function. Isoform 2 acts as a negative regulator of insulin receptor (IR) signaling in skeletal muscle. Regulates insulin-induced tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate 1 (IRS-1), phosphorylation of protein kinase B and glycogen synthase kinase-3 and insulin induced stimulation of glucose uptake. Isoform 1 and isoform 2 act as a negative regulator of FceRI-mediated signal transduction leading to cytokine production and degranulation, most likely by acting at the level of SYK to affect downstream events such as phosphorylation of SLP76 and LAT and mobilization of Ca(2+).

Subunit / interactions. Monomer. Isoform 2: Homodimer. Can form oligomers. Dimerization is increased by oxidative stress and decreased by EGFR. Isoform 2 interacts with GRB2.

Subcellular location. Cell membrane Cytoplasm Cytoplasm.

Tissue specificity. Expressed in giant cell tumor (osteoclastoma rich in multinucleated osteoclastic cells).

Post-translational modifications. A catalytically active cytoplasmic form (p65) is produced by proteolytic cleavage of either isoform 1, isoform 2 or isoform 3. Isoform 1 and isoform 2 are phosphorylated on tyrosine residues by tyrosine kinase Neu. Isoform 1 is glycosylated.

Domain organisation. The tyrosine-protein phosphatase 2 domain (D2) mediates dimerization. The extreme N- and C- termini of the D2 domain act to inhibit dimerization and removal of these sequences increases dimerization and inhibits enzyme activity.

Induction. Up-regulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) in HL-60 cells.

Miscellaneous. Produced by alternative promoter usage. Produced by alternative promoter usage. Produced by alternative initiation at Met-86 of isoform 1.

Similarity. Belongs to the protein-tyrosine phosphatase family. Receptor class 4 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P23469-1	1, PTPeM, RPTPe, tm-PTPe	yes
P23469-2	2, PTPeC, cyt-PTPe
P23469-3	3, p67

RefSeq proteins (8): NP_001303605, NP_001303606, NP_001310283, NP_001310284, NP_001310285, NP_001310286, NP_006495, NP_569119 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000242	PTP_cat	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR016130	Tyr_Pase_AS	Active_site
IPR016336	Tyr_Pase_rcpt_a/e-type	Family
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR050348	Protein-Tyr_Phosphatase	Family

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 (73 total): strand 28, helix 21, turn 6, binding site 3, glycosylation site 2, splice variant 2, topological domain 2, domain 2, active site 2, signal peptide 1, chain 1, modified residue 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6D4D	X-RAY DIFFRACTION	1.76
6D4F	X-RAY DIFFRACTION	1.91
6D3F	X-RAY DIFFRACTION	2.27
2JJD	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23469-F1	86.42	0.74

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 (2): 335 (phosphocysteine intermediate); 630 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (3): 335–341; 379; 303

Post-translational modifications (1): 696

Glycosylation sites (2): 23, 30

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 431 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, YAGI_AML_WITH_INV_16_TRANSLOCATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_45, MODULE_64, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, ATGTTAA_MIR302C, BILD_HRAS_ONCOGENIC_SIGNATURE

GO Biological Process (6): protein dephosphorylation (GO:0006470), signal transduction (GO:0007165), cell surface receptor protein tyrosine phosphatase signaling pathway (GO:0007185), regulation of mast cell activation (GO:0033003), negative regulation of insulin receptor signaling pathway (GO:0046627), dephosphorylation (GO:0016311)

GO Molecular Function (6): protein tyrosine phosphatase activity (GO:0004725), transmembrane receptor protein tyrosine phosphatase activity (GO:0005001), identical protein binding (GO:0042802), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	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
enzyme-linked receptor protein signaling pathway	1
regulation of leukocyte activation	1
mast cell activation	1
insulin receptor signaling pathway	1
negative regulation of signal transduction	1
regulation of insulin receptor signaling pathway	1
negative regulation of cellular response to insulin stimulus	1
phosphate-containing compound metabolic process	1
phosphoprotein phosphatase activity	1
protein tyrosine phosphatase activity	1
transmembrane receptor protein phosphatase activity	1
protein binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPRE	WDR5	P61964	701
PTPRE	PTS	Q03393	611
PTPRE	PTGDR	Q13258	511
PTPRE	CYSLTR1	Q9Y271	497
PTPRE	SMAD3	P84022	449
PTPRE	ARHGAP6	O43182	444
PTPRE	GCSAML	Q5JQS6	417
PTPRE	TNIK	Q9UKE5	399
PTPRE	PDE7B	Q9NP56	398
PTPRE	PTPRJ	Q12913	392
PTPRE	CALHM3	Q86XJ0	390
PTPRE	PITPNC1	Q9UKF7	389
PTPRE	WNT3A	P56704	381
PTPRE	A8MSY1	A8MSY1	379
PTPRE	WDR55	Q9H6Y2	347

IntAct

20 interactions, top by confidence:

A	B	Type	Score
PTPRA	PTPRE	psi-mi:“MI:0914”(association)	0.640
PTPRA	LGALS1	psi-mi:“MI:0914”(association)	0.640
PTPRA	LGALS8	psi-mi:“MI:0914”(association)	0.530
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
PTPRA	PTPRE	psi-mi:“MI:0914”(association)	0.420
Yes1	PTPRE	psi-mi:“MI:0915”(physical association)	0.400
FYN	PTPRE	psi-mi:“MI:0915”(physical association)	0.400
EGFR	PTPRE	psi-mi:“MI:0915”(physical association)	0.370
NLRP12	PTPRE	psi-mi:“MI:0915”(physical association)	0.370
PTPRE	KIF1B	psi-mi:“MI:0914”(association)	0.350
PTPRE	XPO1	psi-mi:“MI:0914”(association)	0.350
SARAF	A2ML1	psi-mi:“MI:0914”(association)	0.350
PTPRE	YES1	psi-mi:“MI:0914”(association)	0.350
PTPRA	RCCD1	psi-mi:“MI:0914”(association)	0.350
PTPRE	PTPRE	psi-mi:“MI:0914”(association)	0.310
PTPRA	EXOC3	psi-mi:“MI:2364”(proximity)	0.270
PTPRE	DLG1	psi-mi:“MI:2364”(proximity)	0.270
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
PTPRE	PDGFRB	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000

BioGRID (79): PTPRE (Affinity Capture-MS), BZW2 (Affinity Capture-MS), CPVL (Affinity Capture-MS), CSE1L (Affinity Capture-MS), GRB2 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS), XPO1 (Affinity Capture-MS), XPO4 (Affinity Capture-MS), XPOT (Affinity Capture-MS), PTPRE (Proximity Label-MS), WASF1 (Proximity Label-MS), CYFIP2 (Proximity Label-MS), ABI2 (Proximity Label-MS), EFR3A (Proximity Label-MS), BAIAP2 (Proximity Label-MS)

ESM2 similar proteins: A2ALK8, A5D6R3, B2GV87, O08617, O35239, O55082, P0C599, P0C5A1, P18052, P18433, P23469, P25044, P26045, P28202, P28204, P28205, P28206, P28209, P28219, P29350, P29351, P35234, P35235, P35236, P41499, P43378, P49445, P49446, P54755, P54830, P81718, Q03348, Q06124, Q15256, Q4JDL3, Q4RQD3, Q5I127, Q5I139, Q5I141, Q5I142

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
PTPRE	“down-regulates activity”	MAPK1	dephosphorylation
PTPRE	“down-regulates activity”	KCNB1	dephosphorylation
PTPRE	“down-regulates activity”	INSR	dephosphorylation
PTPRE	“up-regulates activity”	SRC	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 20 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RAF/MAP kinase cascade	6	24.4×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	81
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
146431	GRCh38/hg38 10q26.2-26.3(chr10:127640489-132776585)x1	Pathogenic
153718	GRCh38/hg38 10q26.11-26.3(chr10:119707856-133613639)x3	Pathogenic

SpliceAI

4615 predictions. Top by Δscore:

Variant	Effect	Δscore
10:128040989:AGGTA:A	donor_loss	1.0000
10:128040990:GGTAA:G	donor_loss	1.0000
10:128040991:G:GA	donor_loss	1.0000
10:128040992:T:A	donor_loss	1.0000
10:128047485:TTCAG:T	donor_loss	1.0000
10:128047486:TCAG:T	donor_loss	1.0000
10:128047487:CAG:C	donor_loss	1.0000
10:128047488:AG:A	donor_loss	1.0000
10:128047489:GG:G	donor_loss	1.0000
10:128047490:GT:G	donor_loss	1.0000
10:128047491:T:A	donor_loss	1.0000
10:128047761:AAG:A	acceptor_gain	1.0000
10:128047762:A:G	acceptor_gain	1.0000
10:128047763:GG:G	acceptor_loss	1.0000
10:128047833:GCAAG:G	donor_gain	1.0000
10:128047834:CAAGG:C	donor_loss	1.0000
10:128047835:AAGG:A	donor_loss	1.0000
10:128047836:AGG:A	donor_loss	1.0000
10:128047838:GT:G	donor_loss	1.0000
10:128047839:T:A	donor_loss	1.0000
10:128049519:T:TA	acceptor_gain	1.0000
10:128049526:ACAG:A	acceptor_loss	1.0000
10:128049527:C:G	acceptor_gain	1.0000
10:128049527:CA:C	acceptor_loss	1.0000
10:128049528:A:AC	acceptor_loss	1.0000
10:128049528:A:AG	acceptor_gain	1.0000
10:128049529:G:GA	acceptor_gain	1.0000
10:128049529:GA:G	acceptor_gain	1.0000
10:128049663:CAACG:C	donor_loss	1.0000
10:128049664:AAC:A	donor_gain	1.0000

AlphaMissense

4652 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:128056193:G:C	R164T	1.000
10:128056194:A:C	R164S	1.000
10:128056194:A:T	R164S	1.000
10:128063112:T:A	W219R	1.000
10:128063112:T:C	W219R	1.000
10:128063149:T:A	V231D	1.000
10:128066081:T:C	C244R	1.000
10:128066083:C:G	C244W	1.000
10:128066093:T:A	W248R	1.000
10:128066093:T:C	W248R	1.000
10:128066175:G:C	R275P	1.000
10:128068180:T:A	W301R	1.000
10:128068180:T:C	W301R	1.000
10:128068182:G:C	W301C	1.000
10:128068182:G:T	W301C	1.000
10:128068282:T:C	C335R	1.000
10:128068284:T:G	C335W	1.000
10:128069697:G:A	G338D	1.000
10:128069703:G:A	G340D	1.000
10:128069796:G:C	R371P	1.000
10:128070850:G:C	G446R	1.000
10:128070851:G:A	G446D	1.000
10:128070899:C:A	P462Q	1.000
10:128072150:G:C	R467P	1.000
10:128072201:C:A	A484E	1.000
10:128073365:C:A	A498D	1.000
10:128077674:T:A	W595R	1.000
10:128077674:T:C	W595R	1.000
10:128077676:G:C	W595C	1.000
10:128077676:G:T	W595C	1.000

dbSNP variants (sampled 300 via entrez): RS1000035285 (10:127989947 G>A), RS1000044364 (10:128081520 T>C), RS1000056326 (10:128060111 A>G), RS1000077605 (10:128002468 G>A), RS1000087885 (10:127915725 T>C,G), RS1000092127 (10:127943780 C>A,G,T), RS1000094156 (10:127905639 G>A), RS1000112115 (10:127926937 A>C,G), RS1000113044 (10:128049988 G>A), RS1000124721 (10:127944177 A>G), RS1000141854 (10:128039587 A>C), RS1000203309 (10:128008393 A>T), RS1000234881 (10:128050237 G>C), RS1000235544 (10:128014714 C>G), RS1000242435 (10:128011052 A>G)

Disease associations

OMIM: gene MIM:600926 | 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
GCST000083_2	Select biomarker traits	1.000000e-06
GCST001651_44	Response to amphetamines	7.000000e-06
GCST009615_12	Triglyceride levels x loop diuretics use interaction	5.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004618	vitamin K measurement
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4850 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Receptor tyrosine phosphatase (RTP) family

Binding affinities (BindingDB)

1 measured of 2 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-hydroxy-3-iodo-1-methyl-2-[3-[[2-oxo-2-(4-thiophen-3-ylanilino)acetyl]amino]phenyl]indole-5-carboxylic acid	IC50	2900 nM	US-9522881: Hydroxyindole carboxylic acid based inhibitors for oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2)

ChEMBL bioactivities

5 potent at pChembl≥5 of 11 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.73	IC50	1860	nM	CHEMBL4174865
5.70	IC50	2010	nM	CHEMBL4160163
5.61	IC50	2470	nM	CHEMBL4170383
5.43	IC50	3700	nM	CHEMBL4168082
5.38	IC50	4170	nM	CHEMBL4159748

PubChem BioAssay actives

5 with measured affinity, of 67 total; 5 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
1-(3-chloro-4-fluorophenyl)-3-[5-[(2,4-dimethylphenoxy)methyl]-1,3,4-thiadiazol-2-yl]urea	1363112: Inhibition of recombinant human cytosolic PTPepsilon expressed in Escherichia coli BL21 (DE3) using E527-P-Q-pY530-Q-P-G-E-N-L536 as substrate after 60 mins by malachite green assay	ic50	1.8600	uM
2-(1,3-benzodioxol-5-yloxy)-N-[5-[(4-chlorophenoxy)methyl]-1,3,4-thiadiazol-2-yl]acetamide	1363112: Inhibition of recombinant human cytosolic PTPepsilon expressed in Escherichia coli BL21 (DE3) using E527-P-Q-pY530-Q-P-G-E-N-L536 as substrate after 60 mins by malachite green assay	ic50	2.0100	uM
1-[5-[(2,4-dimethylphenoxy)methyl]-1,3,4-thiadiazol-2-yl]-3-(4-methylphenyl)urea	1363112: Inhibition of recombinant human cytosolic PTPepsilon expressed in Escherichia coli BL21 (DE3) using E527-P-Q-pY530-Q-P-G-E-N-L536 as substrate after 60 mins by malachite green assay	ic50	2.4700	uM
2-(2-methoxyphenoxy)-N-[5-(phenoxymethyl)-1,3,4-thiadiazol-2-yl]acetamide	1363112: Inhibition of recombinant human cytosolic PTPepsilon expressed in Escherichia coli BL21 (DE3) using E527-P-Q-pY530-Q-P-G-E-N-L536 as substrate after 60 mins by malachite green assay	ic50	3.7000	uM
1-[5-[(4-butan-2-ylphenoxy)methyl]-1,3,4-thiadiazol-2-yl]-3-(2-methoxyphenyl)urea	1363112: Inhibition of recombinant human cytosolic PTPepsilon expressed in Escherichia coli BL21 (DE3) using E527-P-Q-pY530-Q-P-G-E-N-L536 as substrate after 60 mins by malachite green assay	ic50	4.1700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	6
Benzo(a)pyrene	affects methylation, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	3
Tretinoin	increases expression	3
sodium arsenite	affects methylation, decreases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Arsenic	affects expression, affects methylation, increases abundance, increases expression	2
Formaldehyde	decreases expression, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tamoxifen	affects expression, affects cotreatment, increases expression	2
Aflatoxin B1	increases expression, affects methylation	2
Raloxifene Hydrochloride	affects expression, affects cotreatment, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenate	increases abundance, increases expression	1
benzo(e)pyrene	decreases methylation	1
vanadyl sulfate	increases expression	1
isobutyl alcohol	increases abundance, increases expression, affects cotreatment	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
2-(oxalylamino)benzoic acid	decreases activity	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1

ChEMBL screening assays

23 unique, capped per target: 22 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1050901	Binding	Inhibition of PTPRE	Knowledge-based characterization of similarity relationships in the human protein-tyrosine phosphatase family for rational inhibitor design. — J Med Chem
CHEMBL4626318	ADMET	Inhibition of PTPE (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.