PTPRM

Summary

PTPRM (protein tyrosine phosphatase receptor type M, HGNC:9675) is a protein-coding gene on chromosome 18p11.23, encoding Receptor-type tyrosine-protein phosphatase mu (P28827). Receptor protein-tyrosine phosphatase that mediates homotypic cell-cell interactions and plays a role in adipogenic differentiation via modulation of p120 catenin/CTNND1 phosphorylation.

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 possesses an extracellular region, a single transmembrane region, and two tandem catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP mu (MAM) domain, an Ig-like domain and four fibronectin type III-like repeats. This PTP has been shown to mediate cell-cell aggregation through the interaction with another molecule of this PTP on an adjacent cell. This PTP can interact with scaffolding protein RACK1/GNB2L1, which may be necessary for the downstream signaling in response to cell-cell adhesion. Alternative splicing results in multiple transcripts encoding distinct isoforms.

Source: NCBI Gene 5797 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 242 total
• Druggable target: yes
• MANE Select transcript: NM_001105244

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9675
Approved symbol	PTPRM
Name	protein tyrosine phosphatase receptor type M
Location	18p11.23
Locus type	gene with protein product
Status	Approved
Aliases	RPTPU, hR-PTPu
Ensembl gene	ENSG00000173482
Ensembl biotype	protein_coding
OMIM	176888
Entrez	5797

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 6 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000332175, ENST00000400053, ENST00000400060, ENST00000577468, ENST00000577827, ENST00000578093, ENST00000578571, ENST00000578600, ENST00000578698, ENST00000578916, ENST00000580170, ENST00000580838, ENST00000580949, ENST00000583153, ENST00000583289

RefSeq mRNA: 8 — MANE Select: NM_001105244 NM_001105244, NM_001378142, NM_001378143, NM_001378144, NM_001378145, NM_001378146, NM_001378147, NM_002845

CCDS: CCDS11840, CCDS58613

Canonical transcript exons

ENST00000580170 — 33 exons

Exon	Start	End
ENSE00001541391	8406109	8406856
ENSE00002698802	8252488	8252499
ENSE00003459520	8069686	8069994
ENSE00003460216	8376046	8376200
ENSE00003468384	8343423	8343520
ENSE00003470700	8384561	8384686
ENSE00003498902	7774149	7774271
ENSE00003527386	8247845	8247919
ENSE00003532593	8379167	8379340
ENSE00003532602	8244058	8244209
ENSE00003539104	8085671	8085872
ENSE00003543156	8088749	8088851
ENSE00003570183	8370890	8371006
ENSE00003583745	8076455	8076564
ENSE00003586628	8143647	8143779
ENSE00003594330	8248150	8248176
ENSE00003616295	8394476	8394611
ENSE00003621794	8253227	8253414
ENSE00003644741	8314781	8314857
ENSE00003666597	8380296	8380427
ENSE00003668903	8387072	8387235
ENSE00003677149	8319178	8319214
ENSE00003687969	8296368	8296455
ENSE00003715939	7949181	7949355
ENSE00003722241	8113486	8113759
ENSE00003723795	7888106	7888377
ENSE00003724701	8378265	8378414
ENSE00003730604	7955121	7955414
ENSE00003736253	7906505	7906583
ENSE00003739240	8114791	8114827
ENSE00003743485	7926568	7926683
ENSE00003747240	8376462	8376597
ENSE00003903874	7567316	7567891

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 98.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.8443 / max 176.6645, expressed in 1565 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169275	9.0262	1433
169288	5.0058	1168
169278	1.1328	691
169277	0.7053	468
169276	0.3999	224
169274	0.3036	164
169279	0.1677	64
169284	0.0465	20
169289	0.0413	8
169295	0.0077	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.11	gold quality
visceral pleura	UBERON:0002401	98.00	gold quality
right lung	UBERON:0002167	97.91	gold quality
calcaneal tendon	UBERON:0003701	97.68	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.36	gold quality
tibia	UBERON:0000979	97.12	gold quality
left lobe of thyroid gland	UBERON:0001120	97.01	gold quality
thyroid gland	UBERON:0002046	96.99	gold quality
right lobe of thyroid gland	UBERON:0001119	96.97	gold quality
tendon	UBERON:0000043	96.85	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.78	gold quality
adipose tissue	UBERON:0001013	96.72	gold quality
cardiac ventricle	UBERON:0002082	96.60	gold quality
heart left ventricle	UBERON:0002084	96.60	gold quality
apex of heart	UBERON:0002098	96.48	gold quality
seminal vesicle	UBERON:0000998	96.47	gold quality
connective tissue	UBERON:0002384	96.46	gold quality
tendon of biceps brachii	UBERON:0008188	96.41	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.36	gold quality
omental fat pad	UBERON:0010414	96.34	gold quality
peritoneum	UBERON:0002358	96.32	gold quality
stromal cell of endometrium	CL:0002255	96.31	gold quality
heart right ventricle	UBERON:0002080	96.31	gold quality
pleura	UBERON:0000977	96.20	gold quality
upper lobe of left lung	UBERON:0008952	95.93	gold quality
upper lobe of lung	UBERON:0008948	95.82	gold quality
parietal pleura	UBERON:0002400	95.81	gold quality
mucosa of stomach	UBERON:0001199	95.76	gold quality
metanephros cortex	UBERON:0010533	95.71	gold quality
ganglionic eminence	UBERON:0004023	95.54	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	6000.79
E-GEOD-131882	yes	5123.84
E-CURD-119	yes	4834.44
E-HCAD-35	yes	72.27
E-HCAD-25	yes	46.26
E-ANND-3	yes	22.81
E-MTAB-11268	no	5432.35
E-MTAB-10137	no	416.62
E-CURD-112	no	3.53

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

95 targeting PTPRM, 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-5692A	100.00	74.40	6850
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-589-3P	99.91	69.62	2088

Literature-anchored findings (GeneRIF, showing 18)

• 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)
• RPTPmu may play a role in the regulation of cardiovascular functions (PMID:12895029)
• PTPmu may regulate Rho-GTPase-dependent functions of IQGAP1 (PMID:16380380)
• a 3.1 angstrom crystal structure of the RPTPmu ectodomain that forms a homophilic trans (antiparallel) dimer with an extended and rigid architecture, matching the dimensions of adherens junctions is described (PMID:17761881)
• BCCIP is phosphorylated by the Src tyrosine kinase and dephosphorylated by the PTPmu tyrosine phosphatase; neurite outgrowth assays suggest that BCCIP and PTPmu are in a common signal transduction pathway. (PMID:18773424)
• Loss of protein tyrosine phosphatase receptor type mu is associated with glioma cell migration and progression. (PMID:19304959)
• loss of cell surface PTPmu by proteolysis generates catalytically active PTPmu fragments that contribute to migration and survival of glioblastoma cells (PMID:19690139)
• In A549 cells, diverse injurious stimuli dramatically reduced PTPmu protein expression. (PMID:21649524)
• Results suggest that miR-221 and -222 regulate glioma tumorigenesis at least in part through the control of PTPmu protein expression. (PMID:21743492)
• Loss of PTPmu by proteolysis causes glioblastoma. (PMID:22505657)
• Decreased expression of PTPRM in breast cancer is correlated with poor prognosis and inversely correlated with disease-free survival. (PMID:23185569)
• Study determined that, in addition to the furin-processed form of PTPmicro, a pool of 200 kDa full-length PTPmicro exists at the plasma membrane that is cleaved directly by ADAM to generate a larger shed form of the PTPmicro extracellular segment. (PMID:24771611)
• Results suggest increased post-translational modification of RPTPmu N-glycans by GnT-V attenuates its tyrosine phosphatase activity and promotes glioma cell migration through PLCgamma-PKC pathways. (PMID:30274773)
• PSMD11, PTPRM and PTPRB as novel biomarkers of pancreatic cancer progression. (PMID:32663515)
• High expression of PTPRM predicts poor prognosis and promotes tumor growth and lymph node metastasis in cervical cancer. (PMID:32826853)
• PTPRM methylation induced by FN1 promotes the development of glioblastoma by activating STAT3 signalling. (PMID:34225581)
• Determinants of receptor tyrosine phosphatase homophilic adhesion: Structural comparison of PTPRK and PTPRM extracellular domains. (PMID:36436563)
• A quantitative trait GWAS on lens thickness identifies novel risk loci on PTPRM in the narrow angle individuals susceptible to PACG. (PMID:36927043)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch1073-391i24.1	ENSDARG00000089172
danio_rerio		ENSDARG00000100053
danio_rerio		ENSDARG00000114762
mus_musculus	Ptprm	ENSMUSG00000033278
rattus_norvegicus	Ptprm	ENSRNOG00000011700

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), PTPN9 (ENSG00000169410), PTPN2 (ENSG00000175354), PTPN11 (ENSG00000179295), PTPRT (ENSG00000196090), PTPN1 (ENSG00000196396), PTPN20 (ENSG00000204179)

Protein

Protein identifiers

Receptor-type tyrosine-protein phosphatase mu — P28827 (reviewed: P28827)

All UniProt accessions (7): P28827, E7EPS8, J3KRV2, J3KT55, J3QLI4, J3QRB4, Q49AC9

UniProt curated annotations — full annotation on UniProt →

Function. Receptor protein-tyrosine phosphatase that mediates homotypic cell-cell interactions and plays a role in adipogenic differentiation via modulation of p120 catenin/CTNND1 phosphorylation. Promotes CTNND1 dephosphorylation and prevents its cytoplasmic localization where it inhibits SLC2A4 membrane trafficking. In turn, SLC2A4 is directed to the plasma membrane and performs its glucose transporter function.

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane.

Similarity. Belongs to the protein-tyrosine phosphatase family. Receptor class 2B subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P28827-1	1	yes
P28827-2	2

RefSeq proteins (8): NP_001098714, NP_001365071, NP_001365072, NP_001365073, NP_001365074, NP_001365075, NP_001365076, NP_002836 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000242	PTP_cat	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR000998	MAM_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR013151	Immunoglobulin_dom	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR016130	Tyr_Pase_AS	Active_site
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR045911	R-PTP-mu_cat_rpt1	Domain
IPR051622	R-tyr_protein_phosphatases	Family
IPR057598	Fn3_PTPRU	Domain

Pfam: PF00041, PF00047, PF00102, PF00629, PF23144

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 (130 total): strand 66, helix 15, glycosylation site 12, domain 8, turn 5, mutagenesis site 4, sequence conflict 4, binding site 3, disulfide bond 3, active site 2, topological domain 2, signal peptide 1, chain 1, modified residue 1, transmembrane region 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
1RPM	X-RAY DIFFRACTION	2.3
2C9A	X-RAY DIFFRACTION	2.7
8A16	X-RAY DIFFRACTION	2.89
8A17	X-RAY DIFFRACTION	3.09
2V5Y	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28827-F1	84.38	0.61

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): 1095 (phosphocysteine intermediate); 1389 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (3): 1063; 1095–1101; 1139

Post-translational modifications (1): 821

Disulfide bonds (3): 27–36, 96–182, 206–260

Glycosylation sites (12): 72, 92, 131, 249, 406, 414, 454, 534, 544, 598, 651, 681

Mutagenesis-validated functional residues (4):

Position	Phenotype
239	abolishes dimerization.
240	abolishes dimerization.
297	abolishes dimerization.
299	abolishes dimerization.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 241 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_RETINAL_GANGLION_CELL_AXON_GUIDANCE, MODULE_64, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_NEUROGENESIS, GOBP_NEURAL_RETINA_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, HERNANDEZ_ABERRANT_MITOSIS_BY_DOCETACEL_2NM_UP, YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_DN, GOBP_CELL_CELL_ADHESION, MODULE_120, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS

GO Biological Process (16): negative regulation of endothelial cell proliferation (GO:0001937), homophilic cell-cell adhesion (GO:0007156), signal transduction (GO:0007165), response to xenobiotic stimulus (GO:0009410), negative regulation of endothelial cell migration (GO:0010596), positive regulation of D-glucose transmembrane transport (GO:0010828), retina layer formation (GO:0010842), negative regulation of angiogenesis (GO:0016525), neuron projection development (GO:0031175), retinal ganglion cell axon guidance (GO:0031290), protein dephosphorylation (GO:0006470), cell adhesion (GO:0007155), negative regulation of D-glucose transmembrane transport (GO:0010829), dephosphorylation (GO:0016311), negative regulation of cell migration (GO:0030336), D-glucose transmembrane transport (GO:1904659)

GO Molecular Function (10): protein tyrosine phosphatase activity (GO:0004725), transmembrane receptor protein tyrosine phosphatase activity (GO:0005001), phosphatase activity (GO:0016791), identical protein binding (GO:0042802), cadherin binding (GO:0045296), protein tyrosine kinase activity (GO:0004713), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), kinase activity (GO:0016301), hydrolase activity (GO:0016787)

GO Cellular Component (7): cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), adherens junction (GO:0005912), lamellipodium (GO:0030027), perinuclear region of cytoplasm (GO:0048471), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cellular process	2
regulation of D-glucose transmembrane transport	2
D-glucose transmembrane transport	2
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
cell-cell adhesion	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
response to chemical	1
regulation of endothelial cell migration	1
negative regulation of cell migration	1
endothelial cell migration	1
positive regulation of transmembrane transport	1
neural retina development	1
anatomical structure formation involved in morphogenesis	1
retina morphogenesis in camera-type eye	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
neuron development	1
plasma membrane bounded cell projection organization	1
axon guidance	1
dephosphorylation	1
protein modification process	1
negative regulation of transmembrane transport	1
phosphate-containing compound metabolic process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
hexose transmembrane transport	1
phosphoprotein phosphatase activity	1
protein tyrosine phosphatase activity	1
transmembrane receptor protein phosphatase activity	1
phosphoric ester hydrolase activity	1
protein binding	1
cell adhesion molecule binding	1

Protein interactions and networks

STRING

1540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPRM	CDH17	Q12864	710
PTPRM	CDKL5	O76039	639
PTPRM	SBK2	P0C263	621
PTPRM	PTS	Q03393	573
PTPRM	FN1	P02751	544
PTPRM	LRRC30	A6NM36	491
PTPRM	MAMDC2	Q7Z304	487
PTPRM	MDGA1	Q8NFP4	480
PTPRM	CDH5	P33151	465
PTPRM	PTPRC	P08575	458
PTPRM	MDGA2	Q7Z553	451
PTPRM	ABLIM3	O94929	448
PTPRM	GRP	P07491	443
PTPRM	BCAR3	O75815	418
PTPRM	TSPAN31	Q12999	417

IntAct

29 interactions, top by confidence:

A	B	Type	Score
PTPRM	PTPRM	psi-mi:“MI:0915”(physical association)	0.620
PTPRM	PTPRM	psi-mi:“MI:0914”(association)	0.620
DSCAM	PTPRM	psi-mi:“MI:0915”(physical association)	0.540
DSCAML1	PTPRM	psi-mi:“MI:0915”(physical association)	0.540
PTPRM	DSCAM	psi-mi:“MI:0407”(direct interaction)	0.540
PTPRM	DSCAML1	psi-mi:“MI:0407”(direct interaction)	0.540
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
PTPRM	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
PTPRM	H2BC5	psi-mi:“MI:0915”(physical association)	0.400
PTPRM	DTNBP1	psi-mi:“MI:0915”(physical association)	0.400
PTPRM	SELENBP1	psi-mi:“MI:0915”(physical association)	0.400
PTPRM	Cdh4	psi-mi:“MI:0915”(physical association)	0.400
Cdh1	PTPRM	psi-mi:“MI:0915”(physical association)	0.400
PTPRM	Cdh2	psi-mi:“MI:0915”(physical association)	0.400
PTPRM	Cdh1	psi-mi:“MI:0915”(physical association)	0.400
NS3	C15orf61	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
	TNFRSF10A	psi-mi:“MI:0914”(association)	0.350
SAAL1	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC30A5	NBAS	psi-mi:“MI:0914”(association)	0.350
PTPRM	NHSL1	psi-mi:“MI:2364”(proximity)	0.270
PTPRM	LCK	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000
PTPRM	nagA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (82): DTNBP1 (Affinity Capture-MS), LMTK2 (Proximity Label-MS), EHD4 (Proximity Label-MS), CDC42BPA (Proximity Label-MS), NHSL1 (Proximity Label-MS), PTPRM (Affinity Capture-RNA), CDH1 (Affinity Capture-Western), PTPRM (Proximity Label-MS), PTPRM (Proximity Label-MS), PTPRM (Affinity Capture-Western), IQGAP1 (Reconstituted Complex), PTPRM (Affinity Capture-RNA), PTPRM (Affinity Capture-Western), Ptpre (Affinity Capture-Western), Ptprs (Affinity Capture-Western)

ESM2 similar proteins: A0A1S4GGP7, B1Q236, B8V7Q1, B8VIW9, F1QSQ0, F8W3X3, G5EDK5, H2A0L8, O02466, O15943, O44386, O44730, P28827, P34616, P35822, P55289, P70408, Q02763, Q02858, Q03600, Q03763, Q06807, Q09165, Q15262, Q19319, Q24247, Q24298, Q5RJH3, Q60ZN5, Q61495, Q68SP4, Q6W3B0, Q7TMD7, Q7TSF0, Q7TSF1, Q86SJ6, Q86WI1, Q8JHW2, Q8VHN7, Q8WXG9

Diamond homologs: A0A6I8TCE0, A1L1L3, A2A8L5, A2ALK8, A4IFW2, A7MBJ4, B0V2N1, B0X4T2, B1AUH1, B2RU80, B3DK56, B9EKR1, E9Q0N2, E9Q612, F1NWE3, O13016, O14522, O35239, O55082, O82656, O88488, P04157, P06800, P08575, P0C5E4, P10586, P16621, P17706, P18031, P20417, P23467, P23468, P23470, P23471, P26045, P28191, P28192, P28827, P28828, P29074

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PTPRM	“down-regulates activity”	STAT3	dephosphorylation
PTPRM	“down-regulates quantity”	CTNND1	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	169
Likely benign	19
Benign	16

Top pathogenic / likely-pathogenic (0)

SpliceAI

6554 predictions. Top by Δscore:

Variant	Effect	Δscore
18:7572061:G:GG	donor_gain	1.0000
18:7774142:A:AG	acceptor_gain	1.0000
18:7774143:TTTTA:T	acceptor_loss	1.0000
18:7774144:TTTAG:T	acceptor_loss	1.0000
18:7774145:TTA:T	acceptor_loss	1.0000
18:7774146:TAGG:T	acceptor_loss	1.0000
18:7774147:A:T	acceptor_loss	1.0000
18:7774148:G:T	acceptor_loss	1.0000
18:7774267:ATCAG:A	donor_loss	1.0000
18:7774268:TCAGG:T	donor_loss	1.0000
18:7774269:CAG:C	donor_loss	1.0000
18:7774270:AGGT:A	donor_loss	1.0000
18:7774271:GGT:G	donor_loss	1.0000
18:7774272:GTTT:G	donor_loss	1.0000
18:7774273:T:G	donor_loss	1.0000
18:7888100:TTGCA:T	acceptor_loss	1.0000
18:7888101:TGCA:T	acceptor_loss	1.0000
18:7888102:GCA:G	acceptor_loss	1.0000
18:7888103:CA:C	acceptor_loss	1.0000
18:7888104:AGGTT:A	acceptor_loss	1.0000
18:7906499:TTCCA:T	acceptor_loss	1.0000
18:7906500:TCCAG:T	acceptor_loss	1.0000
18:7906501:CCAGG:C	acceptor_loss	1.0000
18:7906502:CAGG:C	acceptor_loss	1.0000
18:7906503:A:AT	acceptor_loss	1.0000
18:7906504:GGT:G	acceptor_gain	1.0000
18:7906581:GTA:G	donor_gain	1.0000
18:7906584:G:GG	donor_gain	1.0000
18:7926563:T:G	acceptor_gain	1.0000
18:7926563:T:TA	acceptor_gain	1.0000

AlphaMissense

9658 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:7774217:T:A	W48R	1.000
18:7774217:T:C	W48R	1.000
18:7774219:G:C	W48C	1.000
18:7774219:G:T	W48C	1.000
18:7888195:T:A	C96S	1.000
18:7888195:T:C	C96R	1.000
18:7888196:G:C	C96S	1.000
18:7888197:C:G	C96W	1.000
18:7926583:T:G	F188C	1.000
18:7926636:T:C	C206R	1.000
18:7926638:C:G	C206W	1.000
18:7949295:T:A	C260S	1.000
18:7949295:T:C	C260R	1.000
18:7949296:G:C	C260S	1.000
18:7949297:C:G	C260W	1.000
18:7955133:C:A	P284H	1.000
18:7955145:C:A	P288H	1.000
18:7955310:T:C	L343P	1.000
18:7955327:T:G	Y349D	1.000
18:7955346:T:C	L355P	1.000
18:8253353:T:C	L885P	1.000
18:8253356:T:C	L886P	1.000
18:8296395:T:A	W915R	1.000
18:8296395:T:C	W915R	1.000
18:8296433:C:A	N927K	1.000
18:8296433:C:G	N927K	1.000
18:8296435:G:C	R928T	1.000
18:8296436:A:C	R928S	1.000
18:8296436:A:T	R928S	1.000
18:8296440:G:T	G930W	1.000

dbSNP variants (sampled 300 via entrez): RS1000001785 (18:8306567 A>G), RS1000002622 (18:8015480 A>G), RS1000014393 (18:7945009 A>G), RS1000015212 (18:7817639 C>T), RS1000018843 (18:8159785 C>T), RS1000019410 (18:8241412 C>T), RS1000021728 (18:8143801 A>G), RS1000021831 (18:7604697 A>G), RS1000024837 (18:7814839 T>C), RS1000029136 (18:8115973 A>G), RS1000035193 (18:7855439 T>G), RS1000038239 (18:7607476 C>G), RS1000038671 (18:8272132 G>A), RS1000039094 (18:7704865 G>A), RS1000040974 (18:7845825 G>C)

Disease associations

OMIM: gene MIM:176888 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001066_19	Dialysis-related mortality	4.000000e-06
GCST001066_24	Dialysis-related mortality	8.000000e-06
GCST002375_2	Response to methotrexate in rheumatoid arthritis	7.000000e-06
GCST002726_44	Glucose homeostasis traits	5.000000e-06
GCST002843_2	Sitting height ratio	7.000000e-07
GCST004286_8	Midgestational circulating levels of PBDEs (fetal genetic effect)	5.000000e-07
GCST004361_3	Estrone/androstenedione ratio in resected early stage-receptor positive breast cancer	2.000000e-06
GCST004691_4	Huntington’s disease progression	2.000000e-06
GCST005175_64	Coronary artery calcified atherosclerotic plaque (90 or 130 HU threshold) in type 2 diabetes	6.000000e-06
GCST005175_65	Coronary artery calcified atherosclerotic plaque (90 or 130 HU threshold) in type 2 diabetes	8.000000e-06
GCST006134_11	Hippocampal volume	4.000000e-06
GCST007742_36	Iris heterochromicity	9.000000e-06
GCST009218_34	Lateral ventricle temporal horn volume	1.000000e-06
GCST009514_5	Recurrence of mild malaria attacks	1.000000e-06
GCST010566_12	Benign childhood epilepsy with centro-temporal spikes	4.000000e-06
GCST010988_71	Adult body size	2.000000e-09

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0006831	acute insulin response measurement
EFO:0007118	sitting height ratio
EFO:0007959	fetal genotype effect measurement
EFO:0007961	polybrominated biphenyl measurement
EFO:0007962	polybrominated diphenyl ether measurement
EFO:0007964	gestational serum measurement
EFO:0007970	estrone measurement
EFO:0007972	androstenedione measurement
EFO:0008336	disease progression measurement
EFO:0004723	coronary artery calcification
EFO:0005035	hippocampal volume
EFO:0009764	eye colour measurement
EFO:0004952	disease recurrence

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4661 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs6506569	Efficacy	4	methotrexate	Rheumatoid arthritis

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6506569	PTPRM	4	-1.00	1	methotrexate

GtoPdb / IUPHAR curated pharmacology

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

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

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 8a [PMID: 23713581]	Inhibition	5.15	pIC50

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

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

pChembl	Type	Value	Unit	Molecule
5.48	IC50	3300	nM	CHEMBL3319356
5.16	IC50	7000	nM	CHEMBL2396718

PubChem BioAssay actives

2 with measured affinity, of 41 total; 2 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
6-hydroxy-3-iodo-1-methyl-2-[3-[[2-oxo-2-(4-thiophen-3-ylanilino)acetyl]amino]phenyl]indole-5-carboxylic acid	1182552: Inhibition of PTPmu (unknown origin)	ic50	3.3000	uM
3-[2-(3-chlorophenyl)ethynyl]-6-hydroxy-2-[4-[2-oxo-2-(propylamino)ethoxy]phenyl]-1-benzofuran-5-carboxylic acid	755765: Inhibition of recombinant PTPmu (unknown origin) using pNPP as substrate by spectrophotometric analysis	ic50	7.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases mutagenesis	8
sodium arsenite	increases expression, affects methylation, decreases expression	4
Valproic Acid	affects expression, increases expression, increases methylation	4
bisphenol A	affects methylation, affects cotreatment, increases methylation, increases expression	2
Calcitriol	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
1-Methyl-4-phenylpyridinium	affects expression, increases expression	2
Aflatoxin B1	affects expression, increases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
ethyl-p-hydroxybenzoate	increases expression	1
arsenite	decreases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases 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	affects cotreatment, increases expression	1
candoxin	decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
Grape Seed Proanthocyanidins	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Catechin	affects cotreatment, decreases expression	1

ChEMBL screening assays

15 unique, capped per target: 14 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2401187	Binding	Inhibition of recombinant PTPmu (unknown origin) using pNPP as substrate by spectrophotometric analysis	A potent and selective small-molecule inhibitor for the lymphoid-specific tyrosine phosphatase (LYP), a target associated with autoimmune diseases. — J Med Chem
CHEMBL4626316	ADMET	Inhibition of PTPM (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.