PTN

Summary

PTN (pleiotrophin, HGNC:9630) is a protein-coding gene on chromosome 7q33, encoding Pleiotrophin (P21246). Secreted growth factor that mediates its signal through cell-surface proteoglycan and non-proteoglycan receptors.

The protein encoded by this gene is a secreted heparin-binding growth factor. The protein has significant roles in cell growth and survival, cell migration, angiogenesis and tumorigenesis. Alternative splicing and the use of alternative promoters results in multiple transcript variants.

Source: NCBI Gene 5764 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 19 total
• Druggable target: yes
• MANE Select transcript: NM_002825

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9630
Approved symbol	PTN
Name	pleiotrophin
Location	7q33
Locus type	gene with protein product
Status	Approved
Aliases	HBNF, HBGF8
Ensembl gene	ENSG00000105894
Ensembl biotype	protein_coding
OMIM	162095
Entrez	5764

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 15 protein_coding

ENST00000348225, ENST00000393083, ENST00000699293, ENST00000877352, ENST00000877353, ENST00000930407, ENST00000930408, ENST00000930409, ENST00000942614, ENST00000942615, ENST00000942616, ENST00000942617, ENST00000942618, ENST00000942619, ENST00000942620

RefSeq mRNA: 3 — MANE Select: NM_002825 NM_001321386, NM_001321387, NM_002825

CCDS: CCDS5844, CCDS94211

Canonical transcript exons

ENST00000348225 — 5 exons

Exon	Start	End
ENSE00000725133	137253464	137253637
ENSE00001210410	137251230	137251391
ENSE00001241341	137227341	137228075
ENSE00001611939	137254859	137254974
ENSE00001622553	137343439	137343733

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 99.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.3502 / max 3505.2725, expressed in 1012 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86396	18.5412	966
86399	8.5087	609
86401	2.2037	362
86397	1.5472	363
86398	1.4258	322
86400	0.8188	293
86395	0.5795	251
86393	0.3177	57
86390	0.1390	21
86391	0.1347	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.90	gold quality
ganglionic eminence	UBERON:0004023	99.67	gold quality
trigeminal ganglion	UBERON:0001675	99.27	gold quality
cranial nerve II	UBERON:0000941	99.20	gold quality
ventral tegmental area	UBERON:0002691	99.19	gold quality
amygdala	UBERON:0001876	98.91	gold quality
periodontal ligament	UBERON:0008266	98.89	gold quality
corpus callosum	UBERON:0002336	98.78	gold quality
nucleus accumbens	UBERON:0001882	98.77	gold quality
pons	UBERON:0000988	98.72	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.66	gold quality
tongue squamous epithelium	UBERON:0006919	98.66	gold quality
subthalamic nucleus	UBERON:0001906	98.65	gold quality
inferior vagus X ganglion	UBERON:0005363	98.65	gold quality
temporal lobe	UBERON:0001871	98.63	gold quality
caudate nucleus	UBERON:0001873	98.63	gold quality
putamen	UBERON:0001874	98.60	gold quality
paraflocculus	UBERON:0005351	98.56	gold quality
superior vestibular nucleus	UBERON:0007227	98.55	gold quality
lateral globus pallidus	UBERON:0002476	98.53	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.49	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.43	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.41	gold quality
substantia nigra pars compacta	UBERON:0001965	98.39	gold quality
embryo	UBERON:0000922	98.37	gold quality
medulla oblongata	UBERON:0001896	98.36	gold quality
entorhinal cortex	UBERON:0002728	98.34	gold quality
mammary duct	UBERON:0001765	98.32	gold quality
right frontal lobe	UBERON:0002810	98.29	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.25	gold quality

Single-cell (SCXA)

Detected in 40 experiment(s), a significant marker in 38.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	5908.71
E-GEOD-124472	yes	5508.89
E-HCAD-56	yes	3689.27
E-MTAB-8894	yes	2796.09
E-CURD-79	yes	2520.94
E-MTAB-11121	yes	2478.94
E-MTAB-9906	yes	2282.31
E-GEOD-93593	yes	2116.30
E-HCAD-25	yes	2091.61
E-MTAB-10885	yes	2067.63
E-GEOD-114530	yes	2038.96
E-MTAB-8221	yes	1857.49
E-CURD-98	yes	1753.18
E-MTAB-7407	yes	1704.95
E-MTAB-10855	yes	1698.30

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, HOXA5, JUN, JUND, NME1, SOX10, SP1, STAT1, TP53

miRNA regulators (miRDB)

53 targeting PTN, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-1244	99.33	68.38	832
HSA-MIR-4727-5P	99.23	67.55	1154

Literature-anchored findings (GeneRIF, showing 40)

• Pleiotrophin signaling through anaplastic lymphoma kinase is rate-limiting for glioblastoma growth. (PMID:11809760)
• overexpression of Pleiotrophin is associated with inflammation and pancreatic cancer (PMID:11895915)
• induced the stimulation of tritiated thymidine incorporation in quiescent human peripheral blood mononuclear cells in a dose-dependant manner (PMID:11936877)
• PTN induces weak chemotactic and strong haptotactic migration of glioblastoma and cerebral microvascular endothelial cells. (PMID:14692702)
• In the present study, we demonstrate that HARP is secreted in human mature milk with concentrations ranging from 17.68+/-6.4ng/ml in mature milk to 59.9+/-11.22ng/ml in colostrum. (PMID:14715276)
• angiogenic factor HARP can also negatively regulate the angiogenic activity of VEGF165 (PMID:15001987)
• in the OSF1 transgenic line, bone mass increase was evident in female, but not male, mice [OSF1] (PMID:15108072)
• Results describe the influence of mechanical loading on heparin binding growth associated molecule (HB-GAM) expression in bone cells. (PMID:15184074)
• Heparin-binding growth-associated molecule is overexpressed in malignant glioma cells and is involved in tumor growth. (PMID:15684595)
• RPTPbeta/zeta is a receptor of HARP in human endothelial cells (PMID:15797857)
• JUN-dependent expression of PTN and SDF-1 in fibroblasts has a role in keratinocyte proliferation (PMID:15840658)
• report on the presence and purification of two naturally occurring forms of PTN (18 and 15 kDa) that differentially promote glioblastoma migration and proliferation (PMID:15908427)
• HARP seems to act as an important regulator of diverse biological activities in human prostate cancer cells (PMID:15924335)
• PTN signals new blood vessel formation through its ability to stimulate different functions in different cell types not limited to the endothelial cell (PMID:15949466)
• conclude that pleiotrophin(PTN) is a rate-limiting growth factor in glioblastoma (PMID:15986444)
• results demonstrate that PTN inhibits HIV infection and suggest that the cell surface-expressed nucleolin is a low affinity receptor for PTN binding to cells and it is also implicated in PTN entry into cells by an active process (PMID:16156786)
• results show that heparin affin regulatory peptide (HARP) is important for human prostate cancer cell proliferation and migration and establish role of activator protein-1 in up-regulation of HARP expression by low concentrations of hydrogen peroxide (PMID:16199533)
• the binding of pleiotrophin to chondroitin sulfate is regulated by chain length and oversulfated structures (PMID:16373346)
• The data demonstrated that the extracellular signal-regulated kinase (ERK) 1/2 pathway, PKC, PKA, p38, and c-Jun N-terminal kinase MAPK participated in the mechanical downregulation of HB-GAM expression. (PMID:16513091)
• HARP mediates FGF2 stimulatory effects on prostate cancer cells. (PMID:16940294)
• This is the first description of the expression of PTN by human MCs and the data suggest that it is rapidly induced in cells that are triggered to migrate. (PMID:16985521)
• PTN signaling may have a critical role in chromosomal segregation and cell cycle progression. (PMID:17067552)
• Data suggest that increased tyrosine phosphorylation of receptor protein tyrosine phosphatase beta/zeta substrates in pleiotrophin-stimulated cells is sufficient to coordinately stimulate the functions needed for an epithelial-mesenchymal transition. (PMID:17098867)
• Pleiotrophin is a neurotrophic factor for spinal motor neurons (PMID:17360581)
• PTN was identified as a factor that plays a role in the nigrostriatal system during development and in response to disease, and may therefore be useful for neuroprotection or reconstruction of the dopamine (PMID:17368428)
• Inhibition of PTN with a polyclonal anti-PTN antibody reduced growth and enhanced apoptosis of MM cell lines and freshly isolated bone marrow tumor cells from MM patients (PMID:17369488)
• PTN expression is associated with histopathological grade of astrocytomas (PMID:17443289)
• Pleiotrophin is present in pathologic human intervertebral discs, and its prevalence and distribution suggest that it may play a role in neovascularization of diseased or damaged disc tissue (PMID:17515817)
• secretion of PTN through stimulation of the stromal cell microenvironment alone may be sufficient to account for significant features of breast cancer progression. (PMID:17578909)
• Inhibition of the mitogenic, angiogenic, and tumorigenic activities of PTN by a synthetic peptide corresponding to its C-thrombospondin repeat-I domain. (PMID:17607711)
• phosphorylation of ALK in PTN-stimulated cells is mediated through the PTN/RPTPbeta/zeta signaling pathway (PMID:17681947)
• identified the exact molecular domain involved in inhibition of HARP-induced mitogenesis (PMID:17727841)
• An autologous PTN-pleiotrophin receptor (PTPRZ1) signaling loop is present in human embryonic stem cells and functions here predominantly via an antiapoptotic effect. (PMID:17823238)
• HARP negatively affects diverse biological activities in C6 glioma cells, mainly due to binding of HARP to VEGF, which may sequester secreted VEGF from signalling through VEGFR2. (PMID:17881084)
• Pleiotrophin failed to activate anaplastic lymphoma kinase (ALK) in neuroblastoma/glioblastoma cells expressing this receptor. ALK is still an orphan receptor in vertebrates. (PMID:17904822)
• MMP-2 processing of HARP and CTGF released vascular endothelial growth factor (VEGF) from angiogenic inhibitory complexes. (PMID:17908800)
• pleiotrophin potentiates cardiomyocyte cell death, at least partially, through inhibition of AKT signaling (PMID:17925408)
• PTN was expressed in HSCs, Kupffer cells, and hepatocytes in fibrotic liver. We propose that pleitrophin specifically antagonizes the TGFbeta1 activity during liver fibrosis (PMID:18381592)
• These results emphasize the importance of PTN in the regulation of inflammatory processes. (PMID:18486628)
• pleiotrophin (PTN) and syndecan-2 and -3 as direct binding partners of Y-P30. (PMID:18599487)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptn	ENSDARG00000102340
mus_musculus	Ptn	ENSMUSG00000029838
rattus_norvegicus	Ptn	ENSRNOG00000011946

Paralogs (1): MDK (ENSG00000110492)

Protein

Protein identifiers

Pleiotrophin — P21246 (reviewed: P21246)

Alternative names: Heparin-binding brain mitogen, Heparin-binding growth factor 8, Heparin-binding growth-associated molecule, Heparin-binding neurite outgrowth-promoting factor, Heparin-binding neurite outgrowth-promoting factor 1, Osteoblast-specific factor 1

All UniProt accessions (3): P21246, A0A8V8TNI1, C9JR52

UniProt curated annotations — full annotation on UniProt →

Function. Secreted growth factor that mediates its signal through cell-surface proteoglycan and non-proteoglycan receptors. Binds cell-surface proteoglycan receptor via their chondroitin sulfate (CS) groups. Thereby regulates many processes like cell proliferation, cell survival, cell growth, cell differentiation and cell migration in several tissues namely neuron and bone. Also plays a role in synaptic plasticity and learning-related behavior by inhibiting long-term synaptic potentiation. Binds PTPRZ1, leading to neutralization of the negative charges of the CS chains of PTPRZ1, inducing PTPRZ1 clustering, thereby causing the dimerization and inactivation of its phosphatase activity leading to increased tyrosine phosphorylation of each of the PTPRZ1 substrates like ALK, CTNNB1 or AFAP1L2 in order to activate the PI3K-AKT pathway. Through PTPRZ1 binding controls oligodendrocyte precursor cell differentiation by enhancing the phosphorylation of AFAP1L2 in order to activate the PI3K-AKT pathway. Forms a complex with PTPRZ1 and integrin alpha-V/beta-3 (ITGAV:ITGB3) that stimulates endothelial cell migration through SRC dephosphorylation and activation that consequently leads to ITGB3 ‘Tyr-773’ phosphorylation. In adult hippocampus promotes dendritic arborization, spine development, and functional integration and connectivity of newborn granule neurons through ALK by activating AKT signaling pathway. Binds GPC2 and chondroitin sulfate proteoglycans (CSPGs) at the neuron surface, leading to abrogation of binding between PTPRS and CSPGs and neurite outgrowth promotion. Binds SDC3 and mediates bone formation by recruiting and attaching osteoblasts/osteoblast precursors to the sites for new bone deposition. Binds ALK and promotes cell survival and cell proliferation through MAPK pathway activation. Inhibits proliferation and enhances differentiation of neural stem cells by inhibiting FGF2-induced fibroblast growth factor receptor signaling pathway. Mediates regulatory mechanisms in normal hemostasis and in hematopoietic regeneration and in maintaining the balance of myeloid and lymphoid regeneration. In addition may play a role in the female reproductive system, auditory response and the progesterone-induced decidualization pathway.

Subunit / interactions. Interacts with ALK and NEK6. Interacts with PTPRZ1 (via chondroitin sulfate groups); promotes formation of homooligomers; oligomerization impairs tyrosine phosphatase activity. Forms a complex with PTPRZ1 and CTNNB1; this complex inactivates PTPRZ1 protein tyrosine phosphatase activity through PTN interaction and stimulates tyrosine phosphorylation of CTNNB1. Interacts with ITGB3 and ITGA5. Forms a complex with PTPRZ1 and integrin alpha-V/beta-3 (ITGAV:ITGB3) that stimulates endothelial cell migration through ITGB3 ‘Tyr-773’ phosphorylation. Interacts with SDC3 (via heparan sulfate chains); this interaction mediates the neurite outgrowth-promoting signal from PTN to the cytoskeleton of growing neurites; this interaction mediates osteoblast recruitment. Interacts with GPC2 (via heparan sulfate); this interaction promotes neurite outgrowth through binding of PTN with chondroitin sulfate of proteoglycans, thereby releasing PTPRS of chondroitin sulfate proteoglycans (CSPGs) and leading to binding with heparan sulfate of GPC2.

Subcellular location. Secreted.

Tissue specificity. Osteoblast and brain.

Post-translational modifications. Phosphorylated by NEK6.

Induction. By heparin and retinoic acid.

Similarity. Belongs to the pleiotrophin family.

RefSeq proteins (3): NP_001308315, NP_001308316, NP_002816* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000762	Midkine_heparin-bd_GF	Family
IPR020089	PTN/MK_N_dom	Domain
IPR020090	PTN/MK_C_dom	Domain
IPR020091	PTN/MK_diS_sf	Homologous_superfamily
IPR020092	PTN_MK_heparin-bd_GF_CS	Conserved_site
IPR037122	PTN/MK_N_dom_sf	Homologous_superfamily
IPR038130	PTN/MK_C_dom_sf	Homologous_superfamily

Pfam: PF01091, PF05196

UniProt features (25 total): strand 9, disulfide bond 5, region of interest 4, sequence conflict 3, turn 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2N6F	SOLUTION NMR
8VOH	SOLUTION NMR
8VOI	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21246-F1	75.07	0.18

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (5): 109–141, 47–76, 55–85, 62–89, 99–131

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-201556	Signaling by ALK
R-HSA-9851151	MDK and PTN in ALK signaling

MSigDB gene sets: 365 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_MEMORY, GOBP_REGULATION_OF_HEPATOCYTE_PROLIFERATION, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_COGNITION, GOBP_GLAND_MORPHOGENESIS, GOBP_BEHAVIOR, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, PAL_PRMT5_TARGETS_UP, TTTGTAG_MIR520D, GOBP_POSITIVE_REGULATION_OF_GLIAL_CELL_DIFFERENTIATION, GOBP_GROWTH, GOBP_OOGENESIS

GO Biological Process (38): leukocyte chemotaxis involved in inflammatory response (GO:0002232), positive regulation of leukocyte chemotaxis (GO:0002690), cell surface receptor protein tyrosine phosphatase signaling pathway (GO:0007185), integrin-mediated signaling pathway (GO:0007229), nervous system development (GO:0007399), negative regulation of neuroblast proliferation (GO:0007406), learning (GO:0007612), memory (GO:0007613), positive regulation of cell population proliferation (GO:0008284), regulation of endothelial cell migration (GO:0010594), positive regulation of neuron projection development (GO:0010976), response to auditory stimulus (GO:0010996), bone mineralization (GO:0030282), positive regulation of bone mineralization (GO:0030501), dendrite regeneration (GO:0031104), regulation of myelination (GO:0031641), tissue regeneration (GO:0042246), receptor clustering (GO:0043113), ossification involved in bone remodeling (GO:0043932), estrous cycle (GO:0044849), positive regulation of ossification (GO:0045778), decidualization (GO:0046697), regulation of synaptic plasticity (GO:0048167), oogenesis (GO:0048477), positive regulation of axon regeneration (GO:0048680), positive regulation of oligodendrocyte differentiation (GO:0048714), positive regulation of cell division (GO:0051781), dendrite arborization (GO:0140059), positive regulation of dendrite development (GO:1900006), negative regulation of long-term synaptic potentiation (GO:1900272), regulation of hemopoiesis (GO:1903706), regulation of stem cell population maintenance (GO:2000036), positive regulation of hepatocyte proliferation (GO:2000347), positive regulation of stem cell differentiation (GO:2000738), ossification (GO:0001503), signal transduction (GO:0007165), positive regulation of cell differentiation (GO:0045597), modulation of chemical synaptic transmission (GO:0050804)

GO Molecular Function (9): protein phosphatase inhibitor activity (GO:0004864), integrin binding (GO:0005178), growth factor activity (GO:0008083), heparin binding (GO:0008201), protein kinase binding (GO:0019901), carbohydrate binding (GO:0030246), chondroitin sulfate binding (GO:0035374), molecular function activator activity (GO:0140677), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), protein-containing complex (GO:0032991), Schaffer collateral - CA1 synapse (GO:0098685)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Receptor Tyrosine Kinases	1
Signaling by ALK	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
leukocyte chemotaxis	2
learning or memory	2
ossification	2
glycosaminoglycan binding	2
sulfur compound binding	2
binding	2
leukocyte migration involved in inflammatory response	1
inflammatory response	1
positive regulation of leukocyte migration	1
regulation of leukocyte chemotaxis	1
positive regulation of chemotaxis	1
enzyme-linked receptor protein signaling pathway	1
cell surface receptor signaling pathway	1
system development	1
neuroblast proliferation	1
negative regulation of neurogenesis	1
regulation of neuroblast proliferation	1
negative regulation of neural precursor cell proliferation	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of cell migration	1
endothelial cell migration	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
response to mechanical stimulus	1
biomineral tissue development	1
bone mineralization	1
regulation of bone mineralization	1
positive regulation of ossification	1
positive regulation of biomineral tissue development	1
dendrite development	1
neuron projection regeneration	1
myelination	1
regulation of cellular process	1
regulation of nervous system development	1
regeneration	1
developmental growth	1
plasma membrane	1

Protein interactions and networks

STRING

2230 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTN	PTPRZ1	P23471	998
PTN	SDC3	O75056	993
PTN	PTPRB	P23467	991
PTN	ALK	Q9UM73	991
PTN	PLXNB2	O15031	902
PTN	HDGF	P51858	813
PTN	AZU1	P20160	802
PTN	SLC2A1	P11166	792
PTN	SPARC	P09486	783
PTN	AKR1D1	P51857	719
PTN	FGF2	P09038	709
PTN	SPARCL1	Q14515	699
PTN	SDC4	P31431	698
PTN	PTPRS	Q13332	685
PTN	SDC1	P18827	665

IntAct

121 interactions, top by confidence:

A	B	Type	Score
ITGAM	PTN	psi-mi:“MI:0407”(direct interaction)	0.620
PTN	ASPH	psi-mi:“MI:0915”(physical association)	0.560
SERPINH1	PTN	psi-mi:“MI:0915”(physical association)	0.560
PRKACA	PTN	psi-mi:“MI:0915”(physical association)	0.560
KLK6	PTN	psi-mi:“MI:0915”(physical association)	0.560
TGFBR2	PTN	psi-mi:“MI:0915”(physical association)	0.560
PTN	SGTA	psi-mi:“MI:0915”(physical association)	0.550
CHD3	PTN	psi-mi:“MI:0915”(physical association)	0.550
DNAJB11	PTN	psi-mi:“MI:0915”(physical association)	0.550
PTN	TAF1D	psi-mi:“MI:0915”(physical association)	0.550
PTN	CWF19L2	psi-mi:“MI:0915”(physical association)	0.400
PTN	CYP2E1	psi-mi:“MI:0915”(physical association)	0.370
BAG6	PTN	psi-mi:“MI:0915”(physical association)	0.370
TSC22D1	PTN	psi-mi:“MI:0915”(physical association)	0.370
PTN	UBQLN1	psi-mi:“MI:0915”(physical association)	0.370
BARD1	PTN	psi-mi:“MI:0915”(physical association)	0.370
KPNB1	PTN	psi-mi:“MI:0915”(physical association)	0.370
PTN	GADD45G	psi-mi:“MI:0915”(physical association)	0.370
PTN	FEZ1	psi-mi:“MI:0915”(physical association)	0.370
PTN	PTN	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (113): PTN (Co-localization), PTN (Co-localization), PTN (Affinity Capture-Western), PTN (Affinity Capture-Western), PTN (Two-hybrid), PTN (Two-hybrid), PTN (Two-hybrid), PTN (Two-hybrid), PTN (Two-hybrid), PTN (Two-hybrid), PTN (Two-hybrid), PTN (Two-hybrid), PTN (Two-hybrid), PTN (Two-hybrid), PTN (Two-hybrid)

ESM2 similar proteins: A0A1D5PUP4, A5YT95, O62650, O73612, O95980, P10669, P19883, P21246, P21674, P21782, P31514, P31515, P32760, P47931, P48532, P48533, P49767, P50291, P52799, P52800, P54198, P55884, P63089, P63090, P79281, P79987, Q17QD6, Q1RMU5, Q5RA73, Q5SQF8, Q5ZJ65, Q6PFE7, Q6V9H4, Q8C4U3, Q8IYR6, Q8N474, Q8N475, Q90844, Q90YC9, Q91590

Diamond homologs: P12025, P21246, P21741, P21782, P24052, P32760, P48530, P48531, P48532, P48533, P63089, P63090, P79281, Q6P8F3, Q9R1S9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PTN	up-regulates	ALK	binding
NME1	“down-regulates quantity by repression”	PTN	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1434 predictions. Top by Δscore:

Variant	Effect	Δscore
7:137228071:TTCTG:T	acceptor_gain	1.0000
7:137228073:CTG:C	acceptor_gain	1.0000
7:137228074:TG:T	acceptor_gain	1.0000
7:137228076:C:CC	acceptor_gain	1.0000
7:137228082:T:C	acceptor_gain	1.0000
7:137228082:T:TC	acceptor_gain	1.0000
7:137228085:C:CT	acceptor_gain	1.0000
7:137228086:A:T	acceptor_gain	1.0000
7:137228098:C:CT	acceptor_gain	1.0000
7:137228099:A:T	acceptor_gain	1.0000
7:137251224:ACTT:A	donor_loss	1.0000
7:137251226:TTA:T	donor_loss	1.0000
7:137251227:TACCT:T	donor_loss	1.0000
7:137251228:A:AG	donor_loss	1.0000
7:137253458:GCTTA:G	donor_loss	1.0000
7:137253459:CTTAC:C	donor_loss	1.0000
7:137253461:TACCG:T	donor_loss	1.0000
7:137253462:A:AC	donor_gain	1.0000
7:137253462:A:T	donor_loss	1.0000
7:137253462:ACCG:A	donor_gain	1.0000
7:137253463:C:CC	donor_gain	1.0000
7:137253463:C:CT	donor_loss	1.0000
7:137253463:CCG:C	donor_gain	1.0000
7:137253463:CCGC:C	donor_gain	1.0000
7:137253636:TT:T	acceptor_gain	1.0000
7:137253637:TC:T	acceptor_loss	1.0000
7:137253638:C:CC	acceptor_gain	1.0000
7:137253639:T:C	acceptor_loss	1.0000
7:137254438:A:AC	donor_gain	1.0000
7:137254439:C:CC	donor_gain	1.0000

AlphaMissense

1099 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:137251264:C:A	K139N	1.000
7:137251264:C:G	K139N	1.000
7:137251289:C:G	C131S	1.000
7:137251290:A:G	C131R	1.000
7:137251290:A:T	C131S	1.000
7:137251322:C:T	G120E	1.000
7:137251323:C:G	G120R	1.000
7:137251323:C:T	G120R	1.000
7:137251327:T:A	R118S	1.000
7:137251327:T:G	R118S	1.000
7:137251328:C:G	R118T	1.000
7:137251355:C:G	C109S	1.000
7:137251356:A:T	C109S	1.000
7:137251363:C:A	W106C	1.000
7:137251363:C:G	W106C	1.000
7:137251365:A:G	W106R	1.000
7:137251365:A:T	W106R	1.000
7:137251372:G:C	F103L	1.000
7:137251372:G:T	F103L	1.000
7:137251373:A:C	F103C	1.000
7:137251373:A:G	F103S	1.000
7:137251374:A:G	F103L	1.000
7:137251379:T:C	Y101C	1.000
7:137251379:T:G	Y101S	1.000
7:137251380:A:C	Y101D	1.000
7:137251380:A:G	Y101H	1.000
7:137251381:T:A	K100N	1.000
7:137251381:T:G	K100N	1.000
7:137251383:T:C	K100E	1.000
7:137251384:G:C	C99W	1.000

dbSNP variants (sampled 300 via entrez): RS1000004664 (7:137340592 A>G), RS1000020528 (7:137284046 A>T), RS1000040939 (7:137241981 C>T), RS1000056406 (7:137284191 C>T), RS1000067838 (7:137302437 A>C), RS1000113069 (7:137266036 A>G), RS1000127323 (7:137254442 A>G), RS1000143526 (7:137261945 C>G), RS1000229671 (7:137265748 A>C,G), RS1000259979 (7:137247466 A>G), RS1000295237 (7:137265275 A>G), RS1000326778 (7:137277230 T>C), RS1000347161 (7:137314964 T>C), RS1000370956 (7:137295641 T>A,C), RS1000386049 (7:137271416 G>C,T)

Disease associations

OMIM: gene MIM:162095 | 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
GCST002539_70	Schizophrenia	3.000000e-09
GCST002931_6	Aluminium levels	9.000000e-06
GCST005352_29	Paclitaxel disposition in epithelial ovarian cancer	5.000000e-06
GCST006585_1862	Blood protein levels	3.000000e-11
GCST006803_103	Schizophrenia	7.000000e-11
GCST006940_99	Neurociticism	6.000000e-09
GCST009391_340	Metabolite levels	4.000000e-06
GCST009600_77	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0010433	triacylglycerol 56:6 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523199 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.11	Kd	77.8	nM	CHEMBL4540967
6.44	Kd	364.5	nM	CHEMBL4436421

PubChem BioAssay actives

2 with measured affinity, of 6 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
(2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2-(6-azidohexoxy)-5-hydroxy-6-(sulfooxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(sulfooxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid	1612776: Binding affinity to PTN (unknown origin) by SPR assay	kd	0.0778	uM
(2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5R,6R)-3-acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5R,6R)-3-acetamido-2-(6-azidohexoxy)-5-sulfooxy-6-(sulfooxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-sulfooxy-6-(sulfooxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid	1612776: Binding affinity to PTN (unknown origin) by SPR assay	kd	0.3645	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	6
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	affects methylation, decreases expression, increases expression	3
bisphenol A	decreases methylation, increases expression	2
Chondroitin Sulfates	affects binding	2
Nickel	decreases expression	2
Tretinoin	increases expression, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
pyrazolo(3,4-d)pyrimidine	affects expression	1
butyraldehyde	increases expression	1
rutecarpine	decreases expression	1
1-nitropyrene	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
bisphenol S	affects cotreatment, increases methylation	1
incobotulinumtoxinA	increases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	increases expression	1
Microplastics	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation, affects methylation	1
Cannabidiol	decreases expression	1
Cocaine	decreases expression	1
Cycloheximide	affects cotreatment, increases expression	1
Dermatan Sulfate	affects binding	1
Diethylhexyl Phthalate	decreases expression, increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4412189	Binding	Binding affinity to PTN (unknown origin) by SPR assay	Unravel a neuroactive sHA sulfation pattern with neurogenesis activity by a library of defined oligosaccharides. — Eur J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8NE	Abcam HCT 116 PTN KO	Cancer cell line	Male
CVCL_B9QP	Abcam A-549 PTN KO	Cancer cell line	Male
CVCL_D2H3	Abcam MCF-7 PTN KO	Cancer cell line	Female

Clinical trials (associated diseases)

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