PDPN

Summary

PDPN (podoplanin, HGNC:29602) is a protein-coding gene on chromosome 1p36.21, encoding Podoplanin (Q86YL7). Mediates effects on cell migration and adhesion through its different partners.

This gene encodes a type-I integral membrane glycoprotein with diverse distribution in human tissues. The physiological function of this protein may be related to its mucin-type character. The homologous protein in other species has been described as a differentiation antigen and influenza-virus receptor. The specific function of this protein has not been determined but it has been proposed as a marker of lung injury. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 10630 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 47 total
• Phenotypes (HPO): 99
• MANE Select transcript: NM_006474

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29602
Approved symbol	PDPN
Name	podoplanin
Location	1p36.21
Locus type	gene with protein product
Status	Approved
Aliases	T1A-2, Gp38, aggrus, GP40, PA2.26, D2-40
Ensembl gene	ENSG00000162493
Ensembl biotype	protein_coding
OMIM	608863
Entrez	10630

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 13 protein_coding, 2 nonsense_mediated_decay

ENST00000294489, ENST00000376057, ENST00000376061, ENST00000475043, ENST00000487038, ENST00000488631, ENST00000506205, ENST00000509009, ENST00000510906, ENST00000513143, ENST00000621990, ENST00000921771, ENST00000921772, ENST00000921773, ENST00000921774

RefSeq mRNA: 5 — MANE Select: NM_006474 NM_001006624, NM_001006625, NM_001385053, NM_006474, NM_198389

CCDS: CCDS30602, CCDS41266, CCDS44060, CCDS53270

Canonical transcript exons

ENST00000621990 — 6 exons

Exon	Start	End
ENSE00001065761	13610387	13610516
ENSE00001065763	13614300	13614411
ENSE00001928338	13615905	13617957
ENSE00003570212	13607173	13607306
ENSE00003678690	13613687	13613725
ENSE00003738660	13583832	13584100

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 99.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.1763 / max 841.7179, expressed in 1134 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
754	45.1234	1121
756	0.2916	159
759	0.2668	127
755	0.2066	124
757	0.1590	73
201363	0.1288	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.82	gold quality
cartilage tissue	UBERON:0002418	97.58	gold quality
ventricular zone	UBERON:0003053	96.40	gold quality
germinal epithelium of ovary	UBERON:0001304	96.17	gold quality
pigmented layer of retina	UBERON:0001782	95.46	gold quality
retina	UBERON:0000966	95.43	gold quality
secondary oocyte	CL:0000655	93.86	gold quality
ganglionic eminence	UBERON:0004023	93.07	gold quality
gall bladder	UBERON:0002110	92.88	gold quality
mucosa of stomach	UBERON:0001199	92.57	gold quality
parietal pleura	UBERON:0002400	92.56	gold quality
left uterine tube	UBERON:0001303	92.52	gold quality
ectocervix	UBERON:0012249	92.48	gold quality
endocervix	UBERON:0000458	92.42	gold quality
omental fat pad	UBERON:0010414	91.69	gold quality
peritoneum	UBERON:0002358	91.60	gold quality
decidua	UBERON:0002450	91.03	gold quality
right ovary	UBERON:0002118	91.02	gold quality
placenta	UBERON:0001987	90.97	gold quality
ovary	UBERON:0000992	90.07	gold quality
upper lobe of left lung	UBERON:0008952	90.07	gold quality
pleura	UBERON:0000977	89.95	gold quality
right lung	UBERON:0002167	89.76	gold quality
left ovary	UBERON:0002119	89.74	gold quality
upper lobe of lung	UBERON:0008948	89.25	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.00	gold quality
gastrocnemius	UBERON:0001388	88.96	gold quality
muscle of leg	UBERON:0001383	88.59	gold quality
vermiform appendix	UBERON:0001154	88.42	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	1508.69
E-MTAB-6308	yes	550.99
E-HCAD-11	yes	474.00
E-GEOD-93593	yes	317.32
E-CURD-114	yes	69.81
E-HCAD-1	yes	22.04
E-ANND-3	yes	21.09
E-MTAB-6701	yes	20.31
E-CURD-46	yes	14.69
E-MTAB-8530	no	378.10

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, E2F1, ETS1, FOS, MAZ, NFATC1, SP1, SP3, TBXT

miRNA regulators (miRDB)

97 targeting PDPN, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-548AW	99.99	72.57	3559
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4503	99.85	71.45	1869

Literature-anchored findings (GeneRIF, showing 40)

• Aggrus is a platelet aggregation-inducing factor expressed in colorectal tumors (PMID:14522983)
• a novel biomarker for oral squamous cell carcinomas that might be involved in migration/invasion (PMID:15515019)
• podoplanin may have a role in tumor progression (PMID:15743802)
• Interstitial cells in the endolymphatic duct express poloplanin protein. (PMID:16408168)
• Podoplanin expression in pretreatment biopsy material may be a useful marker to predict lymphatic metastasis and patient outcome. (PMID:16528371)
• Ki-67/podoplanin-immunoreactivity was useful to identify proliferating lymphatic vessels. (PMID:16574316)
• These data suggest that podoplanin expression might be associated with malignancy of astrocytic tumors. (PMID:16596424)
• podoplanin induces an alternative pathway of tumor cell invasion in the absence of epithelial-mesenchymal transition (PMID:16616332)
• podoplanin expression may be a sensitive immunohistochemical marker for germinoma (PMID:16718353)
• Podoplanin is a small mucin-like transmembrane protein, widely expressed in various specialised cell types throughout the body and podoplanin-mediated tumour invasion. (PMID:17179989)
• Total glycosylation profile of podoplanin weas surveyed by lectin microarray. (PMID:17222411)
• Strong immunostaining with D2-40 antibody was observed at the periphery of sebaceous glands and in skin lymphatic endothelium of all specimens, demonstrating that podoplanin is expressed in sebaceous glands of normal skin. (PMID:17284957)
• in human osteoblast-like MG63 cells, Sp1 and Sp3 stimulate basal PDPN transcription in a concerted, yet independent manner, whereas Saos-2 cells lack sufficient nuclear Sp protein amounts for transcriptional activation. (PMID:17343736)
• Evaluation of lymphangiogenesis using podoplanin immunohistochemistry may be useful in predicting lymph node metastasis and the prognosis in patients with esophageal carcinoma. (PMID:17348451)
• Data showed podoplanin (D2-40 monoclonal antibody) was positive in thin-wall branching vessels and confirmed the current concept of lymphangiogenic origin of the tumor vessels in lymphangioleiomyoma/lymphangioleiomyomatosis. (PMID:17377811)
• conformational comparison of MGP40 and HUMGP39 (PMID:17543889)
• CLEC-2 is a physiological target protein of podoplanin and imply that it is involved in podoplanin-induced platelet aggregation, tumor metastasis (PMID:17616532)
• Diffuse membranous immunoreactivity for podoplanin as detected by monoclonal antibody D2-40 is highly sensitive and specific for primary and metastatic seminoma. (PMID:17951198)
• Podoplanin is a highly sensitive marker for follicular dendritic cell tumors that is useful in the differential diagnosis of dendritic cell and histiocytic lesions. (PMID:17951199)
• cytoplasmic podoplanin expression may be useful in the diagnosis of sarcomatoid mesothelioma (PMID:18162779)
• podoplanin may have a role in axillary lymph node metastases of breast neoplasms (PMID:18165897)
• Overexpression of PDPN protein is associated with oral premalignancy (PMID:18202409)
• Three of the 4 Retiform hemangioendothelioma (RH) biopsies failed to demonstrate D2-40, none expressed VEGFR-3…RH is a vascular entity which usually does not have lymphatic differentiation, but may rarely express D2-40. (PMID:18212541)
• a direct interaction between CLEC-2 and podoplanin was confirmed; podoplanin is a ligand for CLEC-2 on renal cells. (PMID:18215137)
• Podoplanin is a novel marker to enrich tumor-initiating cells with stem-cell-like properties from squamous cell carcinoma cell line A431. (PMID:18539139)
• Because HT1080 cells express the metastasis-promoting, platelet aggregation-inducing factor Aggrus/podoplanin on their surface, we examined the relationship between CD9 and Aggrus. (PMID:18541721)
• Podoplanin-positive CAFs (Cancer-Associated Fibroblasts) were found only in invasive adenocarcinoma and none were found in noninvasive adenocarcinoma. Conventional prognostic factors were significantly correlated with podoplanin expression by CAFs. (PMID:18546264)
• This study adds Microvenular hemangioma to the list of vascular lesions that fail to express the allegedly lymphatic marker podoplanin (PMID:18650031)
• Patient age and a novel biological prognostic marker, podoplanin, are useful for predicting a poor outcome of patients after complete resection of stage IB SqCC of the lung. (PMID:18657337)
• Podoplanin silencing in human lung lymphatic microvascular endothelial cells has no effect on cell viability or cell morphology in tissue culture. (PMID:18658274)
• NZ-1 neutralizes the interaction between podoplanin and CLEC-2, which may lead to the development of therapeutic antibodies against podoplanin-dependent cancer metastasis. (PMID:18707544)
• CCR10+ T cells accumulate preferentially both around and within CCL27+ lymphatic endothelial cells (LEC) podo-low precollector vessels in skin biopsies of human inflammatory disease. (PMID:18772332)
• Podoplanin still remains the only positive marker for chondrosarcoma, though its accuracy is less than previously reported (PMID:18820665)
• PDPN) is transcribed in cells derived from sarcomas, embryonal carcinomas, squamous cell carcinomas and endometrial tumours, while cell lines derived from colon, pancreatic, ovarian and ductal breast carcinomas do not express PDPN transcripts. (PMID:19146981)
• These data suggest a role for galectin-8 and podoplanin in supporting the connection of the lymphatic endothelium to the surrounding extracellular matrix, most likely in cooperation with other glycoproteins on the surface of lymphatic endothelial cells. (PMID:19268462)
• Lymph vessel invasion was detected in higher ratios by immunostaining with podoplanin monoclonal antibody D2-40. (PMID:19356249)
• one should always interpret results of podoplanin staining in the context of the histologic appearance and/or consider evaluation of additional endothelial or ME immunostains (PMID:19363443)
• Internal ligand for CLEC-2. (review) (PMID:19483399)
• This study evaluates the use of the markers, podoplanin, SOX2, NANOG, and OCT3/4 in ovarian tumors (PMID:19483629)
• increased expression in gingival epithelium is related to the progression of chronic periodontitis (PMID:19550098)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pdpn	ENSMUSG00000028583
rattus_norvegicus	Pdpn	ENSRNOG00000014961

Protein

Protein identifiers

Podoplanin — Q86YL7 (reviewed: Q86YL7)

Alternative names: Aggrus, Glycoprotein 36, PA2.26 antigen, T1-alpha

All UniProt accessions (5): Q86YL7, D6RH07, E7ETC6, H0Y8Q3, H0YA72

UniProt curated annotations — full annotation on UniProt →

Function. Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activation in platelets and leading to platelet activation and/or aggregation. Interaction with CD9, on the contrary, attenuates platelet aggregation induced by PDPN. Through MSN or EZR interaction promotes epithelial-mesenchymal transition (EMT) leading to ERZ phosphorylation and triggering RHOA activation leading to cell migration increase and invasiveness. Interaction with CD44 promotes directional cell migration in epithelial and tumor cells. In lymph nodes (LNs), controls fibroblastic reticular cells (FRCs) adhesion to the extracellular matrix (ECM) and contraction of the actomyosin by maintaining ERM proteins (EZR; MSN and RDX) and MYL9 activation through association with unknown transmembrane proteins. Engagement of CLEC1B by PDPN promotes FRCs relaxation by blocking lateral membrane interactions leading to reduction of ERM proteins (EZR; MSN and RDX) and MYL9 activation. Through binding with LGALS8 may participate in connection of the lymphatic endothelium to the surrounding extracellular matrix. In keratinocytes, induces changes in cell morphology showing an elongated shape, numerous membrane protrusions, major reorganization of the actin cytoskeleton, increased motility and decreased cell adhesion. Controls invadopodia stability and maturation leading to efficient degradation of the extracellular matrix (ECM) in tumor cells through modulation of RHOC activity in order to activate ROCK1/ROCK2 and LIMK1/LIMK2 and inactivation of CFL1. Required for normal lung cell proliferation and alveolus formation at birth. Does not function as a water channel or as a regulator of aquaporin-type water channels. Does not have any effect on folic acid or amino acid transport.

Subunit / interactions. Homodimer. Interacts with CLEC1B; the interaction is independent of CLEC1B glycosylation and activates CLEC1B; the interaction is dependent of sialic acid on O-glycans. Interacts with CD9; this interaction is homophilic and attenuates platelet aggregation and pulmonary metastasis induced by PDPN. Interacts with LGALS8; the interaction is glycosylation-dependent; may participate in connection of the lymphatic endothelium to the surrounding extracellular matrix. Interacts with HSPA9. Interacts (via extracellular domain) with CD44; this interaction is required for PDPN-mediated directional migration and regulation of lamellipodia extension/stabilization during cell spreading and migration. Interacts (via cytoplasmic domain) with MSN and EZR; activates RHOA and promotes epithelial-mesenchymal transition. Interacts with CCL21; relocalized PDPN to the basolateral membrane.

Subcellular location. Membrane. Cell projection. Lamellipodium membrane. Filopodium membrane. Microvillus membrane. Ruffle membrane. Membrane raft. Apical cell membrane. Basolateral cell membrane. Invadopodium Cytoplasm. Cytosol.

Tissue specificity. Highly expressed in placenta, lung, skeletal muscle and brain. Weakly expressed in brain, kidney and liver. In placenta, expressed on the apical plasma membrane of endothelium. In lung, expressed in alveolar epithelium. Up-regulated in colorectal tumors and expressed in 25% of early oral squamous cell carcinomas.

Post-translational modifications. Extensively O-glycosylated. Contains sialic acid residues. O-glycosylation is necessary for platelet aggregation activity. Disialylated at Thr-52; sialic acid is critical for platelet-aggregating activity and for CLEC1B interaction. The N-terminus is blocked. Cleaved by a metalloprotease within its extracellular (EC) domain, generating a membrane-bound C-terminal fragment (PCTF33) and an extracellular fragment. The resulting membrane-bound C-terminal fragment (PCTF33) is further processed between Val-150 and Val-151 by PSEN1/gamma-secretase generating the intracellular domain of podoplanin (PICD).

Domain organisation. The cytoplasmic domain controls FRC elongation but is dispensable for contraction. The cytoplasmic domain is essential for recruitment to invadopodia and ECM degradation.

Similarity. Belongs to the podoplanin family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q86YL7-1	1, hT1alpha-2	yes
Q86YL7-2	2, hT1alpha-1
Q86YL7-3	3
Q86YL7-4	4
Q86YL7-5	5
Q86YL7-6	6

RefSeq proteins (5): NP_001006625, NP_001006626, NP_001371982, NP_006465, NP_938203 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR052684	Podoplanin_domain	Family

Pfam: PF05808

UniProt features (52 total): glycosylation site 24, splice variant 7, mutagenesis site 5, region of interest 4, compositionally biased region 2, topological domain 2, sequence variant 2, signal peptide 1, chain 1, site 1, peptide 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
4YO0	X-RAY DIFFRACTION	1.56
3WSR	X-RAY DIFFRACTION	1.91
5XCV	X-RAY DIFFRACTION	2.14
7CQC	X-RAY DIFFRACTION	2.5
7C94	X-RAY DIFFRACTION	2.84
7CQD	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86YL7-F1	58.12	0.07

Antibody-complex structures (SAbDab): 5 — 4YO0, 5XCV, 7C94, 7CQC, 7CQD

Functional residue map

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

Catalytic / active sites (1): 150–151 (cleavage; by gamma-secretase)

Glycosylation sites (24): 25, 32, 34, 35, 52, 55, 65, 66, 76, 85, 86, 88, 89, 96, 98, 100, 102, 106, 107, 109 …

Mutagenesis-validated functional residues (5):

Position	Phenotype
52	eliminates induction of platelet aggregation.
137	prevents self-assembly and association to lipid rafts. reduces the recruitment to invadopodium. disrupts assembly into a
154–159	does not affect localization at cell surface protrusions. does not induce reorganization of the actin cytoskeleton. incr
154–155	impairs interaction with the ezr and msn. impairs epithelial to mesenchymal transition. does not affect localization at
159	highly decreases interaction with the ezr and msn. induces an intermediate phenotype between epithelial and mesenchymal.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-114604	GPVI-mediated activation cascade
R-HSA-9827857	Specification of primordial germ cells

MSigDB gene sets: 565 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_TO_MESENCHYMAL_TRANSITION, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_PLATELET_ACTIVATION, GOBP_MODIFIED_AMINO_ACID_TRANSPORT, MODULE_64, GOBP_LYMPH_NODE_DEVELOPMENT, GOCC_RUFFLE, GOBP_REGULATION_OF_EXTRACELLULAR_MATRIX_ORGANIZATION, MORF_RAD51L3, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP

GO Biological Process (21): lymphangiogenesis (GO:0001946), cell adhesion (GO:0007155), signal transduction (GO:0007165), Rho protein signal transduction (GO:0007266), negative regulation of cell population proliferation (GO:0008285), regulation of cell shape (GO:0008360), positive regulation of epithelial to mesenchymal transition (GO:0010718), cell migration (GO:0016477), platelet activation (GO:0030168), lung development (GO:0030324), positive regulation of cell migration (GO:0030335), negative regulation of apoptotic process (GO:0043066), wound healing, spreading of cells (GO:0044319), lymph node development (GO:0048535), lymphatic endothelial cell fate commitment (GO:0060838), actin-mediated cell contraction (GO:0070252), positive regulation of extracellular matrix disassembly (GO:0090091), regulation of substrate adhesion-dependent cell spreading (GO:1900024), positive regulation of platelet aggregation (GO:1901731), regulation of myofibroblast contraction (GO:1904328), regulation of lamellipodium morphogenesis (GO:2000392)

GO Molecular Function (4): signaling receptor binding (GO:0005102), chemokine binding (GO:0019956), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515)

GO Cellular Component (21): ruffle (GO:0001726), mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), lamellipodium (GO:0030027), cell junction (GO:0030054), filopodium (GO:0030175), lamellipodium membrane (GO:0031258), cytoplasmic vesicle (GO:0031410), filopodium membrane (GO:0031527), microvillus membrane (GO:0031528), ruffle membrane (GO:0032587), cell projection (GO:0042995), membrane raft (GO:0045121), leading edge of lamellipodium (GO:0061851), tetraspanin-enriched microdomain (GO:0097197), cytoplasm (GO:0005737), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Platelet activation, signaling and aggregation	1
Reproduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cell projection membrane	4
cell leading edge	3
cytoplasm	3
cellular process	2
cell migration	2
protein binding	2
plasma membrane bounded cell projection	2
plasma membrane region	2
lamellipodium	2
leading edge membrane	2
anatomical structure morphogenesis	1
lymph vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
small GTPase-mediated signal transduction	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
regulation of cell morphogenesis	1
regulation of biological quality	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
positive regulation of cell differentiation	1
positive regulation of multicellular organismal process	1
cell motility	1
cell activation	1
blood coagulation	1
respiratory tube development	1
animal organ development	1
respiratory system development	1
regulation of cell migration	1
positive regulation of cell motility	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
epiboly involved in wound healing	1

Protein interactions and networks

STRING

2108 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDPN	CLEC1B	Q9P126	999
PDPN	PROX1	Q92786	913
PDPN	EZR	P15311	891
PDPN	LYVE1	Q9Y5Y7	874
PDPN	GP6	Q9HCN6	844
PDPN	CCL21	O00585	843
PDPN	MSN	P26038	835
PDPN	RDX	P35241	806
PDPN	TNFRSF10B	O14763	794
PDPN	PECAM1	P16284	777
PDPN	FLT4	P35916	773
PDPN	LGALS8	O00214	765
PDPN	VEGFC	P49767	723
PDPN	TNFSF4	P23510	697
PDPN	PODXL	O00592	694

IntAct

12 interactions, top by confidence:

A	B	Type	Score
CLEC1B	PDPN	psi-mi:“MI:0407”(direct interaction)	0.560
PDPN	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
RBCK1	UMAD1	psi-mi:“MI:0914”(association)	0.350
SHARPIN	MAP3K7	psi-mi:“MI:0914”(association)	0.350
TRADD	HNRNPCL2	psi-mi:“MI:0914”(association)	0.350
PDPN	KIF14	psi-mi:“MI:0914”(association)	0.350
PDPN	ORC4	psi-mi:“MI:0914”(association)	0.350
PDPN	TMEM14B	psi-mi:“MI:0915”(physical association)	0.000
PDPN	TOM1L1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): PDPN (Affinity Capture-MS), PDPN (Affinity Capture-MS), PDPN (Affinity Capture-MS), TOM1L1 (Two-hybrid), PDPN (Two-hybrid), PDPN (Affinity Capture-RNA), KIF14 (Affinity Capture-MS), MBLAC2 (Affinity Capture-MS), IL17F (Affinity Capture-MS), SLC38A7 (Affinity Capture-MS), TMEM177 (Affinity Capture-MS), MAGT1 (Affinity Capture-MS), MPDU1 (Affinity Capture-MS), ORC4 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8Y7Y5, A1KXC4, A6QLF8, J3KML8, O00592, O35188, O55145, O57604, P06484, P07141, P13838, P14220, P15702, P16150, P18827, P20934, P26260, P34740, P47951, P59647, P78423, P97808, Q08DZ5, Q1ECS6, Q28270, Q28645, Q29RT9, Q3MIW9, Q3TNW5, Q52S86, Q58Y74, Q5RAF8, Q62170, Q64314, Q6MG22, Q6P9X9, Q6UWI2, Q6UXF1, Q86YL7, Q8BHE4

Diamond homologs: Q62011, Q64294, Q86YL7, Q95152

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

952 predictions. Top by Δscore:

Variant	Effect	Δscore
1:13607320:G:T	donor_gain	1.0000
1:13610376:A:AG	acceptor_gain	1.0000
1:13610377:C:G	acceptor_gain	1.0000
1:13610382:A:AG	acceptor_gain	1.0000
1:13610382:AATAG:A	acceptor_gain	1.0000
1:13610515:GG:G	donor_gain	1.0000
1:13610516:GG:G	donor_gain	1.0000
1:13613679:A:AG	acceptor_gain	1.0000
1:13613685:A:AG	acceptor_gain	1.0000
1:13613686:G:GG	acceptor_gain	1.0000
1:13613724:AG:A	donor_loss	1.0000
1:13613725:GG:G	donor_loss	1.0000
1:13613726:GT:G	donor_loss	1.0000
1:13613727:T:A	donor_loss	1.0000
1:13614296:TCA:T	acceptor_loss	1.0000
1:13614297:CAGAT:C	acceptor_loss	1.0000
1:13614298:A:AG	acceptor_gain	1.0000
1:13614298:A:G	acceptor_loss	1.0000
1:13614298:AGAT:A	acceptor_gain	1.0000
1:13614299:G:GG	acceptor_gain	1.0000
1:13614299:GAT:G	acceptor_gain	1.0000
1:13614299:GATG:G	acceptor_gain	1.0000
1:13614412:G:GG	donor_gain	1.0000
1:13614416:G:GG	donor_gain	1.0000
1:13584097:GGAG:G	donor_gain	0.9900
1:13584098:GAGG:G	donor_gain	0.9900
1:13585712:GTG:G	donor_gain	0.9900
1:13585714:G:GA	donor_gain	0.9900
1:13607171:A:AG	acceptor_gain	0.9900
1:13607172:G:GT	acceptor_gain	0.9900

AlphaMissense

1028 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:13614338:G:A	G137R	0.980
1:13614338:G:C	G137R	0.980
1:13614339:G:A	G137E	0.964
1:13614356:G:C	G143R	0.963
1:13614365:G:C	G146R	0.957
1:13614366:G:A	G146D	0.957
1:13614326:G:A	G133R	0.956
1:13614326:G:C	G133R	0.956
1:13614357:G:A	G143D	0.956
1:13614327:G:A	G133E	0.944
1:13614333:T:A	I135K	0.930
1:13614348:T:G	L140R	0.918
1:13584067:G:A	G12R	0.912
1:13584067:G:C	G12R	0.912
1:13614351:C:A	A141D	0.912
1:13614336:T:A	V136D	0.898
1:13584068:G:A	G12E	0.873
1:13614333:T:G	I135R	0.872
1:13584062:T:A	V10D	0.866
1:13614348:T:A	L140Q	0.863
1:13614369:C:A	A147E	0.854
1:13614321:T:C	L131P	0.834
1:13614390:G:C	R154P	0.833
1:13614338:G:T	G137W	0.830
1:13614330:T:C	I134T	0.824
1:13614394:A:C	K155N	0.818
1:13614394:A:T	K155N	0.818
1:13614368:G:C	A147P	0.807
1:13584037:T:A	W2R	0.806
1:13584037:T:C	W2R	0.806

dbSNP variants (sampled 300 via entrez): RS1000053183 (1:13587118 C>G,T), RS1000109461 (1:13586071 G>A), RS1000166979 (1:13590038 G>A), RS1000247617 (1:13598072 G>A), RS1000279498 (1:13582284 A>G), RS1000523061 (1:13592563 T>C), RS1000583300 (1:13596730 G>A), RS1000627447 (1:13585038 A>C), RS1000658457 (1:13584854 T>C), RS1000762665 (1:13608531 A>G,T), RS1000878959 (1:13608101 G>A), RS1000892539 (1:13605166 G>A), RS1000922192 (1:13605333 C>T), RS1000938649 (1:13614082 C>T), RS1001181656 (1:13586913 A>G)

Disease associations

OMIM: gene MIM:608863 | disease phenotypes: MIM:120000

GenCC curated gene-disease

Mondo (2): aorta coarctation (MONDO:0007345), specific learning disability (MONDO:0016225)

Orphanet (2): Coarctation of aorta (Orphanet:1457), Specific learning disability (Orphanet:211047)

HPO phenotypes

99 total (30 of 99 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000055	Abnormal female external genitalia morphology
HP:0000077	Abnormality of the kidney
HP:0000107	Renal cyst
HP:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000160	Narrow mouth
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000270	Delayed cranial suture closure
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000457	Depressed nasal ridge
HP:0000464	Abnormality of the neck
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000504	Abnormality of vision
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000534	Abnormal eyebrow morphology
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000708	Atypical behavior
HP:0000717	Autism

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001017	Aortic Coarctation	C14.240.400.090; C14.280.400.090; C16.131.240.400.090
D000067559	Specific Learning Disorder	C10.597.606.150.550.700; C23.888.592.604.150.550.700; F03.625.374.188.700; F03.625.562.700

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment	6
sodium arsenite	affects methylation, decreases expression, increases expression	4
trichostatin A	increases expression, affects cotreatment	3
bisphenol A	increases expression, affects cotreatment	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
bisphenol S	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Estradiol	increases expression, affects cotreatment	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Particulate Matter	increases abundance, decreases expression	2
bisphenol F	affects cotreatment, increases expression	1
methylmercuric chloride	increases expression	1
nickel sulfate	decreases expression	1
1-nitropyrene	decreases expression	1
lysophosphatidic acid	decreases reaction, increases expression	1
3-nitrobenzanthrone	decreases expression	1
3-(4-dimethylamino-naphthalen-1-ylmethylene)-1,3-dihydro-indol-2-one	decreases reaction, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
MRK 003	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Celecoxib	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Calcitriol	increases expression	1

Cellosaurus cell lines

15 cell lines: 10 cancer cell line, 4 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8MC	Abcam HCT 116 PDPN KO	Cancer cell line	Male
CVCL_B9PI	Abcam A-549 PDPN KO	Cancer cell line	Male
CVCL_D2GU	Abcam MCF-7 PDPN KO	Cancer cell line	Female
CVCL_D2U0	Lec1/hPDPN	Spontaneously immortalized cell line	Female
CVCL_D2U1	Lec2/hPDPN	Spontaneously immortalized cell line	Female
CVCL_D2U2	Lec8/hPDPN	Spontaneously immortalized cell line	Female
CVCL_D2U3	Y-MESO-14/hPDPN	Cancer cell line	Male
CVCL_D2U4	RERF-LC-A1/hPDPN	Cancer cell line	Male
CVCL_D2U5	CHO/hPDPN	Spontaneously immortalized cell line	Female
CVCL_D2U6	LN229/hPDPN	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00767572	PHASE4	TERMINATED	Statins and Endothelial Function in Patients With Coarctation of the Aorta
NCT04330755	PHASE4	COMPLETED	Levosimendan Versus Combination With Magnesium Sulphate on Spine Protection by NIRS in Infants Undergoing Coarctectomy
NCT04128540	PHASE3	COMPLETED	Erector Spinae Plane Block Versus Fentanyl Infusion in Pediatric Patients Undergoing Aortic Coarcitectomy
NCT01278303	PHASE2	COMPLETED	Covered CP Stents for the Prevention or Treatment of Aortic Wall Injury Associated With Coarctation of the Aorta
NCT00552812	Not specified	COMPLETED	Coarctation Of the Aorta Stent Trial
NCT00978952	Not specified	COMPLETED	Large Diameter Advanta™ V12 Covered Stent Trial for Coarctation of the Aorta
NCT01032876	Not specified	COMPLETED	Cerebral Perfusion During Neonatal Cardiac Surgery
NCT01340378	Not specified	COMPLETED	A Pilot Study of Thrombin Generation Changes in Neonates Undergoing Placement of a Blalock-Taussig Shunt
NCT02161471	Not specified	COMPLETED	Haemodynamics and Function of the Atria in Congenital Heart Disease by Cardiovascular Magnetic Resonance
NCT02591940	Not specified	UNKNOWN	Proof of Concept of Model Based Cardiovascular Prediction
NCT02700737	Not specified	COMPLETED	Evaluation of Image-Based Modelling on Clinical Decisions in Coarctation of the Aorta
NCT02739087	Not specified	UNKNOWN	Radiation-Free Heart Catheterization Using MRI
NCT03147014	Not specified	UNKNOWN	Cardiovascular Response to Maternal Hyperoxygenation in Fetal Congenital Heart Disease
NCT03262753	Not specified	UNKNOWN	Long-term Outcomes and Vascular Evaluation After Coarctation of the Aorta Treatment
NCT03999073	Not specified	COMPLETED	Carotid Atherosclerosis in Patients With Aortic Coarctation
NCT04307888	Not specified	UNKNOWN	Spanish Percutaneous Aortic INtervention REGISTRY (SPAIN REGISTRY)
NCT05086016	Not specified	ACTIVE_NOT_RECRUITING	Growth Trial: Study of the Renata Minima Stent
NCT05203874	Not specified	UNKNOWN	Contribution of Multimodal Imaging in Early Coarctation
NCT05880576	Not specified	ENROLLING_BY_INVITATION	The Arch Watch Study: An Integrated Evaluation of Hemodynamics in Infants With Suspected Coarctation of the Aorta
NCT06567275	Not specified	COMPLETED	Comparison Between Serratus Anterior Plane Block and Erector Spinae Plane Block in Coarctectomy
NCT06740461	Not specified	NOT_YET_RECRUITING	Aortic Stiffness by CMR in Aortic Coarctation
NCT06759103	Not specified	RECRUITING	Electronic Archive of Patients With Diagnosis and Suspected Prenatal Diagnosis of Aortic Coarctation
NCT06828770	Not specified	RECRUITING	Minima Stent System Post- Approval Study (PAS)
NCT07134621	Not specified	ENROLLING_BY_INVITATION	Target Organ Damage in Patients With Repaired Coarctation of Aorta and Exercise Induced Hypertension
NCT07316855	Not specified	RECRUITING	Evaluating the Feasibility of Bioresorbable Iron-Based Covered Stent: A Clinical Trial
NCT07499609	Not specified	COMPLETED	Prevalence and Risk Factors for Hypertension and Recoarctation in Patients Operated for Aortic Coarctation
NCT07568431	Not specified	NOT_YET_RECRUITING	Correlation of Cardiac Index Measured by the PRAM Method With NIRS and Lactate Levels in Pediatric Aortic Coarctation Surgery
NCT03261076	Not specified	UNKNOWN	Reading Remediation and Outcomes in Detention
NCT04122820	Not specified	UNKNOWN	Ambulatory Screening for Specific Learning Disabilities (SLD) and Developmental Coordination Disorder (DCD).
NCT04783987	Not specified	UNKNOWN	Single and Dual Task Gait Parameters in Children With Specific Learning Difficulties
NCT05319197	Not specified	COMPLETED	HAND FUNCTIONS OF CHILDREN WITH A SPECIFIC LEARNING DISORDER
NCT05780853	Not specified	RECRUITING	A Game-based Neurodevelopmental Assessment for Young Children
NCT05787483	Not specified	COMPLETED	Biopsychosocial Outcomes of Mindfulness-based Instruction
NCT05872737	Not specified	RECRUITING	FAB Programme for Parents of Children With NDD
NCT05902143	Not specified	UNKNOWN	Fine Motor Function in Children With Specific Learning Disorders
NCT05923645	Not specified	UNKNOWN	Efficacy of rTMS as an Adjunct to AI Enabled Remedial Intervention in Children With Dyslexia
NCT05998083	Not specified	COMPLETED	The Effectiveness of Purposeful Exercises in Children Diagnosed With Special Learning Disabilities
NCT06086951	Not specified	RECRUITING	Pai.ACT - An Artificial Intelligence Driven Chatbot Assisted ACT
NCT06112483	Not specified	UNKNOWN	SWELE Program: An Unstructured Outdoor Play With Mindfulness-based Interventions to Promote Mental Health Among Students With Special Education Needs
NCT06262646	Not specified	COMPLETED	Video-conferencing FACT for Young Children With Special Needs