PDPN
podoplanin
Basic information
Region (hg38): 1:13583465-13617957
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDPN gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | |||||
| missense | 9 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 2 | |||||
| Total | 0 | 0 | 9 | 2 | 3 |
Variants in PDPN
This is a list of pathogenic ClinVar variants found in the PDPN region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-13583838-A-G | Likely benign (Oct 01, 2022) | |||
| 1-13583851-C-T | Benign/Likely benign (Oct 01, 2024) | |||
| 1-13583873-C-G | not specified | Uncertain significance (Dec 19, 2022) | ||
| 1-13583875-C-T | not specified | Likely benign (Jan 03, 2024) | ||
| 1-13607224-G-C | not specified | Uncertain significance (Sep 07, 2022) | ||
| 1-13607226-G-A | not specified | Uncertain significance (Jul 02, 2024) | ||
| 1-13607232-A-G | Benign (Aug 01, 2024) | |||
| 1-13607244-G-A | not specified | Uncertain significance (Feb 21, 2024) | ||
| 1-13607280-C-A | not specified | Uncertain significance (Apr 17, 2023) | ||
| 1-13610403-A-G | not specified | Uncertain significance (Dec 14, 2022) | ||
| 1-13610458-C-T | Benign (Dec 31, 2019) | |||
| 1-13610459-G-A | not specified | Uncertain significance (Jan 30, 2024) | ||
| 1-13610479-C-T | Benign (Mar 01, 2024) | |||
| 1-13610502-C-G | not specified | Uncertain significance (Jan 24, 2024) | ||
| 1-13613708-A-G | not specified | Uncertain significance (Jan 26, 2023) | ||
| 1-13614333-T-C | not specified | Uncertain significance (Jun 11, 2024) | ||
| 1-13614345-T-C | not specified | Uncertain significance (Sep 01, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PDPN | protein_coding | protein_coding | ENST00000294489 | 6 | 34493 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000320 | 0.826 | 125603 | 0 | 5 | 125608 | 0.0000199 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.520 | 158 | 141 | 1.12 | 0.00000755 | 1483 |
| Missense in Polyphen | 41 | 39.111 | 1.0483 | 407 | ||
| Synonymous | -2.18 | 79 | 57.9 | 1.36 | 0.00000327 | 534 |
| Loss of Function | 1.21 | 7 | 11.4 | 0.613 | 5.83e-7 | 126 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000291 | 0.0000291 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000177 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000331 | 0.0000327 |
| Other | 0.000164 | 0.000163 |
dbNSFP
Source:
- Function
- 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 (PubMed:14522983, PubMed:15231832, PubMed:17616532, PubMed:18215137, PubMed:17222411). Interaction with CD9, on the contrary, attenuates platelet aggregation induced by PDPN (PubMed:18541721). 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 (PubMed:17046996, PubMed:21376833). Interaction with CD44 promotes directional cell migration in epithelial and tumor cells (PubMed:20962267). 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 (By similarity). Through binding with LGALS8 may participate to connection of the lymphatic endothelium to the surrounding extracellular matrix (PubMed:19268462). 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 (PubMed:15515019). 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 (PubMed:25486435). Required for normal lung cell proliferation and alveolus formation at birth (By similarity). Does not function as a water channel or as a regulator of aquaporin-type water channels (PubMed:9651190). Does not have any effect on folic acid or amino acid transport (By similarity). {ECO:0000250|UniProtKB:Q62011, ECO:0000269|PubMed:14522983, ECO:0000269|PubMed:15231832, ECO:0000269|PubMed:15515019, ECO:0000269|PubMed:17046996, ECO:0000269|PubMed:17222411, ECO:0000269|PubMed:17616532, ECO:0000269|PubMed:18215137, ECO:0000269|PubMed:18541721, ECO:0000269|PubMed:19268462, ECO:0000269|PubMed:20962267, ECO:0000269|PubMed:21376833, ECO:0000269|PubMed:25486435, ECO:0000269|PubMed:9651190}.;
- Pathway
- GPVI-mediated activation cascade;Platelet activation, signaling and aggregation;Hemostasis
(Consensus)
Recessive Scores
- pRec
- 0.186
Intolerance Scores
- loftool
- 0.847
- rvis_EVS
- 0.02
- rvis_percentile_EVS
- 55.61
Haploinsufficiency Scores
- pHI
- 0.558
- hipred
- N
- hipred_score
- 0.123
- ghis
- 0.463
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.480
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pdpn
- Phenotype
- integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; muscle phenotype; homeostasis/metabolism phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; digestive/alimentary phenotype;
Gene ontology
- Biological process
- cell morphogenesis;lymphangiogenesis;amino acid transmembrane transport;water transport;amino acid transport;Rho protein signal transduction;negative regulation of cell population proliferation;regulation of cell shape;positive regulation of epithelial to mesenchymal transition;folic acid transport;platelet activation;lung development;positive regulation of cell migration;negative regulation of apoptotic process;wound healing, spreading of cells;lymph node development;positive regulation of cellular component movement;lymphatic endothelial cell fate commitment;actin-mediated cell contraction;positive regulation of extracellular matrix disassembly;regulation of substrate adhesion-dependent cell spreading;positive regulation of platelet aggregation;regulation of myofibroblast contraction;invadopodium organization;regulation of lamellipodium morphogenesis
- Cellular component
- ruffle;cytosol;plasma membrane;integral component of plasma membrane;membrane;basolateral plasma membrane;apical plasma membrane;lamellipodium;cell junction;filopodium;lamellipodium membrane;cytoplasmic vesicle;filopodium membrane;microvillus membrane;ruffle membrane;cell projection;membrane raft;leading edge of lamellipodium;invadopodium;tetraspanin-enriched microdomain
- Molecular function
- signaling receptor binding;water transmembrane transporter activity;protein binding;folic acid transmembrane transporter activity;amino acid transmembrane transporter activity;water channel activity;chemokine binding;chaperone binding