PTN
protein-codingpleiotrophin, the group of Receptor ligands
Gene summary
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. [provided by RefSeq, Oct 2016]
- NEGF1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~116.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PTN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002825.7. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 10 | 1 | 11 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 13 | 1 | 0 | 14 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002816.1 | 4 | MANE Select | |
| Ensembl | ENSP00000341170.2 | 4 | MANE Select | |
| RefSeq | NP_001308315.1 | 4 | Standard | |
| RefSeq | NP_001308316.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Syndecan-3-mediated signaling events
Biological Process
- liver development
- transmembrane receptor protein tyrosine phosphatase signaling pathway
- nervous system development
- heart development
- learning
Molecular Function
- protein phosphatase inhibitor activity
- growth factor activity
- heparin binding
- protein kinase binding
- chondroitin sulfate proteoglycan binding
Cellular Component
- extracellular region
- basement membrane
- extracellular space
- endoplasmic reticulum
- cell surface
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000348225
- Coding exons
- 4
- Length
- 116524
- Individuals with no LoFs
- 125706
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125715
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.18 | 58 | 89.3 | 0.649 | 0.00000468 | 1092 |
| Missense (PolyPhen) | 11 | 30.764 | 0.35756 | 373 | ||
| Synonymous | 0.480 | 27 | 30.4 | 0.889 | 0.00000140 | 298 |
| Loss of Function | 1.62 | 5 | 10.7 | 0.467 | 6.05e-7 | 117 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000030 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Secreted growth factor that induces neurite outgrowth and which is mitogenic for fibroblasts, epithelial, and endothelial cells (PubMed:1768439, PubMed:1733956). Binds anaplastic lymphoma kinase (ALK) which induces MAPK pathway activation, an important step in the anti-apoptotic signaling of PTN and regulation of cell proliferation (PubMed:11278720). Binds to cell-surface target proteins via their chondroitin sulfate groups (PubMed:26896299). Down-regulates PTPRZ1 activity (PubMed:16814777). {ECO:0000269|PubMed:11278720, ECO:0000269|PubMed:16814777, ECO:0000269|PubMed:1768439, ECO:0000269|PubMed:26896299}.;
Recessive Scores
- pRec
- 0.370
Intolerance Scores
- LoFtool
- 0.496
- RVIS EVS
- 0.28
- RVIS percentile EVS
- 70.87
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |