PSPN
protein-codingpersephin, the group of GDNF family ligands
Gene summary
This gene encodes a secreted ligand of the GDNF (glial cell line-derived neurotrophic factor) subfamily and TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein signals through the RET receptor tyrosine kinase and a GPI-linked coreceptor, and promotes survival of neuronal populations. This protein may play a role in cell death, and nervous system development and function. Elevated expression of this gene has been observed in oral squamous cell carcinoma. [provided by RefSeq, Aug 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.9 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 PSPN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004158.5. 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 | 0 | |||||
| missense | 36 | 4 | 40 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 37 | 4 | 0 | 41 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004149.1 | 2 | MANE Select | |
| Ensembl | ENSP00000245810.1 | 2 | MANE Select | |
| Ensembl | ENSP00000469884.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Developmental Biology
- Signal Transduction
- RAF/MAP kinase cascade
- MAPK1/MAPK3 signaling
- MAPK family signaling cascades
Biological Process
- MAPK cascade
- nervous system development
- axon guidance
- central nervous system development
- regulation of signaling receptor activity
Molecular Function
- Ras guanyl-nucleotide exchange factor activity
- signaling receptor binding
- growth factor activity
Cellular Component
- extracellular region
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000245810
- Coding exons
- 2
- Length
- 3911
- Individuals with no LoFs
- 124543
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 124547
- p
- 0.0000161
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.252 | 80 | 86.6 | 0.924 | 0.00000618 | 922 |
| Missense (PolyPhen) | 24 | 31.448 | 0.76315 | 397 | ||
| Synonymous | -0.757 | 46 | 39.9 | 1.15 | 0.00000269 | 361 |
| Loss of Function | 0.0797 | 6 | 6.21 | 0.965 | 4.08e-7 | 48 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000027 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Exhibits neurotrophic activity on mesencephalic dopaminergic and motor neurons.;
Recessive Scores
- pRec
- 0.148
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.407
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |