PEBP1
protein-codingphosphatidylethanolamine binding protein 1
Gene summary
This gene encodes a member of the phosphatidylethanolamine-binding family of proteins and has been shown to modulate multiple signaling pathways, including the MAP kinase (MAPK), NF-kappa B, and glycogen synthase kinase-3 (GSK-3) signaling pathways. The encoded protein can be further processed to form a smaller cleavage product, hippocampal cholinergic neurostimulating peptide (HCNP), which may be involved in neural development. This gene has been implicated in numerous human cancers and may act as a metastasis suppressor gene. Multiple pseudogenes of this gene have been identified in the genome. [provided by RefSeq, Jul 2015]
- PBP
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.5 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 PEBP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002567.4. 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 | 8 | 1 | 2 | 11 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 10 | 1 | 2 | 13 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002558.1 | 4 | MANE Select | |
| Ensembl | ENSP00000261313.2 | 4 | MANE Select | |
| Ensembl | ENSP00000544158.1 | 4 | Standard | |
| Ensembl | ENSP00000544158.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- EGF-Ncore
- EGF-EGFR Signaling Pathway
- MAP2K and MAPK activation
- Disease
- Signal Transduction
Biological Process
- MAPK cascade
- regulation of neurotransmitter levels
- regulation of the force of heart contraction
- response to oxidative stress
- aging
Molecular Function
- RNA binding
- serine-type endopeptidase inhibitor activity
- signaling receptor binding
- protein binding
- ATP binding
Cellular Component
- extracellular space
- nucleus
- mitochondrion
- mitochondrial outer membrane
- Golgi apparatus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261313
- Coding exons
- 4
- Length
- 9727
- Individuals with no LoFs
- 125713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 35
- Defined
- 125748
- p
- 0.000139
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.942 | 83 | 111 | 0.748 | 0.00000638 | 1202 |
| Missense (PolyPhen) | 20 | 26.198 | 0.76341 | 278 | ||
| Synonymous | -0.127 | 53 | 51.8 | 1.02 | 0.00000348 | 371 |
| Loss of Function | 1.80 | 3 | 8.75 | 0.343 | 4.57e-7 | 94 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00027 | 0.00026 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds ATP, opioids and phosphatidylethanolamine. Has lower affinity for phosphatidylinositol and phosphatidylcholine. Serine protease inhibitor which inhibits thrombin, neuropsin and chymotrypsin but not trypsin, tissue type plasminogen activator and elastase (By similarity). Inhibits the kinase activity of RAF1 by inhibiting its activation and by dissociating the RAF1/MEK complex and acting as a competitive inhibitor of MEK phosphorylation. {ECO:0000250, ECO:0000269|PubMed:18294816}.;
Recessive Scores
- pRec
- 0.284
Intolerance Scores
- LoFtool
- 0.554
- RVIS EVS
- 0.35
- RVIS percentile EVS
- 73.97
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.988
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |