PAEP
protein-codingprogestagen associated endometrial protein, the group of Lipocalins
Gene summary
This gene is a member of the kernel lipocalin superfamily whose members share relatively low sequence similarity but have highly conserved exon/intron structure and three-dimensional protein folding. Most lipocalins are clustered on the long arm of chromosome 9. The encoded glycoprotein has been previously referred to as pregnancy-associated endometrial alpha-2-globulin, placental protein 14, and glycodelin, but has been officially named progestagen-associated endometrial protein. Three distinct forms, with identical protein backbones but different glycosylation profiles, are found in amniotic fluid, follicular fluid and seminal plasma of the reproductive system. These glycoproteins have distinct and essential roles in regulating a uterine environment suitable for pregnancy and in the timing and occurrence of the appropriate sequence of events in the fertilization process. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.2 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 PAEP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002571.4. 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 | 3 | 4 | |||
| missense | 27 | 5 | 32 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 2 | 3 | |||
| Total | 1 | 0 | 29 | 6 | 3 | 39 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002562.2 | 6 | MANE Select | |
| Ensembl | ENSP00000417898.1 | 6 | MANE Select | |
| RefSeq | NP_001018058.1 | 6 | Standard | |
| RefSeq | NP_001018059.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- apoptotic process
- multicellular organism development
- positive regulation of granulocyte macrophage colony-stimulating factor production
- negative regulation of sperm capacitation
- regulation of binding of sperm to zona pellucida
Molecular Function
- protein binding
- small molecule binding
Cellular Component
- extracellular region
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000479141
- Coding exons
- 6
- Length
- 5200
- Individuals with no LoFs
- 125728
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125744
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.518 | 85 | 99.5 | 0.854 | 0.00000508 | 1166 |
| Missense (PolyPhen) | 28 | 29.11 | 0.96187 | 376 | ||
| Synonymous | -1.42 | 57 | 44.9 | 1.27 | 0.00000290 | 335 |
| Loss of Function | -0.269 | 11 | 10.1 | 1.09 | 4.28e-7 | 119 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Glycoprotein that regulates critical steps during fertilization and also has immunomonomodulatory effects. Four glycoforms, namely glycodelin-S, -A, -F and -C have been identified in reproductive tissues that differ in glycosylation and biological activity. Glycodelin-A has contraceptive and immunosuppressive activities (PubMed:9918684, PubMed:7531163). Glycodelin-C stimulates binding of spermatozoa to the zona pellucida (PubMed:17192260). Glycodelin-F inhibits spermatozoa- zona pellucida binding and significantly suppresses progesterone- induced acrosome reaction of spermatozoa (PubMed:12672671). Glycodelin-S in seminal plasma maintains the uncapacitated state of human spermatozoa (PubMed:15883155). {ECO:0000269|PubMed:12672671, ECO:0000269|PubMed:15883155, ECO:0000269|PubMed:17192260, ECO:0000269|PubMed:7531163, ECO:0000269|PubMed:9918684}.;
Recessive Scores
- pRec
- 0.204
Intolerance Scores
- LoFtool
- 0.782
- RVIS EVS
- 0.35
- RVIS percentile EVS
- 74.18
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.702
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |