APEH
protein-codingacylaminoacyl-peptide hydrolase
Gene summary
This gene encodes the enzyme acylpeptide hydrolase, which catalyzes the hydrolysis of the terminal acetylated amino acid preferentially from small acetylated peptides. The acetyl amino acid formed by this hydrolase is further processed to acetate and a free amino acid by an aminoacylase. This gene is located within the same region of chromosome 3 (3p21) as the aminoacylase gene, and deletions at this locus are also associated with a decrease in aminoacylase activity. The acylpeptide hydrolase is a homotetrameric protein of 300 kDa with each subunit consisting of 732 amino acid residues. It can play an important role in destroying oxidatively damaged proteins in living cells. Deletions of this gene locus are found in various types of carcinomas, including small cell lung carcinoma and renal cell carcinoma. [provided by RefSeq, Jul 2008]
- D3F15S2
- DNF15S2
- D3S48E
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.0 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 APEH variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001640.4. 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 | 4 | 2 | 6 | |||
| missense | 76 | 76 | ||||
| nonsense | 4 | 4 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 91 | 2 | 0 | 93 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001631.3 | 22 | MANE Select | |
| Ensembl | ENSP00000296456.5 | 22 | MANE Select | |
| Ensembl | ENSP00000415862.1 | 22 | Standard | |
| Ensembl | ENSP00000402365.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neutrophil degranulation
- Eukaryotic Translation Termination
- Translation
- Metabolism of proteins
- Innate Immune System
Biological Process
- translational termination
- proteolysis
- neutrophil degranulation
- amyloid-beta metabolic process
Molecular Function
- RNA binding
- serine-type endopeptidase activity
- protein binding
- omega peptidase activity
- identical protein binding
Cellular Component
- extracellular region
- cytosol
- nuclear membrane
- extracellular exosome
- ficolin-1-rich granule lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000296456
- Coding exons
- 22
- Length
- 9962
- Individuals with no LoFs
- 125667
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 81
- Defined
- 125748
- p
- 0.000322
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.21 | 356 | 426 | 0.835 | 0.0000246 | 4747 |
| Missense (PolyPhen) | 83 | 120.48 | 0.68888 | 1293 | ||
| Synonymous | 1.13 | 147 | 166 | 0.888 | 0.00000930 | 1450 |
| Loss of Function | 2.48 | 27 | 44.9 | 0.601 | 0.00000200 | 508 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000080 | 0.000062 | rare |
| Latino/Admixed American | 0.00032 | 0.00032 | rare |
| Ashkenazi Jewish | 0.0013 | 0.0013 | notable |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.00033 | 0.00032 | rare |
| European (Non-Finnish) | 0.00026 | 0.00025 | rare |
| South Asian | 0.00036 | 0.00036 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: This enzyme catalyzes the hydrolysis of the N-terminal peptide bond of an N-acetylated peptide to generate an N- acetylated amino acid and a peptide with a free N-terminus. It preferentially cleaves off Ac-Ala, Ac-Met and Ac-Ser. {ECO:0000269|PubMed:1861871, ECO:0000269|PubMed:2006156}.;
Recessive Scores
- pRec
- 0.304
Intolerance Scores
- LoFtool
- 0.724
- RVIS EVS
- -0.78
- RVIS percentile EVS
- 12.97
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.797
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |