PAFAH2
protein-codingplatelet activating factor acetylhydrolase 2
Gene summary
This gene encodes platelet-activating factor acetylhydrolase isoform 2, a single-subunit intracellular enzyme that catalyzes the removal of the acetyl group at the SN-2 position of platelet-activating factor (identified as 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine). However, this lipase exhibits a broader substrate specificity than simply platelet activating factor. Two other isoforms of intracellular platelet-activating factor acetylhydrolase exist, and both are multi-subunit enzymes. Additionally, there is a single-subunit serum isoform of this enzyme. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~38.4 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 PAFAH2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000437.4. 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 | 79 | 1 | 80 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 83 | 1 | 0 | 84 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000428.2 | 10 | MANE Select | |
| Ensembl | ENSP00000363400.3 | 10 | MANE Select | |
| Ensembl | ENSP00000363402.1 | 10 | Standard | |
| Ensembl | ENSP00000363402.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ether lipid metabolism - Homo sapiens (human)
- Hemostasis
- Platelet homeostasis
Biological Process
- lipid metabolic process
- blood coagulation
- lipid catabolic process
- negative regulation of apoptotic process
Molecular Function
- 1-alkyl-2-acetylglycerophosphocholine esterase activity
- phospholipid binding
Cellular Component
- endoplasmic reticulum membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000374282
- Coding exons
- 10
- Length
- 38391
- Individuals with no LoFs
- 125473
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 274
- Defined
- 125748
- p
- 0.00109
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.120 | 239 | 234 | 1.02 | 0.0000136 | 2559 |
| Missense (PolyPhen) | 90 | 85.112 | 1.0574 | 990 | ||
| Synonymous | -0.255 | 88 | 85.0 | 1.04 | 0.00000457 | 765 |
| Loss of Function | 1.16 | 16 | 21.8 | 0.733 | 0.00000113 | 244 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0012 | 0.0012 | notable |
| Latino/Admixed American | 0.00078 | 0.00078 | rare |
| Ashkenazi Jewish | 0.0032 | 0.0032 | notable |
| East Asian | 0.0035 | 0.0034 | notable |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00044 | 0.00044 | rare |
| South Asian | 0.0026 | 0.0026 | notable |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Has a marked selectivity for phospholipids with short acyl chains at the sn-2 position. May share a common physiologic function with the plasma-type enzyme. {ECO:0000269|PubMed:9494101}.;
Intolerance Scores
- LoFtool
- 0.935
- RVIS EVS
- -0.4
- RVIS percentile EVS
- 26.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |