PAFAH1B3
protein-codingplatelet activating factor acetylhydrolase 1b catalytic subunit 3
Gene summary
This gene encodes an acetylhydrolase that catalyzes the removal of an acetyl group from the glycerol backbone of platelet-activating factor. The encoded enzyme is a subunit of the platelet-activating factor acetylhydrolase isoform 1B complex, which consists of the catalytic beta and gamma subunits and the regulatory alpha subunit. This complex functions in brain development. A translocation between this gene on chromosome 19 and the CDC-like kinase 2 gene on chromosome 1 has been observed, and was associated with cognitive disability, ataxia, and atrophy of the brain. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.5 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 PAFAH1B3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002573.4. 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 | 0 | |||||
| missense | 35 | 1 | 36 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 38 | 1 | 0 | 39 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002564.1 | 5 | MANE Select | |
| Ensembl | ENSP00000262890.2 | 5 | MANE Select | |
| RefSeq | NP_001139411.1 | 5 | Standard | |
| RefSeq | NP_001139412.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ether lipid metabolism - Homo sapiens (human)
- Vesicle-mediated transport
- Membrane Trafficking
- COPI-independent Golgi-to-ER retrograde traffic
- Golgi-to-ER retrograde transport
Biological Process
- lipid metabolic process
- spermatogenesis
- nervous system development
- brain development
- lipid catabolic process
Molecular Function
- 1-alkyl-2-acetylglycerophosphocholine esterase activity
- phospholipase A2 activity
- protein binding
- identical protein binding
- protein heterodimerization activity
Cellular Component
- cytoplasm
- cytosol
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000538771
- Coding exons
- 5
- Length
- 6514
- Individuals with no LoFs
- 125734
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 14
- Defined
- 125748
- p
- 0.0000557
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.06 | 112 | 148 | 0.755 | 0.00000889 | 1473 |
| Missense (PolyPhen) | 28 | 43.116 | 0.64941 | 470 | ||
| Synonymous | 0.166 | 59 | 60.6 | 0.973 | 0.00000339 | 494 |
| Loss of Function | 1.63 | 6 | 12.1 | 0.494 | 7.76e-7 | 100 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000091 | 0.000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inactivates paf by removing the acetyl group at the sn-2 position. This is a catalytic subunit. Plays an important role during the development of brain.;
Recessive Scores
- pRec
- 0.145
Intolerance Scores
- LoFtool
- 0.531
- RVIS EVS
- -0.3
- RVIS percentile EVS
- 32.62
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |