ABHD4
protein-codingabhydrolase domain containing 4, N-acyl phospholipase B, the group of Abhydrolase domain containing
Gene summary
Predicted to enable lysophosphatidic acid acyltransferase activity and phosphatidylcholine lysophospholipase A1 activity. Predicted to be involved in N-acylphosphatidylethanolamine metabolic process; lipid homeostasis; and phosphatidic acid biosynthetic process. Predicted to act upstream of or within N-acylethanolamine metabolic process. Predicted to be located in endoplasmic reticulum membrane. Predicted to be active in lipid droplet. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.7 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 ABHD4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022060.3. 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 | 57 | 57 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 59 | 0 | 0 | 59 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_071343.2 | 7 | MANE Select | |
| Ensembl | ENSP00000414558.2 | 7 | MANE Select | |
| RefSeq | NP_001378938.1 | 6 | Standard | |
| Ensembl | ENSP00000216327.7 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of lipids
- Metabolism
- Glycerophospholipid biosynthesis
- Phospholipid metabolism
- Acyl chain remodelling of PE
Biological Process
- lipid catabolic process
- phosphatidylethanolamine acyl-chain remodeling
- lipid homeostasis
Molecular Function
- hydrolase activity
- carboxylic ester hydrolase activity
Cellular Component
- endoplasmic reticulum membrane
- lipid droplet
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000428304
- Coding exons
- 7
- Length
- 14120
- Individuals with no LoFs
- 125526
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 222
- Defined
- 125748
- p
- 0.000883
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.701 | 191 | 220 | 0.867 | 0.0000134 | 2242 |
| Missense (PolyPhen) | 58 | 63.743 | 0.90991 | 637 | ||
| Synonymous | -0.827 | 94 | 84.3 | 1.11 | 0.00000519 | 694 |
| Loss of Function | 1.30 | 15 | 21.5 | 0.697 | 0.00000148 | 178 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00050 | 0.00049 | rare |
| Latino/Admixed American | 0.00044 | 0.00043 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.0015 | 0.0015 | notable |
| European (Non-Finnish) | 0.0012 | 0.0012 | notable |
| South Asian | 0.00063 | 0.00062 | rare |
| Other | 0.0013 | 0.0013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Lysophospholipase selective for N-acyl phosphatidylethanolamine (NAPE). Contributes to the biosynthesis of N-acyl ethanolamines, including the endocannabinoid anandamide by hydrolyzing the sn-1 and sn-2 acyl chains from N-acyl phosphatidylethanolamine (NAPE) generating glycerophospho-N-acyl ethanolamine (GP-NAE), an intermediate for N-acyl ethanolamine biosynthesis. Hydrolyzes substrates bearing saturated, monounsaturated, polyunsaturated N-acyl chains. Shows no significant activity towards other lysophospholipids, including lysophosphatidylcholine, lysophosphatidylethanolamine and lysophosphatidylserine (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- RVIS EVS
- -0.98
- RVIS percentile EVS
- 8.75
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.804
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |