FAAH2
protein-codingfatty acid amide hydrolase 2
Gene summary
This gene encodes a fatty acid amide hydrolase that shares a conserved protein motif with the amidase signature family of enzymes. The encoded enzyme is able to catalyze the hydrolysis of a broad range of bioactive lipids, including those from the three main classes of fatty acid amides; N-acylethanolamines, fatty acid primary amides and N-acyl amino acids. This enzyme has a preference for monounsaturated acyl chains as a substrate. Alternate splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2017]
- AMDD
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~202.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0100148
Submitter: ClinGen
*FAAH2* was first reported in relation to X-linked intellectual disability in 2010 (Whibley et al., PMID: 20655035). Since this first report, additional studies have reported variants in *FAAH2* in individuals with neurological disorders. However, the phenotypic spectrum in reported individuals is wide, ranging from severe neonatal presentation with early death to late onset neuromuscular and psychiatric presentations. Four variants (loss of function and deletions) that have been reported in four probands in three publications (PMIDs: 20655035, 34645488, 36964972 and SCV: 004804629.1) are included in this curation. *FAAH2* is not constrained for loss-of-function variants (pLI = 0, gnomAD v2.1.1) or missense variants (Z = –3.63). Therefore, all cases were scored 0. This gene-disease relationship is not supported by experimental evidence. In summary, the evidence supporting the relationship between *FAAH2* and X-linked complex neurodevelopmental disorder has been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role *FAAH2* plays in this disease. This gene-disease relationship was originally evaluated in September 2024. In June of 2025, it was recurated; no new evidence was added, but the gruop reconsidered the original scoring due to constraint information. As a result, the classification changed from limited to disputed. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on June 12, 2025 (SOP Version 11).
Inheritance Pattern: XL
Disease ID:MONDO:0005258
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FAAH2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_174912.4. 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 | 14 | 5 | 19 | |||
| missense | 142 | 8 | 1 | 151 | ||
| nonsense | 1 | 12 | 1 | 14 | ||
| start loss | 0 | |||||
| frameshift | 1 | 2 | 3 | |||
| splice donor/acceptor (+/-2bp) | 22 | 22 | ||||
| Total | 2 | 0 | 192 | 14 | 1 | 209 |
Highest pathogenic variant AF is 0.00000331088
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_777572.2 | 11 | MANE Select | |
| Ensembl | ENSP00000364035.4 | 11 | MANE Select | |
| RefSeq | NP_001340769.1 | 10 | Standard | |
| RefSeq | NP_001340770.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of lipids
- anandamide degradation
- Arachidonic acid metabolism
- Metabolism
- Fatty acid metabolism
Biological Process
- arachidonic acid metabolic process
Molecular Function
- fatty acid amide hydrolase activity
- oleamide hydrolase activity
- anandamide amidohydrolase activity
Cellular Component
- lipid droplet
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000374900
- Coding exons
- 11
- Length
- 202491
- Individuals with no LoFs
- 125393
- Homozygous LoFs
- 118
- Heterozygous LoFs
- 232
- Defined
- 125743
- p
- 0.00139
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -3.63 | 325 | 186 | 1.75 | 0.0000129 | 3428 |
| Missense (PolyPhen) | 93 | 60.035 | 1.5491 | 1027 | ||
| Synonymous | -4.66 | 115 | 66.6 | 1.73 | 0.00000445 | 1054 |
| Loss of Function | -2.20 | 26 | 16.4 | 1.59 | 0.00000117 | 319 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0011 | 0.00086 | notable |
| Latino/Admixed American | 0.0027 | 0.0021 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0019 | 0.0014 | notable |
| Finnish | 0.000064 | 0.000046 | rare |
| European (Non-Finnish) | 0.0027 | 0.0019 | notable |
| South Asian | 0.00075 | 0.00042 | rare |
| Other | 0.0014 | 0.00098 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Degrades bioactive fatty acid amides like oleamide, the endogenous cannabinoid, anandamide and myristic amide to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Hydrolyzes monounsaturated substrate anandamide preferentially as compared to polyunsaturated substrates. {ECO:0000269|PubMed:17015445}.;
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- LoFtool
- 0.922
- RVIS EVS
- -0.29
- RVIS percentile EVS
- 33.42
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.180
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |