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26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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FAAH
fatty acid amide hydrolase
Chromosome 1 · 1p33
NCBI Gene: 2166Ensembl: ENSG00000117480.17HGNC: HGNC:3553UniProt: O00519
184PubMed Papers
20Diseases
3Drugs
1Pathogenic Variants
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingfatty acid amide hydrolase activityfatty acid catabolic processorganelle membranemigraine disorderPainHeadacheNasal congestion
✦AI Summary

FAAH (fatty acid amide hydrolase) is a membrane-bound amidase that catalyzes the hydrolysis of endogenous amidated lipids, serving as the primary catabolic enzyme for endocannabinoids and related signaling molecules 1. The enzyme hydrolyzes anandamide (N-arachidonoylethanolamine) to arachidonic acid and ethanolamine, with preferential activity toward polyunsaturated substrates 1. FAAH also metabolizes oleamide (a sleep-inducing lipid) and 2-arachidonoylglycerol (2-AG), another endocannabinoid 1. The enzyme belongs to the amidase signature family and contains a catalytic serine residue 1. Beyond canonical substrates, bacterial FAAH variants regulate bioactive molecules including N-acyl amino acids and quorum-sensing molecules, affecting intestinal immune function 2. FAAH's role in endocannabinoid regulation has significant clinical implications. A common human polymorphism (C385A; rs324420) that reduces FAAH expression enhances fronto-amygdala connectivity and improves fear extinction learning while decreasing anxiety 3. Conversely, this variant associates with lower subjective well-being and increased alcohol dependence risk 4. FAAH inhibition shows therapeutic potential for migraine through CB1 receptor-mediated anti-nociceptive effects in meningeal tissues 5. Additionally, loss-of-function FAAH mutations interact with DGAT2 variants in obesity development 6, while the rs324420 polymorphism associates with generalized epilepsy susceptibility 7. These findings suggest FAAH modulation as a therapeutic target, though previous adverse events in clinical trials warrant careful development 8.

Sources cited
1
FAAH hydrolyzes anandamide, oleamide, and 2-AG; belongs to amidase signature family with catalytic serine residue
PMID: 12432941
2
Bacterial FAAH regulates bioactive molecules including N-acyl amino acids and affects intestinal immune function pathways
PMID: 39446943
3
C385A polymorphism reduces FAAH expression, enhances fronto-amygdala function, improves fear extinction, and decreases anxiety
PMID: 25731744
4
rs324420 A-allele (reduced FAAH activity) associates with lower well-being and increased alcohol dependence risk
PMID: 37761966
5
FAAH inhibition reduces meningeal nociception through CB1 receptor-mediated mechanisms, with therapeutic potential for migraine
PMID: 37038131
6
Loss-of-function FAAH mutations interact with DGAT2 variants to affect obesity susceptibility
PMID: 28243972
7
rs324420 polymorphism associates with generalized epilepsy susceptibility
PMID: 37018974
8
FAAH inhibitors have experienced serious adverse events in clinical trials, warranting careful drug development
PMID: 27191771
Disease Associationsⓘ20
migraine disorderOpen Targets
0.61Moderate
PainOpen Targets
0.61Moderate
HeadacheOpen Targets
0.61Moderate
Nasal congestionOpen Targets
0.60Moderate
FeverOpen Targets
0.60Moderate
common coldOpen Targets
0.60Moderate
CoughOpen Targets
0.60Moderate
pharyngitisOpen Targets
0.60Moderate
seasonal allergic rhinitisOpen Targets
0.59Moderate
toothacheOpen Targets
0.59Moderate
Back painOpen Targets
0.58Moderate
arthritisOpen Targets
0.58Moderate
osteoarthritisOpen Targets
0.57Moderate
muscle crampOpen Targets
0.56Moderate
influenzaOpen Targets
0.56Moderate
sinusitisOpen Targets
0.53Moderate
DysmenorrheaOpen Targets
0.53Moderate
drug dependenceOpen Targets
0.47Moderate
Low back painOpen Targets
0.39Weak
Patent ductus arteriosusOpen Targets
0.38Weak
Pathogenic Variants1
NM_001441.3(FAAH):c.549del (p.His184fs)Likely pathogenic
Polysubstance abuse, susceptibility to
★☆☆☆2024→ Residue 184
View on ClinVar ↗
Drug Targets3
ACETAMINOPHENApproved
Cyclooxygenase inhibitor
Pain
JNJ-42165279Phase II
Anandamide amidohydrolase inhibitor
anxiety disorder
REDAFAMDASTATPhase II
Anandamide amidohydrolase inhibitor
liver disease
Related Genes
MGLLProtein interaction97%CNR1Protein interaction97%EPRS1Protein interaction95%NAPEPLDProtein interaction93%DARS2Protein interaction90%FABP5Protein interaction89%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
79%
Brain
24%
Lung
17%
Ovary
12%
Heart
8%
Gene Interaction Network
Click a node to explore
FAAHMGLLCNR1EPRS1NAPEPLDDARS2FABP5
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt O00519
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.15LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.93 [0.76–1.15]
RankingsWhere FAAH stands among ~20K protein-coding genes
  • #2,345of 20,598
    Most Researched184 · top quartile
  • #878of 1,025
    FDA-Approved Drug Targets1
  • #4,743of 5,498
    Most Pathogenic Variants1
  • #11,925of 17,882
    Most Constrained (LOEUF)1.15
Genes detectedFAAH
Sources retrieved26 papers
Response time—
📄 Sources
26â–¼
1
A human gut
PMID: 39446943
Science · 2024
1.00
2
Endocannabinoid hydrolases.
PMID: 12432941
Prostaglandins Other Lipid Mediat · 2002
0.90
3
Impact of FAAH gene, hyperactivation in emotion processing brain regions and Lavender oil preparation Silexan in anxiety.
PMID: 30680488
Eur Arch Psychiatry Clin Neurosci · 2019
0.80
4
New Insights of Uterine Leiomyoma Pathogenesis: Endocannabinoid System.
PMID: 30842391
Med Sci Monit Basic Res · 2019
0.76
5
Potent dual MAGL/FAAH inhibitor AKU-005 engages endocannabinoids to diminish meningeal nociception implicated in migraine pain.
PMID: 37038131
J Headache Pain · 2023
0.70