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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
FAAH2
fatty acid amide hydrolase 2
Chromosome X Β· Xp11.21
NCBI Gene: 158584Ensembl: ENSG00000165591.8HGNC: HGNC:26440UniProt: Q6GMR7
11PubMed Papers
20Diseases
0Drugs
2Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
fatty acid amide hydrolase activityarachidonate metabolic processlipid dropletmembranehypogonadismtype 2 diabetes mellitushypertensionsystemic lupus erythematosus
✦AI Summary

FAAH2 is an X-linked enzyme that catalyzes hydrolysis of endogenous fatty amides, including the endocannabinoid anandamide and sleep-inducing oleamide, to their corresponding fatty acids 12. The enzyme preferentially hydrolyzes monounsaturated substrates and contains a critical amidase signature domain required for catalytic activity 3. FAAH2 is expressed in multiple tissues, including seminal vesicles where it localizes to epithelial cells, skeletal muscle, and adipose tissue, regulating endocannabinoid signaling and stress responses 456. Loss-of-function mutations in FAAH2 are associated with neuropsychiatric and metabolic phenotypes. A hemizygous variant (p.Gln330Lys) presented with anxiety disorder, autistic-like traits, borderline intellectual functioning, obesity, and hepatic steatosis 3, while a maternally-inherited missense mutation (p.Ala458Ser) caused autism with subsequent anxiety, ataxia, and learning disabilities accompanied by lipid metabolism abnormalities 7. Clinical exome sequencing identified FAAH2 as a candidate disease gene 8, and molecular autopsy studies support its role in lethal conditions 9. FAAH2 dysregulation has been implicated in late-onset preeclampsia pathophysiology 10. These findings suggest FAAH2 variants contribute to X-linked neurodevelopmental disorders with metabolic involvement through altered endocannabinoid signaling.

Sources cited
1
FAAH2 catalyzes hydrolysis of oleamide and anandamide
PMID: 17015445
2
FAAH2 catalyzes hydrolysis of oleamide and anandamide
PMID: 19926788
3
Hemizygous FAAH2 c.988C>A variant causes anxiety, autistic traits, borderline intellectual functioning, obesity, and hepatic steatosis; mutation affects amidase signature domain
PMID: 40744325
4
FAAH2 is expressed in human seminal vesicles, localizing to epithelial cells
PMID: 28786134
5
FAAH2a disruption attenuates stress-associated behavior in zebrafish; FAAH2 mediates stress responses
PMID: 29304078
6
FAAH2 is expressed in skeletal muscle; altered expression correlates with metabolic traits
PMID: 30070030
7
FAAH2 p.Ala458Ser mutation causes autism, anxiety, ataxia, learning disabilities, and altered lipid metabolism; partial enzyme inactivation confirmed
PMID: 25885783
8
FAAH2 identified as candidate disease gene in clinical exome sequencing cohort
PMID: 36964972
9
FAAH2 supported as disease gene in molecular autopsy study of lethal phenotypes
PMID: 34645488
10
FAAH2 dysregulated in late-onset preeclampsia proteomics analysis
PMID: 41031401
Disease Associationsβ“˜20
hypogonadismOpen Targets
0.33Weak
type 2 diabetes mellitusOpen Targets
0.24Weak
hypertensionOpen Targets
0.22Weak
systemic lupus erythematosusOpen Targets
0.04Suggestive
depressive disorderOpen Targets
0.02Suggestive
heart diseaseOpen Targets
0.02Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.01Suggestive
psychiatric disorderOpen Targets
0.01Suggestive
autism spectrum disorderOpen Targets
0.01Suggestive
Intellectual disabilityOpen Targets
0.01Suggestive
lung adenocarcinomaOpen Targets
0.01Suggestive
metabolic diseaseOpen Targets
0.01Suggestive
preeclampsiaOpen Targets
0.01Suggestive
obesityOpen Targets
0.00Suggestive
neurotic disorderOpen Targets
0.00Suggestive
COVID-19Open Targets
0.00Suggestive
autismOpen Targets
0.00Suggestive
neoplasmOpen Targets
0.00Suggestive
Neurodevelopmental disorderOpen Targets
0.00Suggestive
Turner syndromeOpen Targets
0.00Suggestive
Pathogenic Variants2
NM_174912.4(FAAH2):c.267_275+2delPathogenic
not provided
β˜…β˜†β˜†β˜†2017
NM_174912.4(FAAH2):c.1175G>A (p.Trp392Ter)Pathogenic
Meckel-like syndrome
β˜†β˜†β˜†β˜†2021β†’ Residue 392
View on ClinVar β†—
Related Genes
CYP4Z1Shared pathway100%EPRS1Protein interaction99%DARS2Protein interaction99%EARS2Protein interaction96%ALDH18A1Protein interaction87%GMPSProtein interaction86%
Tissue Expression6 tissues
Liver
100%
Brain
16%
Lung
12%
Bone Marrow
10%
Ovary
3%
Heart
1%
Gene Interaction Network
Click a node to explore
FAAH2CYP4Z1EPRS1DARS2EARS2ALDH18A1GMPS
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q6GMR7
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
2.02LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.63 [1.32–2.02]
RankingsWhere FAAH2 stands among ~20K protein-coding genes
  • #16,746of 20,598
    Most Researched11
  • #4,585of 5,498
    Most Pathogenic Variants2
  • #17,841of 17,882
    Most Constrained (LOEUF)2.02
Genes detectedFAAH2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Clinical exome sequencing findings in 1589 patients.
PMID: 36964972
Am J Med Genet A Β· 2023
1.00
2
Lethal variants in humans: lessons learned from a large molecular autopsy cohort.
PMID: 34645488
Genome Med Β· 2021
0.90
3
Large-Scale Proteomics Reveals New Candidate Biomarkers for Late-Onset Preeclampsia.
PMID: 41031401
Hypertension Β· 2026
0.80
4
Investigating the role of a novel hemizygous FAAH2 variant in neurological and metabolic disorders.
PMID: 40744325
Gene Β· 2025
0.70
5
Expression and distribution of key proteins of the endocannabinoid system in the human seminal vesicles.
PMID: 28786134
Andrologia Β· 2018
0.60