Fatty acid amide hydrolase-2 | <i>N</i>-Acylethanolamine turnover | IUPHAR/BPS Guide to PHARMACOLOGY

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Fatty acid amide hydrolase-2

Target not currently curated in GtoImmuPdb

Target id: 1401

Nomenclature: Fatty acid amide hydrolase-2

Abbreviated Name: FAAH2

Family: N-Acylethanolamine turnover

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 532 Xp11.21 FAAH2 fatty acid amide hydrolase 2 5
Previous and Unofficial Names
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
Enzyme Reaction
EC Number: anandamide + H2O <=> arachidonic acid + ethanolamine
oleamide + H2O <=> oleic acid + NH3
Description Reaction Reference
The enzyme is responsible for the catabolism of neuromodulatory fatty acid amides, including anandamide and oleamide anandamide + H2O <=> arachidonic acid + ethanolamine
oleamide + H2O <=> oleic acid + NH3
Rank order of affinity (Human)
oleamide > N-oleoylethanolamide > anandamide > N-palmitoylethanolamine  [5]

Download all structure-activity data for this target as a CSV file

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
LY2077855 Hs Inhibition 8.5 pIC50 1
pIC50 8.5 (IC50 3x10-9 M) [1]
OL135 Hs Inhibition 7.9 – 8.4 pIC50 1,5
pIC50 7.9 – 8.4 (IC50 1.26x10-8 – 4x10-9 M) [1,5]
URB597 Hs Inhibition 7.5 – 8.3 pIC50 1,5
pIC50 7.5 – 8.3 (IC50 3.16x10-8 – 5.01x10-9 M) [1,5]
ASP8477 Hs Inhibition 7.2 pIC50 4
pIC50 7.2 (IC50 5.73x10-8 M) [4]
JNJ1661010 Hs Inhibition 5.2 pIC50 1
pIC50 5.2 (IC50 5.7x10-6 M) [1]
Description: 20 min preincubation
Clinically-Relevant Mutations and Pathophysiology
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Type Species Amino acid change Nucleotide change Description Reference
Missense Human Ala458Ser 1372 G>T This mutation causes partial inactivation of FAAH2 in vitro. 3
Clinically-Relevant Mutations and Pathophysiology Comments
The missense mutation Ala458Ser was identified in a male with autistic features identified in early development, accompanied by later developing features including anxiety, pseudoseizures, ataxia, supranuclear gaze palsy, and isolated learning disabilities [3]. The authors propose that compromised FAAH2 activity and altered endocannabinoid signaling underlies the patent's phenotype.
General Comments
FAAH and FAAH2 show distinct but overlapping tissue expression patterns [5]. The absence of FAAH2 in mice and rats should be considered when extrapolating experimental findings in the endocannabinoid pathway across species.
Genome wide association studies (GWAS) have identified FAAH2 as a possible candidate gene for X-linked intellectual disability [6] and autism spectrum disorders [2].


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1. Karbarz MJ, Luo L, Chang L, Tham CS, Palmer JA, Wilson SJ, Wennerholm ML, Brown SM, Scott BP, Apodaca RL et al.. (2009) Biochemical and biological properties of 4-(3-phenyl-[1,2,4] thiadiazol-5-yl)-piperazine-1-carboxylic acid phenylamide, a mechanism-based inhibitor of fatty acid amide hydrolase. Anesth. Analg., 108 (1): 316-29. [PMID:19095868]

2. Lim ET, Raychaudhuri S, Sanders SJ, Stevens C, Sabo A, MacArthur DG, Neale BM, Kirby A, Ruderfer DM, Fromer M et al.. (2013) Rare complete knockouts in humans: population distribution and significant role in autism spectrum disorders. Neuron, 77 (2): 235-42. [PMID:23352160]

3. Sirrs S, van Karnebeek CD, Peng X, Shyr C, Tarailo-Graovac M, Mandal R, Testa D, Dubin D, Carbonetti G, Glynn SE et al.. (2015) Defects in fatty acid amide hydrolase 2 in a male with neurologic and psychiatric symptoms. Orphanet J Rare Dis, 10: 38. [PMID:25885783]

4. Watabiki T, Tsuji N, Kiso T, Ozawa T, Narazaki F, Kakimoto S. (2017) In vitro and in vivo pharmacological characterization of ASP8477: A novel highly selective fatty acid amide hydrolase inhibitor. Eur. J. Pharmacol., 815: 42-48. [PMID:29017758]

5. Wei BQ, Mikkelsen TS, McKinney MK, Lander ES, Cravatt BF. (2006) A second fatty acid amide hydrolase with variable distribution among placental mammals. J. Biol. Chem., 281 (48): 36569-78. [PMID:17015445]

6. Whibley AC, Plagnol V, Tarpey PS, Abidi F, Fullston T, Choma MK, Boucher CA, Shepherd L, Willatt L, Parkin G et al.. (2010) Fine-scale survey of X chromosome copy number variants and indels underlying intellectual disability. Am. J. Hum. Genet., 87 (2): 173-88. [PMID:20655035]


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