Biology:FAAH2
Fatty acid amide hydrolase 2 or FAAH2 is a member of the serine hydrolase family of enzymes.[1]
Fatty acid amide hydrolase 2 degrades many types of fatty acid amides, including the sleep-inducing oleamide and endocannabinoids such as anandamide.[2] It has a tissue distribution quite distinct from the paralogous FAAH (or "FAAH1"). Compared to FAAH, it is less active on N-acyl ethanolamines (e.g. anandamide) and N-acyl taurines.[1]
OrthoDB indicates that FAAH2 (as a gene distinct from FAAH) has orthologs all across Metazoa, with the notable exclusion of rodents.[3] This complicates the translation of FAAH-related results from rodent models to human biology.[1]
Clinical significance
Defects in this enzyme have been associated with neurologic and psychiatric disorders. Specifically, a Canadian male with autism, anxiety, severe dysarthria, and a number of other issues have a Ala458Ser mutation inherited from his healthy carrier mother. In cell models this mutation is associated with a decreased function of this gene. This patient has a very abnormal blood lipid composition consistent with a loss of function.[4]
ClinVar reports a missense mutation that produces an early stop codon (Trp392Ter) is associated with Meckel-like syndrome.[5]
UniProt Variant Viewer lists a large number of other variants found in surveyed human genomes. Several are predicted to have consequences by PolyPhen and/or SIFT.[2]
References
- ↑ 1.0 1.1 1.2 "A second fatty acid amide hydrolase with variable distribution among placental mammals". The Journal of Biological Chemistry 281 (48): 36569–78. December 2006. doi:10.1074/jbc.M606646200. PMID 17015445.
- ↑ 2.0 2.1 "UniProt Q6GMR7" (in en). https://www.uniprot.org/uniprotkb/Q6GMR7/.
- ↑ "9606_0:0045e6". https://www.orthodb.org/?query=9606_0%3A0045e6.
- ↑ "Defects in fatty acid amide hydrolase 2 in a male with neurologic and psychiatric symptoms". Orphanet Journal of Rare Diseases 10. March 2015. doi:10.1186/s13023-015-0248-3. PMID 25885783.
- ↑ "NM_174912.4(FAAH2):c.1175G>A (p.Trp392Ter) AND Meckel-like syndrome - ClinVar - NCBI". https://www.ncbi.nlm.nih.gov/clinvar/RCV001844344/.
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