FAAH2
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Also known as RP11-479E16.1FLJ31204FAAH-2
Summary
FAAH2 (fatty acid amide hydrolase 2, HGNC:26440) is a protein-coding gene on chromosome Xp11.21, encoding Fatty-acid amide hydrolase 2 (Q6GMR7). Catalyzes the hydrolysis of endogenous amidated lipids like the sleep-inducing lipid oleamide ((9Z)-octadecenamide), the endocannabinoid anandamide (N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine), as well as other fatty amides, to their corresponding fatty acids, thereby regul….
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.
Source: NCBI Gene 158584 — RefSeq curated summary.
At a glance
- Gene–disease (curated): autism spectrum disorder (Limited, GenCC) — +1 more curated relationship
- GWAS associations: 4
- Clinical variants (ClinVar): 268 total — 2 pathogenic
- Druggable target: yes — 1 molecules with ChEMBL bioactivity
- MANE Select transcript:
NM_174912
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:26440 |
| Approved symbol | FAAH2 |
| Name | fatty acid amide hydrolase 2 |
| Location | Xp11.21 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | RP11-479E16.1, FLJ31204, FAAH-2 |
| Ensembl gene | ENSG00000165591 |
| Ensembl biotype | protein_coding |
| OMIM | 300654 |
| Entrez | 158584 |
Gene structure
Transcript identifiers
Ensembl transcripts: 13 — 11 protein_coding, 2 protein_coding_CDS_not_defined
ENST00000374900, ENST00000465623, ENST00000491179, ENST00000886034, ENST00000886035, ENST00000886036, ENST00000886037, ENST00000886038, ENST00000886039, ENST00000886040, ENST00000928697, ENST00000928698, ENST00000972153
RefSeq mRNA: 3 — MANE Select: NM_174912
NM_001353840, NM_001353841, NM_174912
CCDS: CCDS14375
Canonical transcript exons
ENST00000374900 — 11 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001094475 | 57380912 | 57381029 |
| ENSE00001094485 | 57378651 | 57378786 |
| ENSE00001094487 | 57341271 | 57341390 |
| ENSE00001094490 | 57292498 | 57292580 |
| ENSE00001094492 | 57331598 | 57331807 |
| ENSE00001094496 | 57431918 | 57432037 |
| ENSE00001306973 | 57310593 | 57310729 |
| ENSE00001465068 | 57286706 | 57287017 |
| ENSE00001897083 | 57488757 | 57489193 |
| ENSE00003558174 | 57448524 | 57448718 |
| ENSE00003649775 | 57446928 | 57447039 |
Expression profiles
Bgee: expression breadth ubiquitous, 190 present calls, max score 91.62.
FANTOM5 (CAGE): breadth broad, TPM avg 3.0167 / max 137.0702, expressed in 655 samples.
FANTOM5 promoters (3 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 196513 | 1.5578 | 543 |
| 196512 | 0.8013 | 254 |
| 196511 | 0.6576 | 265 |
Top tissues by expression
249 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| right uterine tube | UBERON:0001302 | 91.62 | gold quality |
| body of pancreas | UBERON:0001150 | 91.18 | gold quality |
| right lobe of liver | UBERON:0001114 | 89.88 | gold quality |
| epithelial cell of pancreas | CL:0000083 | 89.81 | silver quality |
| olfactory segment of nasal mucosa | UBERON:0005386 | 89.33 | gold quality |
| pancreas | UBERON:0001264 | 88.94 | gold quality |
| pituitary gland | UBERON:0000007 | 88.81 | gold quality |
| adenohypophysis | UBERON:0002196 | 88.63 | gold quality |
| islet of Langerhans | UBERON:0000006 | 88.28 | gold quality |
| skin of abdomen | UBERON:0001416 | 87.65 | gold quality |
| skin of leg | UBERON:0001511 | 86.97 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 86.10 | gold quality |
| zone of skin | UBERON:0000014 | 85.16 | gold quality |
| minor salivary gland | UBERON:0001830 | 84.80 | gold quality |
| mucosa of transverse colon | UBERON:0004991 | 84.17 | gold quality |
| epithelium of nasopharynx | UBERON:0001951 | 83.14 | gold quality |
| mouth mucosa | UBERON:0003729 | 83.03 | gold quality |
| prostate gland | UBERON:0002367 | 83.00 | gold quality |
| cerebellar hemisphere | UBERON:0002245 | 82.84 | gold quality |
| cerebellar cortex | UBERON:0002129 | 82.69 | gold quality |
| nasal cavity epithelium | UBERON:0005384 | 82.03 | silver quality |
| saliva-secreting gland | UBERON:0001044 | 81.96 | gold quality |
| esophagus mucosa | UBERON:0002469 | 81.89 | gold quality |
| right hemisphere of cerebellum | UBERON:0014890 | 81.81 | gold quality |
| adult mammalian kidney | UBERON:0000082 | 81.46 | gold quality |
| metanephros cortex | UBERON:0010533 | 81.30 | gold quality |
| liver | UBERON:0002107 | 81.26 | gold quality |
| cerebellum | UBERON:0002037 | 81.21 | gold quality |
| right lobe of thyroid gland | UBERON:0001119 | 80.73 | gold quality |
| left lobe of thyroid gland | UBERON:0001120 | 80.46 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 5.87 |
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
30 targeting FAAH2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-1252-5P | 100.00 | 69.80 | 2774 |
| HSA-MIR-8485 | 100.00 | 77.57 | 4731 |
| HSA-MIR-4803 | 99.98 | 71.99 | 3117 |
| HSA-MIR-363-3P | 99.98 | 74.72 | 1821 |
| HSA-MIR-32-5P | 99.98 | 75.21 | 1964 |
| HSA-MIR-92A-3P | 99.98 | 75.21 | 1960 |
| HSA-MIR-92B-3P | 99.98 | 75.25 | 1955 |
| HSA-MIR-25-3P | 99.98 | 74.60 | 1817 |
| HSA-MIR-367-3P | 99.98 | 74.83 | 1819 |
| HSA-MIR-548N | 99.98 | 71.94 | 4170 |
| HSA-MIR-651-3P | 99.94 | 73.48 | 5177 |
| HSA-MIR-145-5P | 99.92 | 71.13 | 1836 |
| HSA-MIR-5195-3P | 99.92 | 70.92 | 1877 |
| HSA-MIR-548E-5P | 99.89 | 72.73 | 4486 |
| HSA-MIR-4496 | 99.88 | 68.89 | 2236 |
| HSA-MIR-556-3P | 99.74 | 68.75 | 1203 |
| HSA-MIR-12124 | 99.68 | 69.17 | 2700 |
| HSA-MIR-4310 | 99.59 | 68.84 | 2527 |
| HSA-MIR-1252-3P | 99.55 | 67.71 | 2862 |
| HSA-MIR-451B | 99.55 | 68.28 | 1380 |
| HSA-MIR-4325 | 99.49 | 72.20 | 1342 |
| HSA-MIR-190B-3P | 99.33 | 68.29 | 1382 |
| HSA-MIR-6770-5P | 98.97 | 66.76 | 1853 |
| HSA-MIR-2355-5P | 98.83 | 65.51 | 1589 |
| HSA-MIR-138-5P | 98.43 | 70.49 | 1292 |
| HSA-MIR-338-3P | 98.14 | 67.38 | 1137 |
| HSA-MIR-676-3P | 97.86 | 65.70 | 668 |
| HSA-MIR-937-5P | 97.43 | 68.39 | 667 |
| HSA-MIR-6802-3P | 97.29 | 65.42 | 613 |
| HSA-MIR-4288 | 97.11 | 67.23 | 1636 |
Literature-anchored findings (GeneRIF, showing 4)
- FAAH2 is the second membrane-associated AS enzyme in humans that displays FAAH activity (PMID:17015445)
- 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. (PMID:19095868)
- results establish FAAH-2 as a bone fide N-acylethanolamine-catabolizing enzyme and suggest that inactivation is spatially separated in cells of higher mammals (PMID:19926788)
- A male patient with neuropsychiatric disorders attributed to a FAAH2 missense mutation is described. (PMID:25885783)
Cross-species orthologs
4 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | faah2a | ENSDARG00000008457 |
| danio_rerio | faah2b | ENSDARG00000054786 |
| drosophila_melanogaster | CG8839 | FBGN0033717 |
| caenorhabditis_elegans | WBGENE00013164 |
Paralogs (2): FAAH (ENSG00000117480), QRSL1 (ENSG00000130348)
Protein
Protein identifiers
Fatty-acid amide hydrolase 2 — Q6GMR7 (reviewed: Q6GMR7)
Alternative names: Amidase domain-containing protein, Anandamide amidohydrolase 2, Oleamide hydrolase 2
All UniProt accessions (2): B2C6G4, Q6GMR7
UniProt curated annotations — full annotation on UniProt →
Function. Catalyzes the hydrolysis of endogenous amidated lipids like the sleep-inducing lipid oleamide ((9Z)-octadecenamide), the endocannabinoid anandamide (N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine), as well as other fatty amides, to their corresponding fatty acids, thereby regulating the signaling functions of these molecules. Hydrolyzes monounsaturated substrate anandamide preferentially as compared to polyunsaturated substrates.
Subunit / interactions. Homodimer.
Subcellular location. Membrane. Lipid droplet.
Tissue specificity. Expressed in kidney, liver, lung, prostate, heart and ovary.
Activity regulation. Inhibited by O-aryl carbamates and alpha-keto heterocytes.
Similarity. Belongs to the amidase family.
RefSeq proteins (3): NP_001340769, NP_001340770, NP_777572* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR020556 | Amidase_CS | Conserved_site |
| IPR023631 | Amidase_dom | Domain |
| IPR036928 | AS_sf | Homologous_superfamily |
| IPR052739 | FAAH2 | Family |
Pfam: PF01425
Enzyme classification (BRENDA):
- EC 3.5.1.4 — amidase (BRENDA: 67 organisms, 400 substrates, 635 inhibitors, 203 Km, 135 kcat entries)
- EC 3.5.1.99 — fatty acid amide hydrolase (BRENDA: 10 organisms, 176 substrates, 1033 inhibitors, 73 Km, 48 kcat entries)
Substrate kinetics (BRENDA)
120 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| ACETAMIDE | 0.27–100 | 25 |
| PROPIONAMIDE | 0.0001–88 | 18 |
| BENZAMIDE | 0.0007–7.25 | 17 |
| ACRYLAMIDE | 1.2–93 | 16 |
| OLEAMIDE | 0.007–0.037 | 11 |
| ISOBUTYRAMIDE | 0.0001–7 | 10 |
| BUTYRAMIDE | 0.1–14 | 7 |
| OLEOYL P-NITROANILIDE | 0.012–0.126 | 7 |
| NICOTINAMIDE | 0.3–135.6 | 6 |
| HEXANAMIDE | 0.3–11.08 | 5 |
| ANANDAMIDE | 0.0018–2.78 | 5 |
| MYRISTOYL P-NITROANILIDE | 0.069–0.099 | 5 |
| NONANOYL P-NITROANILIDE | 0.057–0.57 | 5 |
| 2-TOLUAMIDE | 0.1–0.3 | 4 |
| CYCLOMALTOHEXAOSE | 0.2–0.3 | 4 |
Catalyzed reactions (Rhea), 4 shown:
- N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate (RHEA:26136)
- (9Z)-octadecenamide + H2O = (9Z)-octadecenoate + NH4(+) (RHEA:26506)
- N-(9Z-octadecenoyl) ethanolamine + H2O = ethanolamine + (9Z)-octadecenoate (RHEA:45060)
- N-hexadecanoylethanolamine + H2O = ethanolamine + hexadecanoate (RHEA:45064)
UniProt features (6 total): active site 3, chain 1, transmembrane region 1, sequence conflict 1
Structure
Experimental structures (PDB)
0 structures.
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q6GMR7-F1 | 94.08 | 0.85 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Catalytic / active sites (3): 131 (charge relay system); 206 (charge relay system); 230 (acyl-ester intermediate)
Function
Pathways and Gene Ontology
Reactome pathways
1 pathways
| ID | Pathway |
|---|---|
| R-HSA-2142753 | Arachidonate metabolism |
MSigDB gene sets: 35 (showing top):
GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_LIPID_CATABOLIC_PROCESS, GOBP_UNSATURATED_FATTY_ACID_METABOLIC_PROCESS, GOBP_ARACHIDONATE_METABOLIC_PROCESS, GOBP_FATTY_ACID_METABOLIC_PROCESS, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_CARBON_NITROGEN_BUT_NOT_PEPTIDE_BONDS_IN_LINEAR_AMIDES, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_CARBON_NITROGEN_BUT_NOT_PEPTIDE_BONDS, chrXp11, GOBP_ICOSANOID_METABOLIC_PROCESS, GOCC_LIPID_DROPLET, REACTOME_ARACHIDONATE_METABOLISM, REACTOME_METABOLISM_OF_LIPIDS
GO Biological Process (3): lipid catabolic process (GO:0016042), arachidonate metabolic process (GO:0019369), lipid metabolic process (GO:0006629)
GO Molecular Function (2): fatty acid amide hydrolase activity (GO:0017064), hydrolase activity (GO:0016787)
GO Cellular Component (2): lipid droplet (GO:0005811), membrane (GO:0016020)
Reactome top-level categories
Rollup of top-1 pathways:
| Category | Pathways |
|---|---|
| Fatty acid metabolism | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| lipid metabolic process | 1 |
| catabolic process | 1 |
| long-chain fatty acid metabolic process | 1 |
| icosanoid metabolic process | 1 |
| unsaturated fatty acid metabolic process | 1 |
| olefinic compound metabolic process | 1 |
| primary metabolic process | 1 |
| hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides | 1 |
| catalytic activity | 1 |
| intracellular membraneless organelle | 1 |
| cellular anatomical structure | 1 |
Protein interactions and networks
STRING
1816 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| FAAH2 | NAPEPLD | Q6IQ20 | 791 |
| FAAH2 | NAAA | Q02083 | 749 |
| FAAH2 | ABHD6 | Q9BV23 | 687 |
| FAAH2 | MGLL | Q99685 | 656 |
| FAAH2 | DAGLB | Q8NCG7 | 651 |
| FAAH2 | DAGLA | Q9Y4D2 | 636 |
| FAAH2 | ABHD4 | Q8TB40 | 623 |
| FAAH2 | ABHD12 | Q8N2K0 | 570 |
| FAAH2 | GDE1 | Q9NZC3 | 551 |
| FAAH2 | GPR55 | Q9Y2T6 | 547 |
| FAAH2 | ZNF765 | Q7L2R6 | 525 |
| FAAH2 | TRPV1 | Q8NER1 | 425 |
| FAAH2 | ABHD11 | Q8NFV4 | 419 |
| FAAH2 | CNR1 | P21554 | 418 |
| FAAH2 | GPR119 | Q8TDV5 | 400 |
IntAct
0 interactions, top by confidence:
BioGRID (3): FAAH2 (Protein-RNA), HNRNPA2B1 (Cross-Linking-MS (XL-MS)), APP (Reconstituted Complex)
ESM2 similar proteins: A0JPE9, A2AJL3, A2VD33, O46504, O75191, P12276, P12785, P13439, P17256, P19096, P31754, Q08D86, Q0IH28, Q0VFE7, Q3MIF4, Q3SYZ6, Q3TNA1, Q4V831, Q4V9P6, Q503J2, Q566S6, Q5M7T9, Q5R979, Q5RFE6, Q5U5V2, Q5XH07, Q5XIG6, Q5ZMJ4, Q64FG0, Q68FH4, Q6DCD1, Q6DH69, Q6GMR7, Q6GP95, Q6NUM9, Q6NUW9, Q6ZS86, Q71SP7, Q7TSQ8, Q80SY6
Diamond homologs: A0A348AXX5, A0KBH9, A0L5G0, A0LSR0, A1V776, A1WVR7, A2S8I9, A3MNR6, A3N4F4, A3NQ45, A3PI90, A4JIT0, A4WUQ2, A5I6Z3, A5UXF9, A7FYL3, A7GIK2, A7NKM0, A8M5E6, A9AC51, A9KBI0, A9N8Z4, A9WCD8, B1INF7, B1K0H7, B1L1G9, B1YPV8, B2A5W7, B2JJW2, B2T1M4, B2U7V7, B3DWT4, B4E7X6, B6IZ25, B6J4H5, B8G974, B8HY89, B8J405, B9KPF8, B9LER8
SIGNOR signaling
0 interactions.
Disease & clinical
Clinical variants and AI predictions
ClinVar
268 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 2 |
| Likely pathogenic | 0 |
| Uncertain significance | 138 |
| Likely benign | 14 |
| Benign | 5 |
Top pathogenic / likely-pathogenic (2)
| Variant ID | HGVS | Classification |
|---|---|---|
| 1252027 | NM_174912.4(FAAH2):c.1175G>A (p.Trp392Ter) | Pathogenic |
| 522688 | NM_174912.4(FAAH2):c.267_275+2del | Pathogenic |
SpliceAI
2371 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| X:57292494:GCAG:G | acceptor_loss | 1.0000 |
| X:57292495:CAGGT:C | acceptor_loss | 1.0000 |
| X:57292496:A:AG | acceptor_gain | 1.0000 |
| X:57292496:A:G | acceptor_loss | 1.0000 |
| X:57292496:AG:A | acceptor_gain | 1.0000 |
| X:57292496:AGGT:A | acceptor_gain | 1.0000 |
| X:57292497:G:GT | acceptor_gain | 1.0000 |
| X:57292497:GG:G | acceptor_gain | 1.0000 |
| X:57292497:GGT:G | acceptor_gain | 1.0000 |
| X:57292497:GGTG:G | acceptor_gain | 1.0000 |
| X:57292497:GGTGA:G | acceptor_gain | 1.0000 |
| X:57292578:CAG:C | donor_gain | 1.0000 |
| X:57292579:AGGT:A | donor_loss | 1.0000 |
| X:57292582:T:G | donor_loss | 1.0000 |
| X:57310588:CTTA:C | acceptor_loss | 1.0000 |
| X:57310589:TTA:T | acceptor_loss | 1.0000 |
| X:57310590:TAG:T | acceptor_loss | 1.0000 |
| X:57310591:A:AG | acceptor_gain | 1.0000 |
| X:57310591:A:C | acceptor_loss | 1.0000 |
| X:57310591:AG:A | acceptor_gain | 1.0000 |
| X:57310592:G:A | acceptor_gain | 1.0000 |
| X:57310592:G:GT | acceptor_gain | 1.0000 |
| X:57310592:GGT:G | acceptor_gain | 1.0000 |
| X:57310592:GGTT:G | acceptor_gain | 1.0000 |
| X:57310592:GGTTT:G | acceptor_gain | 1.0000 |
| X:57310711:G:GT | donor_gain | 1.0000 |
| X:57310727:AAGGT:A | donor_loss | 1.0000 |
| X:57310728:AGGT:A | donor_loss | 1.0000 |
| X:57310731:T:G | donor_loss | 1.0000 |
| X:57331797:TGG:T | donor_gain | 1.0000 |
AlphaMissense
3452 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| X:57331746:C:A | N187K | 0.997 |
| X:57331746:C:G | N187K | 0.997 |
| X:57341325:A:T | D226V | 0.997 |
| X:57331616:G:A | G144E | 0.996 |
| X:57331714:A:C | S177R | 0.996 |
| X:57331716:T:A | S177R | 0.996 |
| X:57331716:T:G | S177R | 0.996 |
| X:57331729:T:A | W182R | 0.996 |
| X:57331729:T:C | W182R | 0.996 |
| X:57331801:A:C | S206R | 0.996 |
| X:57331803:T:A | S206R | 0.996 |
| X:57331803:T:G | S206R | 0.996 |
| X:57341336:A:C | S230R | 0.996 |
| X:57341338:C:A | S230R | 0.996 |
| X:57341338:C:G | S230R | 0.996 |
| X:57331739:C:T | S185F | 0.995 |
| X:57341324:G:C | D226H | 0.995 |
| X:57431999:T:A | W360R | 0.995 |
| X:57431999:T:C | W360R | 0.995 |
| X:57331770:C:A | N195K | 0.994 |
| X:57331770:C:G | N195K | 0.994 |
| X:57341324:G:T | D226Y | 0.994 |
| X:57341325:A:C | D226A | 0.994 |
| X:57331710:C:A | N175K | 0.993 |
| X:57331710:C:G | N175K | 0.993 |
| X:57331736:A:T | E184V | 0.993 |
| X:57331805:C:A | S207Y | 0.993 |
| X:57341271:G:A | G208D | 0.993 |
| X:57378728:C:A | R274S | 0.993 |
| X:57488909:T:A | W526R | 0.993 |
dbSNP variants (sampled 300 via entrez): RS1000013366 (X:57150787 A>G), RS1000019058 (X:57443614 C>T), RS1000028869 (X:57329908 G>A), RS1000029782 (X:57284281 G>A), RS1000037964 (X:57330508 G>C,T), RS1000040249 (X:57330193 C>A), RS1000044651 (X:57158902 G>A,C), RS1000052415 (X:57282987 T>A), RS1000065654 (X:57373307 T>C), RS1000088464 (X:57458412 G>T), RS1000108187 (X:57273750 C>A,T), RS1000121324 (X:57402082 G>A,T), RS1000121539 (X:57165796 G>C), RS1000125428 (X:57436610 T>A), RS1000133590 (X:57418399 A>G)
Disease associations
OMIM: gene MIM:300654 | disease phenotypes:
GenCC curated gene-disease
| Disease | Classification | Inheritance |
|---|---|---|
| autism spectrum disorder | Limited | X-linked |
ClinGen Gene-Disease Validity (1)
Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.
| Disease | Classification | Inheritance |
|---|---|---|
| X-linked complex neurodevelopmental disorder | Disputed | XL |
Mondo (1): autism spectrum disorder (MONDO:0005258)
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
4 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST003993_41 | Menarche (age at onset) | 2.000000e-09 |
| GCST007847_104 | Type 2 diabetes | 5.000000e-09 |
| GCST008839_470 | Height | 2.000000e-29 |
| GCST90002384_515 | Hemoglobin | 3.000000e-20 |
EFO canonical traits (2, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0004703 | age at menarche |
| EFO:0004509 | hemoglobin measurement |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL1628475 (SINGLE PROTEIN)
Molecules with ChEMBL bioactivity
1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 417 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL184238 | URB-597 | 1 | 417 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: enzyme — N-Acylethanolamine turnover
Most potent curated ligand interactions (5 total), top 5:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| LY2077855 | Inhibition | 8.52 | pIC50 |
| OL135 | Inhibition | 8.4 | pIC50 |
| URB597 | Inhibition | 8.3 | pIC50 |
| ASP8477 | Inhibition | 7.24 | pIC50 |
| JNJ1661010 | Inhibition | 5.24 | pIC50 |
ChEMBL bioactivities
2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 8.30 | IC50 | 5 | nM | URB-597 |
| 7.87 | IC50 | 13.4 | nM | CHEMBL177577 |
PubChem BioAssay actives
2 with measured affinity, of 12 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| [3-(3-carbamoylphenyl)phenyl] N-cyclohexylcarbamate | 1363927: Inhibition of recombinant human N-terminal FLAG-tagged/C-terminal Myc-His6 tagged FAAH2 (32 to 579 residues) expressed in COS7 cell membranes | ic50 | 0.0050 | uM |
| 7-phenyl-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one | 1363927: Inhibition of recombinant human N-terminal FLAG-tagged/C-terminal Myc-His6 tagged FAAH2 (32 to 579 residues) expressed in COS7 cell membranes | ic50 | 0.0134 | uM |
CTD chemical–gene interactions
15 total (human), top 15 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Aflatoxin B1 | increases methylation, decreases expression | 3 |
| sodium arsenite | decreases expression, affects cotreatment, increases abundance, increases expression | 2 |
| Benzo(a)pyrene | affects methylation, decreases expression, decreases methylation | 2 |
| ASP8477 | decreases activity | 1 |
| triphenyl phosphate | affects expression | 1 |
| bisphenol A | affects cotreatment, decreases methylation | 1 |
| sulforaphane | decreases expression | 1 |
| butyraldehyde | decreases expression | 1 |
| Fulvestrant | decreases methylation, affects cotreatment | 1 |
| Arsenic | affects cotreatment, increases abundance, increases expression, decreases expression | 1 |
| Silicon Dioxide | decreases expression | 1 |
| 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide | decreases expression | 1 |
| Okadaic Acid | decreases expression | 1 |
| Copper Sulfate | decreases expression | 1 |
| Lactic Acid | decreases expression | 1 |
ChEMBL screening assays
4 unique, capped per target: 3 binding, 1 admet
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL2168765 | Binding | Inhibition of FAAH2 | Aryl Piperazinyl Ureas as Inhibitors of Fatty Acid Amide Hydrolase (FAAH) in Rat, Dog, and Primate. — ACS Med Chem Lett |
| CHEMBL4626512 | ADMET | Substrate activity at FAAH2 in human brain S9 fraction assessed as bezafibrate level at 100 uM measured after 15 mins by LC-MS/MS analysis | A CNS-Targeting Prodrug Strategy for Nuclear Receptor Modulators. — J Med Chem |
Clinical trials (associated diseases)
300 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT00391261 | PHASE4 | COMPLETED | An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications. |
| NCT01028820 | PHASE4 | COMPLETED | FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders |
| NCT01333865 | PHASE4 | COMPLETED | A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders |
| NCT01337700 | PHASE4 | COMPLETED | Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism |
| NCT01695200 | PHASE4 | COMPLETED | Omega-3 Fatty Acids in Autism Spectrum Disorders |
| NCT02096952 | PHASE4 | COMPLETED | Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD |
| NCT02235467 | PHASE4 | COMPLETED | Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism |
| NCT02940574 | PHASE4 | COMPLETED | Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders |
| NCT03333629 | PHASE4 | COMPLETED | Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes |
| NCT03337646 | PHASE4 | COMPLETED | Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism |
| NCT03538431 | PHASE4 | COMPLETED | Improving Driving in Young People With Autism Spectrum Disorders |
| NCT03757585 | PHASE4 | COMPLETED | Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD) |
| NCT04903353 | PHASE4 | COMPLETED | Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole |
| NCT05063656 | PHASE4 | COMPLETED | Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin |
| NCT05146245 | PHASE4 | UNKNOWN | Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT |
| NCT05916339 | PHASE4 | RECRUITING | AWARE: Management of ADHD in Autism Spectrum Disorder |
| NCT05954052 | PHASE4 | TERMINATED | A Study of Glutathione in Children With Autism Spectrum Disorder |
| NCT06853665 | PHASE4 | RECRUITING | The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine |
| NCT07054697 | PHASE4 | COMPLETED | Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder |
| NCT07161804 | PHASE4 | COMPLETED | Pilot RCT Using Homeopathic Medicines in ASD |
| NCT07439042 | PHASE4 | NOT_YET_RECRUITING | Buspirone for Anxiety in Autistic Youth |
| NCT01302964 | PHASE3 | COMPLETED | Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders |
| NCT01706523 | PHASE3 | TERMINATED | Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders |
| NCT01825798 | PHASE3 | COMPLETED | Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD) |
| NCT01972074 | PHASE3 | COMPLETED | Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder |
| NCT02985749 | PHASE3 | COMPLETED | A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder |
| NCT03197922 | PHASE3 | COMPLETED | Treatment of Encopresis in Children With Autism Spectrum Disorders |
| NCT03504917 | PHASE3 | TERMINATED | A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension |
| NCT03553875 | PHASE3 | TERMINATED | Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions |
| NCT03640156 | PHASE3 | COMPLETED | Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin |
| NCT03715153 | PHASE3 | TERMINATED | Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder. |
| NCT03715166 | PHASE3 | TERMINATED | Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder |
| NCT04233502 | PHASE3 | WITHDRAWN | Efficacy and Safety of Slenyto for Insomnia in Children With ASD |
| NCT04578756 | PHASE3 | COMPLETED | Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder |
| NCT04623398 | PHASE3 | COMPLETED | Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency) |
| NCT04725383 | PHASE3 | TERMINATED | Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders |
| NCT05212493 | PHASE3 | COMPLETED | The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder |
| NCT05361707 | PHASE3 | UNKNOWN | Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances |
| NCT05439616 | PHASE3 | COMPLETED | Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD |
| NCT06229210 | PHASE3 | RECRUITING | Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder |
Related Atlas pages
- Associated diseases: autism spectrum disorder, X-linked complex neurodevelopmental disorder