AADAC

Summary

AADAC (arylacetamide deacetylase, HGNC:17) is a protein-coding gene on chromosome 3q25.1, encoding Arylacetamide deacetylase (P22760). Displays cellular triglyceride lipase activity in liver, increases the levels of intracellular fatty acids derived from the hydrolysis of newly formed triglyceride stores and plays a role in very low-density lipoprotein assembly.

Microsomal arylacetamide deacetylase competes against the activity of cytosolic arylamine N-acetyltransferase, which catalyzes one of the initial biotransformation pathways for arylamine and heterocyclic amine carcinogens

Source: NCBI Gene 13 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (No Known Disease Relationship, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 69 total — 5 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001086

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17
Approved symbol	AADAC
Name	arylacetamide deacetylase
Location	3q25.1
Locus type	gene with protein product
Status	Approved
Aliases	DAC, CES5A1
Ensembl gene	ENSG00000114771
Ensembl biotype	protein_coding
OMIM	600338
Entrez	13

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000232892, ENST00000488869, ENST00000854454, ENST00000854455, ENST00000854456, ENST00000854457, ENST00000854458, ENST00000854459, ENST00000854460, ENST00000854461

RefSeq mRNA: 1 — MANE Select: NM_001086 NM_001086

CCDS: CCDS33877

Canonical transcript exons

ENST00000232892 — 5 exons

Exon	Start	End
ENSE00000779767	151827576	151828488
ENSE00000779768	151824663	151824834
ENSE00000779769	151820383	151820452
ENSE00000779770	151817366	151817588
ENSE00001919447	151814116	151814300

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 99.10.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.3449 / max 386.8907, expressed in 158 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39244	0.9699	114
39242	0.7222	95
39243	0.5305	107
39241	0.0711	33
39245	0.0512	20

Top tissues by expression

275 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.10	gold quality
right adrenal gland	UBERON:0001233	98.99	gold quality
right adrenal gland cortex	UBERON:0035827	98.91	gold quality
left adrenal gland	UBERON:0001234	98.81	gold quality
left adrenal gland cortex	UBERON:0035825	98.68	gold quality
adrenal cortex	UBERON:0001235	97.79	gold quality
right lobe of liver	UBERON:0001114	97.76	gold quality
liver	UBERON:0002107	97.51	gold quality
duodenum	UBERON:0002114	97.26	gold quality
adrenal gland	UBERON:0002369	96.05	gold quality
ileal mucosa	UBERON:0000331	96.02	gold quality
body of pancreas	UBERON:0001150	92.10	gold quality
gall bladder	UBERON:0002110	90.41	gold quality
decidua	UBERON:0002450	89.86	gold quality
adrenal tissue	UBERON:0018303	89.44	gold quality
pancreas	UBERON:0001264	87.68	gold quality
upper leg skin	UBERON:0004262	86.99	gold quality
islet of Langerhans	UBERON:0000006	85.56	gold quality
parietal pleura	UBERON:0002400	85.22	gold quality
small intestine	UBERON:0002108	82.48	gold quality
germinal epithelium of ovary	UBERON:0001304	82.39	gold quality
small intestine Peyer’s patch	UBERON:0003454	82.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.65	gold quality
epithelium of nasopharynx	UBERON:0001951	81.18	gold quality
tongue squamous epithelium	UBERON:0006919	80.85	silver quality
pericardium	UBERON:0002407	80.10	gold quality
oral cavity	UBERON:0000167	78.14	gold quality
gingival epithelium	UBERON:0001949	77.96	gold quality
gingiva	UBERON:0001828	77.69	gold quality
jejunum	UBERON:0002115	77.41	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.73

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting AADAC, 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-188-3P	100.00	68.76	1240
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-605-5P	98.79	68.24	1161
HSA-MIR-1178-3P	98.57	67.09	890
HSA-MIR-3668	98.52	68.76	951
HSA-MIR-33B-3P	97.92	67.39	529
HSA-MIR-515-3P	97.92	67.98	506
HSA-MIR-519E-3P	97.92	68.25	508
HSA-MIR-6502-3P	97.86	65.43	569
HSA-MIR-708-3P	97.50	68.67	1082
HSA-MIR-6750-3P	96.79	67.50	740

Literature-anchored findings (GeneRIF, showing 25)

• role of mutation in courtship and other behaviors (PMID:12242229)
• Dmca1A is an allele of the N-type calcium channel locus that caused synaptic undergrowth (PMID:12896973)
• Localization of cacophony on presynaptic terminals at neuromuscular synapses. (PMID:14715960)
• Data show that the Drosophila cacophony ts2 mutation reduces presynaptic Ca2+ entry and defines an important element in Cav2.1 channel inactivation (PMID:16820014)
• These data confirm the presynaptic expression of synaptic homeostasis and implicate presynaptic Ca(V)2.1 in a homeostatic retrograde signaling system. (PMID:17114050)
• Cacophony protein plays a key role in developmental regulation of Drosophila neuronal excitability. (PMID:17267561)
• Neuronal overexpression of cac partially rescues the viability and physiological defects in stj mutants, indicating a role for the alpha(2)delta Ca(2+) channel subunit in mediating the proper localization of an alpha(1) subunit at synapses. (PMID:18391075)
• cac encoded Ca(v)2-type calcium channels regulate action potential (AP)-independent release of neurotransmitter at excitatory cholinergic synapses (PMID:19004991)
• Homeostatic increase in Ca(2+) influx and release is blocked by a point mutation in the presynaptic CaV2.1 channel. (PMID:22633807)
• Vesicle exocytosis depends on cacophony, TRP and TRPL. (PMID:22952921)
• cac and Dmca1D Ca(2+) channels differentially contribute to functional and structural aspects of slo-induced synaptic modifications (PMID:23959639)
• Dopaminergic neurons with mutant Ca2+ channel cacophony are inherently resistant to MPP+-induced neurodegeneration. (PMID:25445363)
• Cac regulates lysosomal fusion with endosomes and autophagosomes and is required for neuronal homeostasis. (PMID:25811491)
• Homeostatic depression is achieved by decreased presynaptic Cav2.1 calcium channel abundance and calcium influx. (PMID:25884248)
• cacophony (cacTS2), a mutation of the Drosophila presynaptic Ca++ channel alpha1 subunit gene, is a particularly potent seizure-suppressor mutation, reverting seizure-like phenotypes for parabss1 and other BS mutants (PMID:26771829)
• Strikingly the absence of any of DLG proteins at the presynaptic terminal disrupts the clustering and localization of the calcium channel DmCa1A subunit (Cacophony), decreases the action potential-evoked release probability and alters short-term plasticity. (PMID:27573697)
• the novel R1673P allele of CACNA1A produces neurodegenerative phenotypes in flies and human, likely due to a toxic gain of function (PMID:28742085)
• Motor defects in TDP-43 mutants can be rescued by expression of cacophony in motor neurons and by expression in two pairs of neurons in the brain. (PMID:28847811)
• Deletion of exon 7 caused a decrease in cacophony protein expression but not total transcript levels, caused reduced locomotory activity in adults, and locomotion defects in third instar larvae. (PMID:30397173)
• Study finds that the abundance of endogenous Cac is modulated during presynaptic homeostatic potentiation, but does not change during presynaptic homeostatic depression. (PMID:30692227)
• Juvenile hormone drives the maturation of spontaneous mushroom body neural activity and learned behavior. (PMID:33915110)
• The Drosophila ortholog of the schizophrenia-associated CACNA1A and CACNA1B voltage-gated calcium channels regulate memory, sleep and circadian rhythms. (PMID:34015490)
• Separation of presynaptic Cav2 and Cav1 channel function in synaptic vesicle exo- and endocytosis by the membrane anchored Ca(2+) pump PMCA. (PMID:34244444)
• Despite the high sequence divergence of these proteins, gp13 forms a ring structure with similar dimensions to the spirals observed in the crystal lattices of these other proteins. (PMID:23542344)
• a cell wall degrading enzyme in the bacteriophage phi29 tail (PMID:18606992)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	aadac	ENSDARG00000063621
mus_musculus	Aadac	ENSMUSG00000027761
rattus_norvegicus	Aadac	ENSRNOG00000013950
caenorhabditis_elegans		WBGENE00009186
caenorhabditis_elegans		WBGENE00011642
caenorhabditis_elegans		WBGENE00017515

Paralogs (5): NCEH1 (ENSG00000144959), AFMID (ENSG00000183077), AADACL3 (ENSG00000188984), AADACL2 (ENSG00000197953), AADACL4 (ENSG00000204518)

Protein

Protein identifiers

Arylacetamide deacetylase — P22760 (reviewed: P22760)

All UniProt accessions (2): P22760, C9K0E9

UniProt curated annotations — full annotation on UniProt →

Function. Displays cellular triglyceride lipase activity in liver, increases the levels of intracellular fatty acids derived from the hydrolysis of newly formed triglyceride stores and plays a role in very low-density lipoprotein assembly. Displays serine esterase activity in liver. Deacetylates a variety of arylacetamide substrates, including xenobiotic compounds and procarcinogens, converting them to the primary arylamide compounds and increasing their toxicity.

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Tissue specificity. Detected in liver (at protein level). Mainly expressed in liver, small intestine, colon, adrenal gland and bladder.

Post-translational modifications. Glycosylation is required for enzyme activity.

Induction. Down-regulated following infection with hepatis C virus which results in impaired triacylglycerol lipolysis and impaired assembly of very low density lipoproteins. This may represent a cellular adaptation to infection that is aimed at limiting viral production.

Polymorphism. Three alleles are known: AADAC1, AADAC2 and AADAC3. The sequence shown is that of AADAC1 which is found in European American, African American, Japanese and Korean populations at allelic frequencies of 39.3 to 47.4%. The AADAC2 allele is found in European American, African American, Korean, and Japanese populations at allelic frequencies of 52.6 to 63.5% whereas the AADAC3 allele is found in European American (1.3%) and African American (2.0%) samples but not in Japanese or Korean samples.

Miscellaneous. Can hydrolyze a number of clinical drugs such as flutamide, an antiandrogen drug used for the treatment of prostate cancer; phenacetin, an analgesic antipyretic which has been withdrawn from the market due to its links with renal failure; and rifamycins which have been used as antituberculosis drugs.

Similarity. Belongs to the ‘GDXG’ lipolytic enzyme family.

RefSeq proteins (1): NP_001077* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013094	AB_hydrolase_3	Domain
IPR017157	Arylacetamide_deacetylase	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR033140	Lipase_GDXG_put_SER_AS	Active_site
IPR050300	GDXG_lipolytic_enzyme	Family

Pfam: PF07859

Catalyzed reactions (Rhea), 1 shown:

• a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+) (RHEA:12044)

UniProt features (17 total): active site 3, topological domain 2, sequence variant 2, mutagenesis site 2, sequence conflict 2, glycosylation site 2, chain 1, disulfide bond 1, transmembrane region 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22760-F1	95.64	0.92

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): 189; 343; 373

Disulfide bonds (1): 116–340

Glycosylation sites (2): 78, 282

Mutagenesis-validated functional residues (2):

Position	Phenotype
78	abolishes glycosylation at this site and causes moderate decrease in activity.
282	abolishes glycosylation at this site and causes substantial decrease in activity and reduced substrate affinity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-211945	Phase I - Functionalization of compounds
R-HSA-1430728	Metabolism
R-HSA-211859	Biological oxidations

MSigDB gene sets: 127 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_REGULATION_OF_TRIGLYCERIDE_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, SETLUR_PROSTATE_CANCER_TMPRSS2_ERG_FUSION_DN, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_REGULATION_OF_TRIGLYCERIDE_CATABOLIC_PROCESS, GOBP_NEUTRAL_LIPID_CATABOLIC_PROCESS, HSIAO_LIVER_SPECIFIC_GENES, CORRE_MULTIPLE_MYELOMA_UP, GOBP_LIPID_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_LIPID_CATABOLIC_PROCESS, GOBP_TRIGLYCERIDE_CATABOLIC_PROCESS

GO Biological Process (3): lipid metabolic process (GO:0006629), xenobiotic metabolic process (GO:0006805), positive regulation of triglyceride catabolic process (GO:0010898)

GO Molecular Function (8): catalytic activity (GO:0003824), triacylglycerol lipase activity (GO:0004806), lipase activity (GO:0016298), serine hydrolase activity (GO:0017171), deacetylase activity (GO:0019213), protein binding (GO:0005515), hydrolase activity (GO:0016787), carboxylic ester hydrolase activity (GO:0052689)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Biological oxidations	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hydrolase activity, acting on ester bonds	2
primary metabolic process	1
metabolic process	1
cellular response to xenobiotic stimulus	1
regulation of triglyceride catabolic process	1
triglyceride catabolic process	1
positive regulation of lipid catabolic process	1
positive regulation of triglyceride metabolic process	1
molecular_function	1
lipase activity	1
carboxylic ester hydrolase activity	1
hydrolase activity	1
deacylase activity	1
binding	1
catalytic activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1690 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AADAC	NAT2	P11245	865
AADAC	NAT1	P18440	827
AADAC	CES1	P23141	679
AADAC	CES2	O00748	606
AADAC	ABHD5	Q8WTS1	574
AADAC	CES5A	Q6NT32	462
AADAC	FSCB	Q5H9T9	461
AADAC	MOGAT2	Q3SYC2	455
AADAC	MGLL	Q99685	436
AADAC	CES3	Q6UWW8	429
AADAC	CES4A	Q5XG92	427
AADAC	PLIN1	O60240	424
AADAC	PNPLA2	Q96AD5	418
AADAC	GPAT4	Q86UL3	410
AADAC	ABHD10	Q9NUJ1	403

IntAct

4 interactions, top by confidence:

A	B	Type	Score
AADAC	APPBP2	psi-mi:“MI:0915”(physical association)	0.560
AADAC	APPBP2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (2): AADAC (Two-hybrid), ACP1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2A7Z8, A7LB60, P08910, P0DKC5, P0DKC6, P22760, P70683, P83006, Q05AK6, Q0P5B7, Q13093, Q14032, Q1LZ86, Q28017, Q32LS6, Q4R2Y9, Q4V8A1, Q502J0, Q5EA42, Q5PPS7, Q5VUY0, Q5VUY2, Q5XI64, Q5ZJL8, Q5ZKL5, Q60963, Q63276, Q6DHN0, Q6GLL2, Q6IE26, Q6P093, Q7L211, Q7M370, Q7SY73, Q7Z5M8, Q802V6, Q80UX8, Q8BM81, Q8IUS5, Q8R2Y0

Diamond homologs: A0A0A1EQ07, A0A0H5BMX5, A0A2P1GIW2, A0A2P1GIW3, A0A2P1GIY1, A0A2P1GIY2, B5BLW5, I3PLR2, I4DST8, I4DST9, O06350, O53424, O64640, O64641, P15304, P16386, P22760, P24484, P37967, P54310, P9WK86, P9WK87, Q00675, Q05469, Q0CZH0, Q0P5B7, Q0ZPV7, Q5NUF3, Q5NUF4, Q5R8Y5, Q68J42, Q6PIU2, Q7D5F9, Q7M370, Q940G6, Q9EX73, Q9FG13, Q9FX92, Q9FX93, Q9FX94

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

69 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	2
Uncertain significance	55
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1328449	GRCh37/hg19 3q24-26.1(chr3:143439359-165252122)x1	Pathogenic
1330165	GRCh37/hg19 3q23-25.32(chr3:142729607-157921084)x3	Pathogenic
253377	GRCh37/hg19 3q24-29(chr3:142995020-192997215)x4	Pathogenic
814487	GRCh37/hg19 3q25.1-25.2(chr3:149404255-152786331)x1	Pathogenic
929388	GRCh37/hg19 3q22.3-26.1(chr3:138145289-162275610)x3	Pathogenic
153419	GRCh38/hg38 3q25.1-25.2(chr3:151429416-155118646)x1	Likely pathogenic
442527	GRCh37/hg19 3q25.1-25.2(chr3:150352753-153522663)x1	Likely pathogenic

SpliceAI

709 predictions. Top by Δscore:

Variant	Effect	Δscore
3:151814296:ATTTG:A	donor_gain	1.0000
3:151814297:TTTG:T	donor_gain	1.0000
3:151814297:TTTGG:T	donor_loss	1.0000
3:151814298:TTG:T	donor_gain	1.0000
3:151814301:G:GA	donor_loss	1.0000
3:151814301:G:GG	donor_gain	1.0000
3:151814302:TAAG:T	donor_loss	1.0000
3:151820378:TTCA:T	acceptor_loss	1.0000
3:151820380:CAG:C	acceptor_loss	1.0000
3:151820381:A:AG	acceptor_gain	1.0000
3:151820382:G:GA	acceptor_gain	1.0000
3:151820382:GCT:G	acceptor_gain	1.0000
3:151820382:GCTCT:G	acceptor_gain	1.0000
3:151820449:CCAAG:C	donor_loss	1.0000
3:151820451:AAGTA:A	donor_loss	1.0000
3:151820452:AGTAA:A	donor_loss	1.0000
3:151820453:G:C	donor_loss	1.0000
3:151820453:G:GG	donor_gain	1.0000
3:151820454:T:G	donor_loss	1.0000
3:151814299:TG:T	donor_gain	0.9900
3:151814300:GG:G	donor_gain	0.9900
3:151820376:A:AG	acceptor_gain	0.9900
3:151820382:GCTC:G	acceptor_gain	0.9900
3:151820448:ACCAA:A	donor_gain	0.9900
3:151824060:A:AG	donor_gain	0.9900
3:151824061:G:GG	donor_gain	0.9900
3:151824661:A:AG	acceptor_gain	0.9900
3:151824662:G:GG	acceptor_gain	0.9900
3:151824662:GCTAC:G	acceptor_gain	0.9900
3:151824830:AACAG:A	donor_loss	0.9900

AlphaMissense

2600 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:151824688:T:C	F153L	0.963
3:151824690:C:A	F153L	0.963
3:151824690:C:G	F153L	0.963
3:151817499:T:A	V91D	0.955
3:151817570:T:A	W115R	0.944
3:151817570:T:C	W115R	0.944
3:151824796:A:C	S189R	0.943
3:151824798:T:A	S189R	0.943
3:151824798:T:G	S189R	0.943
3:151817502:G:C	R92P	0.940
3:151828036:G:C	R355P	0.925
3:151824797:G:T	S189I	0.922
3:151820433:G:C	A138P	0.913
3:151820440:T:A	V140D	0.913
3:151828168:T:C	L399P	0.906
3:151828026:T:G	Y352D	0.899
3:151828011:G:C	D347H	0.896
3:151824803:G:T	G191V	0.895
3:151817562:G:T	G112V	0.894
3:151817483:T:C	F86L	0.888
3:151817485:C:A	F86L	0.888
3:151817485:C:G	F86L	0.888
3:151828010:A:C	R346S	0.888
3:151828010:A:T	R346S	0.888
3:151828039:T:C	L356P	0.888
3:151824706:G:C	D159H	0.884
3:151824805:G:T	G192W	0.882
3:151824820:G:C	A197P	0.882
3:151820445:T:C	S142P	0.880
3:151824782:G:A	G184D	0.878

dbSNP variants (sampled 300 via entrez): RS1000171717 (3:151813706 A>C), RS1000238313 (3:151813840 T>G), RS1000306220 (3:151813864 C>T), RS1000839586 (3:151813692 GAAGATT>G), RS1000995062 (3:151825877 T>C), RS1001017284 (3:151818540 C>T), RS1001269768 (3:151826762 A>C,G), RS1001279873 (3:151823894 T>C), RS1001553009 (3:151818974 C>T), RS1001602396 (3:151813345 T>C,G), RS1001633624 (3:151813051 G>A,C), RS1001657367 (3:151828205 A>G), RS1002090351 (3:151828986 C>G,T), RS1002691228 (3:151826677 A>C,G), RS1002802449 (3:151818949 A>G)

Disease associations

OMIM: gene MIM:600338 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (4): microcephaly (MONDO:0001149), attention deficit-hyperactivity disorder (MONDO:0007743), primary ovarian failure (MONDO:0005387), Tourette syndrome (MONDO:0007661)

Orphanet (2): Non-syndromic bicoronal craniosynostosis (Orphanet:35099), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000252	Microcephaly

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000763_8	Immunoglobulin A	3.000000e-06
GCST005116_24	Male-pattern baldness	8.000000e-18
GCST006661_125	Male-pattern baldness	3.000000e-15
GCST006661_292	Male-pattern baldness	1.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004747	protein measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3509584 (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: 99,079 (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
CHEMBL806	FLUTAMIDE	4	99,079

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1803155	Metabolism/PK	3	rifampin

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs144650170	AADAC		0.00	0
rs35084477	AADAC		0.00	0
rs186388618	AADAC		0.00	0
rs1803155	AADAC	3	3.25	1	rifampin
rs140197497	AADAC		0.00	0
rs61733692	AADAC		0.00	0

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.22	Ki	600	nM	FLUTAMIDE
5.27	IC50	5400	nM	CHEMBL4216368

PubChem BioAssay actives

2 with measured affinity, of 48 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
Flutamide	1210925: Inhibition of AADAC in human kidney microsome	ki	0.6000	uM
1-[4-(4-hydroxyphenoxy)cyclohexyl]-3-[4-(trifluoromethoxy)phenyl]urea	1373470: Inhibition of AADAC (unknown origin) expressed in baculovirus system using CMNA substrate by fluorescence based assay	ic50	5.4000	uM

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Rifampin	increases hydrolysis, decreases reaction, affects reaction, increases expression, decreases acetylation	2
Silicon Dioxide	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
dicrotophos	decreases expression	1
bis(4-nitrophenyl)phosphate	decreases acetylation, decreases reaction	1
fenofibric acid	affects binding, increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression, decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
rifapentine	affects reaction, increases expression, decreases acetylation, decreases reaction	1
benazol P	affects expression	1
paricalcitol	affects cotreatment, increases expression	1
abrine	increases expression	1
Rosiglitazone	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Troglitazone	increases expression	1
Acetaminophen	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Carbon Tetrachloride	decreases reaction, increases expression, affects cotreatment, increases reaction	1
Deferoxamine	affects cotreatment, decreases reaction, increases expression, increases reaction	1
Dimethyl Sulfoxide	increases expression	1
Estradiol	decreases expression	1
Flutamide	increases hydrolysis	1
Folic Acid	increases expression, affects cotreatment	1
Isoflurophate	decreases acetylation, decreases reaction	1
Methotrexate	affects cotreatment, increases expression	1
Phenacetin	increases hydrolysis	1
Phenylmethylsulfonyl Fluoride	decreases acetylation, decreases reaction	1

ChEMBL screening assays

20 unique, capped per target: 19 admet, 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3528581	ADMET	Drug metabolism assessed as loperamide-mediated inhibition of human recombinant AADAC-mediated compound hydrolysis expressed in SF21 cells measured as enzyme activity at 5 uM relative to control	Contributions of arylacetamide deacetylase and carboxylesterase 2 to flutamide hydrolysis in human liver. — Drug Metab Dispos
CHEMBL4187637	Binding	Inhibition of AADAC (unknown origin) expressed in baculovirus system using CMNA substrate by fluorescence based assay	Identification and optimization of soluble epoxide hydrolase inhibitors with dual potency towards fatty acid amide hydrolase. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

482 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00181571	PHASE4	COMPLETED	A Double-Blind Comparison of Concerta and Placebo in Adults With Attention Deficit Hyperactivity Disorder
NCT00181675	PHASE4	COMPLETED	A Double-Blind Comparison of Galantamine HBr and Placebo in Adults With Attention Deficit Hyperactivity Disorder
NCT00181714	PHASE4	COMPLETED	Prevention of Cigarette Smoking in Attention Deficit Hyperactivity Disorder (ADHD) Youth With Concerta
NCT00181948	PHASE4	COMPLETED	Strattera Treatment in Children With ADHD Who Have Poor Response to Stimulant Therapy
NCT00181987	PHASE4	COMPLETED	Concerta in the Treatment of ADHD in Youth and Adults With Bipolar Disorder
NCT00190736	PHASE4	COMPLETED	Efficacy and Safety of Once-Daily Atomoxetine Hydrochloride in Adults With ADHD Over an Extended Period of Time (6 Months)
NCT00190775	PHASE4	COMPLETED	A Randomized, Double-Blind Comparison of Placebo and Atomoxetine Hydrochloride Given Once a Day in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)
NCT00190879	PHASE4	COMPLETED	Placebo-Controlled Study of Atomoxetine Hydrochloride in the Treatment of Adults With ADHD and Comorbid Social Anxiety Disorder
NCT00190957	PHASE4	COMPLETED	Atomoxetine Treatment of Adults With ADHD and Comorbid Alcohol Abuse
NCT00191035	PHASE4	COMPLETED	Maintenance of Benefit With Atomoxetine Hydrochloride in Adolescents With ADHD
NCT00191048	PHASE4	COMPLETED	Treatment With Atomoxetine Hydrochloride in Children and Adolescents With ADHD
NCT00191633	PHASE4	COMPLETED	Study of Atomoxetine in Children With ADHD to Assess Symptomatic and Functional Outcomes
NCT00191906	PHASE4	COMPLETED	Comparison of Atomoxetine and Placebo in Children With Attention-Deficit/Hyperactivity Disorder (ADHD) and/or Reading Disorder (RD)
NCT00216918	PHASE4	COMPLETED	Neuropsychological Functioning in Children With Attention-Deficit/Hyperactivity Disorder.
NCT00221962	PHASE4	COMPLETED	Study of Aripiprazole (Abilify) in Children With ADHD (Attention Deficit Hyperactivity Disorder)
NCT00223561	PHASE4	COMPLETED	Methylphenidate and Driving Ability in Adult Patients With Attention-Deficit Hyperactivity Disorder
NCT00299234	PHASE4	TERMINATED	Atomoxetine for Children With Acquired Attentional Disorders Following Completion of Chemotherapy for ALL
NCT00302406	PHASE4	COMPLETED	Naturalistic Substitution of Concerta in Adult Subject With ADHD Receiving Immediate Release Methylphenidate
NCT00305370	PHASE4	COMPLETED	Aripiprazole Associated With Methylphenidate in Children and Adolescents With Bipolar Disorder and ADHD
NCT00381758	PHASE4	COMPLETED	The COMACS Study: A Comparison of Methylphenidates in an Analog Classroom Setting
NCT00406354	PHASE4	COMPLETED	Comparison of Atomoxetine Versus Placebo in Children and Adolescents With ADHD and Comorbid ODD in Germany
NCT00434213	PHASE4	COMPLETED	Characterization of Dermal Reactions in Pediatric Patients With ADHD Using DAYTRANA
NCT00468143	PHASE4	COMPLETED	A Within-Subject Cross-Over Comparison Between Immediate Release and Extended Release Adderall
NCT00471354	PHASE4	COMPLETED	A Study for Patients With Attention-Deficit/Hyperactivity Disorder Treated With Atomoxetine
NCT00483106	PHASE4	COMPLETED	Clinical and Pharmacogenetic Study of Attention Deficit With Hyperactivity Disorder (ADHD)
NCT00485849	PHASE4	COMPLETED	A Study of Atomoxetine for Attention Deficit and Hyperactive/Impulsive Behaviour Problems in Children With ASD
NCT00485875	PHASE4	COMPLETED	Safety and Efficacy of Switching From a Stimulant Medication to Atomoxetine in Children and Adolescents With ADHD
NCT00486122	PHASE4	COMPLETED	Evaluation of Continuous Symptom Treatment of ADHD
NCT00500071	PHASE4	COMPLETED	Dose-Optimization Study Evaluating the Efficacy, Safety and Tolerability of Vyvanse (Lisdexamfetamine Dimesylate) in Children Aged 6-12 Diagnosed With ADHD
NCT00506727	PHASE4	COMPLETED	Analog Classroom Study Comparison of ADDERALL XR With STRATTERA in Children Aged 6-12 With ADHD
NCT00510276	PHASE4	COMPLETED	Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) With Atomoxetine in Young Adults and Its Effects on Functional Outcomes
NCT00517504	PHASE4	COMPLETED	Methylphenidate Study in Young Children With Developmental Disorders
NCT00517647	PHASE4	COMPLETED	Atomoxetine Pilot Study in Preschool Children With ADHD