DAO

Summary

DAO (D-amino acid oxidase, HGNC:2671) is a protein-coding gene on chromosome 12q24.11, encoding D-amino-acid oxidase (P14920). Catalyzes the oxidative deamination of D-amino acids with broad substrate specificity.

This gene encodes the peroxisomal enzyme D-amino acid oxidase. The enzyme is a flavoprotein which uses flavin adenine dinucleotide (FAD) as its prosthetic group. Its substrates include a wide variety of D-amino acids, but it is inactive on the naturally occurring L-amino acids. Its biological function is not known; it may act as a detoxifying agent which removes D-amino acids that accumulate during aging. In mice, it degrades D-serine, a co-agonist of the NMDA receptor. This gene may play a role in the pathophysiology of schizophrenia.

Source: NCBI Gene 1610 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis (Moderate, GenCC)
• Clinical variants (ClinVar): 101 total
• Phenotypes (HPO): 47
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001917

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2671
Approved symbol	DAO
Name	D-amino acid oxidase
Location	12q24.11
Locus type	gene with protein product
Status	Approved
Aliases	DAMOX, DAAO
Ensembl gene	ENSG00000110887
Ensembl biotype	protein_coding
OMIM	124050
Entrez	1610

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 18 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000228476, ENST00000546552, ENST00000547122, ENST00000547166, ENST00000547768, ENST00000548052, ENST00000549215, ENST00000551281, ENST00000903552, ENST00000903553, ENST00000903554, ENST00000903555, ENST00000903556, ENST00000903557, ENST00000903558, ENST00000903559, ENST00000903560, ENST00000903561, ENST00000903562, ENST00000903563, ENST00000903564, ENST00000903565

RefSeq mRNA: 3 — MANE Select: NM_001917 NM_001413634, NM_001413635, NM_001917

CCDS: CCDS9122

Canonical transcript exons

ENST00000228476 — 11 exons

Exon	Start	End
ENSE00001232078	108887450	108887564
ENSE00001232101	108884998	108885200
ENSE00002335214	108900404	108901043
ENSE00002406428	108880092	108880224
ENSE00003464642	108898679	108898796
ENSE00003483643	108894263	108894367
ENSE00003639258	108890208	108890273
ENSE00003652221	108897006	108897088
ENSE00003652399	108889469	108889545
ENSE00003676921	108899377	108899475
ENSE00003688777	108892982	108893036

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 94.42.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.2823 / max 227.2351, expressed in 66 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127907	1.2435	66
127908	0.0389	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	94.42	gold quality
liver	UBERON:0002107	90.00	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.52	gold quality
cerebellar hemisphere	UBERON:0002245	89.11	gold quality
cerebellar cortex	UBERON:0002129	89.08	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.48	gold quality
cerebellum	UBERON:0002037	88.08	gold quality
nephron tubule	UBERON:0001231	86.88	gold quality
spinal cord	UBERON:0002240	86.86	gold quality
adult mammalian kidney	UBERON:0000082	85.71	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.96	gold quality
kidney epithelium	UBERON:0004819	84.89	gold quality
inferior olivary complex	UBERON:0002127	84.69	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	83.28	silver quality
adult organism	UBERON:0007023	81.22	gold quality
renal glomerulus	UBERON:0000074	80.38	gold quality
pancreatic ductal cell	CL:0002079	80.25	gold quality
metanephric glomerulus	UBERON:0004736	80.03	gold quality
kidney	UBERON:0002113	80.00	gold quality
substantia nigra	UBERON:0002038	76.30	gold quality
paraflocculus	UBERON:0005351	75.44	gold quality
midbrain	UBERON:0001891	74.95	gold quality
olfactory bulb	UBERON:0002264	71.82	gold quality
cortex of kidney	UBERON:0001225	71.48	gold quality
medulla oblongata	UBERON:0001896	70.36	gold quality
cranial nerve II	UBERON:0000941	70.35	gold quality
cerebellar vermis	UBERON:0004720	70.23	gold quality
inferior vagus X ganglion	UBERON:0005363	70.07	gold quality
tibialis anterior	UBERON:0001385	69.95	silver quality
lateral globus pallidus	UBERON:0002476	69.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.07

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

• Creatinine (CTN) was found to inhibit D-amino acid oxidase in uremia (PMID:12053066)
• The association of both DAAO and a new gene G72 from 13q34 with schizophrenia together with activation of DAAO activity by a G72 protein product points to the involvement of this N-methyl-d-aspartate receptor regulation pathway in schizophrenia. (PMID:12364586)
• DAAO was associated with schizophrenia, but not with bipolar disorder (PMID:14966479)
• This study indicates that the DAAO gene may play a significant role in the etiology of schizophrenia in the Han Chinese. (PMID:15464270)
• the human enzyme is a stable homodimer even in the apoprotein form and weakly binds the cofactor in the free form. (PMID:16616139)
• We found elevated cerebellar DAAO activities in post-mortem brain samples from schizophrenic versus normal individuals. (PMID:16828464)
• Crystal structure of human D-amino acid oxidase. (PMID:17088322)
• The genes D-Amino-Acid Oxidase is regulate the glutamate neurotransmission in schizophrenia. (PMID:17250995)
• might exert gene-specific modulating effects on schizophrenia endophenotypes at the population level (PMID:17336946)
• evidence for epistatic interaction between the associated SNPs at DAOActivator and D-amino acid oxidase genes in contributing to schizophrenia risk (PMID:17492767)
• Data suggest that the D-amino acid oxidase activator (DAOA/G30) locus, but not D-amino acid oxidase, may play a role in the pathophysiology of schizophrenia. (PMID:17627036)
• significant associations between the rs3918346 and rs3825251 SNPs of the DAO gene and boys with autism spectrum disorders (PMID:17629951)
• Polymorphisms are not associated with homicidal behavior in korean schizophrenics. (PMID:17728673)
• These data suggest a potential role for DAO in susceptibility to depressive symptoms in schizophrenia, but a more general role for DAO in affective disorders cannot be excluded. (PMID:17890006)
• Some support for the individual involvement of DAO and G72(DAOA)/G30 in the etiology of bipolar disorder. (PMID:18165970)
• a decrease in the synaptic concentration of d-serine as the result of an anomalous increase in hDAAO activity related to hypoexpression of pLG72 may represent a molecular mechanism by which hDAAO and pLG72 are involved in schizophrenia susceptibility (PMID:18544534)
• DAO activity and expression are increased in schizophrenia, but are not related to DAO or G72/G30 genotype (PMID:18560437)
• Flavin-Adenine Dinucleotide binding only slightly increases the stability of human DAAO to denaturation by urea or temperature. (PMID:19309736)
• present Scandinavian results do not verify previous associations between the analyzed DTNBP1, NRG1, DAO, DAOA, and GRM3 gene polymorphisms and schizophrenia (PMID:19439994)
• results suggest that an increase in DAO expression in parts of the brain is involved in aberrant D-amino acid metabolism, may be a potential therapeutic target for schizophrenia (PMID:19685198)
• The present association of dysbindin SNPs with negative symptoms and DAO SNPs with anxiety and depression is a replication of earlier findings and strengthens the hypothesis of a genetic association in schizophrenia. (PMID:19729970)
• increased hippocampal DAAO expression in schizophrenia; could be responsible for a decrease in local D-serine levels leading to a NMDA-receptor hypofunction that is hypothesized to play a major role in the pathophysiology of schizophrenia (PMID:19823762)
• The results of this study showed that DAO does not have an apparent degree of association with Japanese schizophrenia. (PMID:20178891)
• Familial amyotrophic lateral sclerosis is associated with a mutation in D-amino acid oxidase (PMID:20368421)
• This study supported the hypothesis that DAO plays a role in schizophrenia, possibly in a gender-dependent manner in Koreans. (PMID:20483168)
• Data describe the the effects on human D-amino acid oxidase conformation and stability of the substrate D-serine, the FAD cofactor, and two inhibitors (benzoate and chlorpromazine. (PMID:20521334)
• The rs3918347 allele nucleotide polymorphism of DAAO is associated with schizophrenia in Chinese. (PMID:20855273)
• results suggest that genetic variation in DAAO has a significant impact on both regional activation and functional connectivity (PMID:21421061)
• Genetic polymorphisms in DAO are associated with reduced prepulse inhibition and worse performance in working memory tasks and a personality pattern characterized by attenuated anxiety. (PMID:21471957)
• Data suggest that newly synthesized D-amino acid oxidase colocalizes and interacts with pLG72 which appears to be exposed on the external membrane of mitochondria. (PMID:21679769)
• D-amino acid oxidase activity is inhibited by an interaction with bassoon protein at the presynaptic active zone. (PMID:21700703)
• A significant 3 way interaction between G72, DAAO and diagnosis is detected in the right middle temporal gyrus (after family-wise error correction), accounting for 8.5% of the individual variance in activation. (PMID:22239582)
• D-Amino acid oxidase-induced oxidative stress, 3-bromopyruvate and citrate inhibit angiogenesis, exhibiting potent anticancer effects. (PMID:22802136)
• The distribution pattern of D-amino-acid oxidase gene and protein expression in the central nervous system is inversely correlated with D-serine content and distribution. (Review) (PMID:22865246)
• The DAO polymorphism rs10156191 which causes impaired metabolism of circulating histamine is associated with the clinical response in crossed-hypersensitivity to NSAIDs and could be used as a biomarker of response. (PMID:23152756)
• Data indicate that the protein aggregation due to the expression of the G331V d-amino acid oxidase (hDAAO) variant affects cell viability. (PMID:23219954)
• study suggests that NMDA receptor-mediated signalling genes, DAO, PPP3CC, DTNBP1 might be involved in schizophrenia pathogenic mechanisms related to gender (PMID:23497497)
• The results suggest that DAO, which is involved in the N-methyl-d-aspartate receptor regulation, signaling and glutamate metabolism, is the master gene of the genetic associations and interactions underlying schizophrenia. (PMID:23555897)
• Data suggest that acyclovir (ACV) can serve as an active site probe to study the structural basis of temperature-induced conformational changes of d-Amino acid oxidase (DAO). (PMID:23859606)
• Accumulation of d-serine contributes to an ALS pathogenesis, and DAO might be a common therapeutic target for ALS. (PMID:24085347)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	dao.3	ENSDARG00000035601
danio_rerio	dao.1	ENSDARG00000035602
danio_rerio	dao.2	ENSDARG00000035603
mus_musculus	Dao	ENSMUSG00000042096
rattus_norvegicus	Dao	ENSRNOG00000054962
drosophila_melanogaster	Daao2	FBGN0031860
drosophila_melanogaster	Daao1	FBGN0033543
caenorhabditis_elegans		WBGENE00008127
caenorhabditis_elegans		WBGENE00017565
caenorhabditis_elegans		WBGENE00017648
caenorhabditis_elegans		WBGENE00022076

Paralogs (1): DDO (ENSG00000203797)

Protein

Protein identifiers

D-amino-acid oxidase — P14920 (reviewed: P14920)

All UniProt accessions (7): A0A024RBI1, A0A0B4J250, A0A0B4J257, P14920, F8VV35, F8VVT2, F8W152

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the oxidative deamination of D-amino acids with broad substrate specificity. Required to catabolize D-amino acids synthesized endogenously, of gastrointestinal bacterial origin or obtained from the diet, and to use these as nutrients. Regulates the level of D-amino acid neurotransmitters in the brain, such as D-serine, a co-agonist of N-methyl D-aspartate (NMDA) receptors, and may modulate synaptic transmission. Catalyzes the first step of the racemization of D-DOPA to L-DOPA, for possible use in an alternative dopamine biosynthesis pathway. Also catalyzes the first step of the chiral inversion of N(gamma)-nitro-D-arginine methyl ester (D-NNA) to its L-enantiomer L-NNA that acts as a nitric oxide synthase inhibitor. The hydrogen peroxide produced in the reaction provides protection against microbial infection; it contributes to the oxidative killing activity of phagocytic leukocytes and protects against bacterial colonization of the small intestine. Enzyme secreted into the lumen of the intestine may not be catalytically active and could instead be proteolytically cleaved into peptides with antimicrobial activity. The hydrogen peroxide produced in the reaction may also play a role in promoting cellular senescence in response to DNA damage. Could act as a detoxifying agent which removes D-amino acids accumulated during aging.

Subunit / interactions. Homodimer. Interacts with DAOA; the interaction is direct, can occur in the presence or absence of FAD or substrate bound to DAO, and results in a complex containing two DAO homodimers and 2 DAOA monomers. Interacts with BSN (via coiled region); the interaction is direct and inhibits DAO enzyme activity.

Subcellular location. Peroxisome matrix. Cytoplasm. Cytosol. Presynaptic active zone. Secreted.

Tissue specificity. Expressed in the cerebellum, in astrocytes of the cortex, in motor neurons and fibers of the lumbar spinal cord (at protein level). Expressed in goblet cells of the small intestine (at protein level). Increased in the cerebellum of schizophrenic patients (at protein level). Decreased in motor neurons of the spinal cord of patients with amyotrophic lateral sclerosis (at protein level). Expressed in the cerebellum, spinal cord, kidney, and thalamus. Abundant in glia of the cerebellum and predominantly neuronal in the dorsolateral prefrontal cortex, hippocampus and substantia nigra.

Post-translational modifications. Phosphorylated in the cerebellum; probably not by PRKACA, PRKCA or PRKCE. May be S-nitrosylated, which partially inactivates the enzyme.

Disease relevance. Schizophrenia (SCZD) [MIM:181500] A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Amyotrophic lateral sclerosis (ALS) [MIM:105400] A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

Activity regulation. Inhibited by benzoate, crotonate, thiolactomycin, chlorpromazine (CPZ), risperidone, haloperidol, sulpiride, aripiprazole, blonanserin, quetiapine, 4H-furo[3,2-b]pyrrole-5-carboxylic acid, and the substrate analog CF3-D-ala (3,3,3-trifluoro-D-alanine). Inhibited by luvadaxistat, and 6-chloro-1,2-benzisoxazol-3(2H)-one (CBIO). Also inhibited by 3-methylpyrazole-5-carboxylic acid (MPC), 3-hydroxyquinolin-2(1h)-one, 3-hydroxy-5-(2-phenylethyl)pyridin-2(1h)-one, 3-hydroxy-6-(2-phenylethyl)pyridazin-4(1h)-one, 4h-thieno[3,2-B]pyrole-5-carboxylic acid, 4-(4-chlorophenethyl)-1h-pyrrole-2-carboxylic acid, 3-phenethyl-4h-furo[3,2-B]pyrrole-5-carboxylic acid, 3-hydroxy-2h-chromen-2-one, 4-hydroxy-6-[2-(7-hydroxy-2-oxo-4-phenyl-2h-chromen-6-Yl)ethyl]pyridazin-3(2h)-one, 3-(7-hydroxy-2-oxo-4-phenyl-2h-chromen-6-Yl)propanoic acid, 5-chloro thiophene-3-carboxylic acid, 5-chloro thiophene-2-carboxylic acid, (3r)-3-(5,6-Dioxo-1,4,5,6-Tetrahydropyrazin-2-Yl)-2,3-dihydro-1,4-benzoxathiine-7-carbonitrile and 5-{2-[4-(trifluoromethyl)phenyl]ethyl}-1,4-dihydropyrazine-2,3-dione. Meso-tartrate, valproate, duloxetine, eschitalopram, sertraline, biperiden, trihexyphenidyl and olanzapine have no effect on activity.

Induction. Induced in cells following exposure to etoposide.

Similarity. Belongs to the DAMOX/DASOX family.

RefSeq proteins (3): NP_001400563, NP_001400564, NP_001908* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006076	FAD-dep_OxRdtase	Domain
IPR006181	D-amino_acid_oxidase_CS	Conserved_site
IPR023209	DAO	Family

Pfam: PF01266

Enzyme classification (BRENDA):

• EC 1.4.3.3 — D-amino-acid oxidase (BRENDA: 56 organisms, 441 substrates, 402 inhibitors, 480 Km, 348 kcat entries)

Substrate kinetics (BRENDA)

68 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-ALANINE	0.036–800	80
CEPHALOSPORIN C	0.83–28	34
O2	0.06–6.1	25
D-ALA	0.23–46	24
D-PHENYLALANINE	0.06–55.9	18
D-SERINE	0.6–310	16
D-METHIONINE	0.21–143	15
D-PROLINE	0.73–86	15
D-ASPARTATE	2–2000	14
D-PHE	0.04–3.6	14
D-PRO	0.33–1280	13
D-SER	0.909–36.6	13
D-ARGININE	1.3–29	12
D-MET	0.2–4.2	12
D-VAL	0.094–46	11

Catalyzed reactions (Rhea), 12 shown:

• a D-alpha-amino acid + O2 + H2O = a 2-oxocarboxylate + H2O2 + NH4(+) (RHEA:21816)
• D-alanine + O2 + H2O = pyruvate + H2O2 + NH4(+) (RHEA:22688)
• D-lysine + O2 + H2O = 6-amino-2-oxohexanoate + H2O2 + NH4(+) (RHEA:37583)
• D-serine + O2 + H2O = 3-hydroxypyruvate + H2O2 + NH4(+) (RHEA:70951)
• D-phenylalanine + O2 + H2O = 3-phenylpyruvate + H2O2 + NH4(+) (RHEA:70963)
• D-dopa + O2 + H2O = 3-(3,4-dihydroxyphenyl)pyruvate + H2O2 + NH4(+) (RHEA:70971)
• D-valine + O2 + H2O = 3-methyl-2-oxobutanoate + H2O2 + NH4(+) (RHEA:78203)
• D-methionine + O2 + H2O = 4-methylsulfanyl-2-oxobutanoate + H2O2 + NH4(+) (RHEA:78207)
• D-leucine + O2 + H2O = 4-methyl-2-oxopentanoate + H2O2 + NH4(+) (RHEA:78211)
• D-tryptophan + O2 + H2O = indole-3-pyruvate + H2O2 + NH4(+) (RHEA:78247)
• D-proline + O2 = 1-pyrroline-2-carboxylate + H2O2 (RHEA:78259)
• D-cysteine + O2 + H2O = 2-oxo-3-sulfanylpropanoate + H2O2 + NH4(+) (RHEA:78791)

UniProt features (81 total): binding site 31, strand 15, helix 15, sequence variant 7, mutagenesis site 6, region of interest 2, sequence conflict 2, chain 1, short sequence motif 1, turn 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
7U9U	X-RAY DIFFRACTION	1.66
3ZNN	X-RAY DIFFRACTION	1.9
7U9S	X-RAY DIFFRACTION	2.1
8HY5	X-RAY DIFFRACTION	2.1
3G3E	X-RAY DIFFRACTION	2.2
6KBP	X-RAY DIFFRACTION	2.25
3ZNO	X-RAY DIFFRACTION	2.3
3ZNP	X-RAY DIFFRACTION	2.4
4QFC	X-RAY DIFFRACTION	2.4
3CUK	X-RAY DIFFRACTION	2.49
2DU8	X-RAY DIFFRACTION	2.5
3W4I	X-RAY DIFFRACTION	2.5
2E4A	X-RAY DIFFRACTION	2.6
5ZJ9	X-RAY DIFFRACTION	2.6
5ZJA	X-RAY DIFFRACTION	2.6
2E82	X-RAY DIFFRACTION	2.7
3W4J	X-RAY DIFFRACTION	2.74
3ZNQ	X-RAY DIFFRACTION	2.75
4QFD	X-RAY DIFFRACTION	2.85
3W4K	X-RAY DIFFRACTION	2.86
2E48	X-RAY DIFFRACTION	2.9
2E49	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14920-F1	96.26	0.94

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (31): 43; 44; 45; 49; 50; 51; 53; 163; 164; 182; 224; 228 …

Mutagenesis-validated functional residues (6):

Position	Phenotype
31	increases affinity for the fad cofactor and d-serine. decreases the cellular ratio of d-serine to l-serine.
120	increases activity and fad-binding. decreases protein localization to peroxisomes with protein mislocalized to the nucle
183	abolishes activity. impairs the ability to bind the fad cofactor. impairs targeting to peroxisomes and results in abnorm
219	increases catalytic efficiency and inhibition by benzoate.
224	decreases activity.
279	increases affinity for the fad cofactor and d-serine. decreases the cellular ratio of d-serine to l-serine.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-389661	Glyoxylate metabolism and glycine degradation
R-HSA-9033241	Peroxisomal protein import

MSigDB gene sets: 228 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, MODULE_93, GOBP_DIGESTION, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, MODULE_545, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_METABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_DOPAMINE_METABOLIC_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (13): L-leucine metabolic process (GO:0006551), L-proline catabolic process (GO:0006562), digestion (GO:0007586), D-amino acid catabolic process (GO:0019478), D-serine catabolic process (GO:0036088), dopamine biosynthetic process (GO:0042416), D-alanine catabolic process (GO:0055130), obsolete D-serine metabolic process (GO:0070178), neutrophil-mediated killing of gram-negative bacterium (GO:0070945), D-amino acid metabolic process (GO:0046416), obsolete killing by host of symbiont cells (GO:0051873), L-amino acid catabolic process (GO:0170035), proteinogenic amino acid catabolic process (GO:0170040)

GO Molecular Function (7): D-amino-acid oxidase activity (GO:0003884), D-amino-acid dehydrogenase activity (GO:0008718), identical protein binding (GO:0042802), glycine oxidase activity (GO:0043799), FAD binding (GO:0071949), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (10): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), peroxisomal matrix (GO:0005782), cytosol (GO:0005829), presynaptic active zone (GO:0048786), extracellular region (GO:0005576), mitochondrial outer membrane (GO:0005741), peroxisome (GO:0005777), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
L-amino acid metabolic process	2
proteinogenic amino acid metabolic process	2
amino acid catabolic process	2
D-amino acid catabolic process	2
carboxylic acid catabolic process	2
branched-chain amino acid metabolic process	1
L-proline metabolic process	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
multicellular organismal process	1
D-amino acid metabolic process	1
non-proteinogenic amino acid catabolic process	1
dopamine metabolic process	1
catecholamine biosynthetic process	1
defense response to Gram-negative bacterium	1
neutrophil-mediated killing of bacterium	1
non-proteinogenic amino acid metabolic process	1
primary methylamine oxidase activity	1
oxidoreductase activity, acting on the CH-NH2 group of donors	1
protein binding	1
aliphatic amine oxidase activity	1
flavin adenine dinucleotide binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
peroxisome	1
microbody lumen	1
cytoplasm	1
presynapse	1
mitochondrial membrane	1
organelle outer membrane	1
microbody	1
cell junction	1

Protein interactions and networks

STRING

2109 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DAO	DAOA	P59103	983
DAO	SRR	Q9GZT4	899
DAO	DTNBP1	Q96EV8	779
DAO	MPST	P25325	730
DAO	CTH	P32929	704
DAO	PRODH	O43272	694
DAO	PRODH	O43272	682
DAO	DISC1	Q9NRI5	682
DAO	P0DN79	P0DN79	665
DAO	H7C2H4	H7C2H4	663
DAO	RGS4	P49798	613
DAO	ZNF804A	Q7Z570	609
DAO	COMT	P21964	604
DAO	PPP3CC	P48454	586
DAO	AGXT	P21549	561

IntAct

11 interactions, top by confidence:

A	B	Type	Score
DAO	PRKAB2	psi-mi:“MI:0915”(physical association)	0.800
PRKAB2	DAO	psi-mi:“MI:0915”(physical association)	0.800
DAO	KLHL42	psi-mi:“MI:0915”(physical association)	0.620
DAO	EP300	psi-mi:“MI:0915”(physical association)	0.370
DAO	NME2	psi-mi:“MI:0914”(association)	0.350
DAO	HBB	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): PRKAB2 (Two-hybrid), NME2 (Affinity Capture-MS), GSTM1 (Affinity Capture-MS), KLHL42 (Affinity Capture-MS), DAOA (Far Western), DAOA (Co-purification), DAO (Co-purification), DAO (Reconstituted Complex), DAO (Synthetic Lethality), HBB (Affinity Capture-MS), KLHL42 (Affinity Capture-MS), TRAF7 (Affinity Capture-MS), DAO (Protein-peptide), EP300 (Two-hybrid), PRKAB2 (Two-hybrid)

ESM2 similar proteins: A0A095C6S0, A0A095CCB2, A0A0F9XIF1, A0A346RP51, A2QX24, A2V9Y8, A8NF99, A8WXM1, B8NI25, C0HMB0, C0HMB1, C4R4G9, C4R6B0, C5FM59, D4AWH1, D4CZZ4, F2S701, F2T0M2, G3KLH4, J9VPE7, J9VRT1, O01739, O35078, O43029, O45307, P00371, P14920, P18894, P22942, P24552, P36591, P46882, P80324, Q05531, Q0CS93, Q0D1P2, Q0UI02, Q10058, Q19564, Q4WD43

Diamond homologs: A0A7E6FSU6, A2V9Y8, A3KCL7, A8WXM1, A8XJ44, D3ZDM7, J9VRT1, O01739, O35078, O45307, P00371, P14920, P18894, P22942, P31228, Q19564, Q1AYM8, Q556W1, Q922Z0, Q95XG9, Q99042, Q99489, Q9HGY3, Q9X7P6, Q9Z1M5, Q9Z302, T2HG31, A5U3S4, P9WP26, P9WP27, Q7X2D3, Q9Y7N4, A0A499UB99, C0HMB0, A0A095C6S0, A0A095CCB2, J9VPE7, P24552, P80324, Q88Q83

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	28
Benign	19

Top pathogenic / likely-pathogenic (0)

SpliceAI

1595 predictions. Top by Δscore:

Variant	Effect	Δscore
12:108885196:G:GT	donor_gain	1.0000
12:108885196:GAGGC:G	donor_gain	1.0000
12:108885197:AGGC:A	donor_gain	1.0000
12:108885198:GGCG:G	donor_gain	1.0000
12:108885199:GC:G	donor_gain	1.0000
12:108885201:G:GG	donor_gain	1.0000
12:108885205:G:GG	donor_gain	1.0000
12:108898667:A:AG	acceptor_gain	1.0000
12:108898675:CTA:C	acceptor_loss	1.0000
12:108898676:TA:T	acceptor_loss	1.0000
12:108898677:A:AG	acceptor_gain	1.0000
12:108898677:AG:A	acceptor_gain	1.0000
12:108898677:AGG:A	acceptor_loss	1.0000
12:108898678:G:GG	acceptor_gain	1.0000
12:108898678:GG:G	acceptor_gain	1.0000
12:108898794:AAG:A	donor_loss	1.0000
12:108899371:TTCCA:T	acceptor_loss	1.0000
12:108899374:CAGAA:C	acceptor_loss	1.0000
12:108899375:A:AG	acceptor_gain	1.0000
12:108899375:A:T	acceptor_loss	1.0000
12:108899375:AGAAT:A	acceptor_gain	1.0000
12:108899376:G:GC	acceptor_gain	1.0000
12:108899376:GA:G	acceptor_gain	1.0000
12:108899376:GAA:G	acceptor_gain	1.0000
12:108899376:GAAT:G	acceptor_gain	1.0000
12:108899376:GAATG:G	acceptor_gain	1.0000
12:108899473:GAG:G	donor_gain	1.0000
12:108899473:GAGG:G	donor_loss	1.0000
12:108899476:G:T	donor_loss	1.0000
12:108899477:T:G	donor_loss	1.0000

AlphaMissense

2251 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:108894298:C:G	C181W	0.997
12:108894351:G:C	R199P	0.992
12:108894297:G:A	C181Y	0.988
12:108890227:A:C	S136R	0.987
12:108890229:C:A	S136R	0.987
12:108890229:C:G	S136R	0.987
12:108894295:C:A	N180K	0.986
12:108894295:C:G	N180K	0.986
12:108900415:C:A	N308K	0.986
12:108900415:C:G	N308K	0.986
12:108889503:G:C	R115P	0.985
12:108885112:G:C	A36P	0.983
12:108885160:T:A	W52R	0.983
12:108885160:T:C	W52R	0.983
12:108900420:G:A	G310D	0.983
12:108894296:T:C	C181R	0.982
12:108890264:T:C	L148P	0.981
12:108887479:T:C	L75P	0.980
12:108889499:T:C	F114L	0.980
12:108889501:T:A	F114L	0.980
12:108889501:T:G	F114L	0.980
12:108887536:G:A	G94D	0.979
12:108898699:G:A	G239E	0.979
12:108890213:G:A	G131D	0.978
12:108885040:G:T	G12W	0.977
12:108885053:C:A	A16D	0.976
12:108894291:T:A	V179D	0.976
12:108900435:G:A	G315E	0.976
12:108900457:T:G	C322W	0.976
12:108885041:G:A	G12E	0.975

dbSNP variants (sampled 300 via entrez): RS1000026799 (12:108895570 G>A,T), RS1000215365 (12:108879094 C>T), RS1000295499 (12:108882623 T>A), RS1000539784 (12:108901178 A>G,T), RS1000648028 (12:108879994 G>T), RS1000716566 (12:108885784 C>T), RS1001030189 (12:108884086 G>A), RS1001225805 (12:108889580 C>A,T), RS1001256312 (12:108895142 G>A,C), RS1001467203 (12:108882977 C>A,T), RS1001534126 (12:108878225 T>C), RS1001541377 (12:108883910 C>T), RS1001572564 (12:108895386 T>C), RS1001771502 (12:108889641 C>A,G,T), RS1001874850 (12:108885231 G>A)

Disease associations

OMIM: gene MIM:124050 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
amyotrophic lateral sclerosis	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
amyotrophic lateral sclerosis	Refuted	AD

Mondo (1): amyotrophic lateral sclerosis (MONDO:0004976)

Orphanet (1): Amyotrophic lateral sclerosis (Orphanet:803)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000217	Xerostomia
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000739	Anxiety
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001308	Tongue fasciculations
HP:0001347	Hyperreflexia
HP:0001618	Dysphonia
HP:0001824	Weight loss
HP:0002015	Dysphagia
HP:0002094	Dyspnea
HP:0002145	Frontotemporal dementia
HP:0002180	Neurodegeneration
HP:0002307	Drooling
HP:0002313	Spastic paraparesis
HP:0002360	Sleep disturbance
HP:0002380	Fasciculations
HP:0002463	Language impairment
HP:0002878	Respiratory failure
HP:0003202	Skeletal muscle atrophy
HP:0003324	Generalized muscle weakness
HP:0003376	Steppage gait
HP:0003394	Muscle spasm
HP:0003470	Paralysis
HP:0003484	Upper limb muscle weakness
HP:0003487	Babinski sign
HP:0003693	Distal amyotrophy
HP:0004326	Cachexia

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5485 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 71,513 (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
CHEMBL161	CEFTRIAXONE	4	71,135
CHEMBL2338801	LUVADAXISTAT	2	378

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

Binding affinities (BindingDB)

272 measured of 284 human assays (285 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-hydroxy-6-[2-(4-phenylphenyl)ethyl]diazinan-3-one	IC50	1.2 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
6-[2-(3-fluorophenyl)ethyl]-1,2-dihydropyridazine-3,4-dione	IC50	1.4 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
6-[2-(3,5-difluorophenyl)ethyl]-1,2-dihydropyridazine-3,4-dione	IC50	1.5 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
4-hydroxy-6-[2-[3-(hydroxymethyl)phenyl]ethyl]diazinan-3-one	IC50	2.1 nM	US-9212147: Dihydroxy aromatic heterocyclic compound
6-[2-(3-methoxyphenyl)ethyl]-1,2-dihydropyridazine-3,4-dione	IC50	2.1 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
3-hydroxy-6-(phenoxymethyl)diazinan-4-one	IC50	2.2 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
4-hydroxy-6-(2-naphthalen-1-ylethyl)diazinan-3-one	IC50	2.3 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
6-[(3-fluorophenoxy)methyl]-3-hydroxydiazinan-4-one	IC50	2.3 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
3-hydroxy-6-[(E)-2-phenylethenyl]diazinan-4-one	IC50	2.4 nM	US-9212147: Dihydroxy aromatic heterocyclic compound
4-hydroxy-6-[2-(3-methylphenyl)ethyl]diazinan-3-one	IC50	2.5 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
4-hydroxy-6-(4-phenylbutyl)diazinan-3-one	IC50	2.5 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
6-[(4-chlorophenoxy)methyl]pyridazine-3,4-dione	IC50	2.7 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
6-[(4-fluorophenoxy)methyl]-3-hydroxydiazinan-4-one	IC50	2.9 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
6-[2-(4-methoxyphenyl)ethyl]-1,2-dihydropyridazine-3,4-dione	IC50	2.9 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
3-hydroxyquinolin-2(1H)-one, 3	IC50	3 nM
naphthyridinone analog., 27	IC50	3 nM
4-hydroxy-6-[2-(2-methylphenyl)ethyl]diazinan-3-one	IC50	3.3 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
6-[(2-fluorophenoxy)methyl]-3-hydroxydiazinan-4-one	IC50	3.5 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
6-[(4-chlorophenyl)methylsulfanyl]-4-hydroxydiazinan-3-one	IC50	3.7 nM	US-9290456: Pyridazinone compounds and their use as DAAO inhibitors
3-hydroxy-6-(2-phenylethyl)diazinan-4-one	IC50	3.8 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
3-hydroxy-5-(2-phenylethyl)-1H-pyridin-2-one	IC50	3.9 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
3-hydroxyquinolin-2(1H)-one, 10	IC50	4 nM
6-(2-cyclohexylethyl)pyridazine-3,4-dione	IC50	4.7 nM	US-9212147: Dihydroxy aromatic heterocyclic compound
3-hydroxyquinolin-2(1H)-one, 26	IC50	5 nM
3-hydroxy-6-[(4-methoxyphenyl)sulfanylmethyl]diazinan-4-one	IC50	5.2 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
6-[2-(4-fluoro-3-methylphenyl)ethyl]pyridazine-3,4-dione	IC50	6 nM	US-9290456: Pyridazinone compounds and their use as DAAO inhibitors
4-hydroxy-6-[2-(4-methylphenyl)ethyl]diazinan-3-one	IC50	6.1 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
6-[2-(4-tert-butylphenyl)ethyl]-4-hydroxydiazinan-3-one	IC50	6.6 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
6-butylpyridazine-3,4-dione	IC50	6.9 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
3-hydroxyquinolin-2(1H)-one, 6	IC50	8 nM
3-hydroxyquinolin-2(1H)-one, 15	IC50	8 nM
naphthyridinone analog.,18	IC50	8 nM
6-(4-hydroxybutyl)pyridazine-3,4-dione	IC50	8.1 nM	US-9212147: Dihydroxy aromatic heterocyclic compound
6-(3-methoxypropyl)pyridazine-3,4-dione	IC50	8.1 nM	US-10202399: Dihydroxy aromatic heterocyclic compound
6-[2-(3-chlorophenyl)ethyl]pyridazine-3,4-dione	IC50	8.4 nM	US-9290456: Pyridazinone compounds and their use as DAAO inhibitors
4H-furo[3,2-b]pyrrole-5-carboxylic acid	IC50	9 nM
3-hydroxyquinolin-2(1H)-one, 5	IC50	9 nM
4-hydroxy-6-[2-[4-(hydroxymethyl)phenyl]ethyl]diazinan-3-one	IC50	10 nM	US-9212147: Dihydroxy aromatic heterocyclic compound
6-[2-(3,4-difluorophenyl)ethyl]-4-hydroxydiazinan-3-one	IC50	10 nM	US-9290456: Pyridazinone compounds and their use as DAAO inhibitors
6-[2-[3,5-difluoro-4-(trifluoromethyl)phenyl]ethyl]pyridazine-3,4-dione	IC50	10 nM	US-9290456: Pyridazinone compounds and their use as DAAO inhibitors
3-hydroxyquinolin-2(1H)-one, 4	IC50	10 nM
6-(2-phenylethyl)-1,2-dihydropyridazine-3,4-dione	IC50	10 nM	US-9290456: Pyridazinone compounds and their use as DAAO inhibitors
6-[2-(4-fluorophenyl)ethyl]-1,2-dihydropyridazine-3,4-dione	IC50	10 nM	US-9290456: Pyridazinone compounds and their use as DAAO inhibitors
6-Ethyl-4-hydroxypyridazin-3(2H)-one	IC50	11 nM	US-9750748: Pyridazinones as DAAO enzyme inhibitors
3-hydroxy-6-[[4-(hydroxymethyl)phenyl]sulfanylmethyl]diazinan-4-one	IC50	12 nM	US-9212147: Dihydroxy aromatic heterocyclic compound
6-benzyl-4-hydroxydiazinan-3-one	IC50	12 nM	US-9290456: Pyridazinone compounds and their use as DAAO inhibitors
6-[(4-chlorophenyl)methyl]pyridazine-3,4-dione	IC50	12 nM	US-9290456: Pyridazinone compounds and their use as DAAO inhibitors
6-[(3-methylphenyl)methyl]pyridazine-3,4-dione	IC50	12 nM	US-9290456: Pyridazinone compounds and their use as DAAO inhibitors
6-[2-[2-methyl-4-(trifluoromethyl)phenyl]ethyl]pyridazine-3,4-dione	IC50	12 nM	US-9290456: Pyridazinone compounds and their use as DAAO inhibitors
6-[2-[4-(trifluoromethyl)phenyl]ethyl]-1,2-dihydropyridazine-3,4-dione	IC50	12 nM	US-10202399: Dihydroxy aromatic heterocyclic compound

ChEMBL bioactivities

900 potent at pChembl≥5 of 942 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Ki	1	nM	CHEMBL6192688
8.92	IC50	1.2	nM	CHEMBL3904227
8.85	IC50	1.4	nM	CHEMBL2338797
8.85	IC50	1.4	nM	CHEMBL507614
8.82	IC50	1.5	nM	CHEMBL2338803
8.77	Ki	1.7	nM	CHEMBL2375520
8.70	IC50	2	nM	CHEMBL2338795
8.70	Kd	2	nM	CHEMBL468495
8.68	IC50	2.1	nM	CHEMBL2338799
8.68	IC50	2.1	nM	CHEMBL3965781
8.66	IC50	2.2	nM	CHEMBL2338794
8.66	IC50	2.2	nM	CHEMBL3925924
8.64	IC50	2.3	nM	CHEMBL3941866
8.64	IC50	2.3	nM	CHEMBL3899415
8.62	IC50	2.4	nM	CHEMBL2338786
8.62	IC50	2.4	nM	CHEMBL2338798
8.62	IC50	2.4	nM	CHEMBL3900453
8.60	IC50	2.5	nM	CHEMBL3985690
8.60	IC50	2.5	nM	CHEMBL3913880
8.60	Kd	2.5	nM	CHEMBL495187
8.57	IC50	2.7	nM	CHEMBL2338790
8.57	IC50	2.7	nM	CHEMBL5746650
8.54	IC50	2.9	nM	CHEMBL2338802
8.54	IC50	2.9	nM	CHEMBL3964892
8.54	IC50	2.9	nM	CHEMBL3950593
8.52	IC50	3	nM	CHEMBL467661
8.52	IC50	3	nM	CHEMBL494235
8.51	IC50	3.1	nM	CHEMBL2338800
8.51	IC50	3.09	nM	CHEMBL2375520
8.51	Kd	3.1	nM	CHEMBL492591
8.48	IC50	3.3	nM	CHEMBL3948236
8.46	Ki	3.5	nM	CHEMBL507614
8.46	IC50	3.5	nM	CHEMBL3914284
8.43	IC50	3.7	nM	CHEMBL3930320
8.42	IC50	3.8	nM	CHEMBL2338786
8.42	IC50	3.8	nM	CHEMBL3900453
8.41	IC50	3.9	nM	CHEMBL2338785
8.40	IC50	4	nM	CHEMBL495187
8.40	IC50	4	nM	CHEMBL146227
8.36	IC50	4.4	nM	CHEMBL2338795
8.34	IC50	4.6	nM	CHEMBL3985690
8.34	Kd	4.6	nM	CHEMBL467660
8.33	IC50	4.7	nM	CHEMBL2338789
8.31	IC50	4.9	nM	CHEMBL2338787
8.30	IC50	5	nM	CHEMBL467660
8.29	IC50	5.1	nM	CHEMBL2338794
8.28	IC50	5.2	nM	CHEMBL3889972
8.28	IC50	5.2	nM	CHEMBL5904941
8.27	IC50	5.37	nM	CHEMBL507614
8.26	IC50	5.5	nM	CHEMBL3925924

PubChem BioAssay actives

406 with measured affinity, of 672 total; 50 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
4H-thieno[3,2-b]pyrrole-5-carboxylic acid	735291: Inhibition of human recombinant DAAO after 30 mins by plate reader analysis	ic50	0.0014	uM
6-[2-(3-fluorophenyl)ethyl]-1,2-dihydropyridazine-3,4-dione	735291: Inhibition of human recombinant DAAO after 30 mins by plate reader analysis	ic50	0.0014	uM
6-[2-(3,5-difluorophenyl)ethyl]-1,2-dihydropyridazine-3,4-dione	735291: Inhibition of human recombinant DAAO after 30 mins by plate reader analysis	ic50	0.0015	uM
5,6-dichloro-1,2-benzoxazol-3-one	745647: Competitive inhibition of human recombinant DAAO by Michaelis-Menten plot analysis in presence of D-serine	ki	0.0017	uM
3-hydroxy-1H-1,8-naphthyridin-2-one	1799107: Biacore Binding of DAAO Inhibitors from Article 10.1021/jm900128w: “Discovery, SAR, and pharmacokinetics of a novel 3-hydroxyquinolin-2(1H)-one series of potent D-amino acid oxidase (DAAO) inhibitors.”	kd	0.0020	uM
6-[2-(2-fluorophenyl)ethyl]-1,2-dihydropyridazine-3,4-dione	735291: Inhibition of human recombinant DAAO after 30 mins by plate reader analysis	ic50	0.0020	uM
6-[2-(3-methoxyphenyl)ethyl]-1,2-dihydropyridazine-3,4-dione	735291: Inhibition of human recombinant DAAO after 30 mins by plate reader analysis	ic50	0.0021	uM
6-(phenoxymethyl)-1,2-dihydropyridazine-3,4-dione	735291: Inhibition of human recombinant DAAO after 30 mins by plate reader analysis	ic50	0.0022	uM
6-[2-[3-(trifluoromethyl)phenyl]ethyl]-1,2-dihydropyridazine-3,4-dione	735291: Inhibition of human recombinant DAAO after 30 mins by plate reader analysis	ic50	0.0024	uM
6-(2-phenylethyl)-1,2-dihydropyridazine-3,4-dione	735288: Inhibition of human full length DAAO overexpressed in HEK293 cells after 30 mins by plate reader analysis	ic50	0.0024	uM
5-chloro-3-hydroxy-1H-quinolin-2-one	619912: Binding affinity to human recombinant DAAO by isothermal titration calorimeter analysis	kd	0.0025	uM
6-[2-(4-chlorophenyl)ethyl]-1,2-dihydropyridazine-3,4-dione	735291: Inhibition of human recombinant DAAO after 30 mins by plate reader analysis	ic50	0.0027	uM
6-[2-(4-methoxyphenyl)ethyl]-1,2-dihydropyridazine-3,4-dione	735291: Inhibition of human recombinant DAAO after 30 mins by plate reader analysis	ic50	0.0029	uM
5-chloro-6-fluoro-3-hydroxy-1H-1,8-naphthyridin-2-one	1799106: DAAO in Vitro Activity Assay from Article 10.1021/jm900128w: “Discovery, SAR, and pharmacokinetics of a novel 3-hydroxyquinolin-2(1H)-one series of potent D-amino acid oxidase (DAAO) inhibitors.”	ic50	0.0030	uM
8-fluoro-3-hydroxy-1H-quinolin-2-one	1799106: DAAO in Vitro Activity Assay from Article 10.1021/jm900128w: “Discovery, SAR, and pharmacokinetics of a novel 3-hydroxyquinolin-2(1H)-one series of potent D-amino acid oxidase (DAAO) inhibitors.”	ic50	0.0030	uM
6-[2-(4-fluorophenyl)ethyl]-1,2-dihydropyridazine-3,4-dione	735291: Inhibition of human recombinant DAAO after 30 mins by plate reader analysis	ic50	0.0031	uM
4H-furo[3,2-b]pyrrole-5-carboxylic acid	619913: Binding affinity to human recombinant DAAO by kinetic study scintillation proximity assay	kd	0.0031	uM
3-hydroxy-5-(2-phenylethyl)-1H-pyridin-2-one	735291: Inhibition of human recombinant DAAO after 30 mins by plate reader analysis	ic50	0.0039	uM
3-hydroxy-1H-quinolin-2-one	1799106: DAAO in Vitro Activity Assay from Article 10.1021/jm900128w: “Discovery, SAR, and pharmacokinetics of a novel 3-hydroxyquinolin-2(1H)-one series of potent D-amino acid oxidase (DAAO) inhibitors.”	ic50	0.0040	uM
5-chloro-6-fluoro-3-hydroxy-1H-quinolin-2-one	619914: Binding affinity to human recombinant DAAO by steady state study scintillation proximity assay	kd	0.0046	uM
6-(2-cyclohexylethyl)-1,2-dihydropyridazine-3,4-dione	735291: Inhibition of human recombinant DAAO after 30 mins by plate reader analysis	ic50	0.0047	uM
6-(1-phenylethyl)-1,2-dihydropyridazine-3,4-dione	735291: Inhibition of human recombinant DAAO after 30 mins by plate reader analysis	ic50	0.0049	uM
4-[2-(4-chlorophenyl)ethyl]-1H-pyrrole-2-carboxylic acid	745647: Competitive inhibition of human recombinant DAAO by Michaelis-Menten plot analysis in presence of D-serine	ki	0.0072	uM
5-[(3R)-7-[(3-fluorophenyl)methoxymethyl]-2,3-dihydro-1,4-benzoxathiin-3-yl]-1,4-dihydropyrazine-2,3-dione	1909806: Inhibition of recombinant full length human DAO preincubated with compound for 20 mins measured after 4 hrs by Amplex red and horseradish peroxidase based fluorescence assay	ic50	0.0080	uM
5-ethyl-3-hydroxy-1H-quinolin-2-one	1799106: DAAO in Vitro Activity Assay from Article 10.1021/jm900128w: “Discovery, SAR, and pharmacokinetics of a novel 3-hydroxyquinolin-2(1H)-one series of potent D-amino acid oxidase (DAAO) inhibitors.”	ic50	0.0080	uM
5-fluoro-3-hydroxy-1H-quinolin-2-one	1799106: DAAO in Vitro Activity Assay from Article 10.1021/jm900128w: “Discovery, SAR, and pharmacokinetics of a novel 3-hydroxyquinolin-2(1H)-one series of potent D-amino acid oxidase (DAAO) inhibitors.”	ic50	0.0080	uM
6-[2-[2-(trifluoromethyl)phenyl]ethyl]-1,2-dihydropyridazine-3,4-dione	735291: Inhibition of human recombinant DAAO after 30 mins by plate reader analysis	ic50	0.0084	uM
5-[(3R)-3-methyl-7-(trifluoromethyl)-2H-1,4-benzoxathiin-3-yl]-1,4-dihydropyrazine-2,3-dione	1909806: Inhibition of recombinant full length human DAO preincubated with compound for 20 mins measured after 4 hrs by Amplex red and horseradish peroxidase based fluorescence assay	ic50	0.0090	uM
5-[(3R)-7-chloro-3-methyl-2H-1,4-benzoxathiin-3-yl]-1,4-dihydropyrazine-2,3-dione	1909806: Inhibition of recombinant full length human DAO preincubated with compound for 20 mins measured after 4 hrs by Amplex red and horseradish peroxidase based fluorescence assay	ic50	0.0090	uM
6-fluoro-3-hydroxy-1H-quinolin-2-one	1799106: DAAO in Vitro Activity Assay from Article 10.1021/jm900128w: “Discovery, SAR, and pharmacokinetics of a novel 3-hydroxyquinolin-2(1H)-one series of potent D-amino acid oxidase (DAAO) inhibitors.”	ic50	0.0090	uM
7-fluoro-3-hydroxy-1H-quinolin-2-one	1799106: DAAO in Vitro Activity Assay from Article 10.1021/jm900128w: “Discovery, SAR, and pharmacokinetics of a novel 3-hydroxyquinolin-2(1H)-one series of potent D-amino acid oxidase (DAAO) inhibitors.”	ic50	0.0100	uM
5-[2-(4-chlorophenyl)ethyl]-1-hydroxypyrimidine-2,4-dione	1909806: Inhibition of recombinant full length human DAO preincubated with compound for 20 mins measured after 4 hrs by Amplex red and horseradish peroxidase based fluorescence assay	ic50	0.0110	uM
6-[2-[4-(trifluoromethyl)phenyl]ethyl]-1,2-dihydropyridazine-3,4-dione	735291: Inhibition of human recombinant DAAO after 30 mins by plate reader analysis	ic50	0.0120	uM
3-hydroxychromen-2-one	745647: Competitive inhibition of human recombinant DAAO by Michaelis-Menten plot analysis in presence of D-serine	ki	0.0130	uM
5-[(3R)-7-(difluoromethyl)-2,3-dihydro-1,4-benzoxathiin-3-yl]-1,4-dihydropyrazine-2,3-dione	1909806: Inhibition of recombinant full length human DAO preincubated with compound for 20 mins measured after 4 hrs by Amplex red and horseradish peroxidase based fluorescence assay	ic50	0.0130	uM
6-chloro-1,2-benzoxazol-3-one	619913: Binding affinity to human recombinant DAAO by kinetic study scintillation proximity assay	kd	0.0130	uM
6-(3-phenylpropyl)-1,2-dihydropyridazine-3,4-dione	735291: Inhibition of human recombinant DAAO after 30 mins by plate reader analysis	ic50	0.0130	uM
6-[2-(3,5-dimethoxyphenyl)ethyl]-1,2-dihydropyridazine-3,4-dione	735291: Inhibition of human recombinant DAAO after 30 mins by plate reader analysis	ic50	0.0130	uM
3-hydroxy-5-methyl-1H-quinolin-2-one	1799106: DAAO in Vitro Activity Assay from Article 10.1021/jm900128w: “Discovery, SAR, and pharmacokinetics of a novel 3-hydroxyquinolin-2(1H)-one series of potent D-amino acid oxidase (DAAO) inhibitors.”	ic50	0.0160	uM
6-[(4-chlorophenyl)methyl]-1,2-dihydropyridazine-3,4-dione	1909806: Inhibition of recombinant full length human DAO preincubated with compound for 20 mins measured after 4 hrs by Amplex red and horseradish peroxidase based fluorescence assay	ic50	0.0170	uM
(3R)-3-(5,6-dioxo-1,4-dihydropyrazin-2-yl)-2,3-dihydro-1,4-benzoxathiine-7-carbonitrile	1909806: Inhibition of recombinant full length human DAO preincubated with compound for 20 mins measured after 4 hrs by Amplex red and horseradish peroxidase based fluorescence assay	ic50	0.0200	uM
(3R)-3-(5,6-dioxo-1,4-dihydropyrazin-2-yl)-3-methyl-2H-1,4-benzoxathiine-7-carbonitrile	1909806: Inhibition of recombinant full length human DAO preincubated with compound for 20 mins measured after 4 hrs by Amplex red and horseradish peroxidase based fluorescence assay	ic50	0.0200	uM
5-[(3R)-7-chloro-2,3-dihydro-1,4-benzoxathiin-3-yl]-1,4-dihydropyrazine-2,3-dione	1909806: Inhibition of recombinant full length human DAO preincubated with compound for 20 mins measured after 4 hrs by Amplex red and horseradish peroxidase based fluorescence assay	ic50	0.0210	uM
5-[(3R)-7-methylsulfonyl-2,3-dihydro-1,4-benzoxathiin-3-yl]-1,4-dihydropyrazine-2,3-dione	1909806: Inhibition of recombinant full length human DAO preincubated with compound for 20 mins measured after 4 hrs by Amplex red and horseradish peroxidase based fluorescence assay	ic50	0.0250	uM
5-[7-(trifluoromethyl)-2,3-dihydro-1,4-benzoxathiin-3-yl]-1,4-dihydropyrazine-2,3-dione	1909806: Inhibition of recombinant full length human DAO preincubated with compound for 20 mins measured after 4 hrs by Amplex red and horseradish peroxidase based fluorescence assay	ic50	0.0250	uM
1-hydroxy-5-(2-phenylethyl)pyrimidine-2,4-dione	1909806: Inhibition of recombinant full length human DAO preincubated with compound for 20 mins measured after 4 hrs by Amplex red and horseradish peroxidase based fluorescence assay	ic50	0.0280	uM
3-[(6-fluoronaphthalen-2-yl)methylsulfanyl]-1,4-dihydro-1,2,4-triazine-5,6-dione	1291231: Inhibition of recombinant human DAAO assessed as oxidative deamination of D-serine in presence of molecular oxygen and FAD after 20 mins	ic50	0.0300	uM
3-[(4-chlorophenyl)methylsulfanyl]-1,4-dihydro-1,2,4-triazine-5,6-dione	1291231: Inhibition of recombinant human DAAO assessed as oxidative deamination of D-serine in presence of molecular oxygen and FAD after 20 mins	ic50	0.0300	uM
3-hydroxy-1H-1,6-naphthyridin-2-one	1799106: DAAO in Vitro Activity Assay from Article 10.1021/jm900128w: “Discovery, SAR, and pharmacokinetics of a novel 3-hydroxyquinolin-2(1H)-one series of potent D-amino acid oxidase (DAAO) inhibitors.”	ic50	0.0320	uM
8-chloro-3-hydroxy-1H-quinolin-2-one	1799106: DAAO in Vitro Activity Assay from Article 10.1021/jm900128w: “Discovery, SAR, and pharmacokinetics of a novel 3-hydroxyquinolin-2(1H)-one series of potent D-amino acid oxidase (DAAO) inhibitors.”	ic50	0.0330	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, affects methylation, decreases expression, increases expression	4
Aflatoxin B1	affects expression, decreases expression, increases expression	4
Acetaminophen	decreases expression, increases expression	3
Resveratrol	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	affects expression, increases expression	2
Cyclosporine	decreases expression	2
methyleugenol	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
epoxomicin	affects localization	1
perfluoro-n-nonanoic acid	decreases expression	1
Rosiglitazone	decreases expression	1
Chlorpromazine	decreases activity	1
Copper	decreases expression, affects cotreatment	1
Estradiol	decreases expression	1
Methapyrilene	increases methylation	1
Plant Extracts	decreases expression, affects cotreatment	1
Valproic Acid	decreases expression	1
Palmitic Acid	decreases expression	1
Okadaic Acid	decreases expression	1
Sodium Azide	decreases activity	1
Sodium Benzoate	decreases reaction, increases activity, increases expression	1

ChEMBL screening assays

85 unique, capped per target: 85 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1832105	Binding	Inhibition of human recombinant DAAO expressed in Escherichia coli assessed as H2O2 production from D-serine degradation after 30 mins by fluorescence assay	Biophysical and physicochemical methods differentiate highly ligand-efficient human D-amino acid oxidase inhibitors. — Eur J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00542412	PHASE4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	PHASE4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	PHASE4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	PHASE4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	PHASE4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	PHASE4	RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT00021697	PHASE3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	PHASE3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	PHASE3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	PHASE3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	PHASE3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	PHASE3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	PHASE3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	PHASE3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	PHASE3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	PHASE3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	PHASE3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	PHASE3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	PHASE3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	PHASE3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	PHASE3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	PHASE3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	PHASE3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	PHASE3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	PHASE3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	PHASE3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	PHASE3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	PHASE3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	PHASE3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	PHASE3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
NCT03690791	PHASE3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease
NCT03800524	PHASE3	UNKNOWN	Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
NCT03836716	PHASE3	TERMINATED	Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
NCT03948178	PHASE3	TERMINATED	Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
NCT04165824	PHASE3	COMPLETED	Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04248465	PHASE3	TERMINATED	An Efficacy and Safety Study of Ravulizumab in ALS Participants
NCT04569084	PHASE3	TERMINATED	Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS