HAAO

Summary

HAAO (3-hydroxyanthranilate 3,4-dioxygenase, HGNC:4796) is a protein-coding gene on chromosome 2p21, encoding 3-hydroxyanthranilate 3,4-dioxygenase (P46952). Catalyzes the oxidative ring opening of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes to quinolinate.

3-Hydroxyanthranilate 3,4-dioxygenase is a monomeric cytosolic protein belonging to the family of intramolecular dioxygenases containing nonheme ferrous iron. It is widely distributed in peripheral organs, such as liver and kidney, and is also present in low amounts in the central nervous system. HAAO catalyzes the synthesis of quinolinic acid (QUIN) from 3-hydroxyanthranilic acid. QUIN is an excitotoxin whose toxicity is mediated by its ability to activate glutamate N-methyl-D-aspartate receptors. Increased cerebral levels of QUIN may participate in the pathogenesis of neurologic and inflammatory disorders. HAAO has been suggested to play a role in disorders associated with altered tissue levels of QUIN.

Source: NCBI Gene 23498 — RefSeq curated summary.

At a glance

• Gene–disease (curated): vertebral, cardiac, renal, and limb defects syndrome 1 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 18
• Clinical variants (ClinVar): 77 total — 4 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 24
• Druggable target: yes
• MANE Select transcript: NM_012205

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4796
Approved symbol	HAAO
Name	3-hydroxyanthranilate 3,4-dioxygenase
Location	2p21
Locus type	gene with protein product
Status	Approved
Aliases	3-HAO, HAO
Ensembl gene	ENSG00000162882
Ensembl biotype	protein_coding
OMIM	604521
Entrez	23498

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 5 retained_intron

ENST00000294973, ENST00000402268, ENST00000402698, ENST00000404451, ENST00000406007, ENST00000406924, ENST00000431905, ENST00000878437, ENST00000878438, ENST00000878439, ENST00000878440, ENST00000878441, ENST00000878442, ENST00000878443, ENST00000878444, ENST00000878445, ENST00000940903

RefSeq mRNA: 1 — MANE Select: NM_012205 NM_012205

CCDS: CCDS33187

Canonical transcript exons

ENST00000294973 — 10 exons

Exon	Start	End
ENSE00001069472	42770493	42770582
ENSE00001563131	42792457	42792583
ENSE00003493054	42767860	42767928
ENSE00003515034	42783314	42783420
ENSE00003528979	42767595	42767677
ENSE00003644239	42783784	42783867
ENSE00003672224	42767089	42767515
ENSE00003676745	42769713	42769858
ENSE00003677773	42770143	42770186
ENSE00003679112	42788529	42788607

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 98.81.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8437 / max 156.1678, expressed in 688 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
28026	2.2461	636
28025	0.5976	271

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.81	gold quality
liver	UBERON:0002107	93.30	gold quality
descending thoracic aorta	UBERON:0002345	92.77	gold quality
thoracic aorta	UBERON:0001515	92.63	gold quality
ascending aorta	UBERON:0001496	92.62	gold quality
mucosa of transverse colon	UBERON:0004991	91.96	gold quality
body of pancreas	UBERON:0001150	91.72	gold quality
aorta	UBERON:0000947	89.86	gold quality
right coronary artery	UBERON:0001625	89.31	gold quality
left coronary artery	UBERON:0001626	88.66	gold quality
popliteal artery	UBERON:0002250	88.09	gold quality
tibial artery	UBERON:0007610	88.07	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.29	gold quality
coronary artery	UBERON:0001621	87.18	gold quality
metanephros cortex	UBERON:0010533	87.06	gold quality
endocervix	UBERON:0000458	86.98	gold quality
left ovary	UBERON:0002119	86.88	gold quality
right ovary	UBERON:0002118	86.35	gold quality
small intestine	UBERON:0002108	86.13	gold quality
adult mammalian kidney	UBERON:0000082	85.53	gold quality
pancreas	UBERON:0001264	84.51	gold quality
left uterine tube	UBERON:0001303	84.37	gold quality
body of uterus	UBERON:0009853	84.14	gold quality
ectocervix	UBERON:0012249	83.95	gold quality
mucosa of stomach	UBERON:0001199	83.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.33	gold quality
monocyte	CL:0000576	82.84	gold quality
duodenum	UBERON:0002114	82.34	gold quality
rectum	UBERON:0001052	82.20	gold quality
mononuclear cell	CL:0000842	82.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting HAAO, 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-6721-5P	99.93	68.92	2981
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-4632-5P	97.82	65.38	1470
HSA-MIR-6879-5P	97.77	65.52	1521
HSA-MIR-647	97.73	67.79	927
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-346	97.01	66.97	662

Literature-anchored findings (GeneRIF, showing 7)

• GTF2A1 alone, or GTF2A1 plus HAAO are excellent candidate biomarkers for detecting Ovarian cancer (PMID:19724865)
• Methylation status of CIDEA, HAAO and RXFP3 had significant association with microsatellite instability in endometrial tumors. (PMID:20211485)
• Here, the first crystal structure of human 3-HAO with the native iron bound in its active site is presented, together with an additional structure with zinc (a known inhibitor of human 3-HAO) bound in the active site. (PMID:28375145)
• Genetic variations of HAAO and IRX6 influence susceptibility to hypospadias in the Japanese population. (PMID:30063927)
• Dysregulation at multiple points of the kynurenine pathway is a ubiquitous feature of renal cancer: implications for tumour immune evasion. (PMID:32390008)
• Expression analysis of selected genes involved in tryptophan metabolic pathways in Egyptian children with Autism Spectrum Disorder and learning disabilities. (PMID:33767242)
• Re-sequencing of candidate genes FOXF1, HSPA6, HAAO, and KYNU in 522 individuals with VATER/VACTERL, VACTER/VACTERL-like association, and isolated anorectal malformation. (PMID:35362267)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	haao	ENSDARG00000076487
mus_musculus	Haao	ENSMUSG00000000673
rattus_norvegicus	Haao	ENSRNOG00000031263
caenorhabditis_elegans		WBGENE00010595

Protein

Protein identifiers

3-hydroxyanthranilate 3,4-dioxygenase — P46952 (reviewed: P46952)

Alternative names: 3-hydroxyanthranilate oxygenase, 3-hydroxyanthranilic acid dioxygenase

All UniProt accessions (2): C9IY88, P46952

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the oxidative ring opening of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes to quinolinate.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm. Cytosol.

Disease relevance. Vertebral, cardiac, renal, and limb defects syndrome 1 (VCRL1) [MIM:617660] An autosomal recessive congenital malformation syndrome characterized by vertebral segmentation abnormalities, congenital cardiac defects, renal defects, and distal mild limb defects. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Cofactor biosynthesis; NAD(+) biosynthesis; quinolinate from L-kynurenine: step 3/3.

Similarity. Belongs to the 3-HAO family.

Isoforms (2)

UniProt ID	Names	Canonical?
P46952-1	1	yes
P46952-2	2

RefSeq proteins (1): NP_036337* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010329	3hydroanth_dOase	Family
IPR011051	RmlC_Cupin_sf	Homologous_superfamily
IPR014710	RmlC-like_jellyroll	Homologous_superfamily
IPR016700	3hydroanth_dOase_met	Family

Pfam: PF06052

Enzyme classification (BRENDA):

• EC 1.13.11.6 — 3-hydroxyanthranilate 3,4-dioxygenase (BRENDA: 12 organisms, 20 substrates, 35 inhibitors, 17 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
3-HYDROXYANTHRANILIC ACID	0.002–0.105	5
3-HYDROXYANTHRANILATE	0.0102–0.872	4
4-ETHYL-3-HYDROXYANTHRANILIC ACID	0.011	1
4-METHYL-3-HYDROXYANTHRANILIC ACID	0.037	1
4-PROPYL-3-HYDROXYANTHRANILIC ACID	0.01	1
O2	0.615	1

Catalyzed reactions (Rhea), 1 shown:

• 3-hydroxyanthranilate + O2 = (2Z,4Z)-2-amino-3-carboxymuconate 6-semialdehyde (RHEA:17953)

UniProt features (45 total): strand 20, helix 8, binding site 7, sequence variant 4, region of interest 3, chain 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2QNK	X-RAY DIFFRACTION	1.6
5TKQ	X-RAY DIFFRACTION	1.75
5TK5	X-RAY DIFFRACTION	1.88

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46952-F1	95.95	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 (7): 105; 43; 47; 53; 53; 91; 95

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-71240	Tryptophan catabolism
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 235 (showing top): MODULE_93, GOBP_RESPONSE_TO_ZINC_ION, GNF2_GSTM1, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, REACTOME_TRYPTOPHAN_CATABOLISM, GNF2_HPN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TAL1ALPHAE47_01, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, MORF_RAD51L3, GOBP_NADPLUS_METABOLIC_PROCESS

GO Biological Process (11): L-tryptophan catabolic process (GO:0006569), NAD+ biosynthetic process (GO:0009435), response to zinc ion (GO:0010043), quinolinate biosynthetic process (GO:0019805), ‘de novo’ NAD+ biosynthetic process from L-tryptophan (GO:0034354), obsolete anthranilate metabolic process (GO:0043420), response to cadmium ion (GO:0046686), quinolinate metabolic process (GO:0046874), neuron cellular homeostasis (GO:0070050), pyridine nucleotide biosynthetic process (GO:0019363), dicarboxylic acid metabolic process (GO:0043648)

GO Molecular Function (8): 3-hydroxyanthranilate 3,4-dioxygenase activity (GO:0000334), ferrous iron binding (GO:0008198), electron transfer activity (GO:0009055), iron ion binding (GO:0005506), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to metal ion	2
pyridine-containing compound biosynthetic process	2
cellular anatomical structure	2
aromatic amino acid catabolic process	1
indole-containing compound catabolic process	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
purine nucleotide biosynthetic process	1
nicotinamide nucleotide biosynthetic process	1
NAD+ metabolic process	1
dicarboxylic acid biosynthetic process	1
quinolinate metabolic process	1
aromatic amino acid metabolic process	1
NAD+ biosynthetic process	1
indole-containing compound metabolic process	1
L-amino acid metabolic process	1
proteinogenic amino acid metabolic process	1
dicarboxylic acid metabolic process	1
pyridine-containing compound metabolic process	1
cellular homeostasis	1
nucleotide biosynthetic process	1
carboxylic acid metabolic process	1
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	1
iron ion binding	1
molecular_function	1
transition metal ion binding	1
binding	1
catalytic activity	1
cation binding	1
oxidoreductase activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1046 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HAAO	KYNU	Q16719	912
HAAO	KMO	O15229	892
HAAO	QPRT	Q15274	865
HAAO	TDO2	P48775	835
HAAO	ACMSD	Q8TDX5	811
HAAO	AFMID	Q63HM1	787
HAAO	IDO1	P14902	756
HAAO	AADAT	Q8N5Z0	756
HAAO	IDO2	Q6ZQW0	732
HAAO	KYAT1	Q16773	716
HAAO	CCDC124	Q96CT7	669
HAAO	C5orf34	Q96MH7	634
HAAO	KYAT3	Q6YP21	613
HAAO	NAPRT	Q6XQN6	610
HAAO	A0A494C066	A0A494C066	601

IntAct

18 interactions, top by confidence:

A	B	Type	Score
HAAO	GAD1	psi-mi:“MI:0915”(physical association)	0.830
GAD1	HAAO	psi-mi:“MI:0915”(physical association)	0.830
HAAO	GAD1	psi-mi:“MI:0915”(physical association)	0.560
GAD1	HAAO	psi-mi:“MI:0915”(physical association)	0.560
HAAO	POT1	psi-mi:“MI:0915”(physical association)	0.510
HAAO	TERF2IP	psi-mi:“MI:0915”(physical association)	0.370
ARHGDIA	HAAO	psi-mi:“MI:0915”(physical association)	0.370
DKC1	RPS9	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
HAAO	POT1	psi-mi:“MI:0915”(physical association)	0.000
HAAO	GAD1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): HAAO (Two-hybrid), HAAO (Two-hybrid), HAAO (Two-hybrid), HAAO (Affinity Capture-MS), ARHGDIA (Two-hybrid), HAAO (Two-hybrid), HAAO (Two-hybrid), HAAO (Affinity Capture-Luminescence)

ESM2 similar proteins: A1L4T4, A2XCT8, A2Z7C4, A7RIT9, A8BQB4, A9SCJ6, A9SDW6, A9SS00, A9VCM7, B7PRF6, C3ZAH2, C5WWY0, C5X1F5, D7T737, E0W481, F6HDT7, F6QS54, F6W3G8, F7FKV1, O48707, P35573, P35574, P46952, P46953, Q0VCA8, Q10RE5, Q28FT4, Q2LZI9, Q2PQH8, Q3B8C8, Q3ZBL1, Q562C9, Q5U3F8, Q5ZL43, Q6AWN0, Q6DIY2, Q6DIZ0, Q6P7I0, Q6PBX5, Q75HE6

Diamond homologs: A0RD64, A1C408, A1C874, A1DB76, A2R8S7, A3LP72, A4REV8, A5DLW3, A5E0Z9, A6X798, A7RIT9, B0RUZ7, B0XVP0, B0Y9Z9, B1KJM7, B2AAJ5, B2T2S5, B4EFS7, C1ERL1, P0CL86, P0CL87, P46952, P46953, P47096, Q0D1U6, Q0VCA8, Q19341, Q1E5I0, Q1LCS4, Q28SE8, Q2HD63, Q2P320, Q2UB88, Q2UHT9, Q39LI1, Q3BV37, Q46PT7, Q4P2Q7, Q4UT95, Q4WCF1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	6
Uncertain significance	45
Likely benign	5
Benign	8

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
403727	NM_012205.3(HAAO):c.483dup (p.Asp162Ter)	Pathogenic
403728	NM_012205.3(HAAO):c.558G>A (p.Trp186Ter)	Pathogenic
988085	NM_012205.3(HAAO):c.141C>A (p.His47Gln)	Pathogenic
988086	NM_012205.3(HAAO):c.43del (p.Arg15fs)	Pathogenic
1683650	NM_012205.3(HAAO):c.21del (p.Arg8fs)	Likely pathogenic
3065740	NM_012205.3(HAAO):c.251T>C (p.Leu84Pro)	Likely pathogenic
4849493	NM_012205.3(HAAO):c.80+2T>C	Likely pathogenic
804383	NM_012205.3(HAAO):c.243+1G>A	Likely pathogenic
988087	NM_012205.3(HAAO):c.301G>T (p.Gly101Trp)	Likely pathogenic
988088	NM_012205.3(HAAO):c.323G>A (p.Arg108Gln)	Likely pathogenic

SpliceAI

1451 predictions. Top by Δscore:

Variant	Effect	Δscore
2:42767593:A:AC	donor_gain	1.0000
2:42767594:C:CC	donor_gain	1.0000
2:42770491:A:AC	donor_gain	1.0000
2:42770491:ACT:A	donor_gain	1.0000
2:42770492:C:CC	donor_gain	1.0000
2:42770492:CTC:C	donor_gain	1.0000
2:42788524:CCTA:C	donor_loss	1.0000
2:42788525:CTA:C	donor_loss	1.0000
2:42788526:TAC:T	donor_loss	1.0000
2:42788527:A:C	donor_loss	1.0000
2:42792451:ACTCA:A	donor_loss	1.0000
2:42792452:CTCA:C	donor_loss	1.0000
2:42792453:TCA:T	donor_loss	1.0000
2:42792454:CAC:C	donor_loss	1.0000
2:42792455:A:AC	donor_gain	1.0000
2:42792455:AC:A	donor_loss	1.0000
2:42792456:C:CC	donor_gain	1.0000
2:42767514:ACCT:A	acceptor_loss	0.9900
2:42767516:C:A	acceptor_loss	0.9900
2:42767517:T:A	acceptor_loss	0.9900
2:42769826:T:TG	acceptor_gain	0.9900
2:42770493:T:TA	donor_gain	0.9900
2:42770494:C:CA	donor_gain	0.9900
2:42788523:ACCT:A	donor_loss	0.9900
2:42788528:CCT:C	donor_gain	0.9900
2:42792449:GGACT:G	donor_loss	0.9900
2:42792456:CA:C	donor_gain	0.9900
2:42792456:CAT:C	donor_gain	0.9900
2:42792456:CATG:C	donor_gain	0.9900
2:42792456:CATGA:C	donor_gain	0.9900

AlphaMissense

1852 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:42770183:G:C	F148L	0.968
2:42770183:G:T	F148L	0.968
2:42770185:A:G	F148L	0.968
2:42767618:G:C	S253R	0.966
2:42767618:G:T	S253R	0.966
2:42767620:T:G	S253R	0.966
2:42783862:A:C	F55L	0.963
2:42783862:A:T	F55L	0.963
2:42783864:A:G	F55L	0.963
2:42767874:A:G	W229R	0.959
2:42767874:A:T	W229R	0.959
2:42783349:C:A	E105D	0.944
2:42783349:C:G	E105D	0.944
2:42783393:G:C	H91D	0.936
2:42788555:C:G	D45H	0.933
2:42783317:A:G	L116P	0.932
2:42788580:G:C	F36L	0.932
2:42788580:G:T	F36L	0.932
2:42788582:A:G	F36L	0.932
2:42783379:C:A	R95S	0.926
2:42783379:C:G	R95S	0.926
2:42788559:C:A	R43S	0.926
2:42788559:C:G	R43S	0.926
2:42788549:G:C	H47D	0.923
2:42788560:C:G	R43T	0.920
2:42769734:A:C	F203L	0.919
2:42769734:A:T	F203L	0.919
2:42769736:A:G	F203L	0.919
2:42783797:A:G	I77T	0.917
2:42770537:G:C	F132L	0.915

dbSNP variants (sampled 300 via entrez): RS1000006332 (2:42772902 C>CG), RS1000012233 (2:42791460 T>C), RS1000035950 (2:42771318 C>T), RS1000158418 (2:42784971 A>G), RS1000305312 (2:42782150 G>A,C,T), RS1000342961 (2:42774975 A>G), RS1000404083 (2:42780561 A>C), RS1000420819 (2:42787700 C>T), RS1000452061 (2:42787993 G>A), RS1000455075 (2:42775210 A>C,G), RS1000602190 (2:42780794 G>A), RS1000630439 (2:42781017 C>T), RS1000668910 (2:42781842 C>G), RS1000757498 (2:42786415 G>A,T), RS1000851690 (2:42779038 G>A)

Disease associations

OMIM: gene MIM:604521 | disease phenotypes: MIM:617660

GenCC curated gene-disease

Disease	Classification	Inheritance
vertebral, cardiac, renal, and limb defects syndrome 1	Strong	Autosomal recessive
congenital vertebral-cardiac-renal anomalies syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
vertebral, cardiac, renal, and limb defects syndrome 1	Definitive	AR

Mondo (2): vertebral, cardiac, renal, and limb defects syndrome 1 (MONDO:0060554), congenital vertebral-cardiac-renal anomalies syndrome (MONDO:0020831)

Orphanet (0):

HPO phenotypes

24 total (24 of 24 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000076	Vesicoureteral reflux
HP:0000089	Renal hypoplasia
HP:0000176	Submucous cleft hard palate
HP:0000193	Bifid uvula
HP:0000252	Microcephaly
HP:0000376	Incomplete partition of the cochlea type II
HP:0000407	Sensorineural hearing impairment
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001601	Laryngomalacia
HP:0001631	Atrial septal defect
HP:0001650	Aortic valve stenosis
HP:0001718	Mitral stenosis
HP:0001883	Talipes
HP:0002144	Tethered cord
HP:0003316	Butterfly vertebrae
HP:0003577	Congenital onset
HP:0004322	Short stature
HP:0004383	Hypoplastic left ventricle
HP:0005950	Laryngeal web
HP:0010301	Spinal dysraphism
HP:0010305	Absence of the sacrum
HP:0012821	Unilateral vocal cord paresis

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST002563_3	Hypospadias	4.000000e-34
GCST002715_2	Breastfeeding duration	1.000000e-06
GCST002726_33	Glucose homeostasis traits	5.000000e-07
GCST003013_21	White matter hyperintensity burden	4.000000e-08
GCST003013_7	White matter hyperintensity burden	2.000000e-06
GCST004776_32	Systolic blood pressure	2.000000e-14
GCST004776_82	Systolic blood pressure	1.000000e-08
GCST007094_93	Diastolic blood pressure	2.000000e-13
GCST007098_123	Diastolic blood pressure	3.000000e-07
GCST007098_124	Diastolic blood pressure	1.000000e-06
GCST007099_250	Systolic blood pressure	9.000000e-09
GCST008362_100	Birth weight	7.000000e-10
GCST011946_33	White matter hyperintensity volume	6.000000e-13
GCST011947_4	White matter hyperintensity volume	2.000000e-14
GCST011949_3	White matter hyperintensity volume (adjusted for hypertension)	8.000000e-12
GCST011952_8	White matter hyperintensity volume x hypertension interaction (2df)	8.000000e-11
GCST90002397_794	Mean spheric corpuscular volume	2.000000e-11
GCST90011894_3	Retinitis pigmentosa	2.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006864	breastfeeding duration
EFO:0004471	insulin sensitivity measurement
EFO:0005665	white matter hyperintensity measurement
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0004344	birth weight

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3108657 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.96	IC50	1100	nM	CHEMBL3110069

PubChem BioAssay actives

1 with measured affinity, of 58 total; 1 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
1-hydroxy-2-imino-6-methylpyridine-3-carboxylic acid	1065665: Inhibition of 3-HAO in human brain homogenates using [1-14C]-3-HANA as substrate assessed as [14C]-QUIN production after 1 hr by liquid scintillation spectrometric analysis	ic50	1.1000	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, increases methylation	3
Benzo(a)pyrene	decreases expression, increases methylation	2
Cyclosporine	decreases methylation, decreases expression	2
aristolochic acid I	increases expression	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
bisphenol A	affects expression	1
chlortoluron	decreases expression	1
enilconazole	decreases expression	1
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
cyproconazole	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
Acetaminophen	decreases expression	1
Acyclovir	decreases activity	1
Air Pollutants	affects methylation, increases abundance	1
Atrazine	increases expression	1
Cisplatin	increases expression	1
Clozapine	decreases expression	1
Gold	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Lead	affects methylation	1
Nitrogen Oxides	affects methylation, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	affects expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3112336	Binding	Inhibition of 3-HAO in human brain homogenates using [1-14C]-3-HANA as substrate assessed as [14C]-QUIN production after 1 hr by liquid scintillation spectrometric analysis	2-Aminonicotinic acid 1-oxides are chemically stable inhibitors of quinolinic acid synthesis in the mammalian brain: a step toward new antiexcitotoxic agents. — J Med Chem

Clinical trials (associated diseases)

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