HIF1AN

Summary

HIF1AN (hypoxia inducible factor 1 subunit alpha inhibitor, HGNC:17113) is a protein-coding gene on chromosome 10q24.31, encoding Hypoxia-inducible factor 1-alpha inhibitor (Q9NWT6). Hydroxylates HIF-1 alpha at ‘Asn-803’ in the C-terminal transactivation domain (CAD).

Enables several functions, including 2-oxoglutarate-dependent dioxygenase activity; NF-kappaB binding activity; and transition metal ion binding activity. Involved in negative regulation of Notch signaling pathway and positive regulation of myoblast differentiation. Located in cytosol; nucleoplasm; and perinuclear region of cytoplasm.

Source: NCBI Gene 55662 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 36 total — 1 pathogenic
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_017902

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17113
Approved symbol	HIF1AN
Name	hypoxia inducible factor 1 subunit alpha inhibitor
Location	10q24.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20615, DKFZp762F1811, FLJ22027, FIH1
Ensembl gene	ENSG00000166135
Ensembl biotype	protein_coding
OMIM	606615
Entrez	55662

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000299163, ENST00000478787, ENST00000526476, ENST00000528044, ENST00000533589, ENST00000860850, ENST00000935501, ENST00000968718

RefSeq mRNA: 1 — MANE Select: NM_017902 NM_017902

CCDS: CCDS7498

Canonical transcript exons

ENST00000299163 — 8 exons

Exon	Start	End
ENSE00001100128	100545943	100546049
ENSE00001100130	100547140	100547250
ENSE00001212367	100548093	100559998
ENSE00001695622	100535943	100536135
ENSE00003497047	100540634	100540782
ENSE00003588501	100544951	100545096
ENSE00003639978	100536411	100536661
ENSE00003791426	100546518	100546581

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 93.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.3112 / max 242.9265, expressed in 1822 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106594	32.3112	1822

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	93.16	gold quality
muscle of leg	UBERON:0001383	93.05	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.21	gold quality
muscle organ	UBERON:0001630	92.11	gold quality
skeletal muscle organ	UBERON:0014892	92.11	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.07	gold quality
gluteal muscle	UBERON:0002000	91.59	gold quality
tendon of biceps brachii	UBERON:0008188	90.92	gold quality
stromal cell of endometrium	CL:0002255	90.78	gold quality
triceps brachii	UBERON:0001509	90.67	gold quality
skeletal muscle tissue	UBERON:0001134	90.41	gold quality
quadriceps femoris	UBERON:0001377	89.61	gold quality
vastus lateralis	UBERON:0001379	89.49	gold quality
islet of Langerhans	UBERON:0000006	88.81	gold quality
muscle tissue	UBERON:0002385	88.77	gold quality
deltoid	UBERON:0001476	88.42	gold quality
sural nerve	UBERON:0015488	88.31	gold quality
tibialis anterior	UBERON:0001385	88.27	gold quality
endothelial cell	CL:0000115	88.18	gold quality
adrenal tissue	UBERON:0018303	87.49	gold quality
biceps brachii	UBERON:0001507	87.46	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.43	gold quality
monocyte	CL:0000576	86.89	gold quality
leukocyte	CL:0000738	86.79	gold quality
mononuclear cell	CL:0000842	86.69	gold quality
colonic epithelium	UBERON:0000397	86.08	gold quality
diaphragm	UBERON:0001103	85.98	silver quality
upper leg skin	UBERON:0004262	85.76	gold quality
medial globus pallidus	UBERON:0002477	85.22	gold quality
descending thoracic aorta	UBERON:0002345	85.00	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	745.22
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CUX1, HIF1A

miRNA regulators (miRDB)

230 targeting HIF1AN, 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-8485	100.00	77.57	4731
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-1184	99.99	68.19	1458
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-302E	99.96	70.74	2669

Literature-anchored findings (GeneRIF, showing 40)

• Gene name = FIH1Encoded protein (factor inhibiting HIF-1) is a co-repressor that interacts with hypoxia-inducible factor 1 (HIF-1) alpha and the von Hippel-Lindau tumor suppressor protein to mediate repression of HIF-1 transcriptional activity. (PMID:11641274)
• Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha (PMID:11959990)
• FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor (PMID:12080085)
• present the structure of factor-inhibiting HIF-1 (FIH-1); describe the molecular details of the active site architecture mediating Fe(II) and 2-oxoglutarate binding (PMID:12432100)
• FIH-1 has a unique active site pocket and interaction sites for HIF-1 and von Hippel-Lindau protein (PMID:12482756)
• asparaginyl hydroxylase (FIH) catalytic properties in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases (PMID:14701857)
• Molecular modeling of the HIF-1alpha CAD V802A in complex with FIH-1 predicted an alteration in asparagine positioning providing an explanation for the impaired catalysis, confirming the importance of Val-802 in asparaginyl hydroxylation by FIH-1. (PMID:14734545)
• Human HIF asparaginyl hydroxylase, factor inhibiting HIF (FIH), also efficiently hydroxylates specific asparaginyl (Asn)-residues within proteins of the IkappaB family. (PMID:17003112)
• ARD proteins function as natural inhibitors of FIH and that the hydroxylation status of these proteins provides another oxygen-dependent interface that modulates HIF signaling (PMID:17573339)
• Data show that in renal cell carcinoma, the Cut-like homeodomain protein is involved in FIH-1 transcriptional regulation and is controlled by a specific signaling event involving protein kinase C zeta. (PMID:17682059)
• FIH-1 is widely expressed in invasive breast carcinoma. The hypoxic response and survival suggests that tumour regulation of FIH-1 is an additional important mechanism for HIF pathway activation. (PMID:18096060)
• These results suggest that Siah-1 might play a role as a regulator of FIH abundance under normoxic conditions. (PMID:18280659)
• FIH-1 hydroxylates Notch ICD at two residues (N(1945) and N(2012)) that are critical for the function of Notch ICD as a transactivator within cells and during neurogenesis and myogenesis (PMID:18299578)
• two enzyme-derived histidine ligands are sufficient for iron binding and catalysis by factor inhibiting HIF (FIH) (PMID:18611856)
• Overexpression of the oxygen sensor FIH1 is associated with tumor aggressiveness in pancreatic endocrine tumors. (PMID:18927305)
• The work has defined 13 new FIH-dependent hydroxylation sites with a degenerate consensus corresponding to that of the ankyrin repeat and a range of ankyrin repeat domain-containing proteins as actual and potential substrates for FIH. (PMID:18936059)
• functional inactivation of HIF-alpha by stimulation of FIH-dependent p300 contributes to the YC-1-induced deregulation of hypoxia-induced genes (PMID:19074848)
• The expression imbalance of HPH1 and FIH-1 in placenta may play an important role in the pathogenesis and development of severe pre-eclampsia through inhibiting HIF-1alpha. (PMID:19134330)
• Results show that expression of MYPT1 enhances HIF-CAD activity in a manner consistent with competition for FIH and that this property extends to other ARD proteins. (PMID:19245366)
• Substrate length has a much greater influence on FIH-1-dependent hydroxylation of Notch than of HIF-1alpha, predominantly through binding affinity rather than maximal reaction velocity. (PMID:19401150)
• The interplays among HIF-1alpha and Hdm2 and HIF1 could be potential targets for treating tumors overexpressing HIF-1alpha. (PMID:19696166)
• Mint3 binds FIH-1 and inhibits the ability of FIH-1 to modify HIF-1alpha (PMID:19726677)
• miR-31 contributes to the development of head and neck squamous cell carcinoma by impeding FIH to activate HIF under normoxic conditions. (PMID:20145132)
• FIH1 appears to be a suppressor of oxygen-dependent genes in the kidney, operating through HIF-dependent and -independent mechanisms. (PMID:20720525)
• Methylation-induced epigenetic silencing of FIH is unlikely to underlie up-regulated HIF-1alpha expression in human breast cancer but may play a role in other tumour types. (PMID:20727020)
• Bax-mediated apoptosis is suppressed by FIH1 overexpression, but accelerated by FIH1 deficiency. (PMID:21069436)
• FIH also catalyzes the hydroxylation of highly conserved Asn residues within the ubiquitous ankyrin repeat domain (ARD)-containing proteins (PMID:21177872)
• Data report that histidinyl residues within the ankyrin repeat domain of tankyrase-2 can be hydroxylated by factor-inhibiting hypoxia-inducible factor. (PMID:21251231)
• FIH does not uncouple O2 during turnover conditions, nor does it release reactive oxygen species under any tested conditions. (PMID:21443853)
• FIH1 is expressed in the majority of invasive breast carcinomas and shows distinct subcellular localization patterns. (PMID:21732131)
• Quantitative mass spectrometry reveals dynamics of factor-inhibiting hypoxia-inducible factor-catalyzed hydroxylation. (PMID:21808058)
• FIH activity is essential for tumor growth through the suppression of the p53-p21 axis, the major barrier that prevents cancer progression. (PMID:22002313)
• Glycogen regulation in a HIF-1alpha-independent manner is a novel function for FIH-1 and provides new insight into how the corneal epithelium regulates its energy requirements. (PMID:22532441)
• Our results define a previously unknown mechanism for keratinocyte fate decisions where Notch signaling potential is, in part, controlled through a miR-31/FIH-1 nexus. (PMID:22891326)
• The stable Fe-OH2 bond plays an important part in FIH1’s regulatory role over O2 homeostasis in humans and points toward a strategy for tightly coupling O2 activation with C-terminal transactivation domain of HIF-1alpha hydroxylation. (PMID:23351038)
• FIH-1 depletion did lead to impaired binding of Par-3 to ASPP2. (PMID:23606740)
• Comparison of the structure of JMJD5 with that of FIH, a well characterized protein hydroxylase, reveals that human JMJD5 might function as a protein hydroxylase. (PMID:24100311)
• The role of FIH expression in high-risk locally advanced renal cell carcinoma (LARCC) was explored. (PMID:24388053)
• The role of FIH-1 in regulating the transcriptional activity of HIF1A in glioblastoma multiforme. (PMID:24465898)
• The critical role of miR-31/FIH-1 nexus in colorectal cancer (CRC)was revealed and the contribution of miR-31 to CRC development by targeting FIH-1 was clarified. (PMID:24521875)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hif1an	ENSDARG00000031915
mus_musculus	Hif1an	ENSMUSG00000036450
rattus_norvegicus	Hif1an	ENSRNOG00000014234

Paralogs (4): KDM8 (ENSG00000155666), TYW5 (ENSG00000162971), HSPBAP1 (ENSG00000169087), JMJD7 (ENSG00000243789)

Protein

Protein identifiers

Hypoxia-inducible factor 1-alpha inhibitor — Q9NWT6 (reviewed: Q9NWT6)

Alternative names: Factor inhibiting HIF-1, Hypoxia-inducible factor asparagine hydroxylase

All UniProt accessions (3): E9PL41, E9PNR8, Q9NWT6

UniProt curated annotations — full annotation on UniProt →

Function. Hydroxylates HIF-1 alpha at ‘Asn-803’ in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation.

Subunit / interactions. Homodimer; homodimerization is essential for catalytic activity. Interacts with VHL and HIF1A. Part of a complex with VHL, HIF1A and HDAC1 or HDAC2 or HDAC3. Interacts with NFKB1 and NFKBIA. Interacts with NOTCH1, NOTCH2 and NOTCH3 but not with NOTCH4. Interacts with APBA3; binding inhibits HIF1AN binding to HIF1A. Interacts with TNKS2. Interacts with PPP1R12A. Interacts with ASB4. Interacts with UBE3A. Interacts with ANKS3. Interacts with NECAB3; the interaction is indirect and seems to be mediated by APBA3.

Subcellular location. Nucleus. Cytoplasm. Perinuclear region.

RefSeq proteins (1): NP_060372* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003347	JmjC_dom	Domain
IPR014710	RmlC-like_jellyroll	Homologous_superfamily
IPR027452	FIH-1_dom_II	Homologous_superfamily
IPR041667	Cupin_8	Domain

Pfam: PF13621

Enzyme classification (BRENDA):

• EC 1.14.11.16 — peptide-aspartate beta-dioxygenase (BRENDA: 4 organisms, 27 substrates, 85 inhibitors, 25 Km, 8 kcat entries)
• EC 1.14.11.30 — hypoxia-inducible factor-asparagine dioxygenase (BRENDA: 2 organisms, 29 substrates, 29 inhibitors, 15 Km, 7 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
2-OXOGLUTARATE	0.0006–0.125	8
FE2+	0.003–0.093	6
FIRST GROWTH FACTOR-LIKE DOMAIN-L-ASPARTATE	0.019–0.075	6
2-OXOGLUTARATE	0.01–0.026	6
O2	0.07–0.2	4
DESGLPQLTSYDAEVNAPIQGSRNLLQGEELLRALDQVN	0.07–0.078	3
O2	0.09–0.426	2
HIF-1ALPHA PEPTIDE ASP788-LEU822 (L-ASPARAGINE8	0.1	1
[FACTOR X FIRST EGF-LIKE DOMAIN]-L-ASPARTATE	0.086	1
[THIOETHER-LINKED CYCLIC PEPTIDE HFX-CP101-119]-	0.0012	1
PSDLACRLLGQSMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRAL	0.01	1

Catalyzed reactions (Rhea), 4 shown:

• L-histidyl-[ankyrin-repeat domain protein] + 2-oxoglutarate + O2 = (3S)-3-hydroxy-L-histidyl-[ankyrin-repeat domain protein] + succinate + CO2 (RHEA:54264)
• L-asparaginyl-[hypoxia-inducible factor alpha subunit] + 2-oxoglutarate + O2 = (3S)-3-hydroxy-L-asparaginyl-[hypoxia-inducible factor alpha subunit] + succinate + CO2 (RHEA:54268)
• L-asparaginyl-[ankyrin-repeat domain protein] + 2-oxoglutarate + O2 = (3S)-3-hydroxy-L-asparaginyl-[ankyrin-repeat domain protein] + succinate + CO2 (RHEA:54272)
• L-aspartyl-[ankyrin-repeat domain protein] + 2-oxoglutarate + O2 = (3S)-3-hydroxy-L-aspartyl-[ankyrin-repeat domain protein] + succinate + CO2 (RHEA:54280)

UniProt features (73 total): strand 20, helix 16, binding site 14, mutagenesis site 8, sequence conflict 3, turn 3, region of interest 2, initiator methionine 1, chain 1, domain 1, site 1, modified residue 1, sequence variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

64 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7A1Q	X-RAY DIFFRACTION	1.75
7A1P	X-RAY DIFFRACTION	1.76
6H9J	X-RAY DIFFRACTION	1.83
6HC8	X-RAY DIFFRACTION	1.9
6HKP	X-RAY DIFFRACTION	1.9
7A1J	X-RAY DIFFRACTION	1.9
6HL6	X-RAY DIFFRACTION	1.97
6HA6	X-RAY DIFFRACTION	1.98
6HL5	X-RAY DIFFRACTION	1.98
7A1K	X-RAY DIFFRACTION	1.99
7A1N	X-RAY DIFFRACTION	2.01
7A1S	X-RAY DIFFRACTION	2.01
8K73	X-RAY DIFFRACTION	2.02
8II0	X-RAY DIFFRACTION	2.04
9JTX	X-RAY DIFFRACTION	2.08
3D8C	X-RAY DIFFRACTION	2.1
4Z1V	X-RAY DIFFRACTION	2.1
5JWP	X-RAY DIFFRACTION	2.1
2W0X	X-RAY DIFFRACTION	2.12
1H2K	X-RAY DIFFRACTION	2.15
2YC0	X-RAY DIFFRACTION	2.15
9IIF	X-RAY DIFFRACTION	2.16
9M23	X-RAY DIFFRACTION	2.16
7A1M	X-RAY DIFFRACTION	2.18
1MZE	X-RAY DIFFRACTION	2.2
2XUM	X-RAY DIFFRACTION	2.2
3OD4	X-RAY DIFFRACTION	2.2
9FSN	X-RAY DIFFRACTION	2.2
7A1O	X-RAY DIFFRACTION	2.21
8IHZ	X-RAY DIFFRACTION	2.22

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NWT6-F1	92.43	0.87

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 (1): 340 (important for dimer formation)

Ligand- & substrate-binding residues (14): 199; 201–203; 201; 205; 214; 238–239; 279; 294; 300; 321; 145; 152 …

Post-translational modifications (1): 2

Mutagenesis-validated functional residues (8):

Position	Phenotype
199	prevents suppression of hif cad activity. strongly stimulates 2-oxoglutarate turnover. no stimulation of 2-oxoglutarate
201	prevents suppression of hif cad activity.
201	loss of hif1a asn hydroxylation activity. slightly stimulates 2-oxoglutarate turnover.
201	no impact on hif1a asn hydroxylation activity. loss of asp hydroxylation ability. strongly stimulates 2-oxoglutarate tur
239	no effect on asp hydroxylation ability.
296	loss of hif1a asn hydroxylation activity and slight stimulation of 2-oxoglutarate turnover; when associated with g-201.
340	impairs dimer formation, leading to loss of hif1a asn hydroxylation activity. no stimulation of 2-oxoglutarate turnover;
344	no effect on dimer formation and hif1a asn hydroxylation activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1234174	Cellular response to hypoxia

MSigDB gene sets: 190 (showing top): GOBP_REGULATION_OF_VASCULOGENESIS, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, TGCACTT_MIR519C_MIR519B_MIR519A, AAGCCAT_MIR135A_MIR135B, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_NOTCH_SIGNALING_PATHWAY, BEIER_GLIOMA_STEM_CELL_DN, PATIL_LIVER_CANCER, GOBP_REGULATION_OF_MYOBLAST_DIFFERENTIATION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, WCTCNATGGY_UNKNOWN, GOBP_REGULATION_OF_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_BLOOD_VESSEL_MORPHOGENESIS

GO Biological Process (7): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of vascular endothelial growth factor receptor signaling pathway (GO:0030947), positive regulation of myoblast differentiation (GO:0045663), negative regulation of Notch signaling pathway (GO:0045746), positive regulation of vasculogenesis (GO:2001214), regulation of signal transduction (GO:0009966), regulation of developmental process (GO:0050793)

GO Molecular Function (17): transcription corepressor activity (GO:0003714), Notch binding (GO:0005112), ferrous iron binding (GO:0008198), zinc ion binding (GO:0008270), oxygen sensor activity (GO:0019826), carboxylic acid binding (GO:0031406), peptidyl-histidine dioxygenase activity (GO:0036139), [protein]-asparagine 3-dioxygenase activity (GO:0036140), protein homodimerization activity (GO:0042803), NF-kappaB binding (GO:0051059), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), peptidyl-aspartic acid 3-dioxygenase activity (GO:0062101), ankyrin repeat binding (GO:0071532), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
2-oxoglutarate-dependent dioxygenase activity	3
catalytic activity, acting on a protein	3
negative regulation of DNA-templated transcription	2
positive regulation of cell differentiation	2
cytoplasm	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
regulation of signal transduction	1
vascular endothelial growth factor receptor signaling pathway	1
regulation of cellular response to growth factor stimulus	1
myoblast differentiation	1
regulation of myoblast differentiation	1
Notch signaling pathway	1
regulation of Notch signaling pathway	1
negative regulation of signal transduction	1
vasculogenesis	1
regulation of vasculogenesis	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
developmental process	1
regulation of biological process	1
transcription coregulator activity	1
signaling receptor binding	1
iron ion binding	1
transition metal ion binding	1
oxygen binding	1
molecular sensor activity	1
anion binding	1
organic acid binding	1
identical protein binding	1
protein dimerization activity	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
DNA-binding transcription factor binding	1
protein domain specific binding	1
binding	1
catalytic activity	1
cation binding	1

Protein interactions and networks

STRING

1146 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HIF1AN	HIF1A	Q16665	932
HIF1AN	EGLN1	Q9GZT9	796
HIF1AN	VHL	P40337	781
HIF1AN	EGLN3	Q9H6Z9	769
HIF1AN	EGLN2	Q96KS0	768
HIF1AN	ARNT	P27540	762
HIF1AN	EPAS1	Q99814	759
HIF1AN	ELOC	Q15369	731
HIF1AN	CDYL	Q9Y232	695
HIF1AN	TNKS2	Q9H2K2	688
HIF1AN	UBE3A	P78355	682
HIF1AN	CA9	Q16790	660
HIF1AN	EP300	Q09472	613
HIF1AN	ELOB	Q15370	611
HIF1AN	CUL2	Q13617	601

IntAct

181 interactions, top by confidence:

A	B	Type	Score
HIF1A	EP300	psi-mi:“MI:0914”(association)	0.960
HIF1A	HIF1AN	psi-mi:“MI:0407”(direct interaction)	0.920
HIF1AN	HIF1A	psi-mi:“MI:0407”(direct interaction)	0.920
HIF1AN	HIF1A	psi-mi:“MI:0210”(hydroxylation reaction)	0.920
HIF1AN	HIF1A	psi-mi:“MI:0915”(physical association)	0.920
HIF1A	HIF1AN	psi-mi:“MI:0915”(physical association)	0.920
ASB9	HIF1AN	psi-mi:“MI:0915”(physical association)	0.870
ACBD6	NMT2	psi-mi:“MI:0914”(association)	0.870
ASB9	CKM	psi-mi:“MI:0914”(association)	0.870
HIF1AN	ASB9	psi-mi:“MI:0915”(physical association)	0.870
HIF1AN	APBA3	psi-mi:“MI:0915”(physical association)	0.850
HIF1AN	APBA3	psi-mi:“MI:0914”(association)	0.850
APBA3	HIF1AN	psi-mi:“MI:0915”(physical association)	0.850
HIF1AN	TNKS	psi-mi:“MI:0210”(hydroxylation reaction)	0.830
TNKS	HIF1AN	psi-mi:“MI:0210”(hydroxylation reaction)	0.830
HIF1AN	ANKRD49	psi-mi:“MI:0210”(hydroxylation reaction)	0.810
TNKS2	HIF1AN	psi-mi:“MI:0407”(direct interaction)	0.800
HIF1AN	TNKS2	psi-mi:“MI:0210”(hydroxylation reaction)	0.800

BioGRID (489): HIF1A (Biochemical Activity), HIF1AN (Two-hybrid), HIF1AN (Affinity Capture-Western), HIF1AN (Affinity Capture-MS), HIF1AN (Affinity Capture-MS), HIF1AN (Affinity Capture-MS), HIF1AN (Affinity Capture-MS), HIF1AN (Affinity Capture-MS), HIF1AN (Affinity Capture-MS), HIF1AN (Affinity Capture-MS), HIF1AN (Affinity Capture-MS), HIF1AN (Affinity Capture-MS), HIF1AN (Affinity Capture-MS), HIF1AN (Affinity Capture-MS), HIF1AN (Affinity Capture-MS)

ESM2 similar proteins: A2AV36, A2RSX7, A2RUC4, A4IHY0, A6QQV6, A8E534, B2GUS6, B5XF11, E1C7T6, E9PYK3, F1RET2, P0C870, P0C872, P47823, P59723, P83006, Q08BV2, Q08BY5, Q0VCA8, Q0WVR4, Q3UDE2, Q3V3E1, Q58CU3, Q5BKC6, Q5EA24, Q5R673, Q5U4E8, Q5ZHV5, Q5ZIB9, Q66KI9, Q67XX3, Q67ZB6, Q6AXL5, Q6PCI6, Q7T0X7, Q7TMC8, Q8BFT6, Q8BGG7, Q8BK58, Q8BLR9

Diamond homologs: A2RUC4, A8E534, B2GUS6, B5XF11, E1C7T6, Q1JP61, Q497B8, Q54LV7, Q55DF5, Q5BKC6, Q6AXL5, Q8N371, Q8RWR1, Q9CXT6, Q9NWT6, Q9W0M3, Q08BV2, Q54FG7, P59723, Q0WVR4, Q58CU3, Q5UQY3, Q8BK58, Q8BLR9, Q96EW2, A2RSX7, F4K2M8, O94606, Q2U6D4, Q3TA59, Q4IER0, Q4WVD1, Q5BH52, Q67ZB6, Q6AY40, Q6C3P4, Q9P3K9, P0C870, P0C872, Q54CS7

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
HIF1AN	down-regulates	NOTCH1	hydroxylation
HIF1AN	down-regulates	NOTCH	hydroxylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 129 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Class I MHC mediated antigen processing & presentation	10	7.7×	1e-04
Neddylation	14	7.3×	4e-06
Antigen processing: Ubiquitination & Proteasome degradation	14	5.7×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
tumor necrosis factor-mediated signaling pathway	5	14.5×	8e-03
protein ubiquitination	17	6.2×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	25
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2424804	NC_000010.10:g.(?102283594)(102510668_?)del	Pathogenic

SpliceAI

1744 predictions. Top by Δscore:

Variant	Effect	Δscore
10:100529364:AC:A	donor_gain	1.0000
10:100529365:CC:C	donor_gain	1.0000
10:100529365:CCCT:C	donor_gain	1.0000
10:100529392:T:TA	donor_gain	1.0000
10:100529432:T:TA	donor_gain	1.0000
10:100529730:C:CA	donor_gain	1.0000
10:100536052:T:G	donor_gain	1.0000
10:100536594:G:GT	donor_gain	1.0000
10:100536594:G:T	donor_gain	1.0000
10:100536657:GAGAG:G	donor_gain	1.0000
10:100536658:AGAGG:A	donor_loss	1.0000
10:100536659:GAG:G	donor_gain	1.0000
10:100536659:GAGG:G	donor_loss	1.0000
10:100536660:AGGTA:A	donor_loss	1.0000
10:100536661:GGTAA:G	donor_loss	1.0000
10:100536662:G:GC	donor_loss	1.0000
10:100536662:G:GG	donor_gain	1.0000
10:100536663:T:G	donor_loss	1.0000
10:100544949:A:AG	acceptor_gain	1.0000
10:100544950:G:GG	acceptor_gain	1.0000
10:100544950:GGAA:G	acceptor_gain	1.0000
10:100545931:T:A	acceptor_gain	1.0000
10:100545934:A:AG	acceptor_gain	1.0000
10:100545935:C:G	acceptor_gain	1.0000
10:100545937:TCTTA:T	acceptor_loss	1.0000
10:100545939:TTAGG:T	acceptor_loss	1.0000
10:100545940:TAGGT:T	acceptor_loss	1.0000
10:100547138:A:AG	acceptor_gain	1.0000
10:100547138:AG:A	acceptor_gain	1.0000
10:100547138:AGG:A	acceptor_gain	1.0000

AlphaMissense

2327 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:100536451:C:A	A73D	1.000
10:100536459:T:A	W76R	1.000
10:100536459:T:C	W76R	1.000
10:100536460:G:C	W76S	1.000
10:100536461:G:C	W76C	1.000
10:100536461:G:T	W76C	1.000
10:100536475:T:C	L81P	1.000
10:100536531:T:C	F100L	1.000
10:100536532:T:C	F100S	1.000
10:100536533:C:A	F100L	1.000
10:100536533:C:G	F100L	1.000
10:100540642:T:C	L146P	1.000
10:100540654:T:A	L150H	1.000
10:100540698:T:C	F165L	1.000
10:100540700:T:A	F165L	1.000
10:100540700:T:G	F165L	1.000
10:100540704:T:A	W167R	1.000
10:100540704:T:C	W167R	1.000
10:100540706:G:C	W167C	1.000
10:100540706:G:T	W167C	1.000
10:100540740:T:A	W179R	1.000
10:100540740:T:C	W179R	1.000
10:100540760:C:A	N185K	1.000
10:100540760:C:G	N185K	1.000
10:100540762:T:C	L186P	1.000
10:100540765:T:C	L187P	1.000
10:100540768:T:C	L188P	1.000
10:100544968:C:G	H199D	1.000
10:100544970:C:A	H199Q	1.000
10:100544970:C:G	H199Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000149170 (10:100551526 C>A,T), RS1000184123 (10:100534006 C>T), RS1000369682 (10:100551909 C>T), RS1000408468 (10:100546232 T>C), RS1000593922 (10:100535759 T>A), RS1000657594 (10:100534293 A>G), RS1000663826 (10:100558089 T>C), RS1000699669 (10:100550796 A>G), RS1001001153 (10:100556883 A>G), RS1001052550 (10:100551204 A>G), RS1001348785 (10:100556527 T>G), RS1001378339 (10:100554898 A>G), RS1001505882 (10:100539161 A>G), RS1001553077 (10:100557146 G>A), RS1001620658 (10:100539005 A>G)

Disease associations

OMIM: gene MIM:606615 | disease phenotypes: MIM:120330, MIM:616002

GenCC curated gene-disease

Mondo (2): renal coloboma syndrome (MONDO:0007352), focal segmental glomerulosclerosis 7 (MONDO:0014451)

Orphanet (2): Renal coloboma syndrome (Orphanet:1475), Hereditary steroid-resistant nephrotic syndrome (Orphanet:656)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001841_4	Palmitoleic acid (16:1n-7) levels	6.000000e-09
GCST002783_295	Body mass index	2.000000e-11
GCST002783_551	Body mass index	6.000000e-11
GCST002783_62	Body mass index	8.000000e-10
GCST004339_4	Palmitoleic acid (16:1n-7) levels	8.000000e-11
GCST004904_191	Body mass index	1.000000e-09
GCST004904_230	Body mass index	2.000000e-15
GCST007129_2	Cerebrospinal fluid t-tau:AB1-42 ratio	5.000000e-09
GCST009391_1811	Metabolite levels	9.000000e-06
GCST010703_13	Brain morphology (MOSTest)	1.000000e-09
GCST90000025_452	Appendicular lean mass	4.000000e-18

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007973	palmitoleic acid measurement
EFO:0007708	t-tau:beta-amyloid 1-42 ratio measurement
EFO:0010403	triacylglycerol 48:0 measurement
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537168	Papillorenal syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5909 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 75,754 (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
CHEMBL3544988	DAPRODUSTAT	4	308
CHEMBL3646221	VADADUSTAT	4	533
CHEMBL50	QUERCETIN	3	74,559
CHEMBL3646118	MOLIDUSTAT	2	354

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

ChEMBL bioactivities

25 potent at pChembl≥5 of 67 total, top 25 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.96	IC50	1100	nM	CHEMBL316034
5.62	IC50	2380	nM	CHEMBL5404184
5.62	IC50	2380	nM	CHEMBL5418688
5.53	IC50	2970	nM	CHEMBL5410721
5.48	IC50	3310	nM	CHEMBL5410158
5.44	IC50	3600	nM	CHEMBL5436718
5.44	IC50	3600	nM	CHEMBL5426884
5.42	IC50	3780	nM	CHEMBL5437483
5.40	IC50	4000	nM	CHEMBL5091848
5.40	IC50	3990	nM	CHEMBL5421814
5.29	IC50	5190	nM	CHEMBL5421760
5.27	IC50	5380	nM	CHEMBL5436602
5.27	IC50	5400	nM	CHEMBL5407982
5.26	IC50	5550	nM	CHEMBL5407966
5.25	IC50	5650	nM	CHEMBL5412577
5.24	IC50	5750	nM	CHEMBL5420345
5.24	IC50	5760	nM	CHEMBL5416119
5.21	IC50	6230	nM	CHEMBL5426350
5.20	IC50	6290	nM	CHEMBL5407902
5.20	IC50	6300	nM	CHEMBL5424970
5.19	IC50	6450	nM	CHEMBL5433909
5.16	IC50	6980	nM	CHEMBL2043176
5.11	IC50	7800	nM	CHEMBL5072902
5.09	IC50	8090	nM	CHEMBL5426575
5.07	IC50	8600	nM	CHEMBL316034

PubChem BioAssay actives

25 with measured affinity, of 103 total; 24 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
pyridine-2,4-dicarboxylic acid	1926048: Inhibition of FIH (unknown origin)	ic50	1.1000	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-[4-methoxy-3-(3-pyrrolidin-1-ylpropoxy)phenyl]prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	2.3800	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-[4-methoxy-3-(2-pyrrolidin-1-ylethoxy)phenyl]prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	2.3800	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-[3-methoxy-4-(3-pyrrolidin-1-ylpropoxy)phenyl]prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	2.9700	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-[4-methoxy-3-(3-morpholin-4-ylpropoxy)phenyl]prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	3.3100	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-[3-methoxy-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	3.6000	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-[4-methoxy-3-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	3.6000	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-[3-methoxy-4-[3-(4-methylpiperidin-1-yl)propoxy]phenyl]prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	3.7800	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-[4-methoxy-3-[2-(4-methylpiperidin-1-yl)ethoxy]phenyl]prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	3.9900	uM
2-nonylsulfanyl-6-oxo-1H-pyrimidine-5-carboxylic acid	1810103: Inhibition of human FIH using HLEVVKLLLEAGADVNAQDK-CONH2 as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins by RapidFire Mass spectrometry assay	ic50	4.0000	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-[4-methoxy-3-[3-(4-methylpiperazin-1-yl)propoxy]phenyl]prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	5.1900	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-[4-methoxy-3-(3-piperidin-1-ylpropoxy)phenyl]prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	5.3800	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-[3-methoxy-4-(2-piperidin-1-ylethoxy)phenyl]prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	5.4000	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-[3-methoxy-4-(3-piperidin-1-ylpropoxy)phenyl]prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	5.5500	uM
(E)-3-[3-[3-(diethylamino)propoxy]-4-methoxyphenyl]-1-(5-hydroxy-2,2-dimethylchromen-6-yl)prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	5.6500	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-[3-methoxy-4-[2-(4-methylpiperidin-1-yl)ethoxy]phenyl]prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	5.7500	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-[3-methoxy-4-[3-(4-methylpiperazin-1-yl)propoxy]phenyl]prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	5.7600	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-[4-methoxy-3-[3-(4-methylpiperidin-1-yl)propoxy]phenyl]prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	6.2300	uM
(E)-3-[4-[2-(diethylamino)ethoxy]-3-methoxyphenyl]-1-(5-hydroxy-2,2-dimethylchromen-6-yl)prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	6.2900	uM
(E)-3-[4-[3-(diethylamino)propoxy]-3-methoxyphenyl]-1-(5-hydroxy-2,2-dimethylchromen-6-yl)prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	6.3000	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	6.4500	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-(3-hydroxy-4-methoxyphenyl)prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	6.9800	uM
2-(cyclohexylmethylsulfanyl)-6-oxo-1H-pyrimidine-5-carboxylic acid	1810103: Inhibition of human FIH using HLEVVKLLLEAGADVNAQDK-CONH2 as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins by RapidFire Mass spectrometry assay	ic50	7.8000	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-[3-methoxy-4-(2-morpholin-4-ylethoxy)phenyl]prop-2-en-1-one	2033535: Inhibition of HIF-1 alpha transcriptional activity in human U-251 cells incubated for 24 hrs under hypoxia condition by luciferse reporter assay	ic50	8.0900	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
cobaltous chloride	decreases expression, decreases reaction	3
sodium arsenite	decreases expression, increases expression	2
tetraethylenepentamine	affects localization, affects reaction, decreases expression, decreases reaction	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	increases expression	1
bisphenol A	decreases methylation	1
nickel chloride	decreases expression	1
manganese chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
dinophysistoxin 1	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Amphotericin B	increases reaction, affects binding, decreases activity, increases hydroxylation	1
Atrazine	decreases expression	1
Clioquinol	decreases reaction, increases hydroxylation, decreases activity	1
Isoproterenol	decreases expression	1
Ivermectin	decreases expression	1
Manganese	decreases expression	1
Vitamin E	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	affects localization, affects reaction	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

20 unique, capped per target: 20 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1068586	Binding	Inhibition of human recombinant FIH1	Structure-based virtual screening approach to the discovery of novel inhibitors of factor-inhibiting HIF-1: identification of new chelating groups for the active-site ferrous ion. — Bioorg Med Chem

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B5K9	HAP1 HIF1AN (-) 2	Cancer cell line	Male
CVCL_D1N3	Abcam K-562 HIF1AN KO	Cancer cell line	Female
CVCL_D2JN	Abcam Raji HIF1AN KO	Cancer cell line	Male
CVCL_D9G9	Ubigene HEK293 HIF1AN KO	Transformed cell line	Female
CVCL_UQ70	Abcam Jurkat HIF1AN KO	Cancer cell line	Male
CVCL_XP54	HAP1 HIF1AN (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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