HMOX1

Summary

HMOX1 (heme oxygenase 1, HGNC:5013) is a protein-coding gene on chromosome 22q12.3, encoding Heme oxygenase 1 (P09601). Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous iron. In precision oncology, HMOX1 EXPRESSION is associated with resistance to Sorafenib + Sunitinib in Renal Cell Carcinoma (CIViC Level B).

Heme oxygenase, an essential enzyme in heme catabolism, cleaves heme to form biliverdin, which is subsequently converted to bilirubin by biliverdin reductase, and carbon monoxide, a putative neurotransmitter. Heme oxygenase activity is induced by its substrate heme and by various nonheme substances. Heme oxygenase occurs as 2 isozymes, an inducible heme oxygenase-1 and a constitutive heme oxygenase-2. HMOX1 and HMOX2 belong to the heme oxygenase family.

Source: NCBI Gene 3162 — RefSeq curated summary.

At a glance

• Gene–disease (curated): heme oxygenase 1 deficiency (Strong, ClinGen) — +2 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 325 total — 19 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 60
• Druggable target: yes
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_002133

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5013
Approved symbol	HMOX1
Name	heme oxygenase 1
Location	22q12.3
Locus type	gene with protein product
Status	Approved
Aliases	bK286B10, HO-1
Ensembl gene	ENSG00000100292
Ensembl biotype	protein_coding
OMIM	141250
Entrez	3162

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000216117, ENST00000412893, ENST00000481190, ENST00000494998, ENST00000677931, ENST00000678411, ENST00000679074

RefSeq mRNA: 1 — MANE Select: NM_002133 NM_002133

CCDS: CCDS13914

Canonical transcript exons

ENST00000216117 — 5 exons

Exon	Start	End
ENSE00000653517	35386685	35387176
ENSE00000653518	35389864	35389963
ENSE00001380117	35393468	35394207
ENSE00001915869	35381096	35381196
ENSE00003592416	35383106	35383226

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 98.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 130.2421 / max 5103.0333, expressed in 1683 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191982	127.6541	1681
191988	0.7076	314
191986	0.4384	192
191991	0.3201	140
191990	0.2908	137
191985	0.2461	117
191987	0.2261	115
191984	0.1798	91
191983	0.1790	70

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	98.96	gold quality
spleen	UBERON:0002106	98.91	gold quality
monocyte	CL:0000576	97.60	gold quality
granulocyte	CL:0000094	97.26	gold quality
leukocyte	CL:0000738	97.22	gold quality
mononuclear cell	CL:0000842	97.19	gold quality
islet of Langerhans	UBERON:0000006	96.10	gold quality
left ovary	UBERON:0002119	96.10	gold quality
mucosa of transverse colon	UBERON:0004991	95.95	gold quality
skin of leg	UBERON:0001511	95.34	gold quality
gall bladder	UBERON:0002110	95.33	gold quality
right ovary	UBERON:0002118	94.65	gold quality
upper lobe of left lung	UBERON:0008952	94.51	gold quality
trabecular bone tissue	UBERON:0002483	94.32	gold quality
upper lobe of lung	UBERON:0008948	94.32	gold quality
duodenum	UBERON:0002114	93.81	gold quality
right lobe of liver	UBERON:0001114	93.57	gold quality
left adrenal gland	UBERON:0001234	92.89	gold quality
skin of abdomen	UBERON:0001416	92.65	gold quality
lower esophagus mucosa	UBERON:0035834	92.61	gold quality
right lung	UBERON:0002167	92.49	gold quality
zone of skin	UBERON:0000014	92.28	gold quality
ovary	UBERON:0000992	92.02	gold quality
adult mammalian kidney	UBERON:0000082	91.83	gold quality
omental fat pad	UBERON:0010414	91.74	gold quality
right adrenal gland cortex	UBERON:0035827	91.72	gold quality
right adrenal gland	UBERON:0001233	91.67	gold quality
peritoneum	UBERON:0002358	91.60	gold quality
left adrenal gland cortex	UBERON:0035825	91.59	gold quality
liver	UBERON:0002107	91.42	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	5020.55
E-MTAB-7407	yes	4954.64
E-HCAD-32	yes	721.23
E-CURD-122	yes	56.75
E-HCAD-10	yes	39.03
E-MTAB-10553	yes	29.26
E-HCAD-9	yes	23.76
E-CURD-112	yes	18.08
E-CURD-7	no	1262.94
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
BAD	Activation
BCL2	Activation

Upstream regulators (CollecTRI, top): AP1, AR, ARNT, ASCL1, ATF4, BACH1, BACH2, CEBPA, CREB1, CTCF, EGR1, ELK1, ELK3, ERG, ESR2, ETS1, ETS2, FLI1, FOS, FOXO1, FOXP3, GATA2, GLI3, HIF1A, IRF6, JUN, JUNB, JUND, KAT7, KDM5A, KLF2, MAF, MAFG, MAFK, MT3, MYC, NCOA3, NFE2L2, NFKB1, NFKB

miRNA regulators (miRDB)

35 targeting HMOX1, 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-4795-3P	100.00	74.62	4024
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-3065-5P	99.97	71.56	3281
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-6807-3P	99.15	69.23	1275
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-4717-5P	98.19	67.97	894
HSA-MIR-517-5P	97.13	68.43	781
HSA-MIR-3194-5P	96.80	64.90	1027
HSA-MIR-6858-3P	96.37	64.41	771

Literature-anchored findings (GeneRIF, showing 40)

• Expression and regulation in healthy lung and interstitial lung disorders (PMID:11727267)
• Gene transfection of H25A mutant heme oxygenase-1 protects cells against hydroperoxide-induced cytotoxicity (PMID:11786534)
• Induction of HO-1 mRNA and protein expression in cultured endothelial cells by the active pentaerythrityl tetranitrate metabolite pentaerythrityl trinitrate is followed by increased cellular resistance to oxidant injury. (PMID:11820797)
• Has a significant role in endothelial cell cycle progression (PMID:11829463)
• Heme oxygenase-1, a protective gene that prevents the rejection of transplanted organs. (PMID:12086318)
• This enzyme performs the seemingly lackluster function of catabolizing heme to generate bilirubin, carbon monoxide, and free iron. (PMID:12091240)
• protection of grafts by this enzyme and its toxic product carbon monoxide (PMID:12099373)
• Rickettsia rickettsii infection of culture human endothelial cells induces heme oxygenase 1 expression (PMID:12117910)
• hHO-1 is potentially able to reduce the risk factors of atherosclerosis, partially due to its cellular protection against oxidative injury and to its inhibitory effect on cellular proliferation (PMID:12118938)
• Exposure of endothelium to sublethal concentrations of heme-oxidized LDL leads to induction of both HO-1 and ferritin, leading to cytotoxicity. (PMID:12130498)
• transcriptional activation of the human haem oxygenase-1 gene promoter in a hepatoma cell line (PMID:12133007)
• microsatellite polymorphism in promoter of heme oxygenase-1 gene is associated with susceptibility to coronary artery disease in type 2 diabetic patients (PMID:12136229)
• expression in colon carcinoma cells exposed to pyrrolidine dithiocarbamate (PMID:12151344)
• Patients with AAA were less frequently carriers of short repeats in the HO-1 gene promoter than patients with atherosclerosis or healthy subjects. Short alleles facilitating upregulation of HO-1 may be a protective anti-inflammatory factor against AAA. (PMID:12182912)
• HO-1 regulates the cell cycle in vascular endothelial and smooth muscle cells (PMID:12207883)
• Abnormal reduction in endogenous heme oxygenase on the surface of placental trophoblasts may be one of the important mechanisms for the onset of intrauterine growth retardation. (PMID:12376298)
• TGF-beta1 is a potent inducer of HO-1; the signaling pathway by which TGF-beta1 regulates HO-1 expression in human lung epithelial cells (PMID:12376363)
• results indicate that prolonged overexpression of HO-1 ultimately decreases soluble guanylate cyclase activity by limiting the availability of cellular heme (PMID:12376366)
• Length polymorphism in the HO-1 gene promoter is related to coronary artery disease susceptibility in Japanese people who also have coronary risk factors such as hypercholesterolemia, diabetes, and smoking. (PMID:12377749)
• induction of HO-1 gene mediates protection against oxidants and increases cell survival by a mechanism independent of telomerase enzyme activity (PMID:12379283)
• Heme oxygenase 1 mediates the immunomodulatory and antiapoptotic effects of interleukin 13 gene therapy in vivo in rats and in vitro in human cells. (PMID:12396617)
• HO-1 mitigates the TNF-alpha-mediated changes in cell cycle progression and apoptosis, perhaps by a decrease in the levels of COX activity (PMID:12397597)
• This enzyme is expressed in heart transplant recipients during acute rejection episodes, along with apoptosis. (PMID:12431619)
• HO-1 has a specific conformation that allows tight binding to nitric oxide, which may contribute to the pleiotropic responses to NO and CO (PMID:12433915)
• CYP2E1 overexpression up-regulates both non-specific delta-aminolevulinate synthase and this enzyme in a human hepatoma cell line. (PMID:12469218)
• gene expression regulation used as a possible assessment for antioxidant capacity in Alzheimer’s disease (PMID:12480749)
• This enzyme is expressed in heart transplant recipients during acute rejection episodes. (PMID:12493432)
• comparison of heme-gree and -bound crystal structures (PMID:12500973)
• Polymorphism in HMOX1 might be associated with development of emphysematous changes in the lung. (PMID:12579334)
• gene induction by glucose deprivation is mediated by reactive oxygen species via the mitochondrial electron-transport chain (PMID:12585963)
• determination of binding sites on cytochrome P450 reductase and biliverdin reductase (PMID:12626517)
• HO-1 expression occurs in human epidermias and infiltrating leukocytes of patients with chronic inflammation. The basal level of HO expression in the skin may serve as a first protective environment against acute oxidative and inflammatory insults. (PMID:12649161)
• decompensated type 2 diabetes is associated with increased NADPH oxidase subunit p22(phox) and hemeoxygenase-1 gene expressions in circulating monocytes (PMID:12679469)
• antiproliferative effect of the HO-1 pathway in airway smooth muscle in vitro and in vivo through a bilirubin-mediated redox modulation of phosphorylation of ERK1/2 (PMID:12690112)
• These results demonstrate that heme oxygenase-1 operates through distinct molecular mechanisms to confer cytoprotection in the hypoxic and the LPS models of inflammation. (PMID:12709566)
• Data suggest that heme oxygenase-1 gene overexpression may be related to decrease in blood pressure through reduction of the vasodilator 20-hydroxyeicosatetraenoic acid in the urine. (PMID:12709568)
• Results demonstrate that upregulation of heme oxygenase-1 was able to attenuate pyrrolidinedithiocarbamate (PDTC)-mediated cell proliferation, but was unable to reverse the PDTC-induced decrease in angiogenesis in vascular endothelial cells. (PMID:12709569)
• Results suggest that stimulation or overexpression of heme oxygenase-1 attenuates DNA damage caused by exposure to angiotensin II. (PMID:12709590)
• Data suggest that heme oxygenase-1 may be involved in intestinal cell cycle progression. (PMID:12709592)
• heme oxygenase activity up-regulates VEGF production and augments the capability of endothelial cells to respond to exogenous stimulation (PMID:12716475)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hmox1a	ENSDARG00000027529
mus_musculus	Hmox1	ENSMUSG00000005413
rattus_norvegicus	Hmox1	ENSRNOG00000014117
drosophila_melanogaster	Ho	FBGN0037933

Paralogs (1): HMOX2 (ENSG00000103415)

Protein

Protein identifiers

Heme oxygenase 1 — P09601 (reviewed: P09601)

All UniProt accessions (7): P09601, A0A7I2V277, A0A7I2V3I1, A0A7I2V3M0, A0A7I2YQL9, B1AHA8, Q6FH11

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous iron. Affords protection against programmed cell death and this cytoprotective effect relies on its ability to catabolize free heme and prevent it from sensitizing cells to undergo apoptosis. (Microbial infection) During SARS-COV-2 infection, promotes SARS-CoV-2 ORF3A-mediated autophagy but is unlikely to be required for ORF3A-mediated induction of reticulophagy. Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous iron.

Subunit / interactions. (Microbial infection) Interacts with SARS-CoV-2 ORF3A protein; the interaction promotes ORF3A-induced autophagy but is unlikely to be involved in ORF3A-mediated induction of reticulophagy. Homodimer and higher order homooligomer. Oligomerization is crucial for its stability and function in the endoplasmic reticulum. Interacts with FLVCR2; this interaction is potentiated in the presence of heme.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expressed at higher levels in renal cancer tissue than in normal tissue (at protein level).

Post-translational modifications. A soluble form arises by proteolytic removal of the membrane anchor.

Disease relevance. Heme oxygenase 1 deficiency (HMOX1D) [MIM:614034] A disease characterized by impaired stress hematopoiesis, resulting in marked erythrocyte fragmentation and intravascular hemolysis, coagulation abnormalities, endothelial damage, and iron deposition in renal and hepatic tissues. Clinical features include persistent hemolytic anemia, asplenia, nephritis, generalized erythematous rash, growth retardation and hepatomegaly. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The transmembrane domain is necessary for its oligomerization.

Induction. Heme oxygenase 1 activity is highly inducible by its substrate heme and by various non-heme substances such as heavy metals, bromobenzene, endotoxin, oxidizing agents and UVA.

Similarity. Belongs to the heme oxygenase family.

RefSeq proteins (1): NP_002124* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002051	Haem_Oase	Family
IPR016053	Haem_Oase-like	Family
IPR016084	Haem_Oase-like_multi-hlx	Homologous_superfamily
IPR018207	Haem_oxygenase_CS	Conserved_site

Pfam: PF01126

Enzyme classification (BRENDA):

• EC 1.14.14.18 — heme oxygenase (biliverdin-producing) (BRENDA: 33 organisms, 138 substrates, 351 inhibitors, 37 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
HEME	0.0002–0.04	15
[REDUCED CYTOCHROME P450 REDUCTASE]	0.5–21.7	6
PROTOHEME IX	0.0018–0.0164	3
NADPH	0.0061–0.023	2
[REDUCED NADPH-HEMOPROTEIN REDUCTASE]	0.0018–0.0027	2
ALPHA-MESO-OXYPROTOHEME IX	0.0036	1
CO-HEME	0.125	1
FE-HEME	0.017	1
HEMATOHEME	0.01	1
HEME B	0.0009	1
HEME C	0.029	1
HEMIN	0.01	1
PROTOHEME	0.0009	1

Catalyzed reactions (Rhea), 1 shown:

• heme b + 3 reduced [NADPH–hemoprotein reductase] + 3 O2 = biliverdin IXalpha + CO + Fe(2+) + 3 oxidized [NADPH–hemoprotein reductase] + 3 H2O + H(+) (RHEA:21764)

UniProt features (33 total): helix 15, binding site 4, mutagenesis site 3, chain 2, sequence variant 2, modified residue 1, topological domain 1, turn 1, strand 1, transmembrane region 1, region of interest 1, site 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
1N45	X-RAY DIFFRACTION	1.5
3CZY	X-RAY DIFFRACTION	1.54
1OZW	X-RAY DIFFRACTION	1.55
1OZL	X-RAY DIFFRACTION	1.58
1OYL	X-RAY DIFFRACTION	1.59
1OZR	X-RAY DIFFRACTION	1.74
1XJZ	X-RAY DIFFRACTION	1.88
6EHA	X-RAY DIFFRACTION	2
1XK1	X-RAY DIFFRACTION	2.08
1XK3	X-RAY DIFFRACTION	2.08
5BTQ	X-RAY DIFFRACTION	2.08
1NI6	X-RAY DIFFRACTION	2.1
1TWR	X-RAY DIFFRACTION	2.1
1T5P	X-RAY DIFFRACTION	2.11
3K4F	X-RAY DIFFRACTION	2.17
1XK0	X-RAY DIFFRACTION	2.18
1OZE	X-RAY DIFFRACTION	2.19
1S8C	X-RAY DIFFRACTION	2.19
3HOK	X-RAY DIFFRACTION	2.19
1TWN	X-RAY DIFFRACTION	2.2
1XK2	X-RAY DIFFRACTION	2.2
1S13	X-RAY DIFFRACTION	2.29
1N3U	X-RAY DIFFRACTION	2.58
1OYK	X-RAY DIFFRACTION	2.59
3TGM	X-RAY DIFFRACTION	2.85
4WD4	X-RAY DIFFRACTION	2.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09601-F1	83.62	0.74

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): 140 (important for catalytic activity)

Ligand- & substrate-binding residues (4): 18; 25 (axial binding residue); 134; 183

Post-translational modifications (1): 229

Mutagenesis-validated functional residues (3):

Position	Phenotype
140	inactive as a heme oxygenase but active as a peroxidase.
270	no effect on catalytic activity, oligomerization and localization to the endoplasmic reticulum.
270	significant reduction in catalytic activity, reduced oligomerization, reduced endoplasmic reticulum localization with cy

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-189483	Heme degradation
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-844456	The NLRP3 inflammasome
R-HSA-917937	Iron uptake and transport
R-HSA-9609523	Insertion of tail-anchored proteins into the endoplasmic reticulum membrane
R-HSA-9660826	Purinergic signaling in leishmaniasis infection
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-9707587	Regulation of HMOX1 expression and activity
R-HSA-9707616	Heme signaling
R-HSA-9818027	NFE2L2 regulating anti-oxidant/detoxification enzymes

MSigDB gene sets: 660 (showing top): TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN, GOBP_REGULATION_OF_AUTOPHAGY, KOBAYASHI_EGFR_SIGNALING_24HR_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_NEGATIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, HARRIS_HYPOXIA, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, REACTOME_THE_NLRP3_INFLAMMASOME, REACTOME_INFLAMMASOMES, REACTOME_NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEAT_CONTAINING_RECEPTOR_NLR_SIGNALING_PATHWAYS, REACTOME_METABOLISM_OF_PORPHYRINS, CHUANG_OXIDATIVE_STRESS_RESPONSE_UP

GO Biological Process (39): angiogenesis (GO:0001525), endothelial cell proliferation (GO:0001935), wound healing involved in inflammatory response (GO:0002246), negative regulation of leukocyte migration (GO:0002686), regulation of transcription by RNA polymerase II (GO:0006357), heme oxidation (GO:0006788), intracellular iron ion homeostasis (GO:0006879), response to oxidative stress (GO:0006979), smooth muscle hyperplasia (GO:0014806), macroautophagy (GO:0016236), positive regulation of macroautophagy (GO:0016239), negative regulation of macroautophagy (GO:0016242), erythrocyte differentiation (GO:0030218), positive regulation of chemokine production (GO:0032722), erythrocyte homeostasis (GO:0034101), low-density lipoprotein particle clearance (GO:0034383), cellular response to heat (GO:0034605), response to nicotine (GO:0035094), intracellular signal transduction (GO:0035556), heme catabolic process (GO:0042167), response to hydrogen peroxide (GO:0042542), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), regulation of angiogenesis (GO:0045765), positive regulation of angiogenesis (GO:0045766), positive regulation of smooth muscle cell proliferation (GO:0048661), negative regulation of smooth muscle cell proliferation (GO:0048662), multicellular organismal-level iron ion homeostasis (GO:0060586), cellular response to arsenic-containing substance (GO:0071243), cellular response to cadmium ion (GO:0071276), cellular response to cisplatin (GO:0072719), positive regulation of cell migration involved in sprouting angiogenesis (GO:0090050), negative regulation of ferroptosis (GO:0110076), negative regulation of cytokine production involved in inflammatory response (GO:1900016), negative regulation of extrinsic apoptotic signaling pathway via death domain receptors (GO:1902042), positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis (GO:1903589), epithelial cell apoptotic process (GO:1904019), positive regulation of epithelial cell apoptotic process (GO:1904037), apoptotic process (GO:0006915), heme metabolic process (GO:0042168)

GO Molecular Function (9): heme oxygenase (decyclizing) activity (GO:0004392), structural molecule activity (GO:0005198), enzyme binding (GO:0019899), heme binding (GO:0020037), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), metal ion binding (GO:0046872), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (9): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrial outer membrane (GO:0005741), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), membrane (GO:0016020), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Metabolism of porphyrins	1
Signaling by Interleukins	1
Inflammasomes	1
Transport of small molecules	1
Protein localization	1
Cell recruitment (pro-inflammatory response)	1
Cellular response to chemical stress	1
Cytoprotection by HMOX1	1
Cellular responses to stress	1
Nuclear events mediated by NFE2L2	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
porphyrin-containing compound catabolic process	2
heme metabolic process	2
macroautophagy	2
regulation of macroautophagy	2
protein binding	2
intracellular membrane-bounded organelle	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
epithelial cell proliferation	1
inflammatory response	1
wound healing	1
inflammatory response to wounding	1
negative regulation of immune system process	1
regulation of leukocyte migration	1
negative regulation of cell migration	1
leukocyte migration	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
response to stress	1
smooth muscle adaptation	1
muscle hyperplasia	1
autophagosome assembly	1
autophagy	1
positive regulation of autophagy	1
negative regulation of autophagy	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
positive regulation of cytokine production	1
chemokine production	1
regulation of chemokine production	1
myeloid cell homeostasis	1
plasma lipoprotein particle clearance	1
low-density lipoprotein particle disassembly	1
response to heat	1
cellular response to stress	1
response to chemical	1

Protein interactions and networks

STRING

3690 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HMOX1	NFE2L2	Q16236	960
HMOX1	BLVRA	P53004	946
HMOX1	KEAP1	Q14145	934
HMOX1	NQO1	P15559	915
HMOX1	GCLM	P48507	908
HMOX1	GCLC	P48506	897
HMOX1	CRYZ	Q08257	882
HMOX1	BCL2	P10415	857
HMOX1	GPX2	P18283	847
HMOX1	GPX5	O75715	838
HMOX1	GPX6	P59796	838
HMOX1	GPX8	Q8TED1	838
HMOX1	GPX3	P22352	837
HMOX1	GPX7	Q96SL4	837
HMOX1	CYCS	P00001	828

IntAct

195 interactions, top by confidence:

A	B	Type	Score
NFE2L2	MAFG	psi-mi:“MI:0914”(association)	0.940
	HMOX1	psi-mi:“MI:0914”(association)	0.740
HMOX1		psi-mi:“MI:0915”(physical association)	0.740
STIM2	PRKAB2	psi-mi:“MI:0914”(association)	0.640
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
SLC1A1	AGPAT2	psi-mi:“MI:0914”(association)	0.640
HMOX1	STX1A	psi-mi:“MI:0915”(physical association)	0.600
HMOX1	ELOVL6	psi-mi:“MI:0915”(physical association)	0.560
HMOX1	CRB3	psi-mi:“MI:0915”(physical association)	0.560
HMOX1	ELOVL5	psi-mi:“MI:0915”(physical association)	0.560
HMOX1	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
HMOX1	MSMO1	psi-mi:“MI:0915”(physical association)	0.560
HMOX1	CYB561	psi-mi:“MI:0915”(physical association)	0.560
HMOX1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
HMOX1	TM4SF19	psi-mi:“MI:0915”(physical association)	0.560
HMOX1	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
HMOX1	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
HMOX1	FAM174A	psi-mi:“MI:0915”(physical association)	0.560
HMOX1	PDZK1IP1	psi-mi:“MI:0915”(physical association)	0.560
HMOX1	JAGN1	psi-mi:“MI:0915”(physical association)	0.560
HMOX1	AQP6	psi-mi:“MI:0915”(physical association)	0.560
SLC16A7	HMOX1	psi-mi:“MI:0915”(physical association)	0.560
HMOX1	CD79A	psi-mi:“MI:0915”(physical association)	0.560
	HMOX1	psi-mi:“MI:0915”(physical association)	0.560
HMOX1	SEC11C	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (169): CCDC155 (Two-hybrid), HMOX1 (Affinity Capture-MS), HMOX1 (Affinity Capture-MS), HMOX1 (Affinity Capture-MS), UGT8 (Affinity Capture-MS), TEX264 (Affinity Capture-MS), HLA-C (Affinity Capture-MS), HMOX1 (Affinity Capture-MS), HMOX1 (Affinity Capture-MS), HMOX1 (Affinity Capture-MS), HMOX1 (Affinity Capture-MS), HMOX1 (Affinity Capture-MS), HMOX1 (Two-hybrid), HMOX1 (Affinity Capture-MS), HMOX1 (Affinity Capture-MS)

ESM2 similar proteins: E9Q4Z2, F1ND48, O00763, O08796, O70252, O73688, O95870, P06762, P09601, P14791, P14901, P23711, P30519, P32394, P43242, P70531, Q08BI9, Q08BW6, Q0ZHH6, Q1JPD2, Q1LX49, Q28HL3, Q2PG53, Q3SYS9, Q4FZX0, Q4G074, Q4KLN4, Q4R8P0, Q4V7A9, Q5E9F2, Q5E9N5, Q5EBA1, Q5R6S0, Q5R7E3, Q6MG55, Q6NRW5, Q6ZT62, Q7Z3D6, Q80V94, Q80YD1

Diamond homologs: O19998, O70252, O70453, O73688, O78497, P06762, P09601, P14791, P14901, P23711, P30519, P32394, P43242, P51271, P71119, P72849, P74133, Q1XDL5, Q2PG53, Q5E9F2, Q5R7E3, Q8YVS7, I3SL57

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
AKT	unknown	HMOX1	phosphorylation
PRDM2	“up-regulates quantity by expression”	HMOX1	“transcriptional regulation”
HMOX1	“down-regulates activity”	HBA1
HMOX1	“down-regulates quantity”	heme	“chemical modification”
AKT1	unknown	HMOX1	phosphorylation
NFE2L2	“up-regulates quantity by expression”	HMOX1	“transcriptional regulation”
HMOX1	up-regulates	Proliferation
HMOX1	down-regulates	Apoptosis
HMOX1	“up-regulates quantity by expression”	BCL2	“transcriptional regulation”
HMOX1	“up-regulates quantity by expression”	BAD	“transcriptional regulation”
NFE2L2	“up-regulates quantity”	HMOX1	“transcriptional regulation”
BACH1	“down-regulates quantity”	HMOX1	“transcriptional regulation”
HMOX1	“form complex”	STC2/HMOX1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 161 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
R-HSA-425366	7	12.4×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
intracellular zinc ion homeostasis	5	17.2×	4e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	6
Uncertain significance	107
Likely benign	167
Benign	7

Top pathogenic / likely-pathogenic (25)

Variant ID	HGVS	Classification
1184829	NM_002133.3(HMOX1):c.636+2T>A	Pathogenic
1326850	NM_002133.3(HMOX1):c.130C>T (p.Arg44Ter)	Pathogenic
1326851	NM_002133.3(HMOX1):c.416G>T (p.Gly139Val)	Pathogenic
1326852	NM_002133.3(HMOX1):c.610A>T (p.Lys204Ter)	Pathogenic
15895	NM_002133.3(HMOX1):c.24_144del	Pathogenic
15896	NM_002133.3(HMOX1):c.324_325del (p.Pro109fs)	Pathogenic
2759906	NM_002133.3(HMOX1):c.304C>T (p.Gln102Ter)	Pathogenic
2784133	NM_002133.3(HMOX1):c.652C>T (p.Gln218Ter)	Pathogenic
2815052	NM_002133.3(HMOX1):c.135_139del (p.Gly46fs)	Pathogenic
2824188	NM_002133.3(HMOX1):c.57_60dup (p.Thr21fs)	Pathogenic
2837038	NM_002133.3(HMOX1):c.459del (p.Ala154fs)	Pathogenic
2841479	NM_002133.3(HMOX1):c.303_328del (p.Trp101fs)	Pathogenic
2843706	NM_002133.3(HMOX1):c.291C>A (p.Tyr97Ter)	Pathogenic
2845608	NM_002133.3(HMOX1):c.288G>A (p.Trp96Ter)	Pathogenic
2869294	NM_002133.3(HMOX1):c.604G>T (p.Glu202Ter)	Pathogenic
2990917	NM_002133.3(HMOX1):c.227_228del (p.Pro76fs)	Pathogenic
3007963	NM_002133.3(HMOX1):c.228del (p.Val77fs)	Pathogenic
3639915	NM_002133.3(HMOX1):c.431dup (p.Gln145fs)	Pathogenic
3691456	NM_002133.3(HMOX1):c.22dup (p.Ser8fs)	Pathogenic
1523240	NM_002133.3(HMOX1):c.637-1G>A	Likely pathogenic
2424358	NC_000022.10:g.(?35779079)(35779239_?)dup	Likely pathogenic
2764359	NM_002133.3(HMOX1):c.144+1G>A	Likely pathogenic
2840397	NM_002133.3(HMOX1):c.23+1G>T	Likely pathogenic
4796619	NM_002133.3(HMOX1):c.546C>A (p.Tyr182Ter)	Likely pathogenic
809355	NM_002133.3(HMOX1):c.55dup (p.Glu19fs)	Likely pathogenic

SpliceAI

510 predictions. Top by Δscore:

Variant	Effect	Δscore
22:35383104:A:AG	acceptor_gain	1.0000
22:35383104:AGCAT:A	acceptor_gain	1.0000
22:35383105:G:GG	acceptor_gain	1.0000
22:35383105:GC:G	acceptor_gain	1.0000
22:35383105:GCA:G	acceptor_gain	1.0000
22:35383105:GCAT:G	acceptor_gain	1.0000
22:35383105:GCATG:G	acceptor_gain	1.0000
22:35383223:CAAG:C	donor_loss	1.0000
22:35383224:AAGGT:A	donor_loss	1.0000
22:35386680:TTCAG:T	acceptor_loss	1.0000
22:35386682:CA:C	acceptor_loss	1.0000
22:35386683:A:AC	acceptor_loss	1.0000
22:35386683:A:AG	acceptor_gain	1.0000
22:35386683:AGCT:A	acceptor_gain	1.0000
22:35386683:AGCTG:A	acceptor_gain	1.0000
22:35386684:G:GT	acceptor_gain	1.0000
22:35386684:GC:G	acceptor_gain	1.0000
22:35386684:GCT:G	acceptor_gain	1.0000
22:35386684:GCTG:G	acceptor_gain	1.0000
22:35386684:GCTGG:G	acceptor_gain	1.0000
22:35387175:AGGTG:A	donor_loss	1.0000
22:35387177:GT:G	donor_loss	1.0000
22:35387178:T:A	donor_loss	1.0000
22:35389859:TTTA:T	acceptor_loss	1.0000
22:35389861:TAGC:T	acceptor_loss	1.0000
22:35389862:A:AG	acceptor_gain	1.0000
22:35389862:AGCTC:A	acceptor_loss	1.0000
22:35389863:G:GA	acceptor_gain	1.0000
22:35389863:GC:G	acceptor_gain	1.0000
22:35389863:GCT:G	acceptor_gain	1.0000

AlphaMissense

1872 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:35387077:G:C	K179N	0.994
22:35387077:G:T	K179N	0.994
22:35387159:T:C	F207L	0.993
22:35387161:C:A	F207L	0.993
22:35387161:C:G	F207L	0.993
22:35387088:G:C	R183P	0.991
22:35386793:C:A	R85S	0.989
22:35387045:T:C	F169L	0.987
22:35387047:C:A	F169L	0.987
22:35387047:C:G	F169L	0.987
22:35386992:C:A	A151D	0.986
22:35386962:T:C	L141P	0.985
22:35387084:T:G	Y182D	0.985
22:35387072:T:C	F178L	0.984
22:35387074:C:A	F178L	0.984
22:35387074:C:G	F178L	0.984
22:35386956:G:A	G139D	0.983
22:35387075:A:G	K179E	0.981
22:35383155:C:G	H25D	0.980
22:35386932:C:A	A131D	0.980
22:35386947:G:C	R136P	0.980
22:35387087:C:A	R183S	0.980
22:35387147:G:C	A203P	0.980
22:35386794:G:C	R85P	0.978
22:35386946:C:A	R136S	0.978
22:35386959:A:C	D140A	0.976
22:35386959:A:G	D140G	0.976
22:35386968:G:A	G143E	0.976
22:35386814:G:C	D92H	0.975
22:35386955:G:C	G139R	0.974

dbSNP variants (sampled 300 via entrez): RS1000147902 (22:35384728 C>G), RS1000558448 (22:35390788 G>A), RS1001188574 (22:35379763 T>C), RS1001243905 (22:35386458 C>T), RS1001317303 (22:35379171 C>G), RS1001482026 (22:35379435 A>G,T), RS1001630576 (22:35394384 C>G), RS1001945456 (22:35383715 T>C), RS1002128324 (22:35389146 C>T), RS1002244750 (22:35384762 C>A), RS1002398156 (22:35390494 G>A,C), RS1002553686 (22:35380641 C>A,T), RS1002642282 (22:35386201 C>T), RS1002860496 (22:35390220 C>T), RS1003195358 (22:35383481 G>A,C)

Disease associations

OMIM: gene MIM:141250 | disease phenotypes: MIM:614034, MIM:606963

GenCC curated gene-disease

Disease	Classification	Inheritance
heme oxygenase 1 deficiency	Strong	Autosomal recessive
cystic fibrosis	Supportive	Autosomal recessive
chronic obstructive pulmonary disease	Limited	Unknown

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
heme oxygenase 1 deficiency	Strong	AR

Mondo (5): heme oxygenase 1 deficiency (MONDO:0013536), chronic obstructive pulmonary disease (MONDO:0005002), pulmonary disease, chronic obstructive, susceptibility to (MONDO:0100167), COPD, severe early onset (MONDO:0011751), cystic fibrosis (MONDO:0009061)

Orphanet (1): Heme oxygenase-1 deficiency (Orphanet:562509)

HPO phenotypes

60 total (30 of 60 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000123	Nephritis
HP:0000246	Sinusitis
HP:0000365	Hearing impairment
HP:0000421	Epistaxis
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000787	Nephrolithiasis
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0001263	Global developmental delay
HP:0001392	Abnormality of the liver
HP:0001394	Cirrhosis
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001738	Exocrine pancreatic insufficiency
HP:0001746	Asplenia
HP:0001878	Hemolytic anemia
HP:0001894	Thrombocytosis
HP:0002020	Gastroesophageal reflux
HP:0002024	Malabsorption
HP:0002035	Rectal prolapse
HP:0002099	Asthma
HP:0002105	Hemoptysis
HP:0002107	Pneumothorax
HP:0002110	Bronchiectasis
HP:0002205	Recurrent respiratory infections

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001762_694	Obesity-related traits	3.000000e-06
GCST005958_13	Waist-to-hip ratio adjusted for BMI (age >50)	1.000000e-06
GCST005962_33	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	6.000000e-06
GCST006284_15	Plasma proprotein convertase subtilisin/kexin type 9 levels in stable coronary artery disease	2.000000e-06
GCST006284_7	Plasma proprotein convertase subtilisin/kexin type 9 levels in stable coronary artery disease	6.000000e-07
GCST007013_1	Hippocampal volume in mild cognitive impairment	2.000000e-07

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0006899	PCSK9 protein measurement
EFO:0005035	hippocampal volume

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D003550	Cystic Fibrosis	C06.689.202; C08.381.187; C16.320.190; C16.614.213
D029424	Pulmonary Disease, Chronic Obstructive	C08.381.495.389; C23.550.291.500.875
C564200	Heme Oxygenase 1 Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2823 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
HMOX1 EXPRESSION	Sorafenib + Sunitinib	Renal Cell Carcinoma	Resistance	CIViC B	EID829

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Haem oxygenase

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 1 [PMID: 16821802]	Inhibition	5.82	pKi

ChEMBL bioactivities

19 potent at pChembl≥5 of 23 total, top 19 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.22	IC50	60	nM	CHEMBL4161975
6.85	Kd	141	nM	CHEMBL5613041
6.60	IC50	250	nM	CHEMBL4456149
6.19	Kd	648	nM	CHEMBL5614205
6.16	Kd	692	nM	CHEMBL5613604
6.15	Kd	703	nM	CHEMBL5613612
6.10	Kd	794	nM	CHEMBL5613267
6.05	IC50	900	nM	CHEMBL4541767
5.85	Kd	1420	nM	CHEMBL5612022
5.82	IC50	1500	nM	CHEMBL536056
5.74	Kd	1840	nM	CHEMBL5613955
5.72	IC50	1900	nM	CHEMBL539857
5.58	IC50	2600	nM	CHEMBL3621940
5.42	Kd	3790	nM	CHEMBL5613257
5.29	Kd	5100	nM	CHEMBL5612877
5.16	Kd	6920	nM	CHEMBL5614120
5.12	Kd	7590	nM	CHEMBL5613017
5.10	Kd	7930	nM	CHEMBL5614291
5.03	Kd	9290	nM	CHEMBL5613326

PubChem BioAssay actives

18 with measured affinity, of 65 total; 18 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-[4-(4-bromophenyl)phenyl]-2-imidazol-1-ylethanol	1633161: Inhibition of human recombinant HO-1 by spectrometry based assay	ic50	0.0600	uM
N-[2-[[2-(3-bromophenyl)quinazolin-4-yl]amino]ethyl]-4-fluorobenzenesulfonamide	2127386: Binding affinity to avi-tagged HO-1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.1410	uM
1-[4-(4-bromophenyl)butyl]imidazole	1633161: Inhibition of human recombinant HO-1 by spectrometry based assay	ic50	0.2500	uM
5-[7-(1-benzothiophen-3-ylsulfonyl)-6,8-dihydro-5H-imidazo[1,2-a]pyrazin-2-yl]-2-fluoroaniline	2127386: Binding affinity to avi-tagged HO-1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.6480	uM
N-[2-[[7-chloro-2-(4-fluorophenyl)quinazolin-4-yl]amino]ethyl]-4-fluorobenzenesulfonamide	2127386: Binding affinity to avi-tagged HO-1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.6920	uM
5-[5-(3-chloro-4-methoxyphenyl)sulfonyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-2-fluoroaniline	2127386: Binding affinity to avi-tagged HO-1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.7030	uM
N-[3-[2-(1-phenylbenzimidazol-2-yl)ethyl]phenyl]pyrazine-2-carboxamide	2127386: Binding affinity to avi-tagged HO-1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.7940	uM
1-[2-(4-phenylmethoxyphenyl)ethyl]imidazole	1633161: Inhibition of human recombinant HO-1 by spectrometry based assay	ic50	0.9000	uM
1-[3-(5-bromopyrimidin-2-yl)oxypyrrolidin-1-yl]-2,2-diphenylethanone	2127386: Binding affinity to avi-tagged HO-1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	1.4200	uM
1-[[(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-4-methyl-1,3-dioxolan-2-yl]methyl]imidazole;hydrochloride	267298: Inhibition of human spleen HO1	ic50	1.5000	uM
5-[5-[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-2-fluoroaniline	2127386: Binding affinity to avi-tagged HO-1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	1.8400	uM
1-[[2-[2-(4-bromophenyl)ethyl]-1,3-dioxolan-2-yl]methyl]imidazole;hydrochloride	1633161: Inhibition of human recombinant HO-1 by spectrometry based assay	ic50	1.9000	uM
N-[6-(4-ethoxy-2-fluorophenyl)-3-methylquinolin-2-yl]propane-1-sulfonamide	2127386: Binding affinity to avi-tagged HO-1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	3.7900	uM
5-[5-(5-chloro-2-methoxyphenyl)sulfonyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-2-fluoroaniline	2127386: Binding affinity to avi-tagged HO-1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	5.1000	uM
4-methyl-N-[2-[(2-phenylquinazolin-4-yl)amino]ethyl]benzenesulfonamide	2127386: Binding affinity to avi-tagged HO-1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	6.9200	uM
N-(1-benzothiophen-3-ylmethyl)-1-[5-(trifluoromethyl)-2-pyridinyl]pyrrolidin-3-amine	2127386: Binding affinity to avi-tagged HO-1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	7.5900	uM
5-[5-(5-ethyl-2-methoxyphenyl)sulfonyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-2-fluoroaniline	2127386: Binding affinity to avi-tagged HO-1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	7.9300	uM
N-[6-(4-ethoxy-2-fluorophenyl)-3-methylquinolin-2-yl]-1H-pyrazole-4-carboxamide	2127386: Binding affinity to avi-tagged HO-1 (unknown origin) assessed as dissociation constant by SPR analysis	kd	9.2900	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects reaction, decreases expression, increases cleavage, increases abundance, increases activity (+9 more)	102
Acetylcysteine	decreases expression, increases chemical synthesis, affects cotreatment, affects expression, increases abundance (+8 more)	67
Particulate Matter	increases abundance, affects expression, decreases expression, increases reaction, affects cotreatment (+4 more)	44
Arsenic Trioxide	increases reaction, decreases expression, increases activity, decreases response to substance, affects reaction (+6 more)	42
Cadmium Chloride	decreases reaction, increases expression, affects reaction, decreases expression, increases activity (+3 more)	39
cobaltiprotoporphyrin	decreases chemical synthesis, affects binding, affects cotreatment, increases activity, affects expression (+14 more)	35
Cadmium	affects cotreatment, affects expression, increases abundance, increases reaction, increases expression (+4 more)	32
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects expression, affects reaction, decreases reaction, increases expression, affects cotreatment (+5 more)	30
Hydrogen Peroxide	affects expression, affects reaction, decreases expression, increases abundance, decreases response to substance (+8 more)	29
sulforaphane	affects cotreatment, increases activity, decreases reaction, increases expression, increases reaction (+1 more)	25
Vehicle Emissions	decreases reaction, increases abundance, decreases expression, affects expression, affects cotreatment (+4 more)	25
Hemin	affects cotreatment, increases reaction, increases activity, decreases chemical synthesis, decreases response to substance (+4 more)	25
SB 203580	affects cotreatment, decreases reaction, increases activity, increases reaction, increases expression	22
Resveratrol	increases activity, increases degradation, decreases reaction, decreases response to substance, affects expression (+8 more)	22
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	affects cotreatment, decreases reaction, increases activity, decreases expression, decreases response to substance (+4 more)	21
Curcumin	increases reaction, increases activity, decreases response to substance, affects reaction, decreases reaction (+2 more)	20
zinc protoporphyrin	increases reaction, decreases activity, increases response to substance, increases activity, decreases abundance (+6 more)	19
2-tert-butylhydroquinone	increases reaction, increases expression, affects cotreatment, affects reaction, affects binding (+1 more)	18
Arsenic	increases expression, decreases reaction, increases ubiquitination, decreases ubiquitination, increases acetylation (+8 more)	18
Lipopolysaccharides	decreases reaction, increases reaction, increases expression, increases activity, decreases activity (+5 more)	18
bisphenol A	decreases expression, decreases reaction, increases expression, affects cotreatment, affects expression (+2 more)	17
pyrazolanthrone	decreases reaction, increases expression, increases activity, decreases expression, increases reaction	16
Oxygen	decreases reaction, increases expression, increases reaction, decreases expression, affects cotreatment (+2 more)	16
Dactinomycin	decreases reaction, increases expression, decreases expression, decreases response to substance, increases response to substance	15
Air Pollutants	decreases expression, decreases reaction, increases reaction, affects cotreatment, increases abundance (+2 more)	14
Paraquat	affects expression, affects cotreatment, increases expression, decreases reaction, decreases response to substance (+2 more)	14
cobaltous chloride	increases activity, increases expression, increases stability, affects reaction, decreases reaction (+1 more)	13
Copper	decreases reaction, increases expression, affects binding, affects cotreatment, increases abundance (+5 more)	13
cinnamaldehyde	decreases reaction, increases expression, increases reaction, affects cotreatment	12
tin protoporphyrin IX	decreases reaction, increases chemical synthesis, affects cotreatment, increases expression, increases reaction (+6 more)	12

ChEMBL screening assays

23 unique, capped per target: 22 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1035716	Binding	Inhibition of human recombinant HO1 expressed in Escherichia coli DH5alpha assessed as heme degradation at 25 uM by spectrophotometry in presence of L-ascorbic acid relative to control	X-ray crystal structure of human heme oxygenase-1 in complex with 1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone: a common binding mode for imidazole-based heme oxygenase-1 inhibitors. — J Med Chem
CHEMBL3418068	ADMET	Effect on heme oxygenase-1 (unknown origin)-mediated HCV replication in human MH14 cells transfected with pHO-1-Luc by luciferase reporter gene assay	Discovery of the 2-phenyl-4,5,6,7-Tetrahydro-1H-indole as a novel anti-hepatitis C virus targeting scaffold. — Eur J Med Chem

Cellosaurus cell lines

9 cell lines: 5 cancer cell line, 4 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B2N5	Abcam A-549 HMOX1 KO	Cancer cell line	Male
CVCL_C7FV	DMBi005-A	Induced pluripotent stem cell	Male
CVCL_C7FW	DMBi005-A-1	Induced pluripotent stem cell	Male
CVCL_C7FX	DMBi006-A	Induced pluripotent stem cell	Male
CVCL_C7FY	DMBi006-A-1	Induced pluripotent stem cell	Male
CVCL_E1E1	Ubigene U-251 MG HMOX1 KO	Cancer cell line	Male
CVCL_E1EG	Ubigene U-87 MG HMOX1 KO	Cancer cell line	Male
CVCL_SR57	HAP1 HMOX1 (-) 1	Cancer cell line	Male
CVCL_XP58	HAP1 HMOX1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00120978	PHASE4	UNKNOWN	Can Advair and Flovent Reduce Systemic Inflammation Related to Chronic Obstructive Pulmonary Disease (COPD)? A Multi-Center Randomized Controlled Trial
NCT00134979	PHASE4	COMPLETED	Formoterol Certihaler, Tiotropium HandiHaler and Tiotropium HandiHaler in Combination With Formoterol Certihaler in Patients With Stable Chronic Obstructive Pulmonary Disease
NCT00158847	PHASE4	TERMINATED	Modification Of Disease Outcome In COPD
NCT00170222	PHASE4	COMPLETED	Placebo Versus Antibiotics in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)
NCT00175565	PHASE4	COMPLETED	Inhaled Steroid Reduces Systemic Inflammation in COPD
NCT00181207	PHASE4	COMPLETED	Airway Clearance for Prevention of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
NCT00186706	PHASE4	COMPLETED	Selenium Supplementation in Chronic Obstructive Pulmonary Disease (COPD) Patients
NCT00190437	PHASE4	COMPLETED	ANTEAB: a Study of Early Antibiotherapy in the ICU Management of Acute Exacerbations of COPD
NCT00202176	PHASE4	COMPLETED	Effects of Bronchodilators in Mild Chronic Obstructive Pulmonary Disease (COPD)
NCT00202189	PHASE4	COMPLETED	Effects of Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease (COPD)
NCT00232674	PHASE4	COMPLETED	Efficacy Study of the Effect of Budesonide on Emphysema
NCT00288548	PHASE4	UNKNOWN	Metoprolol and Formoterol in Chronic Obstructive Pulmonary Disease (COPD)
NCT00291408	PHASE4	WITHDRAWN	Effect of Symbicort on HAT and HDAC in Sputum Macrophages of COPD
NCT00291460	PHASE4	UNKNOWN	Inspiratory Muscle Training in Hypercapnic COPD
NCT00292838	PHASE4	COMPLETED	Relative Potency of Inhaled Corticosteroids
NCT00311961	PHASE4	COMPLETED	Intravenous Versus Oral Administration of Prednisolone in Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)
NCT00316992	PHASE4	COMPLETED	Safety of Ramelteon in Subjects With Chronic Obstructive Pulmonary Disease
NCT00331656	PHASE4	UNKNOWN	Comparative Study of Non-Invasive Mask Ventilation vs Cuirass Ventilation in Patients With Acute Respiratory Failure.
NCT00335621	PHASE4	WITHDRAWN	Replacement of Nebulised Ipratropium With Inhaled Tiotropium in Stable Chronic Obstructive Pulmonary Disease (COPD)
NCT00354354	PHASE4	COMPLETED	Bronchodilators and Oxygen Kinetics With Exercise in Chronic Obstructive Pulmonary Disease (COPD) Patients
NCT00379028	PHASE4	COMPLETED	Airway Clearance Study
NCT00405236	PHASE4	COMPLETED	Effect of Tiotropium on Inflammation and Exacerbations in COPD
NCT00412204	PHASE4	COMPLETED	Study to Evaluate the Effects of Tiotropium Bromide on Chronic Obstructive Pulmonary Disease (COPD) During Exercise
NCT00424528	PHASE4	COMPLETED	Efficacy Safety Study of Arformoterol/Tiotropium Combination Versus Either Therapy Alone in Chronic Obstructive Pulmonary Disease (COPD)
NCT00440245	PHASE4	COMPLETED	Bronchoprotection of Salbutamol in Asthma and Chronic Obstructive Pulmonary Disease
NCT00440687	PHASE4	COMPLETED	Withdrawal of Inhaled Corticosteroids in Patients With COPD in Primary Care
NCT00489853	PHASE4	COMPLETED	Evaluation of Efficacy on Exercise Tolerance of Symbicort (Budesonide/Formoterol) Compared to Placebo and Oxis in Patients With Severe COPD
NCT00491803	PHASE4	COMPLETED	Sildenafil Effects on Pulmonary Haemodynamics and Gas Exchange in Chronic Obstructive Pulmonary Disease (COPD)
NCT00495586	PHASE4	COMPLETED	Effectiveness of Antibiotic Therapy for Exacerbations of Chronic Obstructive Pulmonary Disease
NCT00525564	PHASE4	COMPLETED	Effects of Salmeterol on Walking Capacity in Patients With COPD
NCT00532584	PHASE4	WITHDRAWN	Effect of Steroids on Gene Expression in the Healthy Smokers Lungs
NCT00542880	PHASE4	COMPLETED	Evaluation of Onset of Effect in Patients With Severe Chronic Obstructive Pulmonary Disease (COPD) Treated With Symbicort® Compared to Seretide®
NCT00561886	PHASE4	COMPLETED	Change of Inspiratory Peak Flow in COPD
NCT00569270	PHASE4	COMPLETED	Dynamic Hyperinflation and Tiotropium
NCT00571428	PHASE4	COMPLETED	Efficacy Safety Study of Arformoterol QD Dosing Versus BID Dosing in COPD
NCT00578968	PHASE4	COMPLETED	Cardiac Limitations in Chronic Obstructive Pulmonary Disease: Benefits of Bronchodilation
NCT00592033	PHASE4	COMPLETED	Effect of Oxygen in Normoxaemic COPD Patients Who Desaturate During Exercise
NCT00628225	PHASE4	COMPLETED	Smoking Cessation in Patients With COPD (SMOCC) in General Practice
NCT00633776	PHASE4	WITHDRAWN	Perforomist Versus Foradil Evaluated by Inspiratory Capacity and High Resolution Computed Tomography (HRCT)
NCT00639236	PHASE4	COMPLETED	Effectiveness and Safety of Inhaling Hypertonic Saline in Patients With Chronic Obstructive Pulmonary Disease