HMOX1

heme oxygenase 1

Basic information

Region (hg38): 22:35380360-35394214

Links

ENSG00000100292 ∙ NCBI:3162 ∙ OMIM:141250 ∙ HGNC:5013 ∙ Uniprot:P09601 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• heme oxygenase 1 deficiency (Limited), mode of inheritance: AR
• heme oxygenase 1 deficiency (Supportive), mode of inheritance: AR
• chronic obstructive pulmonary disease (Limited), mode of inheritance: Unknown
• heme oxygenase 1 deficiency (Strong), mode of inheritance: AR
• heme oxygenase 1 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Heme oxygenase 1 deficiency	AR	Allergy/Immunology/Infectious; Hematologic	Although the disease may ultimately be fatal, the condition includes immunodeficiency (includind due to asplenia), and prophylaxis and prompt and aggressive treatment of infections may be beneficial; RBC transfusions may be indicated for anemia	Allergy/Immunology/Infectious; Craniofacial; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Renal	9884342; 21088618; 22023467

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HMOX1 gene.

• not provided (177 variants)
• Inborn genetic diseases (14 variants)
• Heme oxygenase 1 deficiency (4 variants)
• HMOX1-related condition (2 variants)
• Heme oxygenase 1 deficiency;COPD, severe early onset (1 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HMOX1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	59	5	65
missense			70	3	3	76
nonsense	2					2
start loss						0
frameshift		2				2
inframe indel						0
splice donor/acceptor (+/-2bp)	1	2				3
splice region			4	3	1	8
non coding			3	19	3	25
Total	3	4	74	81	11

Highest pathogenic variant AF is 0.0000197

Variants in HMOX1

This is a list of pathogenic ClinVar variants found in the HMOX1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
22-35381161-C-T			Uncertain significance (Jul 09, 2021)
22-35381167-C-T			Uncertain significance (Oct 10, 2019)
22-35381190-C-A		HMOX1-related disorder	Uncertain significance (May 09, 2023)
22-35381191-C-T			Likely benign (Dec 14, 2023)
22-35381192-G-C			Benign (Feb 01, 2024)
22-35381194-C-G			Uncertain significance (Oct 11, 2022)
22-35381197-G-T			Likely pathogenic (Feb 24, 2023)
22-35381200-AGCGCGGGGCGCGGGAC-A			Likely benign (Jan 17, 2023)
22-35381200-A-AGCGCGGG			Likely benign (Jun 14, 2023)
22-35381202-C-T			Uncertain significance (Aug 16, 2022)
22-35381206-G-A			Likely benign (Nov 14, 2023)
22-35381207-G-A			Likely benign (Nov 17, 2023)
22-35381208-G-A			Likely benign (Dec 09, 2023)
22-35381208-GCGCGGGA-G			Likely benign (Apr 05, 2023)
22-35381208-G-GCGCGGGA			Benign (Jan 31, 2024)
22-35381208-G-GCGCGGGACGCGGGA			Likely benign (Apr 13, 2023)
22-35381210-G-A			Benign (Jan 19, 2024)
22-35381211-C-T			Likely benign (Dec 22, 2023)
22-35381213-G-A			Likely benign (Aug 23, 2023)
22-35381213-G-C			Likely benign (Jun 17, 2023)
22-35381215-A-G			Likely benign (Oct 04, 2023)
22-35383094-T-C			Likely benign (Jul 29, 2022)
22-35383101-C-T			Likely benign (Aug 02, 2023)
22-35383107-A-C		not specified	Uncertain significance (Jan 26, 2022)
22-35383107-A-T			Uncertain significance (Apr 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HMOX1	protein_coding	protein_coding	ENST00000216117	5	13854

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00968	0.946	125726	0	22	125748	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.520	190	171	1.11	0.0000111	1860
Missense in Polyphen		63	53.113	1.1862		663
Synonymous	-0.955	79	68.9	1.15	0.00000400	595
Loss of Function	1.75	5	11.3	0.441	5.84e-7	126

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000587	0.0000587
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000168	0.000167
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed. Exhibits cytoprotective effects since excess of free heme sensitizes cells to undergo apoptosis.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:9884342}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: HIF-1 signaling pathway - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Porphyrin and chlorophyll metabolism - Homo sapiens (human);Mineral absorption - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Ferroptosis - Homo sapiens (human);Hereditary Coproporphyria (HCP);Porphyria Variegata (PV);Congenital Erythropoietic Porphyria (CEP) or Gunther Disease;Acute Intermittent Porphyria;Porphyrin Metabolism;miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Nuclear Receptors Meta-Pathway;NRF2 pathway;Transcriptional activation by NRF2;Overview of nanoparticle effects;Photodynamic therapy-induced NFE2L2 (NRF2) survival signaling;Lung fibrosis;Interleukin-4 and 13 signaling;Oxidative Stress;oxidative stress induced gene expression via nrf2;il-10 anti-inflammatory signaling pathway;heme degradation;Heme degradation;Metabolism of porphyrins;Metabolism;Transport of small molecules;Porphyrin metabolism;Iron uptake and transport;HIF-1-alpha transcription factor network;Validated transcriptional targets of AP1 family members Fra1 and Fra2 (Consensus)

Recessive Scores

• pRec: 0.862

Intolerance Scores

• loftool: 0.611
• rvis_EVS: -0.6
• rvis_percentile_EVS: 17.91

Haploinsufficiency Scores

• pHI: 0.110
• hipred: Y
• hipred_score: 0.583
• ghis: 0.454

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hmox1
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: hmox1a
• Affected structure: cardiac ventricle
• Phenotype tag: abnormal
• Phenotype quality: increased volume

Gene ontology

• Biological process: angiogenesis;endothelial cell proliferation;wound healing involved in inflammatory response;negative regulation of leukocyte migration;heme oxidation;cellular iron ion homeostasis;response to oxidative stress;small GTPase mediated signal transduction;excretion;regulation of blood pressure;cell death;intrinsic apoptotic signaling pathway in response to DNA damage;negative regulation of muscle cell apoptotic process;smooth muscle hyperplasia;positive regulation of macroautophagy;negative regulation of macroautophagy;cytokine-mediated signaling pathway;cellular response to nutrient;negative regulation of mast cell cytokine production;erythrocyte homeostasis;low-density lipoprotein particle clearance;regulation of transcription from RNA polymerase II promoter in response to iron;cellular response to heat;response to nicotine;intracellular signal transduction;heme catabolic process;response to hydrogen peroxide;positive regulation of apoptotic process;positive regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of mast cell degranulation;negative regulation of DNA binding;negative regulation of DNA-binding transcription factor activity;negative regulation of neuron apoptotic process;regulation of transcription from RNA polymerase II promoter in response to oxidative stress;response to estrogen;positive regulation of chemokine biosynthetic process;regulation of angiogenesis;positive regulation of angiogenesis;positive regulation of smooth muscle cell proliferation;negative regulation of smooth muscle cell proliferation;regulation of DNA-binding transcription factor activity;protein homooligomerization;iron ion homeostasis;cellular response to arsenic-containing substance;cellular response to cadmium ion;cellular response to hypoxia;cellular response to cisplatin;positive regulation of cell migration involved in sprouting angiogenesis;liver regeneration;positive regulation of blood vessel diameter;negative regulation of extrinsic apoptotic signaling pathway via death domain receptors;positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis;negative regulation of epithelial cell apoptotic process;negative regulation of vascular smooth muscle cell proliferation
• Cellular component: extracellular space;nucleus;nucleolus;endoplasmic reticulum;endoplasmic reticulum membrane;cytosol;caveola;membrane;perinuclear region of cytoplasm
• Molecular function: heme oxygenase (decyclizing) activity;phospholipase D activity;protein binding;enzyme binding;heme binding;protein homodimerization activity;metal ion binding