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HMOX1
heme oxygenase 1
HMOX1 is located on the long (q) arm of chromosome 22, at band 22q12.3. Arm ratio per GRCh38 - banding schematic.
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Overview
HMOX1 is located on chromosome 22 and encodes haeme oxygenase-1, an enzyme that degrades haeme molecules. Haeme is a component of haemoglobin and other proteins, and its breakdown must be carefully controlled. The enzyme plays a particularly important role during times of cellular stress, when it is rapidly upregulated to protect cells from damage. HMOX1 expression increases in response to oxidative stress, inflammation, and other challenges, making it a key component of the body's antioxidant defence system. Variation in HMOX1 has been investigated in relation to cardiovascular conditions, inflammatory disorders, and responses to environmental stressors.
What the gene does
Haeme oxygenase-1 catalyses the first and rate-limiting step in haeme degradation, converting haeme to biliverdin whilst releasing carbon monoxide and ferrous iron. Biliverdin is subsequently converted to bilirubin by biliverdin reductase, and bilirubin functions as an antioxidant. The carbon monoxide produced has signalling properties and may influence vascular tone and immune responses. By removing haeme, the enzyme prevents haeme-mediated oxidative damage, as free haeme can generate reactive oxygen species that damage cellular components. The protein is particularly abundant in the spleen and liver, organs central to red blood cell turnover, but it is expressed in many tissues and can be strongly induced by stress signals including heat shock, heavy metals, and inflammatory cytokines. This inducible expression allows cells to mount protective responses when challenged.
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Chromosome location
HMOX1 is located on the long arm of chromosome 22 at position 22q12.3. The gene spans approximately 14 kilobases and contains five exons. Its chromosomal position places it in a region that has been associated with genomic variation influencing immune and metabolic traits, though HMOX1 itself is the primary gene of interest in this locus for oxidative stress pathways.
Protein structure
The HMOX1 protein comprises 288 amino acids and contains a catalytic domain that binds haeme and facilitates its cleavage. The protein includes a C-terminal membrane anchor that tethers it to the endoplasmic reticulum, positioning the catalytic region appropriately for substrate access. A disordered region spanning amino acids 223-260 is present in the protein; such disordered regions often participate in regulatory interactions or provide flexibility for conformational changes during catalysis. The overall structure enables the enzyme to remain membrane-associated whilst processing haeme molecules efficiently.
Key variants
Genetic variation in HMOX1 includes a well-studied polymorphism in the promoter region involving variable numbers of GT dinucleotide repeats, which can influence the gene's inducibility and baseline expression levels. Individuals with shorter repeat sequences generally show higher enzyme activity under stress conditions. Missense variants within the coding sequence are less commonly reported but may affect enzyme stability or catalytic efficiency. The impact of HMOX1 variation is often studied in polygenic contexts, where it may contribute modest effects to disease risk alongside other genetic and environmental factors.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.262_268delinsCC | p.Ala88fs | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.227_228del | p.Pro76fs | Pathogenic | ★☆☆☆ | not provided |
c.228del | p.Val77fs | Pathogenic | ★☆☆☆ | not provided |
c.22dup | p.Ser8fs | Pathogenic | ★☆☆☆ | not provided |
c.288G>A | p.Trp96Ter | Pathogenic | ★☆☆☆ | not provided |
c.291C>A | p.Tyr97Ter | Pathogenic | ★☆☆☆ | not provided |
c.303_328del | p.Trp101fs | Pathogenic | ★☆☆☆ | not provided |
c.431dup | p.Gln145fs | Pathogenic | ★☆☆☆ | not provided |
c.459del | p.Ala154fs | Pathogenic | ★☆☆☆ | not provided |
c.604G>T | p.Glu202Ter | Pathogenic | ★☆☆☆ | not provided |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
HMOX1 variation has been investigated in relation to cardiovascular disease, where oxidative stress and inflammation are key pathogenic mechanisms. Research has explored associations between promoter polymorphisms and outcomes such as coronary artery disease and restenosis following vascular interventions. The gene has also been studied in inflammatory conditions and in responses to infections, given its role in modulating immune signalling. Because HMOX1 operates within complex biological networks, its contribution to disease is typically polygenic, with effects modified by other genes and environmental exposures. Complete loss of haeme oxygenase-1 function is extremely rare but has been described in case reports involving severe oxidative injury and vascular complications.
No disease links recorded for this gene in our reference set.
UK clinical status
HMOX1 appears on two NHS Genomic Medicine Service panels. It is listed as a green gene on the COVID-19 research panel, reflecting interest in its role in inflammatory responses to infection. The gene also has green status with a rating of R15 on the Primary immunodeficiency or monogenic inflammatory bowel disease panel, indicating relevance to immune regulation and gastrointestinal inflammation pathways. These classifications support the gene's inclusion in research and clinical contexts where oxidative stress and immune function intersect.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the HMOX1 gene do?
HMOX1 provides instructions for haeme oxygenase-1, an enzyme that breaks down haeme into biliverdin, carbon monoxide, and iron. This process protects cells from oxidative damage and is particularly important during inflammation and stress.
Is HMOX1 linked to any inherited conditions?
HMOX1 variation is studied in polygenic contexts rather than classic single-gene disorders. Promoter polymorphisms may modestly influence risk for cardiovascular and inflammatory conditions, though effects are typically small and interact with other genetic and environmental factors.
Why is HMOX1 on NHS genomic panels?
HMOX1 appears on NHS panels for COVID-19 research and primary immunodeficiency or inflammatory bowel disease, reflecting its role in immune responses and inflammation. Its inclusion supports investigation of how oxidative stress pathways influence susceptibility to infection and inflammatory disease.