HMOX1 was first reported in relation to autosomal recessive heme oxygenase deficiency in 1999 (Yachie et al., PMID: 9884342). The primary features of this condition include recurrent fever, hemolytic anemia, low serum bilirubin, elevated serum ferritin, and small or absent spleen. The underlying mechanism is a loss of heme oxidase activity leading to increased susceptibility to oxidative damage (PMID: 20055707).
Six variants (nonsense, frameshift, splice site, whole exon deletion) that have been reported in five probands in five publications (PMIDs: 9884342; 210818618; 26526137; 32587840; 33066778) are included in this curation. Co-segregation with disease has not been observed. The mechanism of pathogenicity is biallelic loss of function. This gene-disease association is also supported by the known biological function of HMOX1, its expression pattern, functional alterations in patient and non-patient cells, and a non-human animal model (PMIDs: 9380735; 9380736; 9884342; 20055707; 25613900).
In summary, HMOX1 is definitively associated with autosomal recessive heme oxygenase deficiency 1. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time without the emergence of contradictory evidence. This classification was approved by the ClinGen General Inborn Errors of Metabolism GCEP on 12/18/2023 (SOP Version 10).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.