HMOX2
protein-codingheme oxygenase 2
Gene summary
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. Several alternatively spliced transcript variants encoding three different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~35.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HMOX2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002134.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 44 | 3 | 47 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 48 | 3 | 1 | 52 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002125.3 | 5 | MANE Select | |
| Ensembl | ENSP00000459214.1 | 5 | MANE Select | |
| RefSeq | NP_001120676.1 | 5 | Standard | |
| RefSeq | NP_001120677.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Porphyrin and chlorophyll metabolism - Homo sapiens (human)
- Mineral absorption - Homo sapiens (human)
- Neutrophil degranulation
- oxidative stress induced gene expression via nrf2
- heme degradation
Biological Process
- response to hypoxia
- heme oxidation
- cellular iron ion homeostasis
- response to oxidative stress
- heme catabolic process
Molecular Function
- heme oxygenase (decyclizing) activity
- protein binding
- heme binding
- metal ion binding
Cellular Component
- endoplasmic reticulum membrane
- plasma membrane
- membrane
- specific granule membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000570646
- Coding exons
- 5
- Length
- 35658
- Individuals with no LoFs
- 125560
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 185
- Defined
- 125747
- p
- 0.000744
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.113 | 182 | 186 | 0.977 | 0.0000107 | 2081 |
| Missense (PolyPhen) | 43 | 53.506 | 0.80364 | 620 | ||
| Synonymous | -0.190 | 78 | 75.9 | 1.03 | 0.00000466 | 593 |
| Loss of Function | 1.67 | 8 | 14.9 | 0.535 | 8.02e-7 | 173 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0014 | 0.0013 | notable |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0.013 | 0.013 | notable |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0.00098 | 0.00098 | rare |
dbNSFP Gene Annotations
Source:
- 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. Heme oxygenase 2 could be implicated in the production of carbon monoxide in brain where it could act as a neurotransmitter.;
Recessive Scores
- pRec
- 0.626
Intolerance Scores
- LoFtool
- 0.879
- RVIS EVS
- -0.76
- RVIS percentile EVS
- 13.45
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.999
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |