HMOX2

Chr 16

heme oxygenase 2

Also known as: HO-2

NCBI Gene: 3163ENSG00000103415UniProt: P30519

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]

86
ClinVar variants
30
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HMOX2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 52 VUS of 86 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.97LOEUF
pLI 0.000
Z-score 1.67
OE 0.54 (0.31–0.97)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.11Z-score
OE missense 0.98 (0.86–1.10)
182 obs / 186.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.54 (0.31–0.97)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.86–1.10)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 8 / 15.0Missense obs/exp: 182 / 186.3Syn Z: -0.19

ClinVar Variant Classifications

86 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
VUS52
Likely Benign3
Benign1
30
Pathogenic
52
VUS
3
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
30
0
30
Likely Pathogenic
0
0
0
0
0
VUS
0
40
12
0
52
Likely Benign
0
3
0
0
3
Benign
0
0
0
1
1
Total04342186

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HMOX2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
HEME OXYGENASE 2; HMOX2
MIM #141251 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of sixteen novel candidate genes for late onset Parkinson's disease.
Gialluisi A et al.·Mol Neurodegener
2021
Heme Oxygenases in Cardiovascular Health and Disease.
Ayer A et al.·Physiol Rev
2016Review
Porphyrin and heme metabolism and the porphyrias.
Bonkovsky HL et al.·Compr Physiol
2013Review
Genetic Risk Factors for Essential Tremor: A Review.
Siokas V et al.·Tremor Other Hyperkinet Mov (N Y)
2020Review
Heme Oxygenase-1 and 2 Common Genetic Variants and Risk for Multiple Sclerosis.
Agúndez JA et al.·Sci Rep
2016
Genetic Association Study of Restless Legs Syndrome in Chinese Population.
Chen J et al.·Eur Neurol
2019
Comprehensive analysis of ferroptosis-related genes and prognosis of cutaneous melanoma.
Liu C et al.·BMC Med Genomics
2022
A polymorphism located at an ATG transcription start site of the heme oxygenase-2 gene is associated with classical Parkinson's disease.
Ayuso P et al.·Pharmacogenet Genomics
2011
Heme Oxygenase-1 and 2 Common Genetic Variants and Risk for Restless Legs Syndrome.
García-Martín E et al.·Medicine (Baltimore)
2015
Dysregulation of Iron Metabolism-Linked Genes at Myocardial Tissue and Cell Levels in Dilated Cardiomyopathy.
Massaiu I et al.·Int J Mol Sci
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Dual binding and efflux mechanisms involving HMOX2 and ABCB1 regulate the tumor selectivity of a near-infrared theranostic probe.
Ramos SC et al.·Int J Biol Macromol
2026Functional
Lutein inhibits ferroptosis and reduces neuronal cell death induced by Parkinson's disease through the NRF2-HMOX2 signaling axis.
Duan J et al.·Toxicol Appl Pharmacol
2025
Chemoproteomic Profiling of a Carbon-Stabilized Gold(III) Macrocycle Reveals Cellular Engagement with HMOX2.
Gukathasan S et al.·J Med Chem
2025
The HMOX2 polymorphism contributes to the carotid body chemoreflex in European sea-level residents by regulating hypoxic ventilatory responses.
Fabries P et al.·Front Med (Lausanne)
2022🔓 Open Access
A Near-Infrared Probe Tracks and Treats Lung Tumor Initiating Cells by Targeting HMOX2.
Kim JJ et al.·J Am Chem Soc
2019
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools