HMOX2

Chr 16

heme oxygenase 2

Also known as: HO-2

NCBI Gene: 3163 ENSG00000103415 UniProt: P30519 OMIM: 141251

Heme oxygenase-2 catalyzes the oxidative cleavage of heme to generate biliverdin, carbon monoxide, and iron, serving as the constitutive isoform of this essential heme catabolism enzyme. Mutations in HMOX2 cause autosomal recessive heme oxygenase-2 deficiency, a rare disorder affecting heme metabolism. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.97

Clinical Summary— HMOX2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

41 VUS of 58 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.97LOEUF

pLI 0.000

Z-score 1.67

OE 0.54 (0.31–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.11Z-score

OE missense 0.98 (0.86–1.10)

182 obs / 186.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.54 (0.31–0.97)

0≤0.351.4

Missense OE?0.98 (0.86–1.10)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 8 / 15.0Missense obs/exp: 182 / 186.3Syn Z: -0.19

This gene — mechanism propensity

0.6259th %ile

GOF

0.6247th %ile

LOF

0.2484th %ile

The Badonyi & Marsh model scores gain-of-function highest, but genomic evidence most strongly supports dominant-negative as the primary mechanism.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

58 submitted variants in ClinVar

ClinVar

Classification Summary

VUS41

Likely Benign3

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	41	0	41
Likely Benign	3	0	3
Benign	0	1	1
Total	44	1	45

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 43) ClinVar copy-number / structural variants overlap HMOX2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →