Heme oxygenase 1 deficiency

Summary

Heme oxygenase 1 deficiency (MONDO:0013536) is a disease caused by HMOX1 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: HMOX1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 11

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	heme oxygenase 1 deficiency
Mondo ID	MONDO:0013536
MeSH	C564200
OMIM	614034
Orphanet	562509
UMLS	C1841651
MedGen	333882
GARD	0017995
Is cancer (heuristic)	no

Also known as: heme oxygenase 1 deficiency · heme oxygenase-1 deficiency · HMOX1D

Data availability: 11 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of porphyrin metabolism › heme oxygenase 1 deficiency

Related subtypes (3): inborn disorder of bilirubin metabolism, inherited porphyria, X-linked sideroblastic anemia 1

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

11 retrieved; paginated sample, class counts are floors:

6 pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 benign/likely benign, 1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1184829	NM_002133.3(HMOX1):c.636+2T>A	HMOX1	Pathogenic	criteria provided, single submitter
1326850	NM_002133.3(HMOX1):c.130C>T (p.Arg44Ter)	HMOX1	Pathogenic	criteria provided, single submitter
1326851	NM_002133.3(HMOX1):c.416G>T (p.Gly139Val)	HMOX1	Pathogenic	no assertion criteria provided
1326852	NM_002133.3(HMOX1):c.610A>T (p.Lys204Ter)	HMOX1	Pathogenic	criteria provided, single submitter
1326853	NM_002133.3(HMOX1):c.262_268delinsCC (p.Ala88fs)	HMOX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
15895	NM_002133.3(HMOX1):c.24_144del	HMOX1	Pathogenic	no assertion criteria provided
15896	NM_002133.3(HMOX1):c.324_325del (p.Pro109fs)	HMOX1	Pathogenic	no assertion criteria provided
4796619	NM_002133.3(HMOX1):c.546C>A (p.Tyr182Ter)	HMOX1	Likely pathogenic	criteria provided, single submitter
1318566	NM_002133.3(HMOX1):c.287G>A (p.Trp96Ter)	HMOX1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3366998	NM_002133.3(HMOX1):c.73C>T (p.His25Tyr)	HMOX1	Uncertain significance	criteria provided, single submitter
1617610	NM_002133.3(HMOX1):c.378C>T (p.Pro126=)	HMOX1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
HMOX1	Strong	Autosomal recessive	heme oxygenase 1 deficiency	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HMOX1	Orphanet:562509	Heme oxygenase-1 deficiency
HMOX1	Orphanet:586	Cystic fibrosis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HMOX1	HGNC:5013	ENSG00000100292	P09601	Heme oxygenase 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HMOX1	Heme oxygenase 1	Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous iron.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HMOX1	Enzyme (other)	yes	1.14.14.18	Haem_Oase, Haem_Oase-like, Haem_Oase-like_multi-hlx

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	1
monocyte	1
spleen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HMOX1	230	ubiquitous	marker	cartilage tissue, spleen, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HMOX1	4,054

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HMOX1	P09601	26

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Regulation of HMOX1 expression and activity	1	2284.0×	0.004	HMOX1
Heme degradation	1	815.7×	0.004	HMOX1
The NLRP3 inflammasome	1	671.8×	0.004	HMOX1
NFE2L2 regulating anti-oxidant/detoxification enzymes	1	543.8×	0.004	HMOX1
Insertion of tail-anchored proteins into the endoplasmic reticulum membrane	1	475.8×	0.004	HMOX1
Purinergic signaling in leishmaniasis infection	1	423.0×	0.004	HMOX1
Iron uptake and transport	1	346.1×	0.004	HMOX1
Heme signaling	1	215.5×	0.006	HMOX1
Cytoprotection by HMOX1	1	184.2×	0.006	HMOX1
Interleukin-4 and Interleukin-13 signaling	1	102.9×	0.010	HMOX1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
wound healing involved in inflammatory response	1	8426.0×	0.001	HMOX1
heme oxidation	1	8426.0×	0.001	HMOX1
smooth muscle hyperplasia	1	8426.0×	0.001	HMOX1
cellular response to cisplatin	1	3370.4×	0.003	HMOX1
cellular response to arsenic-containing substance	1	2106.5×	0.003	HMOX1
negative regulation of leukocyte migration	1	1685.2×	0.003	HMOX1
positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis	1	1685.2×	0.003	HMOX1
heme catabolic process	1	1532.0×	0.003	HMOX1
erythrocyte homeostasis	1	1296.3×	0.003	HMOX1
positive regulation of epithelial cell apoptotic process	1	1296.3×	0.003	HMOX1
negative regulation of macroautophagy	1	1123.5×	0.003	HMOX1
low-density lipoprotein particle clearance	1	991.3×	0.003	HMOX1
epithelial cell apoptotic process	1	842.6×	0.003	HMOX1
negative regulation of ferroptosis	1	802.5×	0.003	HMOX1
cellular response to cadmium ion	1	766.0×	0.003	HMOX1
positive regulation of cell migration involved in sprouting angiogenesis	1	732.7×	0.003	HMOX1
negative regulation of smooth muscle cell proliferation	1	624.1×	0.003	HMOX1
multicellular organismal-level iron ion homeostasis	1	581.1×	0.003	HMOX1
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	1	581.1×	0.003	HMOX1
endothelial cell proliferation	1	543.6×	0.003	HMOX1
positive regulation of macroautophagy	1	526.6×	0.003	HMOX1
response to hydrogen peroxide	1	468.1×	0.004	HMOX1
response to nicotine	1	421.3×	0.004	HMOX1
regulation of angiogenesis	1	421.3×	0.004	HMOX1
negative regulation of cytokine production involved in inflammatory response	1	421.3×	0.004	HMOX1
positive regulation of chemokine production	1	374.5×	0.004	HMOX1
cellular response to heat	1	343.9×	0.004	HMOX1
positive regulation of smooth muscle cell proliferation	1	330.4×	0.004	HMOX1
erythrocyte differentiation	1	267.5×	0.005	HMOX1
intracellular iron ion homeostasis	1	244.2×	0.005	HMOX1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HMOX1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
HMOX1	23	Binding:22, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HMOX1	1.14.14.18	heme oxygenase (biliverdin-producing)

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	HMOX1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
HMOX1	23	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.