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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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BLMH
bleomycin hydrolase
Chromosome 17 · 17q11.2
NCBI Gene: 642Ensembl: ENSG00000108578.16HGNC: HGNC:1059UniProt: Q13867
123PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Protease
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolaminopeptidase activityprotein bindingnucleusaortic valve stenosisvertebral joint diseaseneoplasmlamellar ichthyosis
✦AI Summary

BLMH (bleomycin hydrolase) is a cysteine aminopeptidase with two primary functions: inactivating the chemotherapy drug bleomycin and detoxifying homocysteine thiolactone 1. The enzyme catalyzes hydrolysis of bleomycin's carboxamide bond, protecting both normal and malignant cells from drug toxicity 2. Additionally, BLMH metabolizes homocysteine thiolactone, preventing N-homocysteinylation of proteins that compromises their function 3. Mechanistically, BLMH interacts with the Phf8/H4K20me1/mTOR/autophagy pathway and amyloid precursor protein (AβPP) 1. BLMH deletion in mice causes downregulation of Phf8 and autophagy markers (Becn1, Atg5, Atg7) while upregulating mTOR and AβPP, leading to amyloid-β accumulation 1. Elevated homocysteine thiolactone metabolites in Blmh-deficient mice recapitulate these biochemical changes 1. Disease relevance is substantial: BLMH is attenuated in Alzheimer's disease brains, and Blmh deletion worsens cognitive and neuromotor deficits in 5xFAD AD models 1. BLMH variants influence bleomycin-induced pulmonary toxicity in Hodgkin lymphoma patients 4. Additionally, serum BLMH levels serve as a potential biomarker for predicting deep brain stimulation responses in Parkinson's disease 5. Clinically, BLMH characterization enables optimization of bleomycin pharmacokinetics and identification of patients requiring alternative therapies 4.

Sources cited
1
BLMH is a homocysteine thiolactone detoxifying enzyme; Blmh deletion causes cognitive/neuromotor deficits and interacts with Phf8/H4K20me1/mTOR/autophagy pathway and AβPP, leading to Aβ accumulation
PMID: 37718819
2
BLMH is a neutral cysteine aminopeptidase that hydrolyzes bleomycin; activity-based probes and inhibitors can label and inhibit BLMH
PMID: 26256478
3
BLMH is a homocysteine thiolactone-detoxifying enzyme evolved to prevent N-homocysteinylation of proteins; impairment contributes to neurodegeneration in Alzheimer's disease
PMID: 39125665
4
BLMH gene polymorphism (A1450G) influences bleomycin-induced late pulmonary toxicity in ABVD-treated Hodgkin lymphoma patients
PMID: 27327270
5
Serum BLMH is significantly downregulated in responders to deep brain stimulation in Parkinson's disease and serves as a potential biomarker for predicting DBS therapeutic responses
PMID: 38176938
Disease Associationsⓘ20
aortic valve stenosisOpen Targets
0.26Weak
vertebral joint diseaseOpen Targets
0.14Weak
neoplasmOpen Targets
0.08Suggestive
lamellar ichthyosisOpen Targets
0.04Suggestive
Alzheimer diseaseOpen Targets
0.04Suggestive
epidermolytic ichthyosisOpen Targets
0.04Suggestive
ichthyosis with erythrokeratodermaOpen Targets
0.04Suggestive
response to statinOpen Targets
0.04Suggestive
familial reactive perforating collagenosisOpen Targets
0.04Suggestive
psoriasisOpen Targets
0.04Suggestive
peeling skin syndrome 6Open Targets
0.04Suggestive
psoriasis 2Open Targets
0.04Suggestive
erythrokeratodermia variabilisOpen Targets
0.04Suggestive
ulerythema ophryogenesisOpen Targets
0.04Suggestive
epidermolytic hyperkeratosis 2B, autosomal recessiveOpen Targets
0.03Suggestive
ichthyosis, congenital, autosomal recessive 14Open Targets
0.03Suggestive
seborrhea-like dermatitis with psoriasiform elementsOpen Targets
0.03Suggestive
Chronic mucocutaneous candidosisOpen Targets
0.03Suggestive
immunodeficiency 51Open Targets
0.03Suggestive
congenital non-bullous ichthyosiform erythrodermaOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NUDT12Protein interaction87%CASP14Protein interaction82%KERAProtein interaction75%TPP2Shared pathway67%THOP1Shared pathway67%NPEPPSShared pathway33%
Tissue Expression6 tissues
Brain
100%
Lung
63%
Bone Marrow
57%
Heart
48%
Ovary
44%
Liver
38%
Gene Interaction Network
Click a node to explore
BLMHNUDT12CASP14KERATPP2THOP1NPEPPS
PROTEIN STRUCTURE
Preparing viewer…
PDB7V5L · 1.74 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.72LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.51 [0.37–0.72]
RankingsWhere BLMH stands among ~20K protein-coding genes
  • #3,816of 20,598
    Most Researched123 · top quartile
  • #5,601of 17,882
    Most Constrained (LOEUF)0.72
Genes detectedBLMH
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Deletion of the Homocysteine Thiolactone Detoxifying Enzyme Bleomycin Hydrolase, in Mice, Causes Memory and Neurological Deficits and Worsens Alzheimer's Disease-Related Behavioral and Biochemical Traits in the 5xFAD Model of Alzheimer's Disease.
PMID: 37718819
J Alzheimers Dis · 2023
1.00
2
Association of GLOD4 with Alzheimer's Disease in Humans and Mice.
PMID: 39302370
J Alzheimers Dis · 2024
0.90
3
Detection of bleomycin and its hydrolase by the cationic surfactant-doped liquid crystal-based sensing platform.
PMID: 33583545
Anal Chim Acta · 2021
0.80
4
Design and Synthesis of Activity-Based Probes and Inhibitors for Bleomycin Hydrolase.
PMID: 26256478
Chem Biol · 2015
0.70
5
Serum BLMH and CKM as Potential Biomarkers for Predicting Therapeutic Effects of Deep Brain Stimulation in Parkinson's Disease: A Proteomics Study.
PMID: 38176938
J Integr Neurosci · 2023
0.60