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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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DOHH
deoxyhypusine hydroxylase
Chromosome 19 Β· 19p13.3
NCBI Gene: 83475Ensembl: ENSG00000129932.11HGNC: HGNC:28662UniProt: Q9BU89
30PubMed Papers
21Diseases
0Drugs
5Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
iron ion bindingprotein bindingdeoxyhypusine monooxygenase activitypeptidyl-hypusine biosynthetic processneurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairmentcomplex neurodevelopmental disorderneurodegenerative diseaseNeurodevelopmental disorder
✦AI Summary

DOHH (deoxyhypusine hydroxylase) catalyzes the second and final enzymatic step in hypusine biosynthesis, converting the deoxyhypusine intermediate to hypusine on eukaryotic translation initiation factor 5A (eIF5A) 1. This post-translational modification is essential for eIF5A activation and efficient translation of specific gene products 2. DOHH functions as a monooxygenase requiring iron ion cofactors and operates in the cytosol [UniProt annotation]. Hypusinated eIF5A regulates translation of genes involved in critical cellular processes including MYC elongation, mitochondrial oxidative phosphorylation, and cellular proliferation 23. In cancer biology, DOHH expression is upregulated by extracellular aspartate signaling in lung metastases, promoting a translational program that enhances breast cancer aggressiveness through increased collagen synthesis 4. Pathologically, biallelic DOHH variants cause a neurodevelopmental disorder characterized by global developmental delay, intellectual disability, microcephaly, and facial dysmorphism, resulting from reduced enzyme activity and accumulation of non-hypusinated eIF5A 15. DOHH-related disorder patients frequently present with refractory epilepsy, particularly temperature-triggered seizures, with emergence typically between 2-5 years of age 5.

Sources cited
1
DOHH catalyzes the second step of hypusine biosynthesis; biallelic variants cause neurodevelopmental disorder with developmental delay, intellectual disability, microcephaly, and facial dysmorphism
PMID: 35858628
2
Aspartate signaling upregulates DOHH expression in lung metastases to promote aggressive cancer cell phenotype through eIF5A hypusination
PMID: 39743589
3
Hypusinated eIF5A regulates MYC elongation and is required for colorectal cancer cell growth; DOHH inhibition reduces cancer progression
PMID: 33303756
4
DOHH and hypusine signaling promote pulmonary vascular remodeling in pulmonary arterial hypertension through supporting oxidative phosphorylation
PMID: 38261723
5
DOHH-related disorder manifests as neurodevelopmental encephalopathy with microcephaly, epilepsy (often temperature-triggered), and developmental delay
PMID: 40883692
6
DOHH participates in deoxyhypusination complexes with iron-dependent catalytic mechanism essential for eIF5A activation across eukaryotes and Archaea
PMID: 39809274
Disease Associationsβ“˜21
neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairmentOpen Targets
0.71Strong
complex neurodevelopmental disorderOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.36Weak
Neurodevelopmental disorderOpen Targets
0.19Weak
neuronal ceroid lipofuscinosis 1Open Targets
0.04Suggestive
familial isolated congenital aspleniaOpen Targets
0.04Suggestive
non-alcoholic steatohepatitisOpen Targets
0.03Suggestive
prostate cancerOpen Targets
0.03Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.02Suggestive
colitisOpen Targets
0.02Suggestive
glioblastoma multiformeOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.01Suggestive
malariaOpen Targets
0.01Suggestive
glioblastomaOpen Targets
0.01Suggestive
Ischemic strokeOpen Targets
0.01Suggestive
EncephalopathyOpen Targets
0.01Suggestive
myocardial infarctionOpen Targets
0.01Suggestive
infectionOpen Targets
0.01Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.01Suggestive
microcephalyOpen Targets
0.01Suggestive
Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairmentUniProt
Pathogenic Variants5
NM_001145165.2(DOHH):c.898dup (p.Ala300fs)Likely pathogenic
Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment
β˜…β˜†β˜†β˜†2024β†’ Residue 300
NM_001145165.2(DOHH):c.304del (p.Glu102fs)Pathogenic
DOHH related neurodevelopmental disorder|Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment
β˜†β˜†β˜†β˜†2022β†’ Residue 102
NM_001145165.2(DOHH):c.840T>A (p.Tyr280Ter)Pathogenic
DOHH related neurodevelopmental disorder|Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment
β˜†β˜†β˜†β˜†2022β†’ Residue 280
NM_001145165.2(DOHH):c.746T>C (p.Ile249Thr)Pathogenic
DOHH related neurodevelopmental disorder|Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment
β˜†β˜†β˜†β˜†2022β†’ Residue 249
NM_001145165.2(DOHH):c.552C>A (p.Asn184Lys)Pathogenic
DOHH related neurodevelopmental disorder|Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment
β˜†β˜†β˜†β˜†2022β†’ Residue 184
View on ClinVar β†—
Related Genes
DHPSProtein interaction100%EIF5A2Protein interaction100%ADSS1Protein interaction100%EIF5AL1Protein interaction92%PES1Protein interaction90%ZNF593Protein interaction84%
Tissue Expression6 tissues
Brain
100%
Liver
65%
Lung
48%
Ovary
45%
Bone Marrow
45%
Heart
23%
Gene Interaction Network
Click a node to explore
DOHHDHPSEIF5A2ADSS1EIF5AL1PES1ZNF593
PROTEIN STRUCTURE
Preparing viewer…
PDB4D4Z Β· 1.70 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.69LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.13 [0.76–1.69]
RankingsWhere DOHH stands among ~20K protein-coding genes
  • #11,903of 20,598
    Most Researched30
  • #3,620of 5,498
    Most Pathogenic Variants5
  • #16,061of 17,882
    Most Constrained (LOEUF)1.69
Genes detectedDOHH
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Aspartate signalling drives lung metastasis via alternative translation.
PMID: 39743589
Nature Β· 2025
1.00
2
eIF5A and hypusination-related disorders: literature review and case report of DOHH-related encephalopathy.
PMID: 40883692
J Neurodev Disord Β· 2025
0.90
3
Blockade of EIF5A hypusination limits colorectal cancer growth by inhibiting MYC elongation.
PMID: 33303756
Cell Death Dis Β· 2020
0.80
4
Hypusine Signaling Promotes Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.
PMID: 38261723
Am J Respir Crit Care Med Β· 2024
0.70
5
Biophysical and modeling-based approach for the identification of inhibitors against DOHH from Leishmania donovani.
PMID: 35809341
Brief Funct Genomics Β· 2023
0.60