DOHH Gene - Deoxyhypusine Hydroxylase
DOHH: A key enzyme in hypusination, essential for eukaryotic translation factor eIF5A activation and cellular proliferation.
Gene Information Card
| Symbol | DOHH |
|---|---|
| Full Name | Deoxyhypusine Hydroxylase |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | 83475 ncbi.nlm.nih.gov/gene/83475 |
| Ensembl ID | ENSG00000104879 |
| UniProt ID | Q9BU89 |
| OMIM ID | 611262 |
| HGNC ID | 28662 |
| Aliases | HLRC1, MGC13170 |
Description
The DOHH gene encodes deoxyhypusine hydroxylase, a metalloenzyme that catalyzes the second step of hypusine biosynthesis. Hypusine is a unique amino acid modification found only in eukaryotic translation initiation factor 5A (eIF5A). This modification is essential for eIF5A activity, which regulates translation elongation and is critical for cell proliferation, differentiation, and survival. DOHH is highly conserved across eukaryotes and is implicated in cancer and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | DOHH overexpression leads to increased eIF5A hypusination, promoting translation of oncogenic proteins and cell proliferation. | COSMIC, literature |
| Neurodegenerative disorders | Altered hypusination affects neuronal protein synthesis and stress responses, linked to Alzheimer's and Parkinson's disease models. | Literature, OMIM |
| Developmental disorders | Biallelic loss-of-function mutations in DOHH cause a rare syndrome with intellectual disability and growth defects. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Bone marrow | 12.8 | Medium |
| Lymph node | 11.5 | Medium |
| Brain | 8.3 | Low |
| Liver | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.5 | High expression |
| K562 | 14.2 | Moderate expression |
| HeLa | 12.0 | Moderate expression |
| HepG2 | 9.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Loss of start codon, likely loss of function |
| c.287G>A (p.Arg96Gln) | Missense | <0.01% | Impaired enzyme activity, reduced hypusination |
| c.502C>T (p.Arg168Trp) | Missense | <0.01% | Dominant negative effect in some cancers |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations cause developmental syndrome; reduced eIF5A hypusination and impaired translation.
Gain of Function (GOF)
Overexpression or activating mutations increase hypusination, promoting oncogenic translation and cell proliferation.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg168Trp) may interfere with wild-type DOHH, reducing overall enzyme activity.
View complete mutation data：
Gene Ontology (GO)
| • deoxyhypusine hydroxylase activity | • metal ion binding |
| • hypusine biosynthetic process | • translation elongation factor activity |
| • cytoplasm |
Pathways
• Hypusine biosynthesis
• eIF5A regulation of translation
• mTOR signaling (indirect)
Protein Summary
DOHH is a 302-amino acid protein that belongs to the HEAT repeat family. It contains a di-iron center essential for its hydroxylase activity. The enzyme converts deoxyhypusine to hypusine on eIF5A, a modification required for eIF5A's role in translation elongation. DOHH is predominantly cytoplasmic and is expressed in proliferating tissues. Its activity is tightly regulated and linked to cellular stress responses and cancer progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DOHH Knockout HEK293 Cell Line | EDJ-KQ9850 | Human | 83475 | Details Get a Quote |
| DOHH Knockout A-549 Cell Line | EDJ-KQ35500 | Human | 83475 | Details Get a Quote |
| DOHH Knockout HCT 116 Cell Line | EDJ-KQ36710 | Human | 83475 | Details Get a Quote |
| DOHH Knockout HeLa Cell Line | EDJ-KQ36711 | Human | 83475 | Details Get a Quote |
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