DHPS Gene - Deoxyhypusine Synthase
Key enzyme in hypusination, a unique post-translational modification of eukaryotic initiation factor 5A (eIF5A)
Gene Information Card
| Symbol | DHPS |
|---|---|
| Full Name | Deoxyhypusine Synthase |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.13 |
| NCBI Gene ID | 1725 ncbi.nlm.nih.gov/gene/1725 |
| Ensembl ID | ENSG00000105679 |
| UniProt ID | P49366 |
| OMIM ID | 600944 |
| HGNC ID | 2869 |
| Aliases | DS, DHS, NEDDSF, hNEDDSF |
Description
DHPS encodes deoxyhypusine synthase, the enzyme that catalyzes the first step of hypusination, a unique post-translational modification of eukaryotic initiation factor 5A (eIF5A). Hypusination is essential for eIF5A function in translation elongation, mRNA stability, and cell proliferation. Biallelic pathogenic variants in DHPS cause a neurodevelopmental disorder with seizures, microcephaly, and developmental delay (NEDDSF, OMIM 618480).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with seizures, microcephaly, and developmental delay (NEDDSF) | Loss-of-function variants impair hypusination of eIF5A, disrupting translation and neuronal development | ClinVar, OMIM 618480 |
| DHPS deficiency | Biallelic missense/nonsense mutations reduce enzyme activity, leading to eIF5A hypusination defects | OMIM 600944 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.9 | High |
| Brain (cerebellum) | 18.2 | Medium |
| Brain (cortex) | 15.1 | Medium |
| Heart | 12.3 | Medium |
| Liver | 10.5 | Medium |
| Kidney | 9.8 | Medium |
| Lung | 7.2 | Low |
| Pancreas | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 22.5 | High expression |
| HeLa | 18.3 | Medium expression |
| K562 | 15.7 | Medium expression |
| SH-SY5Y | 14.2 | Medium expression |
| HepG2 | 11.9 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.112C>T (p.Arg38Cys) | Missense | Unknown | Reduced enzyme activity; associated with NEDDSF |
| c.323G>A (p.Arg108Gln) | Missense | Unknown | Impaired hypusination; neurodevelopmental phenotype |
| c.1A>G (p.Met1Val) | Start loss | Unknown | Loss of protein expression; severe phenotype |
| c.544C>T (p.Arg182*) | Nonsense | Unknown | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function variants (missense, nonsense, start loss) reduce or abolish deoxyhypusine synthase activity, leading to deficient eIF5A hypusination and neurodevelopmental disease.
Gain of Function (GOF)
No gain-of-function mutations reported in DHPS.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • deoxyhypusine synthase activity (GO:0016903) | • spermidine binding (GO:0005525) |
| • hypusine metabolic process (GO:0006596) | • translation elongation (GO:0006414) |
| • peptidyl-lysine modification to peptidyl-hypusine (GO:0017186) | • cytoplasm (GO:0005737) |
Pathways
• Hypusine biosynthesis (R-HSA-204626)
• Eukaryotic Translation Elongation (R-HSA-156842)
Protein Summary
Deoxyhypusine synthase (DHPS) is a 369-amino acid homotetrameric enzyme that catalyzes the NAD-dependent transfer of the aminobutyl moiety from spermidine to the epsilon-amino group of a specific lysine residue in eIF5A, forming deoxyhypusine. This is the first and rate-limiting step of hypusination, essential for eIF5A activation. The enzyme is highly conserved and expressed in all tissues, with highest levels in testis and brain. Mutations cause autosomal recessive neurodevelopmental disorder with seizures and microcephaly.
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