DPH1 Gene
Diphthamide Biosynthesis 1
Gene Information Card
| Symbol | DPH1 |
|---|---|
| Full Name | Diphthamide Biosynthesis 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 17p13.3 |
| NCBI Gene ID | 1801 ncbi.nlm.nih.gov/gene/1801 |
| Ensembl ID | ENSG00000108924 |
| UniProt ID | Q9BZG8 |
| OMIM ID | 603527 |
| HGNC ID | 3003 |
| Aliases | DEDSS, DPH1L, OVCA1, DPH2L, DPH2L1 |
Description
The DPH1 gene encodes a component of the diphthamide biosynthesis pathway, which modifies translation elongation factor 2 (EEF2) to enable proper protein synthesis. DPH1 is also implicated in tumor suppression and embryonic development. Mutations in DPH1 cause developmental disorders and are associated with various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| DEDSS (Developmental delay, Epilepsy, Dysmorphic features, Skeletal abnormalities, and Sparse hair) | Loss-of-function mutations in DPH1 disrupt diphthamide synthesis, impairing EEF2 function and protein translation, leading to neurodevelopmental defects. | ClinVar, OMIM |
| Ovarian cancer | DPH1 (OVCA1) acts as a tumor suppressor; reduced expression or loss of heterozygosity at 17p13.3 is frequent in ovarian cancer. | COSMIC, NCBI Gene |
| Breast cancer | DPH1 deletion or downregulation contributes to tumorigenesis via altered translation regulation. | COSMIC, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Low |
| Ovary | 8.3 | Low |
| Testis | 15.1 | Low |
| Kidney | 10.2 | Low |
| Liver | 9.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.0 | Embryonic kidney cells |
| HeLa | 11.5 | Cervical cancer cells |
| MCF7 | 9.2 | Breast cancer cells |
| A549 | 10.8 | Lung cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, loss of function |
| c.97C>T (p.Arg33*) | Nonsense | Rare | Premature stop, loss of function |
| c.404G>A (p.Arg135His) | Missense | Rare | Impaired diphthamide synthesis |
| c.556C>T (p.Arg186Trp) | Missense | Rare | Reduced protein stability |
Mutation functional classification
Loss of Function (LOF)
Most DPH1 mutations are loss-of-function, leading to reduced or absent diphthamide modification of EEF2, impairing translation fidelity and causing developmental disorders.
Gain of Function (GOF)
No gain-of-function mutations reported for DPH1.
Dominant Negative (DN)
No dominant-negative mutations reported for DPH1.
View complete mutation data：
Gene Ontology (GO)
| • peptidyl-diphthamide biosynthetic process from peptidyl-histidine (GO:0017183) | • translation elongation factor activity (GO:0003746) |
| • cytosol (GO:0005829) | • cytoplasm (GO:0005737) |
Pathways
• hsa:0017183 - Diphthamide biosynthesis
• hsa:03013 - RNA transport (indirect via EEF2 modification)
Protein Summary
DPH1 is a 42 kDa protein localized to the cytoplasm. It catalyzes the first step of diphthamide biosynthesis, transferring a 3-amino-3-carboxypropyl group to histidine-715 of EEF2. This modification is essential for accurate protein translation and is conserved across eukaryotes. DPH1 also has tumor suppressor activity, particularly in ovarian cancer.
Related Services
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|---|---|---|---|---|
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