DPH1

Chr 17AR

diphthamide biosynthesis 1

Also known as: DEDSSH, DPH2L, DPH2L1, OVCA1

NCBI Gene: 1801ENSG00000108963UniProt: Q9BZG8OMIM: 603527

DPH1 encodes an enzyme that catalyzes the first step of diphthamide biosynthesis, a post-translational modification of histidine in elongation factor 2. Autosomal recessive mutations cause developmental delay with short stature, dysmorphic facial features, and sparse hair. The gene shows extremely high constraint against loss-of-function variants (pLI approaching 1), indicating that heterozygous loss is not tolerated in the general population.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 1.371 OMIM phenotype
Clinical Summary— DPH1
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Gene-Disease Validity (ClinGen)
developmental delay with short stature, dysmorphic facial features, and sparse hair · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 79 VUS of 104 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — DPH1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.37LOEUF
pLI 0.000
Z-score 0.08
OE 0.98 (0.71–1.37)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.18Z-score
OE missense 1.03 (0.93–1.14)
278 obs / 269.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.98 (0.71–1.37)
0≤0.351.4
Missense OE1.03 (0.93–1.14)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 25 / 25.4Missense obs/exp: 278 / 269.8Syn Z: -0.02

ClinVar Variant Classifications

104 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic2
VUS79
Likely Benign7
5
Pathogenic
2
Likely Pathogenic
79
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
2
0
0
0
2
VUS
0
74
5
0
79
Likely Benign
0
4
0
3
7
Benign
0
0
0
0
0
Total27810393

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DPH1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
DPH1 and DPH2 variants that confer susceptibility to diphthamide deficiency syndrome in human cells and yeast models.
Ütkür K et al.·Dis Model Mech
2023Functional
Novel compound heterozygous DPH1 mutations in a patient with the unique clinical features of airway obstruction and external genital abnormalities.
Nakajima J et al.·J Hum Genet
2018Review
DPH1 syndrome: two novel variants and structural and functional analyses of seven missense variants identified in syndromic patients.
Urreizti R et al.·Eur J Hum Genet
2020Case report
Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families.
Alazami AM et al.·Cell Rep
2015
Influence of DPH1 and DPH5 Protein Variants on the Synthesis of Diphthamide, the Target of ADPRibosylating Toxins.
Mayer K et al.·Toxins (Basel)
2017
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Establishment and characterization of a novel imatinib-resistant dermatofibrosarcoma protuberans cell line, DFSP-DPH1.
Jiang H et al.·Hum Cell
2025
Diphthamide formation in Arabidopsis requires DPH1-interacting DPH2 for light and oxidative stress resistance.
Zhang H et al.·Plant Physiol
2025
Recessive loss-of-function variants in DPH1 identified as the molecular cause in a sibling pair previously diagnosed with Fine-Lubinsky syndrome.
Waskow ER et al.·Am J Med Genet A
2025
Functional Integrity of Radical SAM Enzyme Dph1•Dph2 Requires Non-Canonical Cofactor Motifs with Tandem Cysteines.
Ütkür K et al.·Biomolecules
2024Open AccessFunctional
DPH1 Gene Mutations Identify a Candidate SAM Pocket in Radical Enzyme Dph1•Dph2 for Diphthamide Synthesis on EF2.
Ütkür K et al.·Biomolecules
2023Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients