DPH2

Chr 1AR

diphthamide biosynthesis 2

Also known as: DEDSSH2, DPH2L2

NCBI Gene: 1802ENSG00000132768UniProt: Q9BQC3

This gene is one of two human genes similar to the yeast gene dph2. The yeast gene was identified by its ability to complement a diphthamide mutant strain, and thus probably functions in diphthamide biosynthesis. Diphthamide is a post-translationally modified histidine residue present in elongation factor 2 (EF2) that is the target of diphtheria toxin ADP-ribosylation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

Primary Disease Associations & Inheritance

Developmental delay with short stature, dysmorphic facial features, and sparse hair 2MIM #620062
AR
107
ClinVar variants
13
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DPH2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 85 VUS of 107 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.95LOEUF
pLI 0.000
Z-score 1.73
OE 0.57 (0.36–0.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.76Z-score
OE missense 0.88 (0.79–0.97)
261 obs / 297.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.57 (0.36–0.95)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.79–0.97)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 11 / 19.2Missense obs/exp: 261 / 297.9Syn Z: 0.22

ClinVar Variant Classifications

107 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic5
VUS85
Likely Benign7
Conflicting2
8
Pathogenic
5
Likely Pathogenic
85
VUS
7
Likely Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
1
1
3
0
5
VUS
0
78
7
0
85
Likely Benign
0
4
0
3
7
Benign
0
0
0
0
0
Conflicting
—2
Total183183107

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

View in ClinVar →

Protein Context — Lollipop Plot

DPH2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental delay with short stature, dysmorphic facial features, and sparse hair 2

MIM #620062

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
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
Expanding the Phenotypic Spectrum Associated with DPH5-Related Diphthamide Deficiency.
Politano D et al.·Genes (Basel)
2025
Diphthamide-deficiency syndrome: a novel human developmental disorder and ribosomopathy.
Hawer H et al.·Eur J Hum Genet
2020Case report
Expanding the Phenotypic Spectrum of DPH2 -Related Disorder.
Gowda VK et al.·Am J Med Genet A
2025
Genetic modifiers of neurofibromatosis type 1-associated café-au-lait macule count identified using multi-platform analysis.
Pemov A et al.·PLoS Genet
2014
Exploration and validation of a combined Hypoxia and m6A/m5C/m1A regulated gene signature for prognosis prediction of liver cancer.
Ren M et al.·BMC Genomics
2023
A dominant-negative approach that prevents diphthamide formation confers resistance to Pseudomonas exotoxin A and diphtheria toxin.
Roy V et al.·PLoS One
2010
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
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools