DPH3

Chr 3

diphthamide biosynthesis 3

Also known as: DELGIP, DELGIP1, DESR1, DPH3A, KTI11, ZCSL2

The protein encoded by this gene is required for diphthamide biosynthesis, acting as an electron donor to maintain iron-sulfur clusters in the DPH1-DPH2 complex during post-translational modification of elongation factor 2, and also associates with the elongator complex for tRNA wobble base modifications. Mutations cause autosomal recessive intellectual disability with distinctive facial features and growth retardation. The gene shows tolerance to loss-of-function variants (pLI 0.07, LOEUF 1.52), consistent with the recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.52
Clinical SummaryDPH3
Population Constraint (gnomAD)
Low constraint (pLI 0.07) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 unique Pathogenic / Likely Pathogenic· 14 VUS of 44 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.52LOEUF
pLI 0.066
Z-score 0.89
OE 0.51 (0.211.52)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.09Z-score
OE missense 1.04 (0.821.34)
44 obs / 42.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.51 (0.211.52)
00.351.4
Missense OE1.04 (0.821.34)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 2 / 3.9Missense obs/exp: 44 / 42.3Syn Z: -0.05

ClinVar Variant Classifications

44 submitted variants in ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic1
VUS14
Likely Benign2
22
Pathogenic
1
Likely Pathogenic
14
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
1
0
1
VUS
0
12
2
0
14
Likely Benign
0
0
2
0
2
Benign
0
0
0
0
0
Total01227039

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

View in ClinVar →

Protein Context — Lollipop Plot

DPH3 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗