DHDDS

Chr 1ARAD

dehydrodolichyl diphosphate synthase subunit

The protein encoded by DHDDS forms a complex essential for dolichol biosynthesis, producing the glycosyl carrier lipid required for protein glycosylation in the endoplasmic reticulum. Mutations cause retinitis pigmentosa 59, congenital disorder of glycosylation type 1bb, and developmental delay with seizures and movement abnormalities, with both autosomal recessive and autosomal dominant inheritance patterns reported. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.51), and the associated phenotypes affect multiple systems including vision, neurodevelopment, and protein glycosylation pathways.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismAR/ADLOEUF 0.513 OMIM phenotypes
Clinical SummaryDHDDS
🧬
Gene-Disease Validity (ClinGen)
DHDDS-CDG · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.51LOEUF
pLI 0.245
Z-score 3.18
OE 0.24 (0.130.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.09Z-score
OE missense 0.78 (0.680.89)
152 obs / 194.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.24 (0.130.51)
00.351.4
Missense OE0.78 (0.680.89)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 5 / 20.6Missense obs/exp: 152 / 194.8Syn Z: 0.97
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongDHDDS-related epilepsy and intellectual disabilityOTHERAD
definitiveDHDDS-related retinitis pigmentosaOTHERAR
DN
0.6648th %ile
GOF
0.5856th %ile
LOF
0.3454th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median · 1 literature citation

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNWe defined the electroclinical and movement disorder phenotype associated with the monoallelic form of the DHDDS -related neurodevelopmental disease and possible underlying dominant-negative mechanisms.PMID:34504728

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DHDDS · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →