DHDDS

Chr 1

dehydrodolichyl diphosphate synthase subunit

Also known as: CIT, CPT, DEDSM, DS, HDS, RP59, hCIT

NCBI Gene: 79947ENSG00000117682UniProt: Q86SQ9

The protein encoded by this gene catalyzes cis-prenyl chain elongation to produce the polyprenyl backbone of dolichol, a glycosyl carrier lipid required for the biosynthesis of several classes of glycoproteins. Mutations in this gene are associated with retinitis pigmentosa type 59. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

Primary Disease Associations & Inheritance

UniProtRetinitis pigmentosa 59
UniProtDevelopmental delay and seizures with or without movement abnormalities
100
ClinVar variants
6
Pathogenic / LP
0.25
pLI score
1
Active trials
Clinical Summary— DHDDS
🧬
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.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 20 VUS of 100 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.51LOEUF
pLI 0.245
Z-score 3.18
OE 0.24 (0.13–0.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.09Z-score
OE missense 0.78 (0.68–0.89)
152 obs / 194.8 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.0.24 (0.13–0.51)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.68–0.89)
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.0.86
0≤1.21.6
LoF obs/exp: 5 / 20.6Missense obs/exp: 152 / 194.8Syn Z: 0.97

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2
Likely Pathogenic4
VUS20
Likely Benign72
Conflicting2
2
Pathogenic
4
Likely Pathogenic
20
VUS
72
Likely Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
1
0
2
Likely Pathogenic
2
0
2
0
4
VUS
0
17
3
0
20
Likely Benign
0
0
26
46
72
Benign
0
0
0
0
0
Conflicting
—2
Total3173246100

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

View 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.

Gene2Phenotype Curations

DHDDS-related epilepsy and intellectual disability

strong
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

DHDDS-related retinitis pigmentosa

definitive
ARUndeterminedAltered Gene Product Structure
Eye
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — DHDDS
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Refractory myoclonic epilepsy and progressive movement disorder arising from recurrent DHDDS variants in Japanese patients: a case series.
Kobayashi Y et al.·Brain Dev
2025Cohort
Dhdds T206A and Dhdds K42E knock-in mouse models of retinitis pigmentosa 59 are phenotypically similar.
Nguyen MN et al.·Dis Model Mech
2025🔓 Open AccessFunctional
Niemann-Pick C-like Endolysosomal Dysfunction in DHDDS Patient Cells, a Congenital Disorder of Glycosylation, Can Be Treated with Miglustat.
Best HL et al.·Int J Mol Sci
2025🔓 Open Access
DHDDS-related epilepsy with hippocampal atrophy: a case report.
de Oliveira Franco Á et al.·Neurogenetics
2024Case report
Assessing age of onset and clinical symptoms over time in patients with heterozygous pathogenic DHDDS variants.
Muffels IJJ et al.·J Inherit Metab Dis
2024Cohort
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Rare DisordersUndiagnosed DisordersDisorders of Unknown Prevalence

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

RECRUITING
NCT01793168Sanford HealthStarted 2010-07

External Resources

Links to major genomics databases and tools