DHDDS

Chr 1ARAD

dehydrodolichyl diphosphate synthase subunit

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

NCBI Gene: 79947 ENSG00000117682 UniProt: Q86SQ9 OMIM: 608172

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Congenital disorder of glycosylation, type 1bbMIM #621567

Developmental delay and seizures with or without movement abnormalitiesMIM #617836

Retinitis pigmentosa 59MIM #613861

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · DHDDS-CDG · AR · ClinGen 2023

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.51

LOEUF

Mechanism· predicted

📖

GeneReview available — DHDDS

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

1.09Z-score

OE missense 0.78 (0.68–0.89)

152 obs / 194.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.13–0.51)

0≤0.351.4

Missense OE?0.78 (0.68–0.89)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 5 / 20.6Missense obs/exp: 152 / 194.8Syn Z: 0.97

Background carrier burden — how many people carry a rare variant somewhere in DHDDS?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

423 rare PASS variants

Rare truncating (LoF)

1 in 4,500

41 rare PASS variants

Rare synonymous (reference)

1 in 340

191 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DHDDS. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 270	1 in 6,300
South Asian	~43k	1 in 110	1 in 5,400
Remaining (unassigned)	~30k	1 in 84	1 in 6,000
European (Finnish)	~27k	1 in 990	≈ 1 in 26,000
Admixed American	~22k	1 in 140	1 in 2,800
African / African American	~21k	1 in 120	1 in 2,300
East Asian	~20k	1 in 180	1 in 2,300
Ashkenazi Jewish	~13k	1 in 1,300	none seen
Middle Eastern	~2,884	1 in 140	1 in 420

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓