DHDDS

Description

The DHDDS (dehydrodolichyl diphosphate synthase subunit) is a protein-coding gene located on chromosome 1.

Dehydrodolichyl diphosphate synthase is an enzyme encoded by the DHDDS gene in humans. It catalyzes the cis-prenyl chain elongation to produce the polyprenyl backbone of dolichol, a glycosyl carrier lipid necessary for the biosynthesis of various glycoproteins. Mutations in the DHDDS gene have been linked to certain variants of retinitis pigmentosa. Due to its involvement in the early stages of dolichol synthesis, which is crucial for correct N-glycosylation, a disease caused by mutations in DHDDS should be considered a congenital disorder of glycosylation (CDG). Many CDG subtypes feature retinitis pigmentosa as a prominent symptom.

DHDDS forms a complex with NUS1 to create dehydrodolichyl diphosphate synthase (DDS), a critical component in the biosynthesis of dolichol monophosphate (Dol-P). Both subunits contribute to the enzyme's activity, specifically by condensing multiple copies of isopentenyl pyrophosphate (IPP) to farnesyl pyrophosphate (FPP), ultimately producing dehydrodolichyl diphosphate (Dedol-PP), a precursor to dolichol phosphate. This molecule serves as a sugar carrier during protein glycosylation within the endoplasmic reticulum (ER). DHDDS is also responsible for synthesizing long-chain polyprenols, primarily with chain lengths of C95 and C100. Additionally, DHDDS plays a role in regulating the glycosylation and stability of newly synthesized NPC2, facilitating the transportation of LDL-derived cholesterol.

DHDDS is also known as CIT, CPT, DEDSM, DS, HDS, RP59, hCIT.

Associated Diseases

• Retinitis pigmentosa
• Non-specific early-onset epileptic encephalopathy
• Developmental delay and seizures with or without movement abnormalities
• Retinitis pigmentosa 59