GGPS1
Chr 1ARgeranylgeranyl diphosphate synthase 1
Also known as: GGPPS, GGPPS1, MDHLO, MUDHLOV
The protein catalyzes the synthesis of geranylgeranyl diphosphate (GGPP), which is essential for protein prenylation and regulation of nuclear hormone receptors. Biallelic mutations cause muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome with autosomal recessive inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.64), and the syndrome involves multiple organ systems including muscle, auditory, and reproductive systems.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
GGPS1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools