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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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GGPS1
geranylgeranyl diphosphate synthase 1
Chromosome 1 Β· 1q42.3
NCBI Gene: 9453Ensembl: ENSG00000152904.12HGNC: HGNC:4249UniProt: O95749
49PubMed Papers
21Diseases
0Drugs
4Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingidentical protein bindinggeranylgeranyl diphosphate synthase activitycytosolmuscular dystrophy, congenital hearing loss, and ovarian insufficiency syndromeAlzheimer diseaseParkinson diseasemultiple sclerosis
✦AI Summary

GGPS1 (geranylgeranyl diphosphate synthase 1) is a key enzyme in isoprenoid biosynthesis that catalyzes the formation of geranylgeranyl diphosphate (GGPP), an essential precursor for protein geranylgeranylation and carotenoid synthesis 1. The enzyme displays high conservation between mouse and human (94% amino acid identity) and functions by converting isopentenyl diphosphate and farnesyl diphosphate into GGPP 1. GGPS1 operates through interactions with other proteins, including ENKD1, which modulates its enzymatic activity and influences downstream signaling pathways involving RAC1 2. Clinically, biallelic pathogenic variants in GGPS1 cause a rare autosomal recessive muscular dystrophy syndrome that may include hearing loss and ovarian insufficiency, though hearing loss occurs in only 46% of patients 3. The phenotypic spectrum has recently expanded to include hepatic involvement 4. In cancer biology, elevated GGPS1 expression correlates with chemoresistance in small cell lung cancer through the GGPS1-RAB7A-autophagy axis and predicts poor survival outcomes 56. Pan-cancer analyses reveal GGPS1 upregulation across multiple cancer types, particularly breast, liver, and lung cancers, suggesting its role in tumorigenesis 7. Therapeutically, statins targeting the mevalonate-GGPP pathway show promise in overcoming chemoresistance 5.

Sources cited
1
GGPS1 catalyzes GGPP formation from isopentenyl diphosphate and farnesyl diphosphate, with 94% conservation between mouse and human
PMID: 10101267
2
ENKD1 interacts with GGPS1 to modulate its enzymatic activity and influence RAC1-mediated signaling pathways
PMID: 40048432
3
Biallelic GGPS1 variants cause muscular dystrophy syndrome with variable hearing loss (46% of patients) and ovarian insufficiency
PMID: 35869884
4
GGPS1-related muscular dystrophy phenotype can include hepatic involvement
PMID: 38129970
5
High GGPS1 expression associates with chemoresistance in small cell lung cancer through GGPS1-RAB7A-autophagy axis
PMID: 35449308
6
GGPS1 expression predicts chemotherapy response and survival outcomes in small cell lung cancer
PMID: 40613783
7
GGPS1 is upregulated across multiple cancer types and correlates with tumorigenesis
PMID: 39165977
Disease Associationsβ“˜21
muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndromeOpen Targets
0.70Strong
Alzheimer diseaseOpen Targets
0.43Moderate
Parkinson diseaseOpen Targets
0.43Moderate
lysosomal storage diseaseOpen Targets
0.43Moderate
multiple sclerosisOpen Targets
0.43Moderate
neurodegenerative diseaseOpen Targets
0.43Moderate
Perrault syndrome 1Open Targets
0.37Weak
Perrault syndrome 2Open Targets
0.37Weak
tubular aggregate myopathyOpen Targets
0.27Weak
brain injuryOpen Targets
0.24Weak
neuromuscular diseaseOpen Targets
0.15Weak
myopathyOpen Targets
0.14Weak
Sensorineural hearing impairmentOpen Targets
0.14Weak
sensorineural hearing lossOpen Targets
0.14Weak
Premature ovarian insufficiencyOpen Targets
0.11Weak
hypothyroidismOpen Targets
0.11Weak
Abnormality of the skeletal systemOpen Targets
0.09Suggestive
cancerOpen Targets
0.08Suggestive
lung adenocarcinomaOpen Targets
0.08Suggestive
oral squamous cell carcinomaOpen Targets
0.06Suggestive
Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndromeUniProt
Pathogenic Variants4
NM_004837.4(GGPS1):c.770T>G (p.Phe257Cys)Likely pathogenic
Myopathy with tubular aggregates
β˜…β˜†β˜†β˜†2024β†’ Residue 257
NM_004837.4(GGPS1):c.854T>G (p.Val285Gly)Pathogenic
Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome
β˜†β˜†β˜†β˜†2022β†’ Residue 285
NM_004837.4(GGPS1):c.781C>G (p.Arg261Gly)Pathogenic
Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome
β˜†β˜†β˜†β˜†2021β†’ Residue 261
NM_004837.4(GGPS1):c.776A>G (p.Tyr259Cys)Pathogenic
Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome
β˜†β˜†β˜†β˜†2021β†’ Residue 259
View on ClinVar β†—
Related Genes
PMVKProtein interaction99%FNTBProtein interaction96%RSAD2Protein interaction95%DHDDSProtein interaction95%NUS1Protein interaction92%ACAT2Protein interaction89%
Tissue Expression6 tissues
Brain
100%
Heart
57%
Ovary
57%
Lung
54%
Liver
43%
Bone Marrow
11%
Gene Interaction Network
Click a node to explore
GGPS1PMVKFNTBRSAD2DHDDSNUS1ACAT2
PROTEIN STRUCTURE
Preparing viewer…
PDB9CSL Β· 2.10 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.02LoF Tolerant
pLIβ“˜
0.05Tolerant
Observed/Expected LoF0.54 [0.31–1.02]
RankingsWhere GGPS1 stands among ~20K protein-coding genes
  • #8,943of 20,598
    Most Researched49
  • #3,796of 5,498
    Most Pathogenic Variants4
  • #9,934of 17,882
    Most Constrained (LOEUF)1.02
Genes detectedGGPS1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Therapeutic targeting of the mevalonate-geranylgeranyl diphosphate pathway with statins overcomes chemotherapy resistance in small cell lung cancer.
PMID: 35449308
Nat Cancer Β· 2022
1.00
2
Is there genetic susceptibility for atypical femoral fractures?
PMID: 38199157
Injury Β· 2024
0.90
3
Identification of the GGPS1 genes encoding geranylgeranyl diphosphate synthases from mouse and human.
PMID: 10101267
Biochim Biophys Acta Β· 1999
0.80
4
Comprehensive analysis of a real-world cohort identifies geranylgeranyl diphosphate synthase 1 as a predictor of chemoresistance in small cell lung cancer.
PMID: 40613783
Int J Cancer Β· 2025
0.70
5
GGPS1-associated muscular dystrophy with and without hearing loss.
PMID: 35869884
Ann Clin Transl Neurol Β· 2022
0.60