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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
PDSS1
decaprenyl diphosphate synthase subunit 1
Chromosome 10 Β· 10p12.1
NCBI Gene: 23590Ensembl: ENSG00000148459.17HGNC: HGNC:17759UniProt: Q5T2R2
39PubMed Papers
21Diseases
0Drugs
15Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
mitochondrionheterotetrameric polyprenyl diphosphate synthase complexall-trans-decaprenyl-diphosphate synthase activityprotein bindingDeafness - encephaloneuropathy - obesity - valvulopathydeafness-encephaloneuropathy-obesity-valvulopathy syndromecoenzyme Q10 deficiencyneurodegenerative disease
✦AI Summary

PDSS1 (decaprenyl diphosphate synthase subunit 1) is a heterotetrameric enzyme that catalyzes sequential condensation of farnesyl diphosphate with isopentenyl diphosphate molecules to generate prenyl diphosphates with trans stereochemistry 1. It supplies nona- and decaprenyl diphosphate precursors for ubiquinone-9 and ubiquinone-10 side chains, respectively 1. This function is critical for coenzyme Q10 (CoQ10) biosynthesis and mitochondrial respiratory chain function. Biallelic PDSS1 mutations cause primary CoQ10 deficiency type 2, presenting with diverse clinical phenotypes including infantile multisystemic disease, cerebellar ataxia, encephalomyopathy, and retinitis pigmentosa 23. Intronic variants causing cryptic splicing represent important pathogenic mechanisms 3. CoQ10 therapy effectiveness varies, showing limited benefit in advanced disease stages 4. Beyond its canonical biosynthetic role, PDSS1 regulates oncogenic signaling through a non-enzymatic mechanism. In triple-negative breast cancer, PDSS1 upregulation promotes metastasis via CoQ10-dependent activation of CAMK2A-STAT3 signaling, and catalytic activity is essential for this pathological function 5. Similarly, PDSS1 acts as an oncogene in hepatocellular carcinoma through STAT3 pathway activation 67.

Sources cited
1
PDSS1 catalyzes condensation of FPP and IPP to produce prenyl diphosphates; supplies nona- and decaprenyl diphosphate precursors for ubiquinone-9 and ubiquinone-10
PMID: 16262699
2
Primary CoQ10 deficiencies from PDSS1 mutations cause infantile multisystemic disease and cerebellar ataxia phenotypes
PMID: 19096106
3
PDSS1 mutations cause retinitis pigmentosa; intronic variants leading to cryptic splicing are important disease mechanisms
PMID: 36266294
4
PDSS1 mutations cause multisystem mitochondrial disease; CoQ10 therapy showed limited effectiveness in advanced disease
PMID: 39656276
5
PDSS1 catalytic activity promotes triple-negative breast cancer metastasis through CoQ10-dependent CAMK2A-STAT3 pathway activation
PMID: 34408002
6
PDSS1 acts as an oncogene in hepatocellular carcinoma through STAT3 signaling pathway
PMID: 35965499
7
PDSS1 identified as a butyrylation-related gene with prognostic significance in hepatocellular carcinoma
PMID: 39926543
8
PDSS1 mutations cause CoQ10 deficiency and impaired oxidative phosphorylation function
PMID: 17332895
Disease Associationsβ“˜21
Deafness - encephaloneuropathy - obesity - valvulopathyOpen Targets
0.77Strong
deafness-encephaloneuropathy-obesity-valvulopathy syndromeOpen Targets
0.77Strong
coenzyme Q10 deficiencyOpen Targets
0.41Moderate
neurodegenerative diseaseOpen Targets
0.37Weak
lacrimal apparatus diseaseOpen Targets
0.29Weak
esophageal cancerOpen Targets
0.29Weak
tricuspid valve diseaseOpen Targets
0.28Weak
frozen shoulderOpen Targets
0.25Weak
systemic lupus erythematosusOpen Targets
0.21Weak
Myasthenia gravisOpen Targets
0.20Weak
genetic disorderOpen Targets
0.19Weak
mitochondrial diseaseOpen Targets
0.19Weak
diabetes mellitusOpen Targets
0.13Weak
type 2 diabetes mellitusOpen Targets
0.13Weak
schizophreniaOpen Targets
0.11Weak
attention deficit hyperactivity disorderOpen Targets
0.11Weak
substance abuseOpen Targets
0.11Weak
smoking initiationOpen Targets
0.10Weak
hepatocellular carcinomaOpen Targets
0.10Suggestive
neoplasmOpen Targets
0.09Suggestive
Coenzyme Q10 deficiency, primary, 2UniProt
Pathogenic Variants15
NM_014317.5(PDSS1):c.18G>A (p.Trp6Ter)Likely pathogenic
not provided|Deafness-encephaloneuropathy-obesity-valvulopathy syndrome
β˜…β˜…β˜†β˜†2026β†’ Residue 6
NM_014317.5(PDSS1):c.661C>T (p.Arg221Ter)Likely pathogenic
Deafness-encephaloneuropathy-obesity-valvulopathy syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 221
NM_014317.5(PDSS1):c.709_710insCA (p.Asp237fs)Likely pathogenic
Deafness-encephaloneuropathy-obesity-valvulopathy syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 237
NM_014317.5(PDSS1):c.52dup (p.Ala18fs)Likely pathogenic
Deafness-encephaloneuropathy-obesity-valvulopathy syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 18
NM_014317.5(PDSS1):c.436C>T (p.Arg146Ter)Likely pathogenic
Deafness-encephaloneuropathy-obesity-valvulopathy syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 146
NM_014317.5(PDSS1):c.668G>T (p.Gly223Val)Likely pathogenic
Deafness-encephaloneuropathy-obesity-valvulopathy syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 223
NM_014317.5(PDSS1):c.622G>T (p.Gly208Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 208
NM_014317.5(PDSS1):c.173_174insA (p.Ile58_Asn59insTer)Likely pathogenic
Deafness-encephaloneuropathy-obesity-valvulopathy syndrome
β˜…β˜†β˜†β˜†2021β†’ Residue 58
NM_014317.5(PDSS1):c.1164_1165del (p.Ile388fs)Pathogenic
Deafness-encephaloneuropathy-obesity-valvulopathy syndrome
β˜…β˜†β˜†β˜†2018β†’ Residue 388
NM_014317.5(PDSS1):c.336+5G>TLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2014
NM_014317.5(PDSS1):c.968del (p.Thr323fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2013β†’ Residue 323
NM_014317.5(PDSS1):c.1108A>C (p.Ser370Arg)Pathogenic
Deafness-encephaloneuropathy-obesity-valvulopathy syndrome
β˜†β˜†β˜†β˜†2023β†’ Residue 370
NM_014317.5(PDSS1):c.735G>T (p.Gln245His)Pathogenic
Deafness-encephaloneuropathy-obesity-valvulopathy syndrome
β˜†β˜†β˜†β˜†2023β†’ Residue 245
NM_014317.5(PDSS1):c.716T>G (p.Val239Gly)Pathogenic
Deafness-encephaloneuropathy-obesity-valvulopathy syndrome
β˜†β˜†β˜†β˜†2023β†’ Residue 239
NM_014317.5(PDSS1):c.924T>G (p.Asp308Glu)Pathogenic
Deafness-encephaloneuropathy-obesity-valvulopathy syndrome
β˜†β˜†β˜†β˜†2007β†’ Residue 308
View on ClinVar β†—
Related Genes
ETFDHProtein interaction99%COQ8AProtein interaction97%MVDProtein interaction96%DHDDSProtein interaction95%FDFT1Protein interaction94%FDPSProtein interaction94%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
72%
Brain
65%
Lung
64%
Heart
51%
Ovary
40%
Gene Interaction Network
Click a node to explore
PDSS1ETFDHCOQ8AMVDDHDDSFDFT1FDPS
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q5T2R2
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.16LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.81 [0.58–1.16]
RankingsWhere PDSS1 stands among ~20K protein-coding genes
  • #10,373of 20,598
    Most Researched39
  • #2,474of 5,498
    Most Pathogenic Variants15
  • #12,157of 17,882
    Most Constrained (LOEUF)1.16
Genes detectedPDSS1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Biallelic variants in coenzyme Q10 biosynthesis pathway genes cause a retinitis pigmentosa phenotype.
PMID: 36266294
NPJ Genom Med Β· 2022
1.00
2
Human CoQ10 deficiencies.
PMID: 19096106
Biofactors Β· 2008
0.90
3
Association of sleep disturbance and freezing of gait in Parkinson disease: prevention/delay implications.
PMID: 33231167
J Clin Sleep Med Β· 2021
0.80
4
PDSS1 mutations-associated steroid-resistant nephrotic syndrome: case report and review of literature.
PMID: 39656276
Pediatr Nephrol Β· 2025
0.70
5
PDSS1-Mediated Activation of CAMK2A-STAT3 Signaling Promotes Metastasis in Triple-Negative Breast Cancer.
PMID: 34408002
Cancer Res Β· 2021
0.60