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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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PDSS2
decaprenyl diphosphate synthase subunit 2
Chromosome 6 Β· 6q21
NCBI Gene: 57107Ensembl: ENSG00000164494.13HGNC: HGNC:23041UniProt: B4DKU5
44PubMed Papers
21Diseases
0Drugs
6Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
mitochondrioncytosolall-trans-decaprenyl-diphosphate synthase activityprotein bindingcoenzyme Q10 deficiency, primary, 3neurodegenerative diseaseLeigh syndromecoenzyme Q10 deficiency
✦AI Summary

PDSS2 (decaprenyl diphosphate synthase subunit 2) is a heterotetrameric enzyme catalyzing sequential condensation of farnesyl diphosphate and isopentenyl diphosphate molecules to produce prenyl diphosphate precursors 1. The enzyme specifically supplies nona- and decaprenyl diphosphate, which are essential for synthesizing the isoprenoid side chains of ubiquinone-9 and ubiquinone-10 respectively 1. PDSS2 plays critical roles in mitochondrial bioenergetics, as demonstrated by its role in female reproductive aging, where diminished PDSS2 expression in oocytes causes mitochondrial dysfunction, reduced ATP production, and premature ovarian failure reversible by CoQ10 supplementation 2. Beyond CoQ10 biosynthesis, PDSS2 exhibits non-enzymatic tumor-suppressive functions in lung cancer, where it inhibits cell proliferation and migration independently of catalytic activity 3. Mutations in PDSS2 cause primary coenzyme Q10 deficiency, associated with infantile multisystemic disease and cerebellar ataxia 4. Additionally, PDSS2 expression supports metabolic adaptation in tissue-resident memory T cells, where overexpression enhances mitochondrial respiration and antitumor immunity 5. PDSS2 regulation involves transcription factor Sp1-mediated repression, with downregulated expression correlating with poor prognosis in multiple cancer types.

Sources cited
1
PDSS2 catalyzes condensation of FPP and IPP to produce prenyl diphosphates; supplies nona- and decaprenyl diphosphate for ubiquinone side chain synthesis
PMID: 16262699
2
Diminished PDSS2 expression in aging oocytes causes mitochondrial dysfunction and reduced ATP; PDSS2 disruption causes reproductive defects reversible by CoQ10
PMID: 26111777
3
PDSS2 exhibits non-enzymatic tumor-suppressive activity in lung cancer independent of catalytic function; SKA2 represses PDSS2 expression
PMID: 36860919
4
PDSS2 mutations cause primary CoQ10 deficiency associated with infantile multisystemic disease and cerebellar ataxia
PMID: 19096106
5
PDSS2 overexpression promotes mitochondrial respiration and enhances antitumor immunity in tissue-resident memory T cells
PMID: 37648857
6
Sp1 transcription factor mediates PDSS2 promoter repression; negative correlation between Sp1 and PDSS2 expression associates with poor lung cancer prognosis
PMID: 31783675
Disease Associationsβ“˜21
coenzyme Q10 deficiency, primary, 3Open Targets
0.77Strong
neurodegenerative diseaseOpen Targets
0.53Moderate
Leigh syndromeOpen Targets
0.42Moderate
coenzyme Q10 deficiencyOpen Targets
0.41Moderate
lymphoid leukemiaOpen Targets
0.38Weak
prostate carcinomaOpen Targets
0.35Weak
alcohol drinkingOpen Targets
0.34Weak
ovarian neoplasmOpen Targets
0.29Weak
nephrotic syndromeOpen Targets
0.28Weak
lysosomal storage diseaseOpen Targets
0.20Weak
genetic disorderOpen Targets
0.19Weak
tooth diseaseOpen Targets
0.19Weak
thrombophiliaOpen Targets
0.19Weak
benign neoplasm of pituitary glandOpen Targets
0.19Weak
focal segmental glomerulosclerosisOpen Targets
0.17Weak
kidney diseaseOpen Targets
0.16Weak
hepatocellular carcinomaOpen Targets
0.10Suggestive
Abnormality of the skeletal systemOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
lung cancerOpen Targets
0.09Suggestive
Coenzyme Q10 deficiency, primary, 3UniProt
Pathogenic Variants6
NM_020381.4(PDSS2):c.183dup (p.Tyr62fs)Likely pathogenic
Coenzyme Q10 deficiency, primary, 3
β˜…β˜†β˜†β˜†2024β†’ Residue 62
NM_020381.4(PDSS2):c.401_402del (p.Asn134fs)Likely pathogenic
Coenzyme Q10 deficiency, primary, 3
β˜…β˜†β˜†β˜†2024β†’ Residue 134
NM_020381.4(PDSS2):c.129dup (p.Lys44fs)Likely pathogenic
Coenzyme Q10 deficiency, primary, 3
β˜…β˜†β˜†β˜†2024β†’ Residue 44
NM_020381.4(PDSS2):c.874A>G (p.Lys292Glu)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2014β†’ Residue 292
NM_020381.4(PDSS2):c.877-2A>GPathogenic
not provided
β˜…β˜†β˜†β˜†2012
NM_020381.4(PDSS2):c.964C>T (p.Gln322Ter)Pathogenic
Coenzyme Q10 deficiency, primary, 3
β˜†β˜†β˜†β˜†2010β†’ Residue 322
View on ClinVar β†—
Related Genes
ETFDHProtein interaction97%APTXProtein interaction97%DHDDSProtein interaction95%FDFT1Protein interaction92%FDPSProtein interaction92%FNTAProtein interaction92%
Tissue Expression6 tissues
Liver
100%
Heart
93%
Brain
49%
Lung
33%
Ovary
32%
Bone Marrow
29%
Gene Interaction Network
Click a node to explore
PDSS2ETFDHAPTXDHDDSFDFT1FDPSFNTA
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q86YH6
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.82LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.54 [0.36–0.82]
RankingsWhere PDSS2 stands among ~20K protein-coding genes
  • #9,632of 20,598
    Most Researched44
  • #3,407of 5,498
    Most Pathogenic Variants6
  • #6,930of 17,882
    Most Constrained (LOEUF)0.82
Genes detectedPDSS2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging.
PMID: 26111777
Aging Cell Β· 2015
1.00
2
Metabolic programs of T cell tissue residency empower tumour immunity.
PMID: 37648857
Nature Β· 2023
0.90
3
Genetic susceptibility to caffeine intake and metabolism: a systematic review.
PMID: 39438936
J Transl Med Β· 2024
0.80
4
Opicapone for Parkinson's disease-related sleep disturbances: The OASIS clinical trial.
PMID: 39973499
J Parkinsons Dis Β· 2025
0.70
5
Sp1 Mediates the Constitutive Expression and Repression of the PDSS2 Gene in Lung Cancer Cells.
PMID: 31783675
Genes (Basel) Β· 2019
0.60