coenzyme Q10 deficiency, primary, 3

disease
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Also known as coenzyme Q10 deficiency caused by mutation in PDSS2coenzyme Q10 deficiency, primary, type 3COQ10D3PDSS2 coenzyme Q10 deficiency

Summary

coenzyme Q10 deficiency, primary, 3 (MONDO:0013838) is a disease caused by PDSS2 (GenCC Definitive), with 1 cohort gene.

At a glance

  • Causal gene: PDSS2 (GenCC Definitive)
  • Cohort genes: 1
  • ClinVar variants: 61

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namecoenzyme Q10 deficiency, primary, 3
Mondo IDMONDO:0013838
OMIM614652
DOIDDOID:0070240
UMLSC3553358
MedGen766272
GARD0018379
Is cancer (heuristic)no

Also known as: coenzyme Q10 deficiency caused by mutation in PDSS2 · coenzyme Q10 deficiency, primary, 3 · coenzyme Q10 deficiency, primary, type 3 · COQ10D3 · PDSS2 coenzyme Q10 deficiency

Data availability: 61 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic diseasedevelopmental anomaly of metabolic origininborn mitochondrial metabolism disordermitochondrial oxidative phosphorylation disordercoenzyme Q10 deficiencycoenzyme Q10 deficiency, primary, 3

Related subtypes (8): coenzyme Q10 deficiency, primary, 1, autosomal recessive ataxia due to ubiquinone deficiency, familial steroid-resistant nephrotic syndrome with sensorineural deafness, deafness-encephaloneuropathy-obesity-valvulopathy syndrome, encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome, neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome, primary coenzyme Q10 deficiency 8, coenzyme q10 deficiency, primary, 9

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

61 retrieved; paginated sample, class counts are floors:

39 uncertain significance, 8 conflicting classifications of pathogenicity, 6 likely benign, 3 benign/likely benign, 3 likely pathogenic, 1 pathogenic, 1 benign

ClinVarVariant (HGVS)GeneClassificationReview
1200NM_020381.4(PDSS2):c.964C>T (p.Gln322Ter)PDSS2Pathogenicno assertion criteria provided
3592875NM_020381.4(PDSS2):c.401_402del (p.Asn134fs)PDSS2Likely pathogeniccriteria provided, single submitter
3592877NM_020381.4(PDSS2):c.183dup (p.Tyr62fs)PDSS2Likely pathogeniccriteria provided, single submitter
3592878NM_020381.4(PDSS2):c.129dup (p.Lys44fs)PDSS2Likely pathogeniccriteria provided, single submitter
1201NM_020381.4(PDSS2):c.1145C>T (p.Ser382Leu)PDSS2Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
1432907NM_020381.4(PDSS2):c.1003G>A (p.Gly335Arg)PDSS2Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
1954682NM_020381.4(PDSS2):c.1042-1G>APDSS2Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
214987NM_020381.4(PDSS2):c.667G>A (p.Val223Ile)PDSS2Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
214988NM_020381.4(PDSS2):c.700A>G (p.Lys234Glu)PDSS2Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
214989NM_020381.4(PDSS2):c.1046G>A (p.Arg349Gln)PDSS2Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
214991NM_020381.4(PDSS2):c.275A>C (p.His92Pro)PDSS2Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
2174415NM_020381.4(PDSS2):c.1045C>T (p.Arg349Ter)PDSS2Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
1030705NM_020381.4(PDSS2):c.1151C>A (p.Ala384Asp)PDSS2Uncertain significancecriteria provided, single submitter
1032839NM_020381.4(PDSS2):c.837G>A (p.Met279Ile)PDSS2Uncertain significancecriteria provided, single submitter
1430741NM_020381.4(PDSS2):c.382G>A (p.Val128Met)PDSS2Uncertain significancecriteria provided, multiple submitters, no conflicts
1440087NM_020381.4(PDSS2):c.488G>A (p.Arg163His)PDSS2Uncertain significancecriteria provided, multiple submitters, no conflicts
1481116NM_020381.4(PDSS2):c.500A>G (p.Asn167Ser)PDSS2Uncertain significancecriteria provided, multiple submitters, no conflicts
1487136NM_020381.4(PDSS2):c.50C>T (p.Ser17Leu)PDSS2Uncertain significancecriteria provided, multiple submitters, no conflicts
1490204NM_020381.4(PDSS2):c.737C>T (p.Thr246Ile)PDSS2Uncertain significancecriteria provided, multiple submitters, no conflicts
1498538NM_020381.4(PDSS2):c.1096C>T (p.Arg366Cys)PDSS2Uncertain significancecriteria provided, multiple submitters, no conflicts
1498723NM_020381.4(PDSS2):c.602A>G (p.Asn201Ser)PDSS2Uncertain significancecriteria provided, multiple submitters, no conflicts
1508923NM_020381.4(PDSS2):c.277C>T (p.Pro93Ser)PDSS2Uncertain significancecriteria provided, multiple submitters, no conflicts
1902462NM_020381.4(PDSS2):c.76T>G (p.Ser26Ala)PDSS2Uncertain significancecriteria provided, multiple submitters, no conflicts
1919824NM_020381.4(PDSS2):c.526G>C (p.Gly176Arg)PDSS2Uncertain significancecriteria provided, multiple submitters, no conflicts
1985939NM_020381.4(PDSS2):c.538G>C (p.Asp180His)PDSS2Uncertain significancecriteria provided, multiple submitters, no conflicts
2040436NM_020381.4(PDSS2):c.740G>A (p.Trp247Ter)PDSS2Uncertain significancecriteria provided, multiple submitters, no conflicts
2059878NM_020381.4(PDSS2):c.1044G>T (p.Leu348Phe)PDSS2Uncertain significancecriteria provided, multiple submitters, no conflicts
2415087NM_020381.4(PDSS2):c.1154G>C (p.Arg385Thr)PDSS2Uncertain significancecriteria provided, multiple submitters, no conflicts
2434640NM_020381.4(PDSS2):c.1070G>T (p.Gly357Val)PDSS2Uncertain significancecriteria provided, single submitter
2462619NM_020381.4(PDSS2):c.410T>C (p.Met137Thr)PDSS2Uncertain significancecriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

GeneClassificationInheritanceDiseaseRecords
PDSS2DefinitiveAutosomal recessivecoenzyme Q10 deficiency, primary, 34

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
PDSS2HGNC:23041ENSG00000164494Q86YH6All trans-polyprenyl-diphosphate synthase PDSS2gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
PDSS2All trans-polyprenyl-diphosphate synthase PDSS2Heterotetrameric enzyme that catalyzes the condensation of farnesyl diphosphate (FPP), which acts as a primer, and isopentenyl diphosphate (IPP) to produce prenyl diphosphates of varying chain lengths and participates in the determination…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

FamilyGenesFoldFDR
Enzyme (other)112.0×0.083

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
PDSS2Enzyme (other)yes2.5.1.91Polyprenyl_synt, Isoprenoid_synthase_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)1
unknown0

Top tissues across cohort

TissueCohort genes
buccal mucosa cell1
nephron tubule1
secondary oocyte1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
PDSS2256ubiquitousmarkerbuccal mucosa cell, nephron tubule, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
PDSS22,414

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
PDSS2Q86YH680.28

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Ubiquinol biosynthesis1878.5×0.001PDSS2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
regulation of body fluid levels14213.0×9e-04PDSS2
isoprenoid biosynthetic process11685.2×0.001PDSS2
ubiquinone biosynthetic process1936.2×0.001PDSS2
cerebellum development1358.6×0.003PDSS2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

SymbolMoleculesMax phase
PDSS200

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
PDSS22.5.1.91all-trans-decaprenyl-diphosphate synthase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)0
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug1PDSS2
EDifficult family or no structure, no drug0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

SymbolChEMBL assaysDrugged partners (top 3)
PDSS20

Clinical trials & evidence

Clinical trials

Clinical trials: 0.