PDSS1

Chr 10AR

decaprenyl diphosphate synthase subunit 1

Also known as: COQ1, COQ10D2, COQ1A, DPS, SPS, TPRT, TPT, TPT 1

NCBI Gene: 23590ENSG00000148459UniProt: Q5T2R2

The protein encoded by this gene is an enzyme that elongates the prenyl side-chain of coenzyme Q, or ubiquinone, one of the key elements in the respiratory chain. The gene product catalyzes the formation of all trans-polyprenyl pyrophosphates from isopentyl diphosphate in the assembly of polyisoprenoid side chains, the first step in coenzyme Q biosynthesis. The protein may be peripherally associated with the inner mitochondrial membrane, though no transit peptide has been definitively identified to date. Defects in this gene are a cause of coenzyme Q10 deficiency. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Coenzyme Q10 deficiency, primary, 2MIM #614651
AR
428
ClinVar variants
26
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PDSS1
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 175 VUS of 428 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.93LOEUF
pLI 0.000
Z-score 1.85
OE 0.61 (0.41–0.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.32Z-score
OE missense 0.75 (0.66–0.85)
161 obs / 215.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.61 (0.41–0.93)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.66–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.89
0≤1.21.6
LoF obs/exp: 16 / 26.2Missense obs/exp: 161 / 215.5Syn Z: 0.77

ClinVar Variant Classifications

428 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic10
VUS175
Likely Benign142
Benign63
Conflicting22
16
Pathogenic
10
Likely Pathogenic
175
VUS
142
Likely Benign
63
Benign
22
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
4
10
0
16
Likely Pathogenic
3
1
6
0
10
VUS
6
140
26
3
175
Likely Benign
0
4
73
65
142
Benign
0
2
61
0
63
Conflicting
—22
Total1115117668428

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PDSS1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

PDSS1-related coenzyme Q10 deficiency, primary

strong
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Coenzyme Q10 deficiency, primary, 2

MIM #614651

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — PDSS1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
PDSS1 mutations-associated steroid-resistant nephrotic syndrome: case report and review of literature.
Habib C et al.·Pediatr Nephrol
2025Review
Human CoQ10 deficiencies.
Quinzii CM et al.·Biofactors
2008
Association of sleep disturbance and freezing of gait in Parkinson disease: prevention/delay implications.
Tang X et al.·J Clin Sleep Med
2021
Genetic bases and clinical manifestations of coenzyme Q10 (CoQ 10) deficiency.
Desbats MA et al.·J Inherit Metab Dis
2015Review
Missense PDSS1 mutations in CoenzymeQ10 synthesis cause optic atrophy and sensorineural deafness.
Nardecchia F et al.·Ann Clin Transl Neurol
2021Case report
Modelling the human coenzyme Q deficiency in Drosophila melanogaster.
Fernández-Ayala DJM et al.·Free Radic Biol Med
2025Functional
Update on clinical aspects and treatment of selected vitamin-responsive disorders II (riboflavin and CoQ 10).
Horvath R·J Inherit Metab Dis
2012Review
Characterization of human mitochondrial PDSS and COQ proteins and their roles in maintaining coenzyme Q(10) levels and each other's stability.
Yen HC et al.·Biochim Biophys Acta Bioenerg
2020
Nuclear factors: roles related to mitochondrial deafness.
Luo LF et al.·Gene
2013Review
Retinopathy and optic atrophy in a case of COQ2-related primary coenzyme Q(10) deficiency.
Stallworth JY et al.·Ophthalmic Genet
2023Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools