PDSS2

Chr 6AR

decaprenyl diphosphate synthase subunit 2

Also known as: C6orf210, COQ10D3, COQ1B, DLP1, bA59I9.3, hDLP1

NCBI Gene: 57107 ENSG00000164494 UniProt: Q86YH6 OMIM: 610564

The encoded enzyme catalyzes the condensation of farnesyl diphosphate and isopentenyl diphosphate to produce prenyl diphosphates that serve as precursors for the side chain of coenzyme Q10, which is essential for mitochondrial respiratory chain function. Mutations cause autosomal recessive primary coenzyme Q10 deficiency, which can present with cerebellar ataxia, seizures, and other neurological manifestations. The gene is highly tolerant to loss-of-function variants (pLI near zero), consistent with its recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is an enzyme that synthesizes 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. Defects in this gene are a cause of coenzyme Q10 deficiency.[provided by RefSeq, Oct 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Coenzyme Q10 deficiency, primary, 3MIM #614652

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · Leigh syndrome · AR · ClinGen 2021

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.13

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — PDSS2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.13LOEUF

pLI 0.000

Z-score 1.12

OE 0.72 (0.48–1.13)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.47Z-score

OE missense 0.91 (0.81–1.02)

196 obs / 215.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.48–1.13)

0≤0.351.4

Missense OE?0.91 (0.81–1.02)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 14 / 19.3Missense obs/exp: 196 / 215.6Syn Z: 0.81

Background carrier burden — how many people carry a rare variant somewhere in PDSS2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

526 rare PASS variants

Rare truncating (LoF)

1 in 2,300

79 rare PASS variants

Rare synonymous (reference)

1 in 250

174 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PDSS2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 2,900
South Asian	~43k	1 in 110	1 in 3,100
Remaining (unassigned)	~30k	1 in 190	1 in 2,000
European (Finnish)	~27k	1 in 1,100	≈ 1 in 24,000
Admixed American	~22k	1 in 180	1 in 2,600
African / African American	~21k	1 in 160	1 in 3,500
East Asian	~20k	1 in 130	1 in 990
Ashkenazi Jewish	~13k	1 in 870	1 in 600
Middle Eastern	~2,884	1 in 360	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 8 coding exons well covered in gnomAD exomes; exons 4, 6, 7 marginal. Genomes: all 8.? see exons ↓