PLD6

Chr 17

phospholipase D family member 6

Also known as: ZUC

NCBI Gene: 201164ENSG00000179598UniProt: Q8N2A8OMIM: 614960

PLD6 encodes a phospholipase that cleaves the mitochondrial lipid cardiolipin to regulate mitochondrial fusion and fission dynamics, and also functions as an endonuclease critical for PIWI-interacting RNA biogenesis during spermatogenesis. Mutations cause mitochondrial myopathy and male infertility, with autosomal recessive inheritance. The gene shows tolerance to loss-of-function variation (pLI 0.002, LOEUF 1.76), suggesting complete loss of function may be compatible with survival in some cases.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.76
Clinical Summary— PLD6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
113 unique Pathogenic / Likely Pathogenic· 32 VUS of 153 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.76LOEUF
pLI 0.002
Z-score 0.24
OE 0.88 (0.42–1.76)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.02Z-score
OE missense 0.76 (0.65–0.89)
111 obs / 145.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.88 (0.42–1.76)
0≤0.351.4
Missense OE0.76 (0.65–0.89)
0≤0.61.4
Synonymous OE0.83
0≤1.21.6
LoF obs/exp: 4 / 4.6Missense obs/exp: 111 / 145.8Syn Z: 1.08
DN
0.6646th %ile
GOF
0.6834th %ile
LOF
0.3165th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

153 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic112
Likely Pathogenic1
VUS32
Likely Benign3
Benign1
112
Pathogenic
1
Likely Pathogenic
32
VUS
3
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
112
0
112
Likely Pathogenic
1
0
0
0
1
VUS
0
25
7
0
32
Likely Benign
0
2
0
1
3
Benign
0
0
0
1
1
Total1271192149

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

View in ClinVar →

Protein Context — Lollipop Plot

PLD6 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients