PLD5

Chr 1

phospholipase D family member 5

Also known as: PLDC

The protein is predicted to have catalytic activity and localize to cellular membranes, though its specific function remains unclear. PLD5 mutations cause autosomal recessive congenital disorders of glycosylation with severe developmental delay, hypotonia, and multisystem involvement. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.52), suggesting some intolerance to complete protein loss.

ResearchSummary from RefSeq
MultiplemechanismLOEUF 0.52
Clinical SummaryPLD5
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.52LOEUF
pLI 0.031
Z-score 3.46
OE 0.29 (0.170.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.54Z-score
OE missense 0.74 (0.660.83)
207 obs / 279.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.29 (0.170.52)
00.351.4
Missense OE0.74 (0.660.83)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 8 / 27.6Missense obs/exp: 207 / 279.7Syn Z: 0.22
DN
0.7034th %ile
GOF
0.6638th %ile
LOF
0.2968th %ile

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

DNprediction above median
GOFprediction 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PLD5 · 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

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found