GDPD3

Chr 16

glycerophosphodiester phosphodiesterase domain containing 3

Also known as: GDE7

The GDPD3 protein hydrolyzes lysoglycerophospholipids to produce lysophosphatidic acid and corresponding amines, with preference for substrates including lyso-PAF and lysophosphatidylcholine. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and progressive microcephaly. This gene shows extremely high constraint against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.51
Clinical SummaryGDPD3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.51LOEUF
pLI 0.000
Z-score -0.24
OE 1.06 (0.751.51)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.29Z-score
OE missense 0.94 (0.841.06)
187 obs / 198.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.06 (0.751.51)
00.351.4
Missense OE0.94 (0.841.06)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 22 / 20.8Missense obs/exp: 187 / 198.4Syn Z: 0.98
DN
0.6939th %ile
GOF
0.5366th %ile
LOF
0.2777th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GDPD3 · 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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