GDE1

Chr 16

glycerophosphodiester phosphodiesterase 1

Also known as: 363E6.2, MIR16

This glycerophosphodiester phosphodiesterase hydrolyzes glycerophosphodiesters and participates in bioactive N-acylethanolamine biosynthesis including anandamide, with the gene showing low constraint to loss-of-function variants (pLI near 0). Biallelic pathogenic variants cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically with childhood onset. The condition primarily affects the central nervous system with progressive spasticity and developmental delays.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.17
Clinical SummaryGDE1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 44 VUS of 70 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.17LOEUF
pLI 0.000
Z-score 1.09
OE 0.69 (0.421.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.79Z-score
OE missense 0.84 (0.730.96)
155 obs / 185.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.69 (0.421.17)
00.351.4
Missense OE0.84 (0.730.96)
00.61.4
Synonymous OE0.80
01.21.6
LoF obs/exp: 10 / 14.5Missense obs/exp: 155 / 185.2Syn Z: 1.34
DN
0.6260th %ile
GOF
0.5169th %ile
LOF
0.3067th %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

70 submitted variants in ClinVar

Classification Summary

Pathogenic15
VUS44
Benign1
15
Pathogenic
44
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
0
0
0
VUS
0
40
4
0
44
Likely Benign
0
0
0
0
0
Benign
0
0
0
1
1
Total04019160

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

View in ClinVar →

Protein Context — Lollipop Plot

GDE1 · 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.

Search ClinicalTrials.gov →
Clinical Literature
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