GDE1

Chr 16

glycerophosphodiester phosphodiesterase 1

Also known as: 363E6.2, MIR16

NCBI Gene: 51573 ENSG00000006007 UniProt: Q9NZC3 OMIM: 605943

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable glycerophosphodiester phosphodiesterase activity; glycerophosphoinositol glycerophosphodiesterase activity; and lysophospholipase activity. Predicted to be involved in N-acylethanolamine metabolic process; ethanolamine metabolic process; and phospholipid metabolic process. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.17

Clinical Summary— GDE1

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

40 VUS of 51 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?

1.17LOEUF

pLI 0.000

Z-score 1.09

OE 0.69 (0.42–1.17)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.79Z-score

OE missense 0.84 (0.73–0.96)

155 obs / 185.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.69 (0.42–1.17)

0≤0.351.4

Missense OE?0.84 (0.73–0.96)

0≤0.61.4

Synonymous OE?0.80

0≤1.21.6

LoF obs/exp: 10 / 14.5Missense obs/exp: 155 / 185.2Syn Z: 1.34

This gene — mechanism propensity

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

51 submitted variants in ClinVar

ClinVar

Classification Summary

VUS40

Benign1

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	40	0	40
Likely Benign	0	0	0
Benign	0	1	1
Total	40	1	41

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap GDE1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →