GDPD3

Chr 16

glycerophosphodiester phosphodiesterase domain containing 3

Also known as: GDE7

NCBI Gene: 79153 ENSG00000102886 UniProt: Q7L5L3

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.

ResearchSummary from RefSeq, UniProt

Enables phosphoric diester hydrolase activity. Involved in N-acylethanolamine metabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.51

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.51LOEUF

pLI 0.000

Z-score -0.24

OE 1.06 (0.75–1.51)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.29Z-score

OE missense 0.94 (0.84–1.06)

187 obs / 198.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.06 (0.75–1.51)

0≤0.351.4

Missense OE?0.94 (0.84–1.06)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 22 / 20.8Missense obs/exp: 187 / 198.4Syn Z: 0.98

Background carrier burden — how many people carry a rare variant somewhere in GDPD3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

390 rare PASS variants

Rare truncating (LoF)

1 in 590

93 rare PASS variants

Rare synonymous (reference)

1 in 320

146 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GDPD3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 160	1 in 610
South Asian	~43k	1 in 110	1 in 770
Remaining (unassigned)	~30k	1 in 110	1 in 560
European (Finnish)	~27k	1 in 310	1 in 3,300
Admixed American	~22k	1 in 77	1 in 440
African / African American	~21k	1 in 140	1 in 870
East Asian	~20k	1 in 100	1 in 470
Ashkenazi Jewish	~13k	1 in 330	1 in 1,300
Middle Eastern	~2,884	1 in 100	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 10 of 10 coding exons well covered in gnomAD exomes. Genomes: 9 of 10 (exon 9 below).? see exons ↓