GDPD5

Chr 11

glycerophosphodiester phosphodiesterase domain containing 5

Also known as: GDE2, PP1665

NCBI Gene: 81544 ENSG00000158555 UniProt: Q8WTR4

GDPD5 encodes a glycerophosphodiester phosphodiesterase that promotes neurite formation and drives spinal motor neuron differentiation by cleaving glycosylphosphatidylinositol (GPI) anchors from target proteins. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly. The gene shows low constraint against loss-of-function variants (pLI 0.0002, LOEUF 0.602), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

ResearchSummary from RefSeq, UniProt

Predicted to enable glycerophosphodiester phosphodiesterase activity and glycerophospholipase activity. Predicted to be involved in several processes, including negative regulation of Notch signaling pathway; negative regulation of amyloid precursor protein biosynthetic process; and positive regulation of neuron differentiation. Predicted to act upstream of or within neuron differentiation and regulation of timing of cell differentiation. Predicted to be located in axon; neuronal cell body; and perinuclear endoplasmic reticulum. Predicted to be active in plasma membrane raft. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.60

LOEUF

Multiple*

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?

0.60LOEUF

pLI 0.000

Z-score 3.31

OE 0.37 (0.24–0.60)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.70Z-score

OE missense 0.76 (0.69–0.83)

298 obs / 392.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.37 (0.24–0.60)

0≤0.351.4

Missense OE?0.76 (0.69–0.83)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 12 / 32.3Missense obs/exp: 298 / 392.6Syn Z: -0.68

Background carrier burden — how many people carry a rare variant somewhere in GDPD5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 60

764 rare PASS variants

Rare truncating (LoF)

1 in 1,500

131 rare PASS variants

Rare synonymous (reference)

1 in 89

368 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GDPD5. 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 76	1 in 1,800
South Asian	~43k	1 in 52	1 in 840
Remaining (unassigned)	~30k	1 in 56	1 in 1,500
European (Finnish)	~27k	1 in 210	≈ 1 in 6,600
Admixed American	~22k	1 in 59	1 in 2,500
African / African American	~21k	1 in 55	1 in 820
East Asian	~20k	1 in 62	≈ 1 in 4,900
Ashkenazi Jewish	~13k	1 in 300	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 67	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): All 15 coding exons well covered in gnomAD exomes and genomes.? see exons ↓