GPLD1

Chr 6

glycosylphosphatidylinositol specific phospholipase D1

Also known as: GPIPLD, GPIPLDM, PIGPLD, PIGPLD1, PLD

NCBI Gene: 2822ENSG00000112293UniProt: P80108OMIM: 602515

Many proteins are tethered to the extracellular face of eukaryotic plasma membranes by a glycosylphosphatidylinositol (GPI) anchor. The GPI-anchor is a glycolipid found on many blood cells. The protein encoded by this gene is a GPI degrading enzyme. Glycosylphosphatidylinositol specific phospholipase D1 hydrolyzes the inositol phosphate linkage in proteins anchored by phosphatidylinositol glycans, thereby releasing the attached protein from the plasma membrane. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
GOFmechanismLOEUF 0.83
Clinical Summary— GPLD1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 201 VUS of 328 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?
0.83LOEUF
pLI 0.000
Z-score 2.53
OE 0.62 (0.47–0.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-0.30Z-score
OE missense 1.04 (0.96–1.12)
505 obs / 486.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.62 (0.47–0.83)
0≤0.351.4
Missense OE?1.04 (0.96–1.12)
0≤0.61.4
Synonymous OE?0.99
0≤1.21.6
LoF obs/exp: 32 / 51.6Missense obs/exp: 505 / 486.6Syn Z: 0.10

This gene — mechanism propensity

DN
0.6164th %ile
GOF
0.6638th %ile
LOF
0.3357th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

328 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic2
VUS201
Likely Benign72
Benign6
Conflicting8
19
Pathogenic
2
Likely Pathogenic
201
VUS
72
Likely Benign
6
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
3
0
0
19
Likely Pathogenic
0
2
0
0
2
VUS
0
201
0
0
201
Likely Benign
0
11
3
58
72
Benign
1
1
4
0
6
Conflicting
—8
Total17218758308

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 10) ClinVar copy-number / structural variants overlap GPLD1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

GPLD1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients