GPLD1

Chr 6

glycosylphosphatidylinositol specific phospholipase D1

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

NCBI Gene: 2822ENSG00000112293UniProt: P80108

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]

317
ClinVar variants
27
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GPLD1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 204 VUS of 317 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.83LOEUF
pLI 0.000
Z-score 2.53
OE 0.62 (0.47–0.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.30Z-score
OE missense 1.04 (0.96–1.12)
505 obs / 486.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.62 (0.47–0.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (0.96–1.12)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 32 / 51.6Missense obs/exp: 505 / 486.6Syn Z: 0.10

ClinVar Variant Classifications

317 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic3
VUS204
Likely Benign72
Benign6
Conflicting8
24
Pathogenic
3
Likely Pathogenic
204
VUS
72
Likely Benign
6
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
1
9
0
24
Likely Pathogenic
0
2
1
0
3
VUS
0
198
6
0
204
Likely Benign
0
11
3
58
72
Benign
1
1
4
0
6
Conflicting
—8
Total152132358317

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

View in ClinVar →

Protein Context — Lollipop Plot

GPLD1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Associations between physical activity, brain health, cognitive function, and circulating GPLD1 in healthy older (65-85 years) individuals.
Marlatt KL et al.·Geroscience
2025
Network analysis of the progranulin-deficient mouse brain proteome reveals pathogenic mechanisms shared in human frontotemporal dementia caused by GRN mutations.
Huang M et al.·Acta Neuropathol Commun
2020Functional
MASP1, THBS1, GPLD1 and ApoA-IV are novel biomarkers associated with prediabetes: the KORA F4 study.
von Toerne C et al.·Diabetologia
2016
Language impairment and dyslexia genes influence language skills in children with autism spectrum disorders.
Eicher JD et al.·Autism Res
2015Meta-analysis
Combined proteomic and lipidomic studies in Pompe disease allow a better disease mechanism understanding.
Sidorina A et al.·J Inherit Metab Dis
2021Functional
Transfer of Proteins from Cultured Human Adipose to Blood Cells and Induction of Anabolic Phenotype Are Controlled by Serum, Insulin and Sulfonylurea Drugs.
Müller GA et al.·Int J Mol Sci
2023
High-Density Lipoprotein Carries Markers That Track With Recovery From Stroke.
Plubell DL et al.·Circ Res
2020
The Clinical Significance of Glycoprotein Phospholipase D Levels in Distinguishing Early Stage Latent Autoimmune Diabetes in Adults and Type 2 Diabetes.
Qin W et al.·PLoS One
2016
Machine learning-based prognostic modeling of lysosome-related genes for predicting prognosis and immune status of patients with hepatocellular carcinoma.
Li W et al.·Front Immunol
2023Cohort
Biomarkers of Progressive Chronic Heart Failure: The Results of Blood Proteomic Analysis.
Anisimova AS et al.·Kardiologiia
2026
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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