PGAP1

Chr 2AR

post-GPI attachment to proteins inositol deacylase 1

Also known as: Bst1, ISPD3024, MRT42, NEDDSBA, SPG67

NCBI Gene: 80055ENSG00000197121UniProt: Q75T13

The protein encoded by this gene functions early in the glycosylphosphatidylinositol (GPI) biosynthetic pathway, catalyzing the inositol deacylation of GPI. The encoded protein is required for the production of GPI that can attach to proteins, and this may be an important factor in the transport of GPI-anchored proteins from the endoplasmic reticulum to the Golgi. Defects in this gene are a cause an autosomal recessive form of cognitive impairment. [provided by RefSeq, Jul 2017]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with dysmorphic features, spasticity, and brain abnormalitiesMIM #615802
AR
405
ClinVar variants
69
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PGAP1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
69 Pathogenic / Likely Pathogenic· 147 VUS of 405 total submissions
Some data sources returned errors (1)

pubmed: 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
Moderate LoF intolerance
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.
0.60LOEUF
pLI 0.000
Z-score 3.89
OE 0.42 (0.30–0.60)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.26Z-score
OE missense 0.83 (0.77–0.91)
379 obs / 454.6 exp
Tolerant

Mild missense constraint

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.0.42 (0.30–0.60)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.77–0.91)
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.0.92
0≤1.21.6
LoF obs/exp: 22 / 52.4Missense obs/exp: 379 / 454.6Syn Z: 0.80

ClinVar Variant Classifications

405 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic19
VUS147
Likely Benign124
Benign48
Conflicting17
50
Pathogenic
19
Likely Pathogenic
147
VUS
124
Likely Benign
48
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
0
39
0
50
Likely Pathogenic
6
0
13
0
19
VUS
1
124
19
3
147
Likely Benign
0
6
70
48
124
Benign
0
0
45
3
48
Conflicting
—17
Total1813018654405

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

View in ClinVar →

Protein Context — Lollipop Plot

PGAP1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PGAP1-related intellectual disability, encephalopathy, impaired GPI-anchor maturation

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with dysmorphic features, spasticity, and brain abnormalities

MIM #615802

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Th17-related genes PGAP1 and TMBIM1 serve as potential diagnostic and predictive biomarkers in systemic sclerosis: bioinformatic identification and murine model validation.
Li Q et al.·Clin Rheumatol
2026🔓 Open AccessFunctional
PGAP1-Related Encephalopathy in an Infant With Neurodevelopmental Delay: Novel Variant and Review of Literature.
Baris S et al.·Int J Dev Neurosci
2025🔓 Open AccessReview
Molecular basis of the inositol deacylase PGAP1 involved in quality control of GPI-AP biogenesis.
Hong J et al.·Nat Commun
2024🔓 Open Access
Downregulation of lncRNA NEAT1 interacts with miR-374b-5p/PGAP1 axis to aggravate the development of osteoarthritis.
Huang F et al.·J Orthop Surg Res
2023🔓 Open Access
LncRNA LEMD1-AS1 relieves chondrocyte inflammation by targeting miR-944/PGAP1 in osteoarthritis.
Li H et al.·Cell Cycle
2022
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