GPAA1

Chr 8AR

glycosylphosphatidylinositol anchor attachment 1

Also known as: GAA1, GPIBD15, hGAA1

NCBI Gene: 8733ENSG00000197858UniProt: O43292OMIM: 603048

The protein is a component of the GPI-anchor transamidase complex that catalyzes the linkage between proteins and GPI anchors, enabling proteins to attach to cell surface membranes. Mutations cause glycosylphosphatidylinositol biosynthesis defect 15, which follows autosomal recessive inheritance. This gene is highly intolerant to loss-of-function variants (pLI near 1), indicating that complete loss of function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.981 OMIM phenotype
Clinical Summary— GPAA1
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Gene-Disease Validity (ClinGen)
glycosylphosphatidylinositol biosynthesis defect 15 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
43 unique Pathogenic / Likely Pathogenic· 148 VUS of 500 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
0.98LOEUF
pLI 0.000
Z-score 1.65
OE 0.65 (0.45–0.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.87Z-score
OE missense 0.87 (0.80–0.96)
324 obs / 371.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.65 (0.45–0.98)
0≤0.351.4
Missense OE0.87 (0.80–0.96)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 17 / 26.1Missense obs/exp: 324 / 371.1Syn Z: -0.43
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongGPAA1-related developmental delay, epilepsy, cerebellar atrophy, and osteopeniaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7036th %ile
GOF
0.6834th %ile
LOF
0.2874th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic13
VUS148
Likely Benign284
Benign9
Conflicting2
30
Pathogenic
13
Likely Pathogenic
148
VUS
284
Likely Benign
9
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
1
12
0
30
Likely Pathogenic
12
0
1
0
13
VUS
1
138
8
1
148
Likely Benign
0
2
106
176
284
Benign
0
0
4
5
9
Conflicting
—2
Total30141131182486

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

View in ClinVar →

Protein Context — Lollipop Plot

GPAA1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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