GGA1

Chr 22

golgi associated, gamma adaptin ear containing, ARF binding protein 1

The protein regulates trafficking of proteins between the trans-Golgi network and lysosomes, including targeting of membrane receptors and regulation of retrograde transport pathways. Mutations cause neurodevelopmental disorders with intellectual disability, developmental delay, and seizures, with some patients showing additional features like microcephaly or movement disorders. The gene shows autosomal dominant inheritance and is highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.15
Clinical SummaryGGA1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
85 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.15LOEUF
pLI 1.000
Z-score 5.00
OE 0.03 (0.010.15)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.22Z-score
OE missense 0.83 (0.750.91)
323 obs / 391.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.03 (0.010.15)
00.351.4
Missense OE0.83 (0.750.91)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 1 / 31.1Missense obs/exp: 323 / 391.1Syn Z: -0.15

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

VUS85
Likely Benign2
Conflicting1
85
VUS
2
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
84
1
0
85
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Conflicting
1
Total0861088

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

View in ClinVar →

Protein Context — Lollipop Plot

GGA1 · 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

No active trials found for this gene.

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Clinical Literature
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