AP1G1

Chr 16ADAR

adaptor related protein complex 1 subunit gamma 1

The encoded protein is a gamma-adaptin subunit of clathrin-associated adaptor protein complex 1 that mediates protein sorting in the late-Golgi/trans-Golgi network and endosomes by recruiting clathrin to membranes and recognizing sorting signals in transmembrane cargo molecules. Mutations cause Usmani-Riazuddin syndrome, which can follow either autosomal dominant or autosomal recessive inheritance patterns. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.20), indicating that heterozygous loss-of-function mutations are likely pathogenic.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.202 OMIM phenotypes
Clinical SummaryAP1G1
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADStrong

Strong evidence — appropriate for clinical testing

2 total gene-disease associations curated

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.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.20LOEUF
pLI 1.000
Z-score 6.05
OE 0.10 (0.050.20)
Highly constrained

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

Missense Constraint
2.98Z-score
OE missense 0.61 (0.550.67)
277 obs / 456.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.10 (0.050.20)
00.351.4
Missense OE0.61 (0.550.67)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 5 / 52.2Missense obs/exp: 277 / 456.4Syn Z: -0.30
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongAP1G1-related intellectual disability and epilepsyLOFAD
limitedAP1G1-related intellectual disabilityOTHERAR
DN
0.4289th %ile
GOF
0.4480th %ile
LOF
0.61top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOF1 literature citation · LOEUF 0.20

Literature Evidence

LOFThe frameshift mutations caused a loss of AP1G1 protein expression, suggesting haploinsufficiency.PMID:34102099

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

AP1G1 · 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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