AP1G1

Chr 16ADAR

adaptor related protein complex 1 subunit gamma 1

Also known as: ADTG, CLAPG1, USRISD

NCBI Gene: 164 ENSG00000166747 UniProt: O43747 OMIM: 603533

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Adaptins are important components of clathrin-coated vesicles transporting ligand-receptor complexes from the plasma membrane or from the trans-Golgi network to lysosomes. The adaptin family of proteins is composed of four classes of molecules named alpha, beta-, beta prime- and gamma- adaptins. Adaptins, together with medium and small subunits, form a heterotetrameric complex called an adaptor, whose role is to promote the formation of clathrin-coated pits and vesicles. The protein encoded by this gene is a gamma-adaptin protein and it belongs to the adaptor complexes large subunits family. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismAD/ARLOEUF 0.202 OMIM phenotypes

Clinical Summary— AP1G1

🧬

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.

📋

ClinVar Variants

26 unique Pathogenic / Likely Pathogenic· 120 VUS of 220 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.20LOEUF

pLI 1.000

Z-score 6.05

OE 0.10 (0.05–0.20)

Highly constrained

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

Missense Constraint?

2.98Z-score

OE missense 0.61 (0.55–0.67)

277 obs / 456.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.10 (0.05–0.20)

0≤0.351.4

Missense OE?0.61 (0.55–0.67)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

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

This gene — mechanism propensity

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 · 69% of P/LP variants are LoF · LOEUF 0.20

Literature Evidence

LOFThe frameshift mutations caused a loss of AP1G1 protein expression, suggesting haploinsufficiency.1

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

References

1.PMID 34102099 ↗

ClinVar Variant Classifications

220 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15

Likely Pathogenic11

VUS120

Likely Benign37

Benign1

Conflicting4

Pathogenic

Likely Pathogenic

120

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	12	3	0	0	15
Likely Pathogenic	6	3	1	1	11
VUS	12	103	3	2	120
Likely Benign	0	28	4	5	37
Benign	0	0	1	0	1
Conflicting	—				4
Total	30	137	9	8	188

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 44) ClinVar copy-number / structural variants overlap AP1G1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →