AP2M1

Chr 3AD

adaptor related protein complex 2 subunit mu 1

Also known as: AP50, CLAPM1, MRD60, mu2

The AP2M1 protein is a component of the adaptor protein complex 2 (AP-2) that functions in clathrin-mediated endocytosis, cargo selection, and synaptic vesicle recycling. Mutations cause autosomal dominant intellectual developmental disorder with seizures. This represents a neurodevelopmental condition affecting cognitive function and seizure control through disruption of cellular membrane trafficking processes.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.191 OMIM phenotype
Clinical SummaryAP2M1
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.19LOEUF
pLI 0.999
Z-score 4.45
OE 0.04 (0.010.19)
Highly constrained

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

Missense Constraint
4.88Z-score
OE missense 0.17 (0.130.21)
46 obs / 273.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.04 (0.010.19)
00.351.4
Missense OE0.17 (0.130.21)
00.61.4
Synonymous OE0.83
01.21.6
LoF obs/exp: 1 / 25.0Missense obs/exp: 46 / 273.0Syn Z: 1.34
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongAP2M1-related developmental and epileptic encephalopathyOTHERAD
DN
0.3196th %ile
GOF
0.2994th %ile
LOF
0.79top 5%

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

LOFprediction above median · LOEUF 0.19

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

AP2M1 · 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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