AP4E1

Chr 15ARAD

adaptor related protein complex 4 subunit epsilon 1

Also known as: CPSQ4, SPG51, STUT1

This gene encodes a member of the adaptor complexes large subunit protein family. These proteins are components of the heterotetrameric adaptor protein complexes, which play important roles in the secretory and endocytic pathways by mediating vesicle formation and sorting of integral membrane proteins. The encoded protein is a large subunit of adaptor protein complex-4, which is associated with both clathrin- and nonclathrin-coated vesicles. Disruption of this gene may be associated with cerebral palsy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismAR/ADLOEUF 0.432 OMIM phenotypes
Clinical SummaryAP4E1
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Gene-Disease Validity (ClinGen)
AP-4 deficiency syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — AP4E1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.43LOEUF
pLI 0.003
Z-score 4.98
OE 0.28 (0.190.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
0.52Z-score
OE missense 0.94 (0.871.01)
532 obs / 566.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.28 (0.190.43)
00.351.4
Missense OE?0.94 (0.871.01)
00.61.4
Synonymous OE?1.04
01.21.6
LoF obs/exp: 16 / 56.3Missense obs/exp: 532 / 566.9Syn Z: -0.49
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveAP4E1-related cerebral palsy spastic quadriplegicLOFAR

This gene — mechanism propensity

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

DN
0.6745th %ile
GOF
0.5954th %ile
LOF
0.2873th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

AP4E1 · protein map & ClinVar variants

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