AP4E1

Chr 15ARAD

adaptor related protein complex 4 subunit epsilon 1

Also known as: CPSQ4, SPG51, STUT1

The protein is a large subunit of adaptor protein complex-4 that mediates vesicle formation and sorting of integral membrane proteins in secretory and endocytic pathways at the Golgi apparatus and trans-Golgi network. Mutations cause autosomal recessive spastic paraplegia 51 and autosomal dominant familial persistent stuttering through a predicted dominant-negative mechanism. The gene is highly intolerant to loss-of-function variants, indicating haploinsufficiency sensitivity.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
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

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 OE0.28 (0.190.43)
00.351.4
Missense OE0.94 (0.871.01)
00.61.4
Synonymous OE1.04
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

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC