AP4E1

Chr 15

adaptor related protein complex 4 subunit epsilon 1

Also known as: CPSQ4, SPG51, STUT1

NCBI Gene: 23431ENSG00000081014UniProt: Q9UPM8

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]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpastic paraplegia 51, autosomal recessive
UniProtStuttering, familial persistent 1

Clinical highlights

Gene-disease validity (ClinGen)
AP-4 deficiency syndrome · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
8
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.43
LOEUF
LOF
Mechanism· G2P
📖
GeneReview available — AP4E1
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.43LOEUF
pLI 0.003
Z-score 4.98
OE 0.28 (0.19–0.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
0.52Z-score
OE missense 0.94 (0.87–1.01)
532 obs / 566.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.28 (0.19–0.43)
0≤0.351.4
Missense OE?0.94 (0.87–1.01)
0≤0.61.4
Synonymous OE?1.04
0≤1.21.6
LoF obs/exp: 16 / 56.3Missense obs/exp: 532 / 566.9Syn Z: -0.49

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients