AP4E1

adaptor related protein complex 4 subunit epsilon 1

2 disorders 1 untyped 1 susceptibility 15q21.2 gene with protein product

HGNC:573 Monarch NCBI Gene 23431 ENSG00000081014 UniProt Q9UPM8 OMIM 607244

Aliases: AP-4-EPSILON, SPG51.

Normal function · from ai-gene-review (Q9UPM8, commit 79fe13b38970) · AI-generated, not KB evidence

AP4E1 encodes the epsilon large subunit of the heterotetrameric AP-4 adaptor complex. AP-4 forms a nonclathrin coat on the cytoplasmic face of the trans-Golgi network and sorts membrane proteins into transport carriers. The epsilon N-terminal trunk contributes to the complex core and binds activated ARF1 for membrane recruitment, while its C-terminal ear binds the accessory protein tepsin. These interactions support coat assembly and cargo transport in coordination with the mu4 cargo-recognition subunit.

Within AP-4, epsilon contributes the structural and membrane-recruitment side of a cargo-adaptor mechanism. Its trunk assembles into the heterotetramer and directly engages activated ARF1; its ear recruits tepsin. Together these contacts support formation of cytoplasmic carriers at the TGN. Cargo-motif recognition is supplied by mu4, so the cargo-adaptor activity is contributed in the complex rather than attributed to isolated epsilon.

contributes to molecular function: cargo adaptor activity · directly involved in: vesicle-mediated transport · locations: trans-Golgi network membrane · in complex: AP-4 adaptor complex

The epsilon trunk binds activated ARF1 and provides a regulated membrane-recruitment contact for AP-4. Epsilon is an ARF effector rather than a GTPase, exchange factor or activating protein.

molecular function: small GTPase binding · locations: trans-Golgi network membrane · in complex: AP-4 adaptor complex

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Developmental Stuttering	susceptibility
Complex Hereditary Spastic Paraplegia	untyped	mechanism: AP-4-Dependent ATG9A Export and Autophagosome Formation Failure subtype: AP-4-HSP scoped to subtype: AP-4-HSP

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
AP-4 deficiency syndrome MONDO:0100176	AR	Definitive 2020-12-16	Complex Hereditary Spastic Paraplegia untyped

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.