PLEKHF1

Chr 19

pleckstrin homology and FYVE domain containing 1

Also known as: APPD, LAPF, PHAFIN1, ZFYVE15

NCBI Gene: 79156 ENSG00000166289 UniProt: Q96S99

The protein binds phosphatidylinositol phosphates and regulates endosome organization, autophagy, and protein trafficking to the plasma membrane, while also participating in lysosomal-mitochondrial apoptotic pathways. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically presenting in early childhood. The gene shows tolerance to loss-of-function variants (low constraint), which is consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq, UniProt

Enables phosphatidylinositol-3-phosphate binding activity; phosphatidylinositol-4-phosphate binding activity; and phosphatidylinositol-5-phosphate binding activity. Involved in endosome organization; positive regulation of autophagy; and protein localization to plasma membrane. Located in endosome and lysosome. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

1.16

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)