PLEKHF2

Chr 8

pleckstrin homology and FYVE domain containing 2

Also known as: EAPF, PHAFIN2, ZFYVE18

NCBI Gene: 79666 ENSG00000175895 UniProt: Q9H8W4 OMIM: 615208

The protein is predicted to bind phosphatidylinositol and regulate endosome organization and transport from endosomes to lysosomes, potentially functioning in early endosome fusion and receptor trafficking. Mutations cause autosomal recessive intellectual disability with seizures and dysmorphic features, typically presenting in early childhood. The gene is highly constrained against loss-of-function mutations, suggesting that complete loss of protein function is likely pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in endosome organization and endosome to lysosome transport. Located in transport vesicle. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.45

LOEUF

LOF

Mechanism· predicted