ZFYVE28

Chr 4

zinc finger FYVE-type containing 28

Also known as: LST2, LYST2, lst-2

NCBI Gene: 57732 ENSG00000159733 UniProt: Q9HCC9

The protein binds phosphatidylinositol-3-phosphate and negatively regulates epidermal growth factor receptor signaling by promoting receptor degradation in endosomes. Mutations cause spastic tetraplegia with thin corpus callosum and progressive microcephaly, inherited in an autosomal recessive pattern. This gene is highly constrained against loss-of-function variants, suggesting that complete loss of protein function is poorly tolerated.

ResearchSummary from RefSeq, UniProt

Enables phosphatidylinositol-3-phosphate binding activity. Involved in negative regulation of epidermal growth factor-activated receptor activity. Located in cytosol and early endosome membrane. [provided by Alliance of Genome Resources, Jul 2025]

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)

—

P/LP submissions

—

P/LP missense

0.46

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

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