YWHAE

Chr 17

tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon

Also known as: 14-3-3E, HEL2, KCIP-1, MDCR, MDS

NCBI Gene: 7531 ENSG00000108953 UniProt: P62258

The protein mediates signal transduction by binding to phosphoserine-containing proteins and interacts with key regulators of cell division and insulin sensitivity including CDC25 phosphatases, RAF1, and IRS1. Heterozygous mutations cause autosomal dominant developmental and epileptic encephalopathy with intellectual disability, seizures, and developmental delay. The high pLI score (0.98) and low LOEUF score (0.24) indicate the pathogenic mechanism involves haploinsufficiency, where loss of one functional copy is sufficient to cause disease.

GeneReviews ResearchSummary from RefSeq, UniProt

This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 100% identical to the mouse ortholog. It interacts with CDC25 phosphatases, RAF1 and IRS1 proteins, suggesting its role in diverse biochemical activities related to signal transduction, such as cell division and regulation of insulin sensitivity. It has also been implicated in the pathogenesis of small cell lung cancer. Two transcript variants, one protein-coding and the other non-protein-coding, have been found for this gene. [provided by RefSeq, Aug 2008]

GeneReviews 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.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.23

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

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GeneReview available — YWHAE