HEY2

Chr 6

hes related family bHLH transcription factor with YRPW motif 2

Also known as: CHF1, GRIDLOCK, GRL, HERP1, HESR2, HRT2, bHLHb32

NCBI Gene: 23493 ENSG00000135547 UniProt: Q9UBP5

This protein is a transcriptional repressor that functions downstream of Notch signaling and is required for cardiovascular development, binding to E box sequences and repressing cardiac transcriptional activators GATA4 and GATA6. Mutations cause autosomal dominant congenital heart defects including septal defects, conotruncal anomalies, and complex congenital heart disease. The gene is highly constrained against loss-of-function mutations, indicating that haploinsufficiency likely underlies the pathogenic mechanism in affected individuals.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the hairy and enhancer of split-related (HESR) family of basic helix-loop-helix (bHLH)-type transcription factors. The encoded protein forms homo- or hetero-dimers that localize to the nucleus and interact with a histone deacetylase complex to repress transcription. Expression of this gene is induced by the Notch signal transduction pathway. Two similar and redundant genes in mouse are required for embryonic cardiovascular development, and are also implicated in neurogenesis and somitogenesis. Alternatively spliced transcript variants have been found, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)

congenital heart disease · ADLimitednot for standalone diagnostic reporting

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

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P/LP missense

0.41

LOEUF

LOF

Mechanism· predicted

Some data sources returned errors (1)

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