BHLHE41

Chr 12

basic helix-loop-helix family member e41

Also known as: BHLHB3, DEC2, FNSS1, SHARP1, hDEC2

NCBI Gene: 79365 ENSG00000123095 UniProt: Q9C0J9

The encoded protein is a transcriptional repressor that negatively regulates circadian rhythm by competing with CLOCK-BMAL1 for E-box binding sites and repressing clock gene expression. Mutations cause familial natural short sleep syndrome, characterized by individuals who function normally on significantly reduced sleep duration. This gene is highly constrained against loss-of-function variants and follows autosomal dominant inheritance.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a basic helix-loop-helix protein expressed in various tissues. The encoded protein can interact with ARNTL or compete for E-box binding sites in the promoter of PER1 and repress CLOCK/ARNTL's transactivation of PER1. This gene is believed to be involved in the control of circadian rhythm and cell differentiation. Defects in this gene are associated with the short sleep phenotype. [provided by RefSeq, Feb 2014]

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

0.21

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

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