BHLHE40

Chr 3

basic helix-loop-helix family member e40

Also known as: BHLHB2, Clast5, DEC1, HLHB2, SHARP-2, SHARP2, STRA13, Stra14

NCBI Gene: 8553 ENSG00000134107 UniProt: O14503 OMIM: 604256

This gene encodes a transcriptional repressor that regulates circadian rhythm by negatively controlling clock genes and competing with CLOCK-BMAL1 complexes for E-box binding sites in target gene promoters. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.19), but no specific Mendelian disorders have been definitively associated with BHLHE40 mutations in current medical literature. Given its role in circadian regulation and cardiovascular function, mutations would likely affect sleep-wake cycles and potentially blood pressure regulation, though the inheritance pattern and clinical phenotype remain to be established.

OMIM ResearchSummary from RefSeq, 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. [provided by RefSeq, Feb 2014]

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

0.19

LOEUF· LoF intol.

LOF

Mechanism· predicted