BHLHE41
Chr 12ADbasic helix-loop-helix family member e41
Also known as: BHLHB3, DEC2, FNSS1, SHARP1, hDEC2
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.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
139 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 35 | 0 | 35 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 80 | 2 | 0 | 82 |
Likely Benign | 0 | 1 | 1 | 10 | 12 |
Benign | 0 | 2 | 0 | 2 | 4 |
| Total | 0 | 83 | 39 | 12 | 134 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
BHLHE41 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools