BHLHE41 Gene

HGNC Family	Basic helix-loop-helix proteins (BHLH)
Name	basic helix-loop-helix family, member e41
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BHLHE41 (also known as DEC2 or SHARP1) is emerging as a multifaceted transcriptional regulator whose functions span circadian timing, sleep homeostasis, tumor biology, and immune cell differentiation. In the context of the circadian clock, BHLHE41 represses CLOCK/BMAL1–mediated gene activation—a mechanism underscored by studies showing that naturally occurring mutations in BHLHE41 decrease its inhibitory activity on these clock‐driving transcription factors. Such mutations are linked to a short sleep phenotype and resistance to sleep deprivation, highlighting a direct role in setting sleep duration and modulating sleep homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer, BHLHE41 exerts tumor‐suppressive effects by interacting with hypoxia‐inducible factors (HIFs). In triple‐negative breast cancer, for example, BHLHE41 (SHARP1) binds to HIF‐1α and HIF‐2α, promoting their proteasomal degradation and thereby limiting the expression of HIF target genes that drive invasive and metastatic behaviors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, BHLHE41 has key roles in the immune system. Recent studies have shown that it is essential for the proper differentiation and self‐renewal of innate-like B-1a cells"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "and maintains the identity and proliferative capacity of alveolar macrophages."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Although the mechanistic details in T cells are still being clarified, the exhausted CD8 T-cell state—as described in abstract"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "—likely involves similar transcriptional regulatory principles. In exhausted CD8 cells, prolonged antigen exposure leads to a quiescent state; by virtue of its repressive activity, BHLHE41 may help enforce or stabilize this state, limiting overactivation and preventing immunopathology.\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings reveal that BHLHE41 participates in a broad regulatory network. By coupling its clock-regulatory and cell-intrinsic transcriptional repression functions, BHLHE41 not only ensures proper circadian and sleep patterns but also modulates tumor aggressiveness and immune cell fate. In exhausted CD8 T cells"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", its activity may represent a critical checkpoint that balances activation with functional restraint during chronic stimulation.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Renata Pellegrino, Ibrahim Halil Kavakli, Namni Goel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel BHLHE41 variant is associated with short sleep and resistance to sleep deprivation in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sleep (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.5665/sleep.3924"}], "href": "https://doi.org/10.5665/sleep.3924"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25083013"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25083013"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sato Honma, Takeshi Kawamoto, Yumiko Takagi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dec1 and Dec2 are regulators of the mammalian molecular clock."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature01123"}], "href": "https://doi.org/10.1038/nature01123"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12397359"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12397359"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Marco Montagner, Elena Enzo, Mattia Forcato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SHARP1 suppresses breast cancer metastasis by promoting degradation of hypoxia-inducible factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature11207"}], "href": "https://doi.org/10.1038/nature11207"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22801492"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22801492"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Taras Kreslavsky, Bojan Vilagos, Hiromi Tagoh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Essential role for the transcription factor Bhlhe41 in regulating the development, self-renewal and BCR repertoire of B-1a cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.3694"}], "href": "https://doi.org/10.1038/ni.3694"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28250425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28250425"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "René Rauschmeier, Charlotte Gustafsson, Annika Reinhardt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bhlhe40 and Bhlhe41 transcription factors regulate alveolar macrophage self-renewal and identity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.2018101233"}], "href": "https://doi.org/10.15252/embj.2018101233"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31414712"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31414712"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Omar Khan, Josephine R Giles, Sierra McDonald, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TOX transcriptionally and epigenetically programs CD8"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " T cell exhaustion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41586-019-1325-x"}], "href": "https://doi.org/10.1038/s41586-019-1325-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31207603"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31207603"}]}]}]}
Synonyms	BHLHB3, SHARP1, DEC2, HDEC2
Proteins	BHE41_HUMAN
NCBI Gene ID	79365
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

BHLHE41 has 10,290 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 115 datasets.

Click the + buttons to view associations for BHLHE41 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

BHLHE41 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of BHLHE41 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of BHLHE41 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of BHLHE41 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of BHLHE41 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of BHLHE41 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of BHLHE41 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of BHLHE41 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of BHLHE41 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of BHLHE41 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of BHLHE41 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of BHLHE41 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with BHLHE41 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with BHLHE41 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of BHLHE41 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of BHLHE41 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of BHLHE41 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with BHLHE41 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of BHLHE41 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing BHLHE41 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing BHLHE41 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with BHLHE41 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with BHLHE41 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of BHLHE41 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with BHLHE41 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with BHLHE41 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with BHLHE41 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by BHLHE41 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with BHLHE41 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with BHLHE41 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with BHLHE41 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with BHLHE41 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with BHLHE41 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at BHLHE41 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of BHLHE41 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of BHLHE41 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing BHLHE41 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with BHLHE41 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with BHLHE41 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of BHLHE41 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with BHLHE41 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.