BHLHE41 Gene (Protein Coding)

Basic Helix-Loop-Helix Family Member E41

GC12M026120
GIFtS:
42
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 sh... See more...

Aliases for BHLHE41 Gene

Aliases for BHLHE41 Gene

  • Basic Helix-Loop-Helix Family Member E41 2 3 5
  • Enhancer-Of-Split And Hairy-Related Protein 1 2 3 4
  • SHARP1 2 3 4
  • DEC2 2 3 4
  • Basic Helix-Loop-Helix Domain Containing, Class B, 3 2 3
  • Differentially Expressed In Chondrocytes Protein 2 3 4
  • Class E Basic Helix-Loop-Helix Protein 41 3 4
  • SHARP-1 2 4
  • BHLHB3 3 4
  • HDEC2 3 4
  • Differentially Expressed In Chondrocytes 2 2
  • Basic Helix-Loop-Helix Family, Member E41 2
  • Class B Basic Helix-Loop-Helix Protein 3 4
  • BHLHE41 5
  • BHLHe41 4
  • BHLHb3 4
  • FNSS1 3

External Ids for BHLHE41 Gene

Previous HGNC Symbols for BHLHE41 Gene

  • BHLHB3

Previous GeneCards Identifiers for BHLHE41 Gene

  • GC12M026165
  • GC12M026272
  • GC12M026043

Summaries for BHLHE41 Gene

Entrez Gene Summary for BHLHE41 Gene

  • 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]

GeneCards Summary for BHLHE41 Gene

BHLHE41 (Basic Helix-Loop-Helix Family Member E41) is a Protein Coding gene. Diseases associated with BHLHE41 include Short Sleep, Familial Natural, 1 and Advanced Sleep Phase Syndrome, Familial, 1. Among its related pathways are HIF-1-alpha transcription factor network and Circadian rhythm. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and RNA polymerase II proximal promoter sequence-specific DNA binding. An important paralog of this gene is BHLHE40.

UniProtKB/Swiss-Prot Summary for BHLHE41 Gene

  • Transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes (PubMed:11278948, PubMed:14672706, PubMed:15193144, PubMed:15560782, PubMed:18411297, PubMed:19786558, PubMed:25083013). Acts as the negative limb of a novel autoregulatory feedback loop (DEC loop) which differs from the one formed by the PER and CRY transcriptional repressors (PER/CRY loop). Both these loops are interlocked as it represses the expression of PER1 and in turn is repressed by PER1/2 and CRY1/2. Represses the activity of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 heterodimer by competing for the binding to E-box elements (5'-CACGTG-3') found within the promoters of its target genes (PubMed:25083013). Negatively regulates its own expression and the expression of DBP and BHLHE41/DEC2. Acts as a corepressor of RXR and the RXR-LXR heterodimers and represses the ligand-induced RXRA/B/G, NR1H3/LXRA, NR1H4 and VDR transactivation activity. Inhibits HNF1A-mediated transactivation of CYP1A2, CYP2E1 AND CYP3A11 (By similarity).

Gene Wiki entry for BHLHE41 Gene

Additional gene information for BHLHE41 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for BHLHE41 Gene

Genomics for BHLHE41 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for BHLHE41 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around BHLHE41 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for BHLHE41

Top Transcription factor binding sites by QIAGEN in the BHLHE41 gene promoter:
  • C/EBPalpha
  • CHOP-10
  • GCNF
  • GCNF-1
  • GCNF-2
  • Lmo2
  • MyoD
  • PPAR-alpha
  • TBP

Genomic Locations for BHLHE41 Gene

Latest Assembly
chr12:26,120,030-26,125,037
(GRCh38/hg38)
Size:
5,008 bases
Orientation:
Minus strand

Previous Assembly
chr12:26,272,963-26,277,970
(GRCh37/hg19 by Entrez Gene)
Size:
5,008 bases
Orientation:
Minus strand

chr12:26,272,959-26,278,060
(GRCh37/hg19 by Ensembl)
Size:
5,102 bases
Orientation:
Minus strand

Genomic View for BHLHE41 Gene

Genes around BHLHE41 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
BHLHE41 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for BHLHE41 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for BHLHE41 Gene

Proteins for BHLHE41 Gene

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  • Protein details for BHLHE41 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9C0J9-BHE41_HUMAN
    Recommended name:
    Class E basic helix-loop-helix protein 41
    Protein Accession:
    Q9C0J9
    Secondary Accessions:
    • A2I2N8

    Protein attributes for BHLHE41 Gene

    Size:
    482 amino acids
    Molecular mass:
    50498 Da
    Quaternary structure:
    • Homodimer (By similarity). Heterodimer with BHLHE40/DEC1 (PubMed:15193144). Interacts with CIART and ARNTL/BMAL1 (By similarity). Interacts with RXRA (PubMed:19786558). Interacts with NR0B2 and HNF1A (By similarity).

neXtProt entry for BHLHE41 Gene

Protein Expression for BHLHE41 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for BHLHE41 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for BHLHE41 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibodies for research

  • Abcam antibodies for BHLHE41

No data available for DME Specific Peptides for BHLHE41 Gene

Domains & Families for BHLHE41 Gene

Gene Families for BHLHE41 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for BHLHE41 Gene

InterPro:
Blocks:
  • Basic helix-loop-helix dimerization domain bHLH
  • Orange
ProtoNet:

Suggested Antigen Peptide Sequences for BHLHE41 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ61743, highly similar to Class B basic helix-loop-helix protein 3 (B7Z8M6_HUMAN)
  • Enhancer-of-split and hairy-related protein 1 (BHE41_HUMAN)
  • Basic helix-loop-helix protein 3 isoform 2 (Q5SCI4_HUMAN)
  • Basic helix-loop-helix protein 3 isoform 1 (Q8TAT1_HUMAN)
genes like me logo Genes that share domains with BHLHE41: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for BHLHE41 Gene

Function for BHLHE41 Gene

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Molecular function for BHLHE41 Gene

UniProtKB/Swiss-Prot Function:
Transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes (PubMed:11278948, PubMed:14672706, PubMed:15193144, PubMed:15560782, PubMed:18411297, PubMed:19786558, PubMed:25083013). Acts as the negative limb of a novel autoregulatory feedback loop (DEC loop) which differs from the one formed by the PER and CRY transcriptional repressors (PER/CRY loop). Both these loops are interlocked as it represses the expression of PER1 and in turn is repressed by PER1/2 and CRY1/2. Represses the activity of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 heterodimer by competing for the binding to E-box elements (5'-CACGTG-3') found within the promoters of its target genes (PubMed:25083013). Negatively regulates its own expression and the expression of DBP and BHLHE41/DEC2. Acts as a corepressor of RXR and the RXR-LXR heterodimers and represses the ligand-induced RXRA/B/G, NR1H3/LXRA, NR1H4 and VDR transactivation activity. Inhibits HNF1A-mediated transactivation of CYP1A2, CYP2E1 AND CYP3A11 (By similarity).

Phenotypes From GWAS Catalog for BHLHE41 Gene

Gene Ontology (GO) - Molecular Function for BHLHE41 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding ISS --
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISS --
GO:0001102 RNA polymerase II activating transcription factor binding ISS --
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific ISS --
GO:0003677 DNA binding IEA --
genes like me logo Genes that share ontologies with BHLHE41: view
genes like me logo Genes that share phenotypes with BHLHE41: view

Animal Models for research

miRNA for BHLHE41 Gene

miRTarBase miRNAs that target BHLHE41

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for BHLHE41

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for BHLHE41 Gene

Localization for BHLHE41 Gene

Subcellular locations from UniProtKB/Swiss-Prot for BHLHE41 Gene

Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for BHLHE41 gene
Compartment Confidence
nucleus 4
plasma membrane 2
extracellular 2
cytoskeleton 1
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
cytosol 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (4)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for BHLHE41 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin ISA --
GO:0005634 nucleus IBA 21873635
genes like me logo Genes that share ontologies with BHLHE41: view

Pathways & Interactions for BHLHE41 Gene

genes like me logo Genes that share pathways with BHLHE41: view

Pathways by source for BHLHE41 Gene

1 KEGG pathway for BHLHE41 Gene
1 R&D Systems pathway for BHLHE41 Gene
1 Qiagen pathway for BHLHE41 Gene
  • Circadian Clock in Mammals

SIGNOR curated interactions for BHLHE41 Gene

Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for BHLHE41 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IDA 14672706
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006357 regulation of transcription by RNA polymerase II IBA 21873635
GO:0007623 circadian rhythm IEA --
GO:0009952 anterior/posterior pattern specification IBA 21873635
genes like me logo Genes that share ontologies with BHLHE41: view

Drugs & Compounds for BHLHE41 Gene

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(1) Additional Compounds for BHLHE41 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with BHLHE41: view

Transcripts for BHLHE41 Gene

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mRNA/cDNA for BHLHE41 Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for BHLHE41

Alternative Splicing Database (ASD) splice patterns (SP) for BHLHE41 Gene

No ASD Table

Relevant External Links for BHLHE41 Gene

GeneLoc Exon Structure for
BHLHE41

Expression for BHLHE41 Gene

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  1. Primer products for research
  2. Gene Expression Assays for research

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for BHLHE41 Gene

mRNA expression in normal human tissues for BHLHE41 Gene
mRNA expression by BioGPS for BHLHE41 GenemRNA expression by GTEx for BHLHE41 Gene

mRNA differential expression in normal tissues according to GTEx for BHLHE41 Gene

This gene is overexpressed in Brain - Spinal cord (cervical c-1) (x5.2).

Protein differential expression in normal tissues from HIPED for BHLHE41 Gene

This gene is overexpressed in Adipocyte (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for BHLHE41 Gene



Protein tissue co-expression partners for BHLHE41 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for BHLHE41

SOURCE GeneReport for Unigene cluster for BHLHE41 Gene:

Hs.177841

mRNA Expression by UniProt/SwissProt for BHLHE41 Gene:

Q9C0J9-BHE41_HUMAN
Tissue specificity: Highly expressed in skeletal muscle and brain, moderately expressed in pancreas and heart, weakly expressed in placenta, lung, liver and kidney.

Evidence on tissue expression from TISSUES for BHLHE41 Gene

  • Nervous system(3.7)
  • Muscle(3.1)
  • Intestine(2.7)
  • Heart(2.6)
  • Eye(2.6)
  • Stomach(2.5)
  • Skin(2.3)
  • Kidney(2.1)
  • Liver(2.1)
  • Spleen(2.1)
  • Thyroid gland(2.1)
genes like me logo Genes that share expression patterns with BHLHE41: view

Primer products for research

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for BHLHE41 Gene

Orthologs for BHLHE41 Gene

This gene was present in the common ancestor of chordates.

Orthologs for BHLHE41 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia BHLHE41 30 31
  • 99.72 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Bhlhe41 31
  • 74 (a)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia BHLHE41 31
  • 69 (a)
 OneToOne
Cow
(Bos Taurus)
 Mammalia BHLHE41 31
  • 69 (a)
 OneToOne
Dog
(Canis familiaris)
 Mammalia BHLHE41 31
  • 43 (a)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia BHLHE41 31
  • 61 (a)
 OneToOne
Zebrafish
(Danio rerio)
 Actinopterygii bhlhe41 31
  • 51 (a)
 OneToOne
Species where no ortholog for BHLHE41 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rat (Rattus norvegicus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for BHLHE41 Gene

ENSEMBL:
Gene Tree for BHLHE41 (if available)
TreeFam:
Gene Tree for BHLHE41 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for BHLHE41: view image

Paralogs for BHLHE41 Gene

Paralogs for BHLHE41 Gene

(3) SIMAP similar genes for BHLHE41 Gene using alignment to 2 proteins:

  • BHE41_HUMAN
  • Q8TAT1_HUMAN
genes like me logo Genes that share paralogs with BHLHE41: view

Variants for BHLHE41 Gene

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Polymorphic Variants from UniProtKB/Swiss-Prot for BHLHE41 Gene

BHE41_HUMAN-Q9C0J9
Genetic variations in BHLHE41 are associated with the familial natural short sleep 1 (FNSS1) phenotype, an autosomal dominant trait [MIM:612975]. Individuals with this trait require less sleep in any 24-hour period than is typical for their age group.

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for BHLHE41 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
rs121912617 Affects: Short sleep, familial natural, 1. -. - 26,122,364(-) G/Cp.Pro384Argp.Pro384Gln
NM_030762.3(BHLHE41):c.1151C>G (p.Pro384Arg) 		MISSENSE
rs1591838266 Affects: Short sleep, familial natural, 1 26,122,431(-) A/G
NM_030762.3(BHLHE41):c.1084T>C (p.Tyr362His) 		MISSENSE
rs776094709 Likely Benign: not provided 26,122,435(-) G/C
NM_030762.3(BHLHE41):c.1080C>G (p.Ala360=) 		SYNONYMOUS
VAR_082585 - p.Tyr362His

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for BHLHE41 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for BHLHE41 Gene

Variant ID Type Subtype PubMed ID
esv3581126 CNV gain 25503493

Variation tolerance for BHLHE41 Gene

Gene Damage Index Score: 10.12; 90.27% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for BHLHE41 Gene

Human Gene Mutation Database (HGMD)
BHLHE41
SNPedia medical, phenotypic, and genealogical associations of SNPs for
BHLHE41

SNP Genotyping and Copy Number Assays for research

Disorders for BHLHE41 Gene

MalaCards: The human disease database

(5) MalaCards diseases for BHLHE41 Gene - From: OMI, GTR, COP, and GCD

Disorder Aliases PubMed IDs
short sleep, familial natural, 1
  • fnss1
advanced sleep phase syndrome, familial, 1
  • fasps1
advanced sleep phase syndrome
  • familial advanced sleep-phase syndrome
febrile seizures, familial, 5
  • feb5
sleep disorder
  • non-organic sleep disorder
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for BHLHE41

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with BHLHE41: view

No data available for UniProtKB/Swiss-Prot and Genatlas for BHLHE41 Gene

Publications for BHLHE41 Gene

  1. Molecular cloning and characterization of DEC2, a new member of basic helix-loop-helix proteins. (PMID: 11162494) Fujimoto K … Kato Y (Biochemical and biophysical research communications 2001) 2 3 4 23
  2. Functional analysis of the basic helix-loop-helix transcription factor DEC1 in circadian regulation. Interaction with BMAL1. (PMID: 15560782) Sato F … Kato Y (European journal of biochemistry 2004) 3 4 23
  3. A novel BHLHE41 variant is associated with short sleep and resistance to sleep deprivation in humans. (PMID: 25083013) Pellegrino R … Pack AI (Sleep 2014) 3 4
  4. The basic helix-loop-helix proteins differentiated embryo chondrocyte (DEC) 1 and DEC2 function as corepressors of retinoid X receptors. (PMID: 19786558) Cho Y … Makishima M (Molecular pharmacology 2009) 3 4
  5. The transcriptional repressor DEC2 regulates sleep length in mammals. (PMID: 19679812) He Y … Fu YH (Science (New York, N.Y.) 2009) 3 4

ExternalLinks

View latest publications for BHLHE41 gene in Mastermind

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