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Aliases for BHLHE40 Gene

Aliases for BHLHE40 Gene

  • Basic Helix-Loop-Helix Family Member E40 2 3 5
  • Basic Helix-Loop-Helix Domain Containing, Class B, 2 2 3
  • Differentially Expressed In Chondrocytes Protein 1 3 4
  • Enhancer-Of-Split And Hairy-Related Protein 2 3 4
  • Stimulated By Retinoic Acid Gene 13 Protein 3 4
  • Differentially Expressed In Chondrocytes 1 2 3
  • Class B Basic Helix-Loop-Helix Protein 2 3 4
  • SHARP-2 3 4
  • BHLHB2 3 4
  • STRA13 3 4
  • SHARP2 3 4
  • DEC1 3 4
  • Differentiated Embryo Chondrocyte Expressed Gene 1 2
  • Differentiated Embryo Chondrocyte Expressed Gene 1 3
  • Class E Basic Helix-Loop-Helix Protein 40 3
  • Basic Helix-Loop-Helix Family, Member E40 2
  • BHLHe40 4
  • Clast5 3
  • Stra14 3
  • BHLHb2 4
  • HLHB2 3

External Ids for BHLHE40 Gene

Previous HGNC Symbols for BHLHE40 Gene

  • STRA13
  • BHLHB2

Summaries for BHLHE40 Gene

Entrez Gene Summary for BHLHE40 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. [provided by RefSeq, Feb 2014]

GeneCards Summary for BHLHE40 Gene

BHLHE40 (Basic Helix-Loop-Helix Family Member E40) is a Protein Coding gene. Diseases associated with BHLHE40 include Fanconi Anemia, Complementation Group A. Among its related pathways are Circadian rhythm pathway and Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways. Gene Ontology (GO) annotations related to this gene include DNA binding transcription factor activity and protein heterodimerization activity. An important paralog of this gene is BHLHE41.

UniProtKB/Swiss-Prot for BHLHE40 Gene

  • Transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes. 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 PER1/2 and in turn is repressed by PER1/2 and CRY1/2. Represses the activity of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 ARNTL2/BMAL2 heterodimer by competing for the binding to E-box elements (5-CACGTG-3) found within the promoters of its target genes. 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 and NR1H3/LXRA transactivation activity. May be involved in the regulation of chondrocyte differentiation via the cAMP pathway.

Gene Wiki entry for BHLHE40 Gene

Additional gene information for BHLHE40 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for BHLHE40 Gene

Genomics for BHLHE40 Gene

GeneHancer (GH) Regulatory Elements for BHLHE40 Gene

Promoters and enhancers for BHLHE40 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH03J004975 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 672.1 +3.6 3644 14.4 CLOCK MLX ZFP64 FEZF1 DMAP1 IRF4 YY1 SLC30A9 ZNF213 E2F8 BHLHE40 EDEM1 ARL8B ENSG00000235978 EGOT SETMAR ITPR1 GC03M004976 BHLHE40-AS1 LOC105376934
GH03J005002 Enhancer 1.5 FANTOM5 ENCODE dbSUPER 27.1 +23.6 23584 1.4 HDGF PKNOX1 SMAD1 ATF1 ARNT NCOA2 TCF12 ZNF766 CBX5 GATA2 BHLHE40 BHLHE40-AS1 ENSG00000235978 ARL8B EDEM1 LOC105376934
GH03J005015 Enhancer 1.9 FANTOM5 Ensembl ENCODE dbSUPER 18.2 +42.8 42826 12 MLX ZFP64 YBX1 FEZF1 IRF4 SLC30A9 E2F8 ZNF143 SP3 MEF2D BHLHE40 ARL8B EDEM1 LOC105376934 BHLHE40-AS1
GH03J005051 Enhancer 1.5 FANTOM5 Ensembl ENCODE dbSUPER 20.8 +74.9 74869 5.2 HDAC1 HDGF PKNOX1 RB1 ARNT NFXL1 YBX1 BATF KLF5 IRF4 BHLHE40 BHLHE40-AS1 ENSG00000235978 EGOT ARL8B EDEM1 GC03M005068 LOC105376934
GH03J004717 Enhancer 1.7 FANTOM5 Ensembl ENCODE dbSUPER 17.8 -258.4 -258360 5.7 SMAD1 FOXA2 MLX ARNT ARID4B SIN3A YBX1 IRF4 YY1 E2F8 ARL8B BHLHE40 EGOT BHLHE40-AS1 ENSG00000235978 EDEM1 ENSG00000275981 LOC105376933 ITPR1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around BHLHE40 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the BHLHE40 gene promoter:
  • AP-1
  • c-Jun
  • ATF-2
  • p300
  • p53
  • SREBP-1a
  • SREBP-1b
  • SREBP-1c
  • Max1

Genomic Locations for BHLHE40 Gene

Genomic Locations for BHLHE40 Gene
chr3:4,979,116-4,985,323
(GRCh38/hg38)
Size:
6,208 bases
Orientation:
Plus strand
chr3:5,020,801-5,027,008
(GRCh37/hg19)
Size:
6,208 bases
Orientation:
Plus strand

Genomic View for BHLHE40 Gene

Genes around BHLHE40 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
BHLHE40 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for BHLHE40 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for BHLHE40 Gene

Proteins for BHLHE40 Gene

  • Protein details for BHLHE40 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O14503-BHE40_HUMAN
    Recommended name:
    Class E basic helix-loop-helix protein 40
    Protein Accession:
    O14503
    Secondary Accessions:
    • Q96TD3

    Protein attributes for BHLHE40 Gene

    Size:
    412 amino acids
    Molecular mass:
    45510 Da
    Quaternary structure:
    • Homodimer. Heterodimer with BHLHE41/DEC2. Interacts with TCF3/E47. Interacts with ubiquitin-conjugating enzyme UBE2I/UBC9. Interacts with HDAC1, SUMO1, RXRA and ARNTL/BMAL1.

neXtProt entry for BHLHE40 Gene

Post-translational modifications for BHLHE40 Gene

  • Ubiquitinated; which may lead to proteasomal degradation.
  • Sumoylation inhibits its ubiquitination and promotes its negative regulation of the CLOCK-ARNTL/BMAL1 heterodimer transcriptional activator activity.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for BHLHE40 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for BHLHE40 Gene

Domains & Families for BHLHE40 Gene

Gene Families for BHLHE40 Gene

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

Protein Domains for BHLHE40 Gene

Graphical View of Domain Structure for InterPro Entry

genes like me logo Genes that share domains with BHLHE40: view

No data available for UniProtKB/Swiss-Prot for BHLHE40 Gene

Function for BHLHE40 Gene

Molecular function for BHLHE40 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. 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 PER1/2 and in turn is repressed by PER1/2 and CRY1/2. Represses the activity of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 ARNTL2/BMAL2 heterodimer by competing for the binding to E-box elements (5-CACGTG-3) found within the promoters of its target genes. 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 and NR1H3/LXRA transactivation activity. May be involved in the regulation of chondrocyte differentiation via the cAMP pathway.

Phenotypes From GWAS Catalog for BHLHE40 Gene

Gene Ontology (GO) - Molecular Function for BHLHE40 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding NAS,IDA 19274049
GO:0001078 transcriptional repressor activity, RNA polymerase II proximal promoter sequence-specific DNA binding IDA 12624110
GO:0001102 RNA polymerase II activating transcription factor binding IEA,ISS --
GO:0001191 transcriptional repressor activity, RNA polymerase II transcription factor binding IDA 12397359
GO:0003677 DNA binding IEA --
genes like me logo Genes that share ontologies with BHLHE40: view
genes like me logo Genes that share phenotypes with BHLHE40: view

Animal Models for BHLHE40 Gene

MGI Knock Outs for BHLHE40:

Animal Model Products

CRISPR Products

Targeted motifs for BHLHE40 Gene
HOMER Transcription Factor Regulatory Elements motif BHLHE40
  • Consensus sequence: KCACGTGMCN Submotif: canonical Cell Type: HepG2 GEO ID: GSE31477

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for BHLHE40

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology and Transcription Factor Targets for BHLHE40 Gene

Localization for BHLHE40 Gene

Subcellular locations from UniProtKB/Swiss-Prot for BHLHE40 Gene

Cytoplasm. Nucleus. Note=Predominantly localized in the nucleus (PubMed:11278694). {ECO:0000269 PubMed:11278694}.

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 BHLHE40 gene
Compartment Confidence
nucleus 5
golgi apparatus 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear bodies (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for BHLHE40 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA,NAS 9240428
GO:0005737 cytoplasm IEA --
GO:0016604 nuclear body IDA --
genes like me logo Genes that share ontologies with BHLHE40: view

Pathways & Interactions for BHLHE40 Gene

genes like me logo Genes that share pathways with BHLHE40: view

Pathways by source for BHLHE40 Gene

Gene Ontology (GO) - Biological Process for BHLHE40 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IDA 12397359
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated NAS 9240428
GO:0006357 regulation of transcription by RNA polymerase II IEA --
GO:0007623 circadian rhythm IEA --
genes like me logo Genes that share ontologies with BHLHE40: view

No data available for SIGNOR curated interactions for BHLHE40 Gene

Drugs & Compounds for BHLHE40 Gene

(2) Drugs for BHLHE40 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
cyclic amp Experimental Pharma 0

(2) Additional Compounds for BHLHE40 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with BHLHE40: view

Transcripts for BHLHE40 Gene

mRNA/cDNA for BHLHE40 Gene

Unigene Clusters for BHLHE40 Gene

Basic helix-loop-helix family, member e40:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for BHLHE40

Alternative Splicing Database (ASD) splice patterns (SP) for BHLHE40 Gene

No ASD Table

Relevant External Links for BHLHE40 Gene

GeneLoc Exon Structure for
BHLHE40
ECgene alternative splicing isoforms for
BHLHE40

Expression for BHLHE40 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for BHLHE40 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for BHLHE40 Gene

This gene is overexpressed in Serum (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for BHLHE40 Gene



Protein tissue co-expression partners for BHLHE40 Gene

NURSA nuclear receptor signaling pathways regulating expression of BHLHE40 Gene:

BHLHE40

SOURCE GeneReport for Unigene cluster for BHLHE40 Gene:

Hs.744856

mRNA Expression by UniProt/SwissProt for BHLHE40 Gene:

O14503-BHE40_HUMAN
Tissue specificity: Expressed in cartilage, spleen, intestine, lung, and to a lesser extent in heart, brain, liver, muscle and stomach.

Evidence on tissue expression from TISSUES for BHLHE40 Gene

  • Blood(4.4)
  • Skin(4.4)
  • Nervous system(3.4)
  • Muscle(3)
  • Lung(2.9)
  • Liver(2.7)
  • Intestine(2.2)
  • Kidney(2.2)
  • Adrenal gland(2.1)
  • Pancreas(2.1)
genes like me logo Genes that share expression patterns with BHLHE40: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for BHLHE40 Gene

Orthologs for BHLHE40 Gene

This gene was present in the common ancestor of chordates.

Orthologs for BHLHE40 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia BHLHE40 34 33
  • 99.68 (n)
OneToOne
dog
(Canis familiaris)
Mammalia BHLHE40 34 33
  • 92.39 (n)
OneToOne
cow
(Bos Taurus)
Mammalia BHLHE40 34 33
  • 90.61 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Bhlhe40 16 34 33
  • 87.92 (n)
rat
(Rattus norvegicus)
Mammalia Bhlhe40 33
  • 86.78 (n)
oppossum
(Monodelphis domestica)
Mammalia BHLHE40 34
  • 82 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia BHLHE40 34
  • 81 (a)
OneToOne
chicken
(Gallus gallus)
Aves BHLHE40 34 33
  • 72.33 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia BHLHB2 34
  • 70 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii bhlhe40 34 33
  • 64.81 (n)
OneToOne
wufm54h07 33
Species where no ortholog for BHLHE40 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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)
  • 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)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (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 BHLHE40 Gene

ENSEMBL:
Gene Tree for BHLHE40 (if available)
TreeFam:
Gene Tree for BHLHE40 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for BHLHE40: view image

Paralogs for BHLHE40 Gene

Paralogs for BHLHE40 Gene

(2) SIMAP similar genes for BHLHE40 Gene using alignment to 1 proteins:

  • BHE40_HUMAN
genes like me logo Genes that share paralogs with BHLHE40: view

Variants for BHLHE40 Gene

Sequence variations from dbSNP and Humsavar for BHLHE40 Gene

SNP ID Clin Chr 03 pos Variation AA Info Type
rs1000038262 -- 4,977,472(+) A/G upstream_transcript_variant
rs1000070841 -- 4,977,706(+) T/C upstream_transcript_variant
rs1000380056 -- 4,985,675(+) A/G downstream_transcript_variant
rs1000716525 -- 4,984,274(+) A/G 3_prime_UTR_variant
rs1001785054 -- 4,985,029(+) AATAAT/AAT 3_prime_UTR_variant

Structural Variations from Database of Genomic Variants (DGV) for BHLHE40 Gene

Variant ID Type Subtype PubMed ID
nsv1005718 CNV gain 25217958
nsv1073199 CNV deletion 25765185
nsv1126641 CNV deletion 24896259
nsv834606 CNV loss 17160897

Variation tolerance for BHLHE40 Gene

Residual Variation Intolerance Score: 33.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.12; 22.79% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for BHLHE40 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
BHLHE40

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for BHLHE40 Gene

Disorders for BHLHE40 Gene

MalaCards: The human disease database

(1) MalaCards diseases for BHLHE40 Gene - From: DISEASES

Disorder Aliases PubMed IDs
fanconi anemia, complementation group a
  • fanca
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for BHLHE40

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with BHLHE40: view

No data available for UniProtKB/Swiss-Prot and Genatlas for BHLHE40 Gene

Publications for BHLHE40 Gene

  1. Molecular characterization of the novel basic helix-loop-helix protein DEC1 expressed in differentiated human embryo chondrocytes. (PMID: 9240428) Shen M … Kato Y (Biochemical and biophysical research communications 1997) 2 3 4 22 58
  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 22 58
  3. Gene structure and chromosomal location of a human bHLH transcriptional factor DEC1 x Stra13 x SHARP-2/BHLHB2. (PMID: 11226878) Teramoto M … Kato Y (Journal of biochemistry 2001) 3 4 22 58
  4. SUMOylation of DEC1 protein regulates its transcriptional activity and enhances its stability. (PMID: 21829689) Hong Y … Wu H (PloS one 2011) 3 4 58
  5. PER2 variantion is associated with depression vulnerability. (PMID: 19693801) Lavebratt C … Forsell Y (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2010) 3 44 58

Products for BHLHE40 Gene

Sources for BHLHE40 Gene

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