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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
  • Differentiated Embryo Chondrocyte Expressed Gene 1 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
  • Basic Helix-Loop-Helix Family, Member E40 2
  • Class E Basic Helix-Loop-Helix Protein 40 3
  • BHLHe40 4
  • Clast5 3
  • Stra14 3
  • 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 Mesodermal Commitment Pathway and Circadian rhythm pathway. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding 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

Regulatory Elements for BHLHE40 Gene

Enhancers for BHLHE40 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH03H005002 1.7 FANTOM5 ENCODE dbSUPER 27.1 +23.6 23585 1 HDGF PKNOX1 ATF1 ARNT TCF12 ZNF766 CBX5 GATA2 ELK1 ATF7 BHLHE40 BHLHE40-AS1 ENSG00000235978 ARL8B EDEM1 LOC105376934
GH03H004975 1.9 FANTOM5 ENCODE dbSUPER 22.1 +3.6 3645 14 MLX ZFP64 FEZF1 DMAP1 YY1 SLC30A9 ZNF143 SP3 ZC3H11A MEF2D BHLHE40 ARL8B ENSG00000235978 EGOT SETMAR EDEM1 ITPR1 BHLHE40-AS1 LOC105376934
GH03H005015 2.1 FANTOM5 Ensembl ENCODE dbSUPER 18.2 +42.8 42826 12 MLX ZFP64 YBX1 FEZF1 SLC30A9 ZNF143 SP3 ZC3H11A MEF2D SSRP1 BHLHE40 ARL8B EDEM1 LOC105376934 BHLHE40-AS1
GH03H005051 1.7 FANTOM5 Ensembl ENCODE dbSUPER 20.8 +74.9 74870 5 HDGF PKNOX1 RB1 ARNT NFXL1 YBX1 BATF GATA2 ZNF207 ATF7 BHLHE40 BHLHE40-AS1 ENSG00000235978 EGOT ARL8B EDEM1 GC03M005068 LOC105376934
GH03H004717 1.9 FANTOM5 Ensembl ENCODE dbSUPER 17.8 -258.4 -258360 5 FOXA2 ATF1 MLX ARNT ARID4B YBX1 YY1 GATA2 ZNF143 FOS ARL8B BHLHE40 EGOT BHLHE40-AS1 ENSG00000235978 EDEM1 ENSG00000275981 LOC105376933
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around BHLHE40 on UCSC Golden Path with GeneCards custom track

Promoters for BHLHE40 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000302446 1084 5201 MLX FEZF1 DMAP1 YY1 ZNF143 SP3 ZC3H11A MEF2D ZNF610 GLIS1

Genomic Location for BHLHE40 Gene

Chromosome:
3
Start:
4,979,116 bp from pter
End:
4,985,323 bp from pter
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

  • Sumoylation inhibits its ubiquitination and promotes its negative regulation of the CLOCK-ARNTL/BMAL1 heterodimer transcriptional activator activity.
  • Ubiquitinated; which may lead to proteasomal degradation.
  • 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 IDA 12397359
GO:0001078 transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific 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

Clone Products

  • Applied Biological Materials Clones for BHLHE40
  • Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more

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 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 from RNA polymerase II promoter IDA 12397359
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated NAS 9240428
GO:0006357 regulation of transcription from RNA polymerase II promoter 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

Clone Products

  • Applied Biological Materials Clones for BHLHE40
  • Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more

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, PaxDb, 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

Primer Products

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 33 34
  • 99.68 (n)
dog
(Canis familiaris)
Mammalia BHLHE40 33 34
  • 92.39 (n)
cow
(Bos Taurus)
Mammalia BHLHE40 33 34
  • 90.61 (n)
mouse
(Mus musculus)
Mammalia Bhlhe40 33 16 34
  • 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 33 34
  • 72.33 (n)
lizard
(Anolis carolinensis)
Reptilia BHLHB2 34
  • 70 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii bhlhe40 33 34
  • 64.81 (n)
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)

Paralogs for BHLHE40 Gene

Paralogs for BHLHE40 Gene

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

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 Sequence Context AA Info Type
rs1000038262 -- 4,977,472(+) ACCCC(A/G)TTTTT intron-variant, upstream-variant-2KB
rs1000070841 -- 4,977,706(+) TGTTT(C/T)CCCTG intron-variant, upstream-variant-2KB
rs1000380056 -- 4,985,675(+) GCAAC(A/G)TTCCA downstream-variant-500B
rs1000716525 -- 4,984,274(+) ACGGT(A/G)GTGGT utr-variant-3-prime
rs1001785054 -- 4,985,029(+) AGAAG(-/AAT)AATTT cds-indel

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)

Relevant External Links 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
  • fanconi's anemia
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for BHLHE40

Genetic Association Database (GAD)
BHLHE40
Human Genome Epidemiology (HuGE) Navigator
BHLHE40
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
BHLHE40
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 60
  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 60
  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 60
  4. SUMOylation of DEC1 protein regulates its transcriptional activity and enhances its stability. (PMID: 21829689) Hong Y … Wu H (PloS one 2011) 3 4 60
  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 45 60

Products for BHLHE40 Gene

Sources for BHLHE40 Gene

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