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BHLHE40

basic helix-loop-helix family member e40, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): 3:4979436-4985323

Previous symbols: [ "STRA13", "BHLHB2" ]

Links

ENSG00000134107NCBI:8553OMIM:604256HGNC:1046Uniprot:O14503AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BHLHE40 gene.

  • Inborn genetic diseases (11 variants)
  • not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BHLHE40 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
1
clinvar
1
missense
11
clinvar
11
nonsense
0
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
0
non coding
0
Total 0 0 11 1 0

Variants in BHLHE40

This is a list of pathogenic ClinVar variants found in the BHLHE40 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
3-4979750-C-G not specified Uncertain significance (Dec 21, 2022)2338422
3-4979978-A-G not specified Uncertain significance (May 15, 2023)2557855
3-4979988-T-C not specified Uncertain significance (Nov 09, 2021)2259791
3-4982883-T-G not specified Uncertain significance (Oct 05, 2023)3133814
3-4982905-G-A not specified Uncertain significance (Oct 03, 2022)2315914
3-4982985-G-C not specified Uncertain significance (Dec 21, 2023)3133815
3-4983102-A-G not specified Uncertain significance (Oct 22, 2021)3133816
3-4983135-G-A not specified Uncertain significance (Dec 14, 2022)2225144
3-4983309-C-T not specified Uncertain significance (Oct 12, 2022)2213982
3-4983312-A-G not specified Uncertain significance (Sep 01, 2021)2400818
3-4983332-G-A Likely benign (Sep 01, 2022)2653460
3-4983363-A-C not specified Uncertain significance (Jun 01, 2023)2569301
3-4983381-C-A not specified Uncertain significance (Apr 08, 2022)2401461
3-4983390-G-A not specified Uncertain significance (Nov 18, 2022)2327572
3-4983555-C-T not specified Uncertain significance (Feb 07, 2023)2469323
3-4983578-G-T not specified Uncertain significance (Dec 18, 2023)3133812
3-4983579-C-T not specified Uncertain significance (Dec 18, 2023)3133813

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
BHLHE40protein_codingprotein_codingENST00000256495 56208
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9940.00556125647021256490.00000796
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.7872122470.8590.00001432671
Missense in Polyphen3575.1070.466821
Synonymous0.1861041060.9770.00000710834
Loss of Function3.64015.40.006.55e-7195

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00001760.0000176
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
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. {ECO:0000269|PubMed:12397359, ECO:0000269|PubMed:14672706, ECO:0000269|PubMed:15193144, ECO:0000269|PubMed:15560782, ECO:0000269|PubMed:18411297, ECO:0000269|PubMed:19786558}.;
Pathway
Circadian rhythm - Homo sapiens (human);Heart Development;Mesodermal Commitment Pathway;Glucocorticoid Receptor Pathway;Nuclear Receptors Meta-Pathway;BMAL1-CLOCK,NPAS2 activates circadian gene expression;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Circadian Clock;BMAL1:CLOCK,NPAS2 activates circadian gene expression;HIF-2-alpha transcription factor network;Circadian rhythm pathway;HIF-1-alpha transcription factor network (Consensus)

Recessive Scores

pRec
0.290

Intolerance Scores

loftool
rvis_EVS
-0.31
rvis_percentile_EVS
31.93

Haploinsufficiency Scores

pHI
0.260
hipred
Y
hipred_score
0.825
ghis
0.485

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
1.00

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Bhlhe40
Phenotype
growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);

Zebrafish Information Network

Gene name
bhlhe40
Affected structure
locomotor rhythm
Phenotype tag
abnormal
Phenotype quality
process quality

Gene ontology

Biological process
negative regulation of transcription by RNA polymerase II;somitogenesis;regulation of transcription, DNA-templated;Notch signaling pathway;cell differentiation;circadian regulation of gene expression;entrainment of circadian clock by photoperiod;negative regulation of DNA-binding transcription factor activity;negative regulation of transcription, DNA-templated;regulation of neurogenesis
Cellular component
nucleus;cytoplasm;nuclear body
Molecular function
RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II activating transcription factor binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;transcription corepressor activity;protein binding;transcription factor binding;protein domain specific binding;protein homodimerization activity;bHLH transcription factor binding;MRF binding;sequence-specific DNA binding;protein heterodimerization activity;E-box binding;sequence-specific double-stranded DNA binding