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
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (8 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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 8 | 8 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice variant | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 8 | 0 | 0 |
Variants in BHLHE40
This is a list of pathogenic ClinVar variants found in the BHLHE40 region.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-4979750-C-G | Inborn genetic diseases | Uncertain significance (Dec 21, 2022) | ||
| 3-4979978-A-G | Inborn genetic diseases | Uncertain significance (May 15, 2023) | ||
| 3-4979988-T-C | Inborn genetic diseases | Uncertain significance (Nov 09, 2021) | ||
| 3-4982905-G-A | Inborn genetic diseases | Uncertain significance (Oct 03, 2022) | ||
| 3-4983135-G-A | Inborn genetic diseases | Uncertain significance (Dec 14, 2022) | ||
| 3-4983309-C-T | Inborn genetic diseases | Uncertain significance (Oct 12, 2022) | ||
| 3-4983312-A-G | Inborn genetic diseases | Uncertain significance (Sep 01, 2021) | ||
| 3-4983363-A-C | Inborn genetic diseases | Uncertain significance (Jun 01, 2023) | ||
| 3-4983381-C-A | Inborn genetic diseases | Uncertain significance (Apr 08, 2022) | ||
| 3-4983390-G-A | Inborn genetic diseases | Uncertain significance (Nov 18, 2022) | ||
| 3-4983555-C-T | Inborn genetic diseases | Uncertain significance (Feb 07, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| BHLHE40 | protein_coding | protein_coding | ENST00000256495 | 5 | 6208 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.994 | 0.00556 | 125647 | 0 | 2 | 125649 | 0.00000796 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.787 | 212 | 247 | 0.859 | 0.0000143 | 2671 |
| Missense in Polyphen | 35 | 75.107 | 0.466 | 821 | ||
| Synonymous | 0.186 | 104 | 106 | 0.977 | 0.00000710 | 834 |
| Loss of Function | 3.64 | 0 | 15.4 | 0.00 | 6.55e-7 | 195 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000176 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
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