BHLHE40

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

Basic information

Region (hg38): 3:4979437-4985323

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

Links

ENSG00000134107 ∙ NCBI:8553 ∙ OMIM:604256 ∙ HGNC:1046 ∙ Uniprot:O14503 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

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		1
missense			28	2		30
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	28	3	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
3-4979746-C-T		not specified	Uncertain significance (Dec 24, 2024)
3-4979750-C-G		not specified	Uncertain significance (Dec 21, 2022)
3-4979750-C-T		not specified	Uncertain significance (Apr 09, 2024)
3-4979761-C-T		not specified	Uncertain significance (Feb 07, 2025)
3-4979978-A-G		not specified	Uncertain significance (May 15, 2023)
3-4979988-T-C		not specified	Uncertain significance (Nov 09, 2021)
3-4981504-G-C		not specified	Uncertain significance (Mar 01, 2025)
3-4982883-T-G		not specified	Uncertain significance (Oct 05, 2023)
3-4982905-G-A		not specified	Uncertain significance (Oct 03, 2022)
3-4982931-C-T		not specified	Uncertain significance (Oct 28, 2024)
3-4982943-C-T		not specified	Uncertain significance (Dec 09, 2024)
3-4982985-G-C		not specified	Uncertain significance (Dec 21, 2023)
3-4982992-C-T		not specified	Uncertain significance (Nov 13, 2024)
3-4983007-G-T		not specified	Uncertain significance (Aug 12, 2024)
3-4983018-A-G		not specified	Uncertain significance (Oct 09, 2024)
3-4983037-C-T		not specified	Uncertain significance (May 24, 2024)
3-4983102-A-G		not specified	Uncertain significance (Oct 22, 2021)
3-4983127-G-A		not specified	Uncertain significance (Nov 24, 2024)
3-4983135-G-A		not specified	Uncertain significance (Dec 14, 2022)
3-4983282-G-A		not specified	Likely benign (May 29, 2024)
3-4983282-G-T		not specified	Uncertain significance (Nov 09, 2024)
3-4983309-C-T		not specified	Uncertain significance (Oct 12, 2022)
3-4983312-A-G		not specified	Uncertain significance (Sep 01, 2021)
3-4983332-G-A			Likely benign (Sep 01, 2022)
3-4983349-G-A		not specified	Uncertain significance (Nov 26, 2024)

GnomAD

Source: gnomAD

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: 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

• 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