BHLHE41

basic helix-loop-helix family member e41, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): 12:26120030-26125037

Previous symbols: [ "BHLHB3" ]

Links

ENSG00000123095 ∙ NCBI:79365 ∙ OMIM:606200 ∙ HGNC:16617 ∙ Uniprot:Q9C0J9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Short sleeper, familial natural, 1	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	19679812

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BHLHE41 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BHLHE41 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				6	1	7
missense			31	1	2	34
nonsense						0
start loss						0
frameshift						0
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	31	8	3

Variants in BHLHE41

This is a list of pathogenic ClinVar variants found in the BHLHE41 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-26122127-G-C		not specified	Uncertain significance (May 15, 2024)
12-26122134-G-C		not specified	Uncertain significance (Jun 24, 2022)
12-26122137-G-A		not specified	Uncertain significance (Jun 02, 2024)
12-26122151-A-C		not specified	Uncertain significance (Apr 17, 2023)
12-26122178-G-C		not specified	Uncertain significance (Sep 22, 2023)
12-26122181-T-G		not specified	Uncertain significance (Jan 04, 2022)
12-26122192-A-T		BHLHE41-related disorder	Likely benign (Jun 22, 2020)
12-26122193-A-G		not specified	Likely benign (Jan 05, 2022)
12-26122197-G-C		not specified	Uncertain significance (May 30, 2024)
12-26122222-C-CGCG		BHLHE41-related disorder	Likely benign (May 22, 2023)
12-26122233-C-T		BHLHE41-related disorder	Benign (Feb 18, 2020)
12-26122251-G-A		not specified	Uncertain significance (Jan 31, 2024)
12-26122283-G-T		not specified	Uncertain significance (Apr 26, 2023)
12-26122319-G-A		not specified	Uncertain significance (Sep 20, 2023)
12-26122344-C-T		not specified	Uncertain significance (Feb 01, 2023)
12-26122347-G-A		not specified	Uncertain significance (May 20, 2024)
12-26122364-G-C		Short sleep, familial natural, 1	Affects (Aug 14, 2009)
12-26122375-C-T		BHLHE41-related disorder	Likely benign (May 10, 2024)
12-26122399-C-G		BHLHE41-related disorder	Benign (Dec 03, 2019)
12-26122422-G-A		not specified	Uncertain significance (Feb 11, 2022)
12-26122431-A-G		Short sleep, familial natural, 1	Affects (Mar 17, 2020)
12-26122435-G-C			Likely benign (May 08, 2018)
12-26122499-T-G		not specified	Uncertain significance (Nov 15, 2021)
12-26122509-G-A		not specified	Uncertain significance (Oct 30, 2023)
12-26122565-C-T		not specified	Uncertain significance (Sep 17, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BHLHE41	protein_coding	protein_coding	ENST00000242728	5	5102

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.992	0.00788	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.823	158	190	0.832	0.00000888	2965
Missense in Polyphen		37	61.676	0.59991		832
Synonymous	-0.467	91	85.5	1.06	0.00000432	1031
Loss of Function	3.53	0	14.5	0.00	6.82e-7	200

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)	0.00	0.00
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 and in turn is repressed by PER1/2 and CRY1/2. Represses the activity of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 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/B/G, NR1H3/LXRA, NR1H4 and VDR transactivation activity. {ECO:0000269|PubMed:11278948, 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);NOTCH-Ncore;BMAL1-CLOCK,NPAS2 activates circadian gene expression;Pathways in clear cell renal cell carcinoma;Circadian Clock;BMAL1:CLOCK,NPAS2 activates circadian gene expression;HIF-1-alpha transcription factor network (Consensus)

Haploinsufficiency Scores

• pHI: 0.168
• ghis: 0.546

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.962

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Bhlhe41
• 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

Zebrafish Information Network

• Gene name: bhlhe41
• Affected structure: locomotion
• Phenotype tag: abnormal
• Phenotype quality: process quality

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;somitogenesis;Notch signaling pathway;cell population proliferation;animal organ morphogenesis;negative regulation of myotube differentiation;negative regulation of transcription by competitive promoter binding;cell differentiation;circadian regulation of gene expression;negative regulation of transcription, DNA-templated;regulation of neurogenesis
• Cellular component: nucleus
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter 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;transcription corepressor activity;protein binding;transcription factor binding;protein homodimerization activity;histone deacetylase binding;bHLH transcription factor binding;MRF binding;sequence-specific DNA binding;protein heterodimerization activity;E-box binding;sequence-specific double-stranded DNA binding