BMAL1
basic helix-loop-helix ARNT like 1, the group of Basic helix-loop-helix proteins|PAS domain containing
Basic information
Region (hg38): 11:13276651-13387266
Previous symbols: [ "ARNTL" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (5 variants)
- Inborn genetic diseases (4 variants)
- Premature ovarian failure (1 variants)
- See cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the BMAL1 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 | 4 | |||||
| missense | 6 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 1 | |||||
| Total | 0 | 0 | 6 | 3 | 2 |
Variants in BMAL1
This is a list of pathogenic ClinVar variants found in the BMAL1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 11-13354314-A-T | Benign (Jun 26, 2018) | |||
| 11-13354326-G-C | Premature ovarian failure | Uncertain significance (Mar 02, 2020) | ||
| 11-13356772-T-C | Benign (May 21, 2018) | |||
| 11-13356911-G-A | Likely benign (Oct 01, 2022) | |||
| 11-13360412-C-A | not specified | Uncertain significance (Dec 22, 2023) | ||
| 11-13365573-A-G | not specified | Uncertain significance (Jun 01, 2023) | ||
| 11-13366714-T-C | See cases | Uncertain significance (Jun 18, 2020) | ||
| 11-13369641-A-G | not specified | Uncertain significance (Aug 28, 2023) | ||
| 11-13369642-T-C | not specified | Uncertain significance (Jan 22, 2024) | ||
| 11-13369659-C-G | not specified | Uncertain significance (Jun 29, 2023) | ||
| 11-13369762-A-G | not specified | Uncertain significance (Dec 27, 2023) | ||
| 11-13372227-G-T | not specified | Uncertain significance (Mar 01, 2024) | ||
| 11-13372247-A-G | not specified | Uncertain significance (Jun 10, 2022) | ||
| 11-13372284-C-T | Likely benign (Jun 23, 2018) | |||
| 11-13372324-C-T | not specified | Uncertain significance (Sep 16, 2021) | ||
| 11-13372333-G-T | not specified | Uncertain significance (Dec 05, 2022) | ||
| 11-13375633-T-C | not specified | Uncertain significance (Dec 13, 2023) | ||
| 11-13375663-A-G | not specified | Uncertain significance (Jan 19, 2024) | ||
| 11-13381240-C-T | not specified | Uncertain significance (Feb 14, 2023) | ||
| 11-13386656-G-A | not specified | Uncertain significance (Jun 22, 2021) | ||
| 11-13386708-T-C | Likely benign (Oct 01, 2022) | |||
| 11-13386749-C-A | not specified | Uncertain significance (Dec 28, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| BMAL1 | protein_coding | protein_coding | ENST00000389707 | 16 | 110615 |
| 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 | 125725 | 0 | 5 | 125730 | 0.0000199 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.92 | 201 | 356 | 0.564 | 0.0000191 | 4121 |
| Missense in Polyphen | 44 | 129.92 | 0.33866 | 1475 | ||
| Synonymous | 1.29 | 110 | 129 | 0.855 | 0.00000735 | 1195 |
| Loss of Function | 4.68 | 4 | 33.1 | 0.121 | 0.00000195 | 381 |
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) | 0.0000442 | 0.0000440 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time- keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively. ARNTL/BMAL1 positively regulates myogenesis and negatively regulates adipogenesis via the transcriptional control of the genes of the canonical Wnt signaling pathway. Plays a role in normal pancreatic beta-cell function; regulates glucose-stimulated insulin secretion via the regulation of antioxidant genes NFE2L2/NRF2 and its targets SESN2, PRDX3, CCLC and CCLM. Negatively regulates the mTORC1 signaling pathway; regulates the expression of MTOR and DEPTOR. Controls diurnal oscillations of Ly6C inflammatory monocytes; rhythmic recruitment of the PRC2 complex imparts diurnal variation to chemokine expression that is necessary to sustain Ly6C monocyte rhythms. Regulates the expression of HSD3B2, STAR, PTGS2, CYP11A1, CYP19A1 and LHCGR in the ovary and also the genes involved in hair growth. Plays an important role in adult hippocampal neurogenesis by regulating the timely entry of neural stem/progenitor cells (NSPCs) into the cell cycle and the number of cell divisions that take place prior to cell-cycle exit. Regulates the circadian expression of CIART and KLF11. The CLOCK-ARNTL/BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. The NPAS2-ARNTL/BMAL1 heterodimer positively regulates the expression of MAOA, F7 and LDHA and modulates the circadian rhythm of daytime contrast sensitivity by regulating the rhythmic expression of adenylate cyclase type 1 (ADCY1) in the retina. The preferred binding motif for the CLOCK- ARNTL/BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking Ala residue in addition to the canonical 6-nucleotide E- box sequence (PubMed:23229515). CLOCK specifically binds to the half-site 5'-CAC-3', while ARNTL binds to the half-site 5'-GTGA-3' (PubMed:23229515). The CLOCK-ARNTL/BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'- CATGTGA-3' (PubMed:23229515). Essential for the rhythmic interaction of CLOCK with ASS1 and plays a critical role in positively regulating CLOCK-mediated acetylation of ASS1 (PubMed:28985504). {ECO:0000269|PubMed:11441146, ECO:0000269|PubMed:12738229, ECO:0000269|PubMed:18587630, ECO:0000269|PubMed:23785138, ECO:0000269|PubMed:23955654, ECO:0000269|PubMed:24005054, ECO:0000269|PubMed:28985504}.;
- Pathway
- Circadian rhythm - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Circadian Clock;Melatonin metabolism and effects;RORA activates gene expression;NR1D1 (REV-ERBA) represses gene expression;Exercise-induced Circadian Regulation;Hedgehog Signaling Pathway;Circadian Clock;BMAL1:CLOCK,NPAS2 activates circadian gene expression;Circadian rhythm pathway
(Consensus)
Recessive Scores
- pRec
- 0.395
Intolerance Scores
- loftool
- 0.469
- rvis_EVS
- -0.34
- rvis_percentile_EVS
- 30.37
Haploinsufficiency Scores
- pHI
- 0.781
- hipred
- Y
- hipred_score
- 0.719
- ghis
- 0.498
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.982
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Arntl
- Phenotype
- muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland 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); limbs/digits/tail phenotype; vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype;
Zebrafish Information Network
- Gene name
- arntl1a
- Affected structure
- intersegmental vessel
- Phenotype tag
- abnormal
- Phenotype quality
- shortened
Gene ontology
- Biological process
- obsolete protein import into nucleus, translocation;regulation of transcription, DNA-templated;spermatogenesis;circadian rhythm;negative regulation of TOR signaling;circadian regulation of gene expression;regulation of protein catabolic process;regulation of hair cycle;positive regulation of circadian rhythm;proteasome-mediated ubiquitin-dependent protein catabolic process;negative regulation of fat cell differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;regulation of neurogenesis;regulation of insulin secretion;regulation of cell cycle;response to redox state;maternal process involved in parturition;positive regulation of canonical Wnt signaling pathway;oxidative stress-induced premature senescence;negative regulation of cold-induced thermogenesis;positive regulation of protein acetylation;regulation of type B pancreatic cell development;negative regulation of glucocorticoid receptor signaling pathway;regulation of cellular senescence;positive regulation of skeletal muscle cell differentiation
- Cellular component
- nucleus;nucleoplasm;transcription factor complex;PML body;chromatoid body;intracellular membrane-bounded organelle
- Molecular function
- transcription regulatory region sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;protein binding;aryl hydrocarbon receptor binding;bHLH transcription factor binding;sequence-specific DNA binding;protein heterodimerization activity;Hsp90 protein binding;repressing transcription factor binding;E-box binding