BMAL2

basic helix-loop-helix ARNT like 2, the group of Basic helix-loop-helix proteins|PAS domain containing

Basic information

Region (hg38): 12:27332835-27425289

Previous symbols: [ "ARNTL2" ]

Links

ENSG00000029153 ∙ NCBI:56938 ∙ OMIM:614517 ∙ HGNC:18984 ∙ Uniprot:Q8WYA1 ∙ 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 BMAL2 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 BMAL2 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						0
missense			10	1	1	12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	10	1	1

Variants in BMAL2

This is a list of pathogenic ClinVar variants found in the BMAL2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-27344516-G-A		Pulmonary disease, chronic obstructive, susceptibility to	protective (Jul 05, 2022)
12-27346668-T-C		Pulmonary disease, chronic obstructive, susceptibility to	association (May 09, 2022)
12-27368277-A-T		not specified	Uncertain significance (May 17, 2023)
12-27368372-T-A		not specified	Uncertain significance (Feb 06, 2023)
12-27368379-G-A		not specified	Uncertain significance (Feb 05, 2024)
12-27368390-G-A		not specified	Uncertain significance (Apr 07, 2023)
12-27376286-A-C		Pulmonary disease, chronic obstructive, susceptibility to	association (May 10, 2022)
12-27380272-C-T		not specified	Uncertain significance (May 17, 2023)
12-27380273-G-A		not specified	Uncertain significance (Nov 13, 2023)
12-27380359-C-A		not specified	Uncertain significance (Dec 07, 2023)
12-27380359-C-T		not specified	Uncertain significance (Jan 03, 2024)
12-27385489-A-G		not specified	Uncertain significance (Sep 06, 2022)
12-27387238-G-T		not specified	Uncertain significance (Nov 03, 2023)
12-27390164-T-C		not specified	Uncertain significance (Feb 16, 2023)
12-27390173-C-T		not specified	Uncertain significance (Oct 03, 2022)
12-27390208-G-C			Benign (May 24, 2018)
12-27400611-G-C		not specified	Uncertain significance (Oct 27, 2023)
12-27400629-G-A		not specified	Uncertain significance (Feb 27, 2024)
12-27400635-A-G		not specified	Uncertain significance (Aug 10, 2023)
12-27401258-G-A		not specified	Uncertain significance (May 09, 2023)
12-27401267-A-G		not specified	Uncertain significance (Aug 12, 2021)
12-27401323-T-G		not specified	Uncertain significance (Dec 03, 2021)
12-27401587-T-C		not specified	Uncertain significance (Feb 06, 2023)
12-27403478-G-A		not specified	Uncertain significance (Sep 23, 2023)
12-27403489-G-A		not specified	Uncertain significance (May 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BMAL2	protein_coding	protein_coding	ENST00000266503	17	90455

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.04e-10	0.961	125151	7	590	125748	0.00238

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.389	306	326	0.939	0.0000158	4192
Missense in Polyphen		99	113.8	0.86997		1495
Synonymous	1.15	94	109	0.860	0.00000525	1156
Loss of Function	2.11	20	33.1	0.604	0.00000159	459

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0313	0.0313
Ashkenazi Jewish	0.00	0.00
East Asian	0.000547	0.000489
Finnish	0.00	0.00
European (Non-Finnish)	0.000468	0.000466
Middle Eastern	0.000547	0.000489
South Asian	0.0000327	0.0000327
Other	0.00164	0.00163

dbNSFP

Source: dbNSFP

• 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. The CLOCK-ARNTL2/BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. {ECO:0000269|PubMed:11018023, ECO:0000269|PubMed:12738229, ECO:0000269|PubMed:14672706}.

Recessive Scores

• pRec: 0.0965

Intolerance Scores

• loftool: 0.697
• rvis_EVS: 0.55
• rvis_percentile_EVS: 81.55

Haploinsufficiency Scores

• pHI: 0.325
• hipred: Y
• hipred_score: 0.532
• ghis: 0.499

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.828

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Arntl2

Gene ontology

• Biological process: regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;circadian rhythm;entrainment of circadian clock;positive regulation of circadian rhythm;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus;transcription factor complex;nucleolus;cytoplasm
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein dimerization activity;E-box binding