BCL2
BCL2 apoptosis regulator, the group of BCL2 family|Protein phosphatase 1 regulatory subunits
Basic information
Region (hg38): 18:63123346-63320128
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the BCL2 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 | 3 | |||||
| missense | 3 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 3 | 1 | 2 |
Variants in BCL2
This is a list of pathogenic ClinVar variants found in the BCL2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 18-63318171-T-A | not specified | Uncertain significance (Oct 01, 2024) | ||
| 18-63318208-G-A | Likely benign (Aug 15, 2018) | |||
| 18-63318209-A-T | not specified | Uncertain significance (Mar 07, 2024) | ||
| 18-63318269-A-G | Neoplasm | - (-) | ||
| 18-63318329-G-T | not specified | Uncertain significance (Oct 12, 2021) | ||
| 18-63318367-G-A | BCL2-related disorder | Benign (Feb 22, 2019) | ||
| 18-63318596-G-A | not specified | Uncertain significance (Oct 10, 2023) | ||
| 18-63318616-C-G | Neoplasm | - (-) | ||
| 18-63318628-C-G | Neoplasm | - (-) | ||
| 18-63318646-T-C | BCL2-related disorder | Benign (Oct 16, 2019) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| BCL2 | protein_coding | protein_coding | ENST00000398117 | 2 | 196783 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.559 | 0.430 | 117770 | 0 | 2 | 117772 | 0.00000849 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.40 | 94 | 141 | 0.668 | 0.00000669 | 1518 |
| Missense in Polyphen | 29 | 60.607 | 0.47849 | 662 | ||
| Synonymous | -0.283 | 67 | 64.1 | 1.04 | 0.00000309 | 523 |
| Loss of Function | 2.03 | 1 | 6.66 | 0.150 | 2.88e-7 | 65 |
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) | 0.0000190 | 0.0000188 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785). {ECO:0000269|PubMed:17418785, ECO:0000269|PubMed:18570871}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions. {ECO:0000269|PubMed:2875799, ECO:0000269|PubMed:3285301}.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Gastric cancer - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Apoptosis - multiple species - Homo sapiens (human);Protein processing in endoplasmic reticulum - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Necroptosis - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Apoptosis - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Busulfan Pathway, Pharmacodynamics;Colorectal cancer - Homo sapiens (human);Hedgehog signaling pathway - Homo sapiens (human);Vinka Alkaloid Pathway, Pharmacokinetics;IL-5 Signaling Pathway;Influenza A virus infection;TP53 Network;Apoptosis Modulation and Signaling;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Interleukin-11 Signaling Pathway;Corticotropin-releasing hormone signaling pathway;Amyotrophic lateral sclerosis (ALS);Nanoparticle triggered autophagic cell death;Apoptosis;IL-3 Signaling Pathway;Kit receptor signaling pathway;Focal Adhesion;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;Overview of nanoparticle effects;Photodynamic therapy-induced AP-1 survival signaling.;Apoptotic Signaling Pathway;Hematopoietic Stem Cell Gene Regulation by GABP alpha-beta Complex;Regulation of Apoptosis by Parathyroid Hormone-related Protein;VEGFA-VEGFR2 Signaling Pathway;Oxidative Damage;miRNA regulation of prostate cancer signaling pathways;Prion disease pathway;NO-cGMP-PKG mediated Neuroprotection;Interleukin-4 and 13 signaling;apoptotic signaling in response to dna damage;PI3K-Akt Signaling Pathway;Chromosomal and microsatellite instability in colorectal cancer;Hedgehog Signaling Pathway;IL-2 Signaling Pathway;Senescence and Autophagy in Cancer;DNA Damage Response (only ATM dependent);Estrogen signaling pathway;Signal Transduction;inhibition of cellular proliferation by gleevec;prion pathway;telomeres telomerase cellular aging and immortality;melanocyte development and pigmentation pathway;il-7 signal transduction;role of mitochondria in apoptotic signaling;il-2 receptor beta chain in t cell activation;regulation of bad phosphorylation;transcription regulation by methyltransferase of carm1;hiv-1 nef: negative effector of fas and tnf;stress induction of hsp regulation;keratinocyte differentiation;The NLRP1 inflammasome;Inflammasomes;Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways;Activation of BAD and translocation to mitochondria ;Activation of BH3-only proteins;Intrinsic Pathway for Apoptosis;Innate Immune System;Immune System;Apoptosis;Programmed Cell Death;ATF-2 transcription factor network;ceramide signaling pathway;p53 signaling pathway;EGFR1;IL2;Signaling by Nuclear Receptors;IL3;C-MYB transcription factor network;IL2-mediated signaling events;RXR and RAR heterodimerization with other nuclear receptor;Direct p53 effectors;EPO signaling pathway;Estrogen-dependent gene expression;BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members;ESR-mediated signaling;Caspase Cascade in Apoptosis;HIV-1 Nef: Negative effector of Fas and TNF-alpha;IL2 signaling events mediated by STAT5;Validated targets of C-MYC transcriptional repression;IL2 signaling events mediated by PI3K;Signaling events mediated by Stem cell factor receptor (c-Kit);Role of Calcineurin-dependent NFAT signaling in lymphocytes;Ceramide signaling pathway
(Consensus)
Recessive Scores
- pRec
- 0.983
Intolerance Scores
- loftool
- 0.238
- rvis_EVS
- -0.19
- rvis_percentile_EVS
- 39.68
Haploinsufficiency Scores
- pHI
- 0.954
- hipred
- Y
- hipred_score
- 0.800
- ghis
- 0.700
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Bcl2
- Phenotype
- immune system phenotype; renal/urinary system phenotype; digestive/alimentary 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); hearing/vestibular/ear phenotype; vision/eye 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; reproductive 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); pigmentation phenotype; neoplasm; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; craniofacial 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); endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan);
Gene ontology
- Biological process
- protein polyubiquitination;ossification;ovarian follicle development;metanephros development;branching involved in ureteric bud morphogenesis;behavioral fear response;B cell homeostasis;release of cytochrome c from mitochondria;regulation of cell-matrix adhesion;lymphoid progenitor cell differentiation;B cell lineage commitment;response to ischemia;renal system process;protein dephosphorylation;melanin metabolic process;regulation of nitrogen utilization;apoptotic process;humoral immune response;cellular response to DNA damage stimulus;actin filament organization;axonogenesis;female pregnancy;cell aging;male gonad development;extrinsic apoptotic signaling pathway via death domain receptors;intrinsic apoptotic signaling pathway in response to DNA damage;intrinsic apoptotic signaling pathway in response to oxidative stress;response to radiation;response to toxic substance;post-embryonic development;response to iron ion;response to UV-B;response to gamma radiation;regulation of gene expression;negative regulation of autophagy;negative regulation of calcium ion transport into cytosol;regulation of glycoprotein biosynthetic process;mesenchymal cell development;positive regulation of neuron maturation;positive regulation of smooth muscle cell migration;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;cytokine-mediated signaling pathway;cochlear nucleus development;gland morphogenesis;regulation of transmembrane transporter activity;negative regulation of ossification;positive regulation of cell growth;negative regulation of cell growth;melanocyte differentiation;negative regulation of cell migration;positive regulation of B cell proliferation;hair follicle morphogenesis;axon regeneration;regulation of protein stability;endoplasmic reticulum calcium ion homeostasis;glomerulus development;negative regulation of cellular pH reduction;negative regulation of myeloid cell apoptotic process;T cell differentiation in thymus;positive regulation of peptidyl-serine phosphorylation;negative regulation of osteoblast proliferation;response to cytokine;response to nicotine;organ growth;positive regulation of multicellular organism growth;B cell proliferation;cellular response to glucose starvation;response to drug;response to hydrogen peroxide;T cell homeostasis;negative regulation of apoptotic process;positive regulation of catalytic activity;CD8-positive, alpha-beta T cell lineage commitment;regulation of protein homodimerization activity;regulation of protein heterodimerization activity;negative regulation of neuron apoptotic process;ear development;regulation of viral genome replication;positive regulation of melanocyte differentiation;negative regulation of retinal cell programmed cell death;regulation of mitochondrial membrane permeability;focal adhesion assembly;spleen development;thymus development;digestive tract morphogenesis;oocyte development;positive regulation of skeletal muscle fiber development;pigment granule organization;homeostasis of number of cells within a tissue;B cell receptor signaling pathway;response to glucocorticoid;neuron apoptotic process;defense response to virus;regulation of mitochondrial membrane potential;negative regulation of mitochondrial depolarization;regulation of calcium ion transport;transmembrane transport;intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress;cellular response to hypoxia;reactive oxygen species metabolic process;extrinsic apoptotic signaling pathway in absence of ligand;cell-cell adhesion;positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway;negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator;negative regulation of G1/S transition of mitotic cell cycle;negative regulation of reactive oxygen species metabolic process;negative regulation of anoikis;negative regulation of apoptotic signaling pathway;negative regulation of extrinsic apoptotic signaling pathway in absence of ligand;negative regulation of intrinsic apoptotic signaling pathway;positive regulation of intrinsic apoptotic signaling pathway
- Cellular component
- nucleus;nucleoplasm;cytoplasm;mitochondrion;mitochondrial outer membrane;endoplasmic reticulum;endoplasmic reticulum membrane;cytosol;membrane;nuclear membrane;protein-containing complex;myelin sheath;pore complex
- Molecular function
- protease binding;protein binding;transcription factor binding;channel activity;channel inhibitor activity;ubiquitin protein ligase binding;identical protein binding;protein homodimerization activity;sequence-specific DNA binding;protein heterodimerization activity;BH3 domain binding;protein phosphatase 2A binding