GSK3B
glycogen synthase kinase 3 beta
Basic information
Region (hg38): 3:119821320-120094994
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (23 variants)
- Inborn genetic diseases (4 variants)
- Primary dilated cardiomyopathy (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GSK3B 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 | 5 | |||||
| missense | 4 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 18 | 18 | ||||
| Total | 0 | 0 | 4 | 1 | 22 |
Variants in GSK3B
This is a list of pathogenic ClinVar variants found in the GSK3B region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-119843259-C-T | Benign (Jun 08, 2018) | |||
| 3-119843267-T-C | not specified | Uncertain significance (Sep 27, 2021) | ||
| 3-119843303-G-A | not specified | Uncertain significance (May 03, 2023) | ||
| 3-119843538-T-A | Benign (Jun 15, 2019) | |||
| 3-119863444-A-G | Benign (Jun 21, 2019) | |||
| 3-119866592-G-A | Primary dilated cardiomyopathy • not specified | Uncertain significance (Aug 05, 2023) | ||
| 3-119866607-A-C | not specified | Uncertain significance (May 23, 2023) | ||
| 3-119866843-T-A | Benign (Jun 14, 2019) | |||
| 3-119876186-C-T | Benign (Jun 15, 2019) | |||
| 3-119876204-A-G | Benign (Jun 15, 2019) | |||
| 3-119876656-A-G | Benign (Jun 14, 2019) | |||
| 3-119905634-C-T | Benign (Jun 15, 2019) | |||
| 3-119912502-T-G | Benign (Aug 16, 2019) | |||
| 3-119912967-A-G | Benign (Jun 14, 2019) | |||
| 3-119916215-T-C | Benign (Jul 25, 2019) | |||
| 3-119923394-C-T | Benign (Jun 18, 2018) | |||
| 3-119947419-C-T | Benign (Jun 14, 2019) | |||
| 3-120001977-A-G | Benign (Jun 15, 2019) | |||
| 3-120002056-T-C | not specified | Uncertain significance (Feb 15, 2024) | ||
| 3-120002133-T-A | Benign (Jun 15, 2019) | |||
| 3-120002229-G-A | Likely benign (Apr 10, 2018) | |||
| 3-120002324-T-C | Benign (Jun 14, 2019) | |||
| 3-120002344-A-AT | Benign (Aug 15, 2019) | |||
| 3-120002389-T-A | Benign (Jun 15, 2019) | |||
| 3-120002424-C-T | Benign (Jun 21, 2019) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GSK3B | protein_coding | protein_coding | ENST00000316626 | 12 | 273095 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.956 | 0.0443 | 125737 | 0 | 6 | 125743 | 0.0000239 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.80 | 117 | 239 | 0.490 | 0.0000125 | 2761 |
| Missense in Polyphen | 20 | 89.682 | 0.22301 | 1030 | ||
| Synonymous | 0.608 | 80 | 87.2 | 0.917 | 0.00000436 | 886 |
| Loss of Function | 4.14 | 4 | 27.4 | 0.146 | 0.00000172 | 305 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000909 | 0.0000907 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000354 | 0.0000352 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation. Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including ARNTL/BMAL1, CLOCK and PER2. Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation. Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation. Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity. Phosphorylates MYCN in neuroblastoma cells which may promote its degradation (PubMed:24391509). {ECO:0000269|PubMed:11430833, ECO:0000269|PubMed:12554650, ECO:0000269|PubMed:14690523, ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:16484495, ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:1846781, ECO:0000269|PubMed:19946213, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:22514281, ECO:0000269|PubMed:24391509, ECO:0000269|PubMed:8397507, ECO:0000269|PubMed:9072970, ECO:0000269|PubMed:9819408}.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Gastric cancer - Homo sapiens (human);Focal adhesion - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Cell cycle - Homo sapiens (human);Influenza A - Homo sapiens (human);Breast cancer - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Axon guidance - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Basal cell carcinoma - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Measles - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Endometrial cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Hedgehog signaling pathway - Homo sapiens (human);EGF-Core;WNT-Core;HH-Core;TGF-Core;EGF-Ncore;Cell Cycle;IL-5 Signaling Pathway;Androgen receptor signaling pathway;Energy Metabolism;MicroRNAs in cardiomyocyte hypertrophy;Leptin signaling pathway;TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway;Prolactin Signaling Pathway;Regulation of Microtubule Cytoskeleton;IL-7 Signaling Pathway;Alzheimers Disease;Neural Crest Differentiation;IL17 signaling pathway;B Cell Receptor Signaling Pathway;Corticotropin-releasing hormone signaling pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Cardiac Progenitor Differentiation;T-Cell Receptor and Co-stimulatory Signaling;JAK-STAT;Cardiac Hypertrophic Response;Hair Follicle Development- Induction (Part 1 of 3);Focal Adhesion;Copper homeostasis;Melatonin metabolism and effects;Wnt Signaling Pathway;IL-6 signaling pathway;Wnt-beta-catenin Signaling Pathway in Leukemia;Regulation of Wnt-B-catenin Signaling by Small Molecule Compounds;Association Between Physico-Chemical Features and Toxicity Associated Pathways;PI3K-AKT-mTOR signaling pathway and therapeutic opportunities;Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;Regulation of Apoptosis by Parathyroid Hormone-related Protein;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Chemokine signaling pathway;ESC Pluripotency Pathways;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;miRNA regulation of prostate cancer signaling pathways;Wnt Signaling Pathway and Pluripotency;PI3K-AKT-mTOR - VitD3 Signalling;Endometrial cancer;PI3K-Akt Signaling Pathway;Chromosomal and microsatellite instability in colorectal cancer;EMT transition in Colorectal Cancer;Wnt Signaling Pathway;Insulin Signaling;Glycogen Metabolism;Notch Signaling Pathway;Senescence and Autophagy in Cancer;ErbB Signaling Pathway;DNA Damage Response (only ATM dependent);Developmental Biology;TWEAK;Degradation of beta-catenin by the destruction complex;B-WICH complex positively regulates rRNA expression;Positive epigenetic regulation of rRNA expression;Transcriptional regulation by RUNX2;Notch;Disease;Signaling by WNT;Signal Transduction;Epigenetic regulation of gene expression;Gene expression (Transcription);GLI3 is processed to GLI3R by the proteasome;wnt signaling pathway;cell cycle: g1/s check point;segmentation clock;deregulation of cdk5 in alzheimers disease;nfat and hypertrophy of the heart ;multi-step regulation of transcription by pitx2;phosphoinositides and their downstream targets;skeletal muscle hypertrophy is regulated via akt-mtor pathway;Generic Transcription Pathway;Prolactin;Regulation of HSF1-mediated heat shock response;Cellular responses to stress;RNA Polymerase II Transcription;TCR;Hedgehog;KitReceptor;insulin Mam;inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages;Disassembly of the destruction complex and recruitment of AXIN to the membrane;BCR;AndrogenReceptor;regulation of eif2;Aurora A signaling;Ubiquitin-dependent degradation of Cyclin D1;Ubiquitin-dependent degradation of Cyclin D;S Phase;Degradation of GLI2 by the proteasome;Hedgehog ,off, state;Cellular responses to external stimuli;IL-7 signaling;Signaling by Hedgehog;TGF_beta_Receptor;BDNF;EGFR1;Glucocorticoid receptor regulatory network;Semaphorin interactions;PIP3 activates AKT signaling;JAK STAT pathway and regulation;Cellular response to heat stress;EPO signaling;Beta-catenin phosphorylation cascade;IL3;Gastrin;C-MYC pathway;Axon guidance;IL5;Leptin;Constitutive Signaling by AKT1 E17K in Cancer;PI3K/AKT Signaling in Cancer;CRMPs in Sema3A signaling;Cell Cycle;IL6;Wnt;IL-7;Integrin-linked kinase signaling;AKT phosphorylates targets in the cytosol;VEGF;Cell Cycle, Mitotic;Wnt Canonical;Intracellular signaling by second messengers;Degradation of beta catenin;LPA receptor mediated events;Diseases of signal transduction;CDC42 signaling events;Insulin-mediated glucose transport;Validated transcriptional targets of deltaNp63 isoforms;Reelin signaling pathway;TCF dependent signaling in response to WNT;Canonical Wnt signaling pathway;Regulation of Androgen receptor activity;Signaling events mediated by Stem cell factor receptor (c-Kit);Role of Calcineurin-dependent NFAT signaling in lymphocytes;Class I PI3K signaling events mediated by Akt;Trk receptor signaling mediated by PI3K and PLC-gamma;Wnt Mammals;Hedgehog signaling events mediated by Gli proteins;Presenilin action in Notch and Wnt signaling;p53 pathway;LKB1 signaling events;Regulation of RUNX2 expression and activity;insulin
(Consensus)
Recessive Scores
- pRec
- 0.986
Intolerance Scores
- loftool
- 0.157
- rvis_EVS
- -0.29
- rvis_percentile_EVS
- 32.94
Haploinsufficiency Scores
- pHI
- 0.979
- hipred
- Y
- hipred_score
- 0.783
- ghis
- 0.609
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.988
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Gsk3b
- 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); digestive/alimentary 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); liver/biliary system phenotype; normal 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); 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); endocrine/exocrine gland phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- gsk3b
- Affected structure
- heart valve
- Phenotype tag
- abnormal
- Phenotype quality
- aplastic
Gene ontology
- Biological process
- epithelial to mesenchymal transition;positive regulation of cell-matrix adhesion;glycogen metabolic process;protein phosphorylation;ER overload response;dopamine receptor signaling pathway;circadian rhythm;positive regulation of gene expression;positive regulation of mitochondrion organization;Wnt signaling pathway;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;hippocampus development;establishment of cell polarity;maintenance of cell polarity;regulation of axon extension;neuron projection development;negative regulation of protein complex assembly;positive regulation of protein complex assembly;negative regulation of protein binding;positive regulation of protein binding;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;negative regulation of phosphoprotein phosphatase activity;regulation of microtubule-based process;intracellular signal transduction;cellular response to interleukin-3;negative regulation of apoptotic process;positive regulation of GTPase activity;negative regulation of glycogen biosynthetic process;positive regulation of protein catabolic process;protein autophosphorylation;positive regulation of protein export from nucleus;regulation of dendrite morphogenesis;regulation of axonogenesis;excitatory postsynaptic potential;regulation of microtubule cytoskeleton organization;negative regulation of calcineurin-NFAT signaling cascade;superior temporal gyrus development;negative regulation of canonical Wnt signaling pathway;extrinsic apoptotic signaling pathway;extrinsic apoptotic signaling pathway in absence of ligand;neuron projection retraction;regulation of cellular response to heat;negative regulation of protein localization to nucleus;positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway;negative regulation of neuron death;positive regulation of neuron death;negative regulation of protein acetylation;negative regulation of dopaminergic neuron differentiation;cellular response to amyloid-beta;positive regulation of protein localization to centrosome;beta-catenin destruction complex assembly;beta-catenin destruction complex disassembly;negative regulation of type B pancreatic cell development;regulation of synaptic vesicle exocytosis;negative regulation of glycogen (starch) synthase activity
- Cellular component
- nucleus;nucleoplasm;cytoplasm;mitochondrion;centrosome;cytosol;plasma membrane;axon;dendrite;beta-catenin destruction complex;postsynapse;glutamatergic synapse;Wnt signalosome
- Molecular function
- RNA polymerase II transcription factor binding;protease binding;p53 binding;protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;beta-catenin binding;kinase activity;protein kinase binding;ubiquitin protein ligase binding;protein kinase A catalytic subunit binding;dynactin binding;tau protein binding;tau-protein kinase activity;NF-kappaB binding