GSK3A

glycogen synthase kinase 3 alpha

Basic information

Region (hg38): 19:42226225-42242625

Links

ENSG00000105723 ∙ NCBI:2931 ∙ OMIM:606784 ∙ HGNC:4616 ∙ Uniprot:P49840 ∙ 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 GSK3A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GSK3A 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	1	1	7
missense			16			16
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding						0
Total	0	0	23	1	1

Variants in GSK3A

This is a list of pathogenic ClinVar variants found in the GSK3A region.

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

Position	Type	Phenotype	Significance	ClinVar
19-42226234-C-T		Inborn genetic diseases	Uncertain significance (Sep 20, 2023)
19-42226247-C-T		Inborn genetic diseases	Uncertain significance (Jan 04, 2022)
19-42226273-A-G		not specified	Uncertain significance (Dec 17, 2014)
19-42226297-A-G		Inborn genetic diseases	Uncertain significance (Nov 10, 2022)
19-42226384-G-A		not specified • Inborn genetic diseases	Uncertain significance (Oct 27, 2022)
19-42226403-C-T		Inborn genetic diseases	Uncertain significance (Nov 06, 2023)
19-42226405-G-C		not specified • Inborn genetic diseases	Uncertain significance (Sep 27, 2021)
19-42226417-C-T		ZNF526-related disorder	Likely benign (Sep 05, 2019)
19-42230868-C-A			Uncertain significance (Oct 01, 2023)
19-42232519-G-T		not specified	Uncertain significance (Oct 06, 2021)
19-42232623-G-A			Benign (Dec 31, 2019)
19-42233299-A-C		not specified	Uncertain significance (Aug 08, 2022)
19-42233351-G-C		not specified	Uncertain significance (May 23, 2023)
19-42234636-A-G		not specified	Uncertain significance (Jan 04, 2024)
19-42236901-T-C			Uncertain significance (Nov 01, 2021)
19-42240046-T-C		not specified	Uncertain significance (Dec 28, 2022)
19-42240089-G-A		not specified	Uncertain significance (Jul 09, 2021)
19-42242203-G-A		not specified	Uncertain significance (Feb 05, 2024)
19-42242235-G-C		not specified	Uncertain significance (Jan 04, 2024)
19-42242287-A-C		not specified	Uncertain significance (Jul 06, 2021)
19-42242299-A-C		not specified	Uncertain significance (Oct 06, 2021)
19-42242308-A-C		not specified	Uncertain significance (Jul 27, 2021)
19-42242320-C-G		Primary dilated cardiomyopathy	Uncertain significance (Oct 10, 2016)
19-42242324-C-T		not specified	Uncertain significance (Dec 28, 2023)
19-42242342-C-T		not specified	Uncertain significance (Sep 21, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GSK3A	protein_coding	protein_coding	ENST00000222330	11	12440

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000297	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.22	103	245	0.421	0.0000147	3033
Missense in Polyphen		17	105.53	0.16109		1226
Synonymous	1.04	90	103	0.870	0.00000626	1041
Loss of Function	4.47	0	23.3	0.00	0.00000140	258

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: 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), CTNNB1/beta-catenin, APC and AXIN1. Requires primed phosphorylation of the majority of its substrates. Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. Regulates glycogen metabolism in liver, but not in muscle. May also mediate the development of insulin resistance by regulating activation of transcription factors. In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin. Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease. May be involved in the regulation of replication in pancreatic beta-cells. Is necessary for the establishment of neuronal polarity and axon outgrowth. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. {ECO:0000269|PubMed:12761548, ECO:0000269|PubMed:17229088}.
• Pathway: Dopaminergic synapse - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);IL-5 Signaling Pathway;Sterol Regulatory Element-Binding Proteins (SREBP) signalling;Leptin signaling pathway;B Cell Receptor Signaling Pathway;T-Cell Receptor and Co-stimulatory Signaling;JAK-STAT;Chemical Compounds to monitor Proteins;XBP1(S) activates chaperone genes;Wnt Signaling Pathway;Regulation of Apoptosis by Parathyroid Hormone-related Protein;Angiopoietin Like Protein 8 Regulatory Pathway;Insulin Signaling;Glycogen Metabolism;Disease;Signal Transduction;phosphoinositides and their downstream targets;Ghrelin;BCR;IL-7 signaling;EGFR1;PIP3 activates AKT signaling;JAK STAT pathway and regulation;EPO signaling;IL3;IL5;Leptin;Constitutive Signaling by AKT1 E17K in Cancer;PI3K/AKT Signaling in Cancer;Wnt;IL-7;AKT phosphorylates targets in the cytosol;VEGF;Intracellular signaling by second messengers;Degradation of beta catenin;Diseases of signal transduction;Canonical Wnt signaling pathway;FOXM1 transcription factor network;Class I PI3K signaling events mediated by Akt (Consensus)

Recessive Scores

• pRec: 0.820

Intolerance Scores

• rvis_EVS: -0.32
• rvis_percentile_EVS: 31.46

Haploinsufficiency Scores

• pHI: 0.450
• hipred: Y
• hipred_score: 0.677
• ghis: 0.669

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.997

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gsk3a
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; craniofacial 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); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype

Gene ontology

• Biological process: regulation of systemic arterial blood pressure;cardiac left ventricle morphogenesis;glycogen metabolic process;protein phosphorylation;dopamine receptor signaling pathway;nervous system development;insulin receptor signaling pathway;positive regulation of gene expression;negative regulation of UDP-glucose catabolic process;Wnt signaling pathway;peptidyl-threonine phosphorylation;positive regulation of protein ubiquitination;negative regulation of TOR signaling;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;cellular response to insulin stimulus;cellular response to interleukin-3;IRE1-mediated unfolded protein response;proteasome-mediated ubiquitin-dependent protein catabolic process;negative regulation of glycogen biosynthetic process;positive regulation of protein catabolic process;positive regulation of heart contraction;negative regulation of glucose import;negative regulation of insulin receptor signaling pathway;excitatory postsynaptic potential;negative regulation of cell growth involved in cardiac muscle cell development;positive regulation of adenylate cyclase-activating adrenergic receptor signaling pathway;negative regulation of canonical Wnt signaling pathway;extrinsic apoptotic signaling pathway;extrinsic apoptotic signaling pathway in absence of ligand;positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway;positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway;positive regulation of amyloid-beta formation;regulation of autophagy of mitochondrion;positive regulation of protein targeting to mitochondrion;negative regulation of glycogen synthase activity, transferring glucose-1-phosphate;negative regulation of type B pancreatic cell development;negative regulation of glycogen (starch) synthase activity;positive regulation of glycogen (starch) synthase activity
• Cellular component: mitochondrion;cytosol;beta-catenin destruction complex;neuronal cell body;apical dendrite;postsynapse;proximal dendrite
• Molecular function: protein serine/threonine kinase activity;signaling receptor binding;protein binding;ATP binding;protein kinase A catalytic subunit binding;tau protein binding;tau-protein kinase activity