GSK3B

Summary

GSK3B (glycogen synthase kinase 3 beta, HGNC:4617) is a protein-coding gene on chromosome 3q13.33, encoding Glycogen synthase kinase-3 beta (P49841). 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….

The protein encoded by this gene is a serine-threonine kinase belonging to the glycogen synthase kinase subfamily. It is a negative regulator of glucose homeostasis and is involved in energy metabolism, inflammation, ER-stress, mitochondrial dysfunction, and apoptotic pathways. Defects in this gene have been associated with Parkinson disease and Alzheimer disease.

Source: NCBI Gene 2932 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Definitive, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 76 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes — 67 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Transcription factor: yes — 10 downstream targets (CollecTRI)
• MANE Select transcript: NM_001146156

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4617
Approved symbol	GSK3B
Name	glycogen synthase kinase 3 beta
Location	3q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000082701
Ensembl biotype	protein_coding
OMIM	605004
Entrez	2932

Gene structure

Transcript identifiers

Ensembl transcripts: 71 — 26 protein_coding, 21 nonsense_mediated_decay, 20 protein_coding_CDS_not_defined, 4 retained_intron

ENST00000264235, ENST00000316626, ENST00000473886, ENST00000474830, ENST00000650344, ENST00000676566, ENST00000676650, ENST00000676722, ENST00000676723, ENST00000676733, ENST00000676743, ENST00000676775, ENST00000676844, ENST00000676887, ENST00000676890, ENST00000676910, ENST00000676948, ENST00000677034, ENST00000677046, ENST00000677067, ENST00000677069, ENST00000677128, ENST00000677169, ENST00000677338, ENST00000677362, ENST00000677400, ENST00000677423, ENST00000677483, ENST00000677502, ENST00000677530, ENST00000677648, ENST00000677716, ENST00000677788, ENST00000677804, ENST00000677870, ENST00000677875, ENST00000677878, ENST00000677885, ENST00000677903, ENST00000677959, ENST00000677995, ENST00000678013, ENST00000678064, ENST00000678121, ENST00000678159, ENST00000678181, ENST00000678210, ENST00000678245, ENST00000678286, ENST00000678342, ENST00000678350, ENST00000678377, ENST00000678439, ENST00000678509, ENST00000678561, ENST00000678608, ENST00000678678, ENST00000678754, ENST00000678787, ENST00000678967, ENST00000679066, ENST00000679068, ENST00000679085, ENST00000679131, ENST00000679164, ENST00000679188, ENST00000679194, ENST00000679201, ENST00000679206, ENST00000899265, ENST00000899266

RefSeq mRNA: 3 — MANE Select: NM_001146156 NM_001146156, NM_001354596, NM_002093

CCDS: CCDS2996, CCDS54628, CCDS93346

Canonical transcript exons

ENST00000264235 — 11 exons

Exon	Start	End
ENSE00001149998	119843255	119843353
ENSE00001206838	120093347	120094447
ENSE00001863284	119821321	119826855
ENSE00002371679	119923373	119923483
ENSE00002373333	120002046	120002239
ENSE00002375726	119947268	119947351
ENSE00002376570	119916044	119916174
ENSE00002378955	119905755	119905852
ENSE00002423863	119912704	119912810
ENSE00003476725	119876413	119876508
ENSE00003549723	119863419	119863605

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 98.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.7487 / max 357.5144, expressed in 1819 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44044	25.2393	1817
44045	5.8006	1718
44040	2.0009	693
44046	1.9290	1236
44047	1.0313	593
44043	0.9428	680
44042	0.6717	329
44038	0.5186	254
44039	0.4482	191
44041	0.1662	60

Top tissues by expression

299 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.84	gold quality
adrenal tissue	UBERON:0018303	97.76	gold quality
colonic epithelium	UBERON:0000397	96.96	gold quality
sural nerve	UBERON:0015488	96.74	gold quality
buccal mucosa cell	CL:0002336	95.66	gold quality
upper leg skin	UBERON:0004262	95.48	gold quality
cortical plate	UBERON:0005343	95.32	gold quality
tongue squamous epithelium	UBERON:0006919	95.09	gold quality
ventricular zone	UBERON:0003053	94.73	gold quality
ganglionic eminence	UBERON:0004023	94.54	gold quality
postcentral gyrus	UBERON:0002581	94.20	gold quality
left testis	UBERON:0004533	93.97	gold quality
parietal lobe	UBERON:0001872	93.81	gold quality
right testis	UBERON:0004534	93.70	gold quality
testis	UBERON:0000473	93.56	gold quality
skin of hip	UBERON:0001554	93.42	gold quality
superior frontal gyrus	UBERON:0002661	92.99	gold quality
corpus epididymis	UBERON:0004359	92.83	gold quality
islet of Langerhans	UBERON:0000006	92.77	gold quality
middle temporal gyrus	UBERON:0002771	92.75	gold quality
monocyte	CL:0000576	92.61	gold quality
blood	UBERON:0000178	92.57	gold quality
tendon	UBERON:0000043	92.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.29	gold quality
tonsil	UBERON:0002372	92.25	gold quality
skin of abdomen	UBERON:0001416	92.22	gold quality
superior vestibular nucleus	UBERON:0007227	92.18	gold quality
corpus callosum	UBERON:0002336	92.14	gold quality
mononuclear cell	CL:0000842	92.05	gold quality
leukocyte	CL:0000738	91.94	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.28

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

10 targets.

Target	Regulation
CCND1	Activation
CDKN1A	Repression
LGALS3	Activation
MMP9	Activation
MYH6	Activation
NR3C1	Activation
POU5F1	Repression
RELA	Activation
SOX2	Repression
TNNT2	Activation

Upstream regulators (CollecTRI, top): AP1, AR, ARID4B, CDX2, CEBPA, CEBPB, CREB1, EGR1, ELF1, ETS2, FOXO3, HNF4A, KAT7, KLF6, MEF2A, MITF, MYB, MYC, NFATC4, NFE2L2, NFKB1, NFKBIA, PAX3, PITX2, POU4F2, PPARA, RFX2, RFX3, SNAI1, SP3, STAT3, TFCP2, TP53, VEZF1

miRNA regulators (miRDB)

375 targeting GSK3B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-513B-5P	99.99	69.96	2150

Literature-anchored findings (GeneRIF, showing 40)

• The intracellular distribution of GSK-3 beta is dynamically regulated by signaling cascades, and apoptotic stimuli cause increased nuclear levels of GSK-3 beta, which facilitates interactions with nuclear substrates. (PMID:11495916)
• Protein kinase A enhances, whereas glycogen synthase kinase-3 beta inhibits, the activity of the exon 2-encoded transactivator domain of heterogeneous nuclear ribonucleoprotein D in a hierarchical fashion. (PMID:11903055)
• Arg(96) mutant has a dominant-negative effect on GSK-3beta-dependent phosphorylation of beta-catenin and targeting of beta-catenin for degradation requires prior priming through phosphorylation of Ser(45) (PMID:11967263)
• signaling systems determining cell fate appear to be important targets of mood stabilizers, and these may include signaling pathways encompassing GSK3beta, including transcription factors regulated by GSK3beta(REVIEW) (PMID:11986994)
• reacts with p53 protein after dna damage (PMID:12048243)
• Human serum and glucocorticoid-inducible kinase-like kinase (SGKL) phosphorylates glycogen syntheses kinase 3 beta (GSK-3beta) at serine-9 through direct interaction (PMID:12054501)
• improves insulin action and glucose metabolism in skeletal muscle (PMID:12086949)
• GSK3b binds to and phosphorylates serine493 in glutamate E segment of NEFH (PMID:12130654)
• A-kinase anchoring protein AKAP220 binds to this enzyme and mediates protein kinase A-dependent inhibition of GSK-3beta (PMID:12147701)
• GSK3beta functions at the nodal point of converging signaling pathways in endothelial cells to regulate vessel growth through its control of vascular cell migration and survival. (PMID:12167628)
• Glycogen synthase kinase 3 beta influenced post-natal maturation and differentiation of neurons in vivo in transgenic mice that overexpress a constitutively active GSK-3beta. (PMID:12182887)
• Data show that endoplasmic reticulum stress induced by thapsigargin not only activated the apoptosis effector caspase-3 but also caused a large and prolonged increase in the activity of glycogen synthase kinase-3beta. (PMID:12228224)
• GSK-3 beta is inhibited by endothelial cell costimulation, allowing nuclear accumulation of NFAT and prolonging IL-2 synthesis in the presence of cyclosporin A. (PMID:12244165)
• inhibition of GSK3beta activity appears to trigger nuclear accumulation of cyclin D1 and cell cycle progression (PMID:12364325)
• GSK3b expresion is regulated by reelin (PMID:12376533)
• Fresh lymphocytes from schizophrenic patients showed no difference in GSK-3 alpha and GSK-3beta mRNA levels, GSK-3beta protein levels, or total GSK-3 (alpha+beta) enzyme activity compared with findings in control subjects. (PMID:12379450)
• role in phosphorylating tau protein (PMID:12387894)
• Data report the crystal structure of glycogen synthase kinase 3beta (GSK3beta) in complex with a minimal GSK3beta-binding segment of axin, at 2.4 A resolution. (PMID:12554650)
• plays a role in Alzheimer disease and other CNS disorders (REVIEW) (PMID:12566926)
• GSK3 beta functions as a natural activator of MEKK1 (PMID:12584189)
• Messenger RNA of beta-catenin and Tcf-4, but not GSK-3beta, was found to be overexpressed in HCC(hepatocellular carcinoma). (PMID:12603528)
• role in mouse hepatic carcinogenesis (PMID:12663502)
• first demonstration that glycogen synthase kinase-3beta associates with type 1 protein phosphatase/inhibitor-2 (PP1C/I-2) complex and phosphorylates I-2 at T72 in intact cells (PMID:12761178)
• Cell adhesion to the extracellular matrix protein fibronectin modulates radiation-dependent G2 phase arrest and involve this enzyme in vitro. (PMID:12778079)
• GSK-3 regulates its own phosphorylation status (PMID:12796505)
• manipulation of GSK-3beta activity may be a mechanism by which HHV-8 latency-associated nuclear antigen (LANA) may modify transcriptional activity and contribute to the phenotype of HHV-8 primary effusion lymphoma. (PMID:12829841)
• molecular cross-talk between glycogen synthase kinase-3 beta (GSK-3 beta) and the p105 precursor of the NF-kappa B p50 subunit (PMID:12871932)
• glycogen synthase kinase-3beta is suppressed by Akt in prostate cancer cells which leads to the phosphorylation of cAMP-response element-binding protein (PMID:12900420)
• Overexpression of phospho-GSK-3beta is associated with hepatocellular carcinoma (PMID:12969793)
• possible role of GSK-3 beta, a pro-apoptotic factor participating in signal transduction involved in cell survival, is discussed in relation to schizophrenia (PMID:14518171)
• Increased expression of glycogen synthase kinase 3 is associated with ovarian epithelial cell transformation and in tumour progression (PMID:14520463)
• role in binding to and promoting action of p53 (PMID:14523002)
• multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation (PMID:14536078)
• GSK3beta is a potential regulator of platelet function (PMID:14550568)
• activation of Csk and GSK-3beta by Galphaq may contribute to the physiological and pathological effects of Gq-coupled receptors (PMID:14561750)
• a mechanism involving GSK-3beta activation may be responsible for tumor necrosis factor-related apoptosis-inducing ligand resistance in prostate cancer cells (PMID:14617795)
• TSH/cAMP-stimulated p70S6 kinase activity and cell proliferation is regulated by Rap1GAP in thyroid cells (PMID:14660640)
• CF101 inhibits human colon carcinoma growth in mice via modulation of GSK3B. (PMID:14691449)
• GSK3B regulates the cytoskeleton and translocation of Rac1 in keratinocyte lamellipodia. (PMID:14729058)
• No association was detected between GSK3-beta -50 T/C SNP and the presence of bipolar illness. Homozygotes for the wild variant (T/T) showed an earlier age at onset than carriers of the mutant allele (F=5.53, d.f.=2,182, P=0.0047). (PMID:14729229)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	gsk3ba	ENSDARG00000017803
danio_rerio	gsk3bb	ENSDARG00000052468
mus_musculus	Gsk3b	ENSMUSG00000022812
rattus_norvegicus	Gsk3b	ENSRNOG00000002833
drosophila_melanogaster	sgg	FBGN0003371
drosophila_melanogaster	gskt	FBGN0046332
caenorhabditis_elegans	gsk-3	WBGENE00001746

Paralogs (1): GSK3A (ENSG00000105723)

Protein

Protein identifiers

Glycogen synthase kinase-3 beta — P49841 (reviewed: P49841)

Alternative names: Serine/threonine-protein kinase GSK3B

All UniProt accessions (41): P49841, A0A3B3ITW1, A0A7I2V2I5, A0A7I2V2K7, A0A7I2V2N4, A0A7I2V2T2, A0A7I2V2U4, A0A7I2V2V4, A0A7I2V2Y0, A0A7I2V3A4, A0A7I2V3D8, A0A7I2V3G9, A0A7I2V3J4, A0A7I2V3K8, A0A7I2V3N7, A0A7I2V3S5, A0A7I2V3T3, A0A7I2V3Z5, A0A7I2V432, A0A7I2V441, A0A7I2V4F3, A0A7I2V4G2, A0A7I2V4W7, A0A7I2V4X2, A0A7I2V4X3, A0A7I2V589, A0A7I2V5B5, A0A7I2V5G5, A0A7I2V5K9, A0A7I2V5M2, A0A7I2V5P4, A0A7I2V606, A0A7I2V626, A0A7I2V675, A0A7I2YQ81, A0A7I2YQB0, A0A7I2YQG6, A0A7I2YQK0, A0A7I2YQK2, A0A7I2YQU1, Q6FI27

UniProt curated annotations — full annotation on UniProt →

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 (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 inhibition of its activity. Phosphorylates SIK1 at ‘Thr-182’, leading to sustainment of its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SNAI1, leading to its 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 BMAL1, CLOCK and PER2. Phosphorylates FBXL2 at ‘Thr-404’ and primes it for ubiquitination by the SCF(FBXO3) complex and proteasomal degradation. Phosphorylates CLOCK AT ‘Ser-427’ and targets it for proteasomal degradation. Phosphorylates 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. Regulates the circadian rhythmicity of hippocampal long-term potentiation and BMAL1 and PER2 expression. Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, activating KAT5/TIP60 acetyltransferase activity and promoting acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer. Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation. Phosphorylates E2F1, promoting the interaction between E2F1 and USP11, stabilizing E2F1 and promoting its activity. Phosphorylates mTORC2 complex component RICTOR at ‘Ser-1235’ in response to endoplasmic stress, inhibiting mTORC2. Phosphorylates mTORC2 complex component RICTOR at ‘Thr-1695’ which facilitates FBXW7-mediated ubiquitination and subsequent degradation of RICTOR. Phosphorylates FXR1, promoting FXR1 ubiquitination by the SCF(FBXO4) complex and FXR1 degradation by the proteasome. Phosphorylates interleukin-22 receptor subunit IL22RA1, preventing its proteasomal degradation. Phosphorylates and inhibits the CTP synthase and protein-asparagine deamidase activities of CTPS1. Phosphorylates DSP at multiple sequential serine residues in the C-terminus tail, promoting its recruitment to developing desmosome cell-cell junctions.

Subunit / interactions. Monomer. Interacts with ARRB2, DISC1 and ZBED3. Interacts with CABYR, MMP2, MUC1, NIN and PRUNE1. Interacts with AXIN1; the interaction mediates hyperphosphorylation of CTNNB1 leading to its ubiquitination and destruction. Interacts with and phosphorylates SNAI1. Interacts with DNM1L (via a C-terminal domain). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B. Interacts with SGK3. Interacts with DAB2IP (via C2 domain); the interaction stimulates GSK3B kinase activation. Interacts (via C2 domain) with PPP2CA. Interacts with the CLOCK-BMAL1 heterodimer. Interacts with the BMAL1. Interacts with CTNND2. Interacts with NCYM. The complex composed, at least, of APC, CTNNB1 and GSK3B interacts with JPT1; the interaction requires the inactive form of GSK3B (phosphorylated at ‘Ser-9’). Forms a complex composed of PRKAR2A or PRKAR2B, GSK3B and GSKIP through GSKIP interaction; facilitates PKA-induced phosphorylation and regulates GSK3B activity. Interacts with GSKIP. Interacts with GID8. Interacts with PIWIL2. Interacts with LMBR1L. Interacts with DDX3X. Interacts with BIRC2. Interacts with TNFRSF10B; TNFRSF10B stimulation inhibits GSK3B kinase activity. Interacts with RICTOR; the interaction results in phosphorylation of RICTOR at ‘Thr-1695’ by GSK3B which facilitates FBXW7-mediated ubiquitination and subsequent degradation of RICTOR. Found in a complex with SLC39A6, SLC39A10 and with GSK3B that controls NCAM1 phosphorylation. Interacts with PKP3 (via ARM repeats); the interaction may be involved in PKP3 protein degradation.

Subcellular location. Cytoplasm. Nucleus. Cell membrane.

Tissue specificity. Expressed in testis, thymus, prostate and ovary and weakly expressed in lung, brain and kidney. Colocalizes with EIF2AK2/PKR and TAU in the Alzheimer disease (AD) brain.

Post-translational modifications. Phosphorylated by AKT1 and ILK1. Upon insulin-mediated signaling, the activated PKB/AKT1 protein kinase phosphorylates and deactivates GSK3B, resulting in the dephosphorylation and activation of GYS1. Activated by phosphorylation at Tyr-216. Inactivated by phosphorylation at Ser-9. Phosphorylated in a circadian manner in the hippocampus. Mono-ADP-ribosylation by PARP10 negatively regulates kinase activity. Palmitoylated. Palmitoylation by ZDHHC4 prevents AKT1-mediated phosphorylation.

Activity regulation. Activated by phosphorylation at Tyr-216. In response to insulin, inhibited by phosphorylation at Ser-9 by PKB/AKT1 and RPS6KA3; phosphorylation at this site causes a conformational change, preventing access of substrates to the active site. Inhibited by IL22 treatment which also triggers phosphorylation at Ser-9, promoting inactivation. Inhibited by lithium.

Miscellaneous. Higher expression and activity of GSK3B are found in the skeletal muscle (vastus lateralis) of patients with type 2 diabetes. Several potent GSK3 (GSK3A and GSK3B) inhibitors have been identified and characterized in preclinical models for treatments of type 2 diabetes. May play a specific role in axon growth and neurite outgrowth. Reduced binding to AXIN1, reduced ability to phosphorylate MAPT/TAU.

Similarity. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P49841-1	1, GSK-3beta1	yes
P49841-2	2, GSK-3beta2, neuron-specific

RefSeq proteins (3): NP_001139628, NP_001341525, NP_002084 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR039192	STKc_GSK3	Domain
IPR050591	GSK-3	Family

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.11.26 — tau-protein kinase (BRENDA: 18 organisms, 200 substrates, 549 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 4 shown:

• L-seryl-[tau protein] + ATP = O-phospho-L-seryl-[tau protein] + ADP + H(+) (RHEA:12801)
• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)
• L-threonyl-[tau protein] + ATP = O-phospho-L-threonyl-[tau protein] + ADP + H(+) (RHEA:53904)

UniProt features (65 total): helix 19, strand 17, modified residue 5, mutagenesis site 5, turn 5, compositionally biased region 3, region of interest 2, sequence conflict 2, binding site 2, chain 1, domain 1, lipid moiety-binding region 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

122 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9X2V	X-RAY DIFFRACTION	1.39
1O6L	X-RAY DIFFRACTION	1.6
9X2Q	X-RAY DIFFRACTION	1.68
1O6K	X-RAY DIFFRACTION	1.7
9X2X	X-RAY DIFFRACTION	1.79
1J1B	X-RAY DIFFRACTION	1.8
2JDO	X-RAY DIFFRACTION	1.8
7SXJ	X-RAY DIFFRACTION	1.85
3QKL	X-RAY DIFFRACTION	1.9
9X2W	X-RAY DIFFRACTION	1.92
2X39	X-RAY DIFFRACTION	1.93
1Q5K	X-RAY DIFFRACTION	1.94
9X2Y	X-RAY DIFFRACTION	1.96
4AFJ	X-RAY DIFFRACTION	1.98
3CQW	X-RAY DIFFRACTION	2
6Y9S	X-RAY DIFFRACTION	2.03
4PTE	X-RAY DIFFRACTION	2.03
7B6F	X-RAY DIFFRACTION	2.05
9X2U	X-RAY DIFFRACTION	2.07
6Y9R	X-RAY DIFFRACTION	2.08
7SXH	X-RAY DIFFRACTION	2.09
1J1C	X-RAY DIFFRACTION	2.1
1Q41	X-RAY DIFFRACTION	2.1
2UW9	X-RAY DIFFRACTION	2.1
4NM3	X-RAY DIFFRACTION	2.1
9PE9	X-RAY DIFFRACTION	2.11
6NPZ	X-RAY DIFFRACTION	2.12
6TCU	X-RAY DIFFRACTION	2.14
8AV1	X-RAY DIFFRACTION	2.15
6V6L	X-RAY DIFFRACTION	2.19

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49841-F1	89.11	0.79

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 181 (proton acceptor)

Ligand- & substrate-binding residues (2): 62–70; 85

Post-translational modifications (6): 9, 216, 389, 390, 402, 14

Mutagenesis-validated functional residues (5):

Position	Phenotype
9	loss of phosphorylation; abolished inhibition of activity, leading to constitutively active.
14	significantly reduced palmitoylation.
85–86	abolished serine/threonine-protein kinase activity.
96	prevents the phosphorylation of phosphate-primed glycogen synthase.
128	abolishes activity toward axin1.

Function

Pathways and Gene Ontology

Reactome pathways

26 pathways

ID	Pathway
R-HSA-195253	Degradation of beta-catenin by the destruction complex
R-HSA-196299	Beta-catenin phosphorylation cascade
R-HSA-198323	AKT phosphorylates targets in the cytosol
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-399956	CRMPs in Sema3A signaling
R-HSA-4641262	Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-5250924	B-WICH complex positively regulates rRNA expression
R-HSA-5339716	Signaling by GSK3beta mutants
R-HSA-5358747	CTNNB1 S33 mutants aren’t phosphorylated
R-HSA-5358749	CTNNB1 S37 mutants aren’t phosphorylated
R-HSA-5358751	CTNNB1 S45 mutants aren’t phosphorylated
R-HSA-5358752	CTNNB1 T41 mutants aren’t phosphorylated
R-HSA-5467337	APC truncation mutants have impaired AXIN binding
R-HSA-5467340	AXIN missense mutants destabilize the destruction complex
R-HSA-5467348	Truncations of AMER1 destabilize the destruction complex
R-HSA-5610783	Degradation of GLI2 by the proteasome
R-HSA-5610785	GLI3 is processed to GLI3R by the proteasome
R-HSA-5674400	Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-69601	Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A
R-HSA-75815	Ubiquitin-dependent degradation of Cyclin D
R-HSA-8939902	Regulation of RUNX2 expression and activity
R-HSA-9683610	Maturation of nucleoprotein
R-HSA-9694631	Maturation of nucleoprotein
R-HSA-9762114	GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity
R-HSA-9929356	GSK3B-mediated proteasomal degradation of PD-L1(CD274)

MSigDB gene sets: 890 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_DENDRITE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_BINDING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_REGULATION_OF_PROTEIN_BINDING, MOOTHA_GLYCOGEN_METABOLISM, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS

GO Biological Process (106): epithelial to mesenchymal transition (GO:0001837), positive regulation of cell-matrix adhesion (GO:0001954), heart valve development (GO:0003170), glycogen metabolic process (GO:0005977), protein phosphorylation (GO:0006468), ER overload response (GO:0006983), mitochondrion organization (GO:0007005), circadian rhythm (GO:0007623), insulin receptor signaling pathway (GO:0008286), positive regulation of autophagy (GO:0010508), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), negative regulation of epithelial to mesenchymal transition (GO:0010719), regulation of neuron projection development (GO:0010975), Wnt signaling pathway (GO:0016055), peptidyl-serine phosphorylation (GO:0018105), viral protein processing (GO:0019082), hippocampus development (GO:0021766), establishment of cell polarity (GO:0030010), maintenance of cell polarity (GO:0030011), cell differentiation (GO:0030154), negative regulation of cell migration (GO:0030336), regulation of axon extension (GO:0030516), neuron projection development (GO:0031175), negative regulation of protein-containing complex assembly (GO:0031333), positive regulation of protein-containing complex assembly (GO:0031334), positive regulation of protein ubiquitination (GO:0031398), negative regulation of TOR signaling (GO:0032007), positive regulation of protein binding (GO:0032092), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), positive regulation of type I interferon production (GO:0032481), regulation of microtubule-based process (GO:0032886), response to endoplasmic reticulum stress (GO:0034976), intracellular signal transduction (GO:0035556), cellular response to interleukin-3 (GO:0036016), regulation of circadian rhythm (GO:0042752), negative regulation of apoptotic process (GO:0043066), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), positive regulation of neuron apoptotic process (GO:0043525), positive regulation of cell differentiation (GO:0045597)

GO Molecular Function (22): protease binding (GO:0002020), p53 binding (GO:0002039), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), beta-catenin binding (GO:0008013), kinase activity (GO:0016301), protein kinase binding (GO:0019901), ubiquitin protein ligase binding (GO:0031625), protein kinase A catalytic subunit binding (GO:0034236), dynactin binding (GO:0034452), tau protein binding (GO:0048156), tau-protein kinase activity (GO:0050321), NF-kappaB binding (GO:0051059), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), scaffold protein binding (GO:0097110), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), MAP kinase activity (GO:0004707), protein binding (GO:0005515), transferase activity (GO:0016740), phosphatase binding (GO:0019902)

GO Cellular Component (20): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), axon (GO:0030424), dendrite (GO:0030425), beta-catenin destruction complex (GO:0030877), presynapse (GO:0098793), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), Wnt signalosome (GO:1990909), early endosome (GO:0005769), late endosome (GO:0005770), Golgi apparatus (GO:0005794), caveola (GO:0005901), focal adhesion (GO:0005925), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Signaling by CTNNB1 phospho-site mutants	4
Hedgehog ‘off’ state	2
Signaling by WNT	1
Degradation of beta-catenin by the destruction complex	1
PIP3 activates AKT signaling	1
Cellular response to heat stress	1
Semaphorin interactions	1
TCF dependent signaling in response to WNT	1
Positive epigenetic regulation of rRNA expression	1
Signaling by WNT in cancer	1
Signaling by APC mutants	1
Signaling by AXIN mutants	1
Signaling by AMER1 mutants	1
PI3K/AKT Signaling in Cancer	1
p53-Independent G1/S DNA Damage Checkpoint	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein binding	3
intracellular membrane-bounded organelle	3
cytoplasm	3
synapse	3
anatomical structure development	2
gene expression	2
regulation of gene expression	2
establishment or maintenance of cell polarity	2
protein kinase activity	2
cytoskeletal protein binding	2
protein serine/threonine kinase activity	2
neuron projection	2
endosome	2
mesenchymal cell differentiation	1
regulation of cell-matrix adhesion	1
cell-matrix adhesion	1
positive regulation of cell-substrate adhesion	1
heart development	1
energy reserve metabolic process	1
glucan metabolic process	1
phosphorylation	1
protein modification process	1
ER-nucleus signaling pathway	1
response to endoplasmic reticulum stress	1
cellular response to biotic stimulus	1
organelle organization	1
rhythmic process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
negative regulation of cell differentiation	1
negative regulation of multicellular organismal process	1
neuron projection development	1

Protein interactions and networks

STRING

8184 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GSK3B	AXIN1	O15169	999
GSK3B	CTNNB1	P35222	999
GSK3B	APC	P25054	997
GSK3B	AXIN2	Q9Y2T1	997
GSK3B	CSNK1A1	P48729	996
GSK3B	BTRC	Q9Y297	996
GSK3B	DVL1	O14640	995
GSK3B	CHKA	P35790	981
GSK3B	TP53	P04637	981
GSK3B	FRAT1	Q92837	979
GSK3B	AMER1	Q5JTC6	969
GSK3B	DISC1	Q9NRI5	969
GSK3B	TCHP	Q9BT92	966
GSK3B	LRP6	O75581	955
GSK3B	MAPT	P10636	943

IntAct

479 interactions, top by confidence:

A	B	Type	Score
AXIN1	GSK3B	psi-mi:“MI:0407”(direct interaction)	0.980
GSK3B	AXIN1	psi-mi:“MI:0217”(phosphorylation reaction)	0.980
AXIN1	GSK3B	psi-mi:“MI:0217”(phosphorylation reaction)	0.980
AXIN1	GSK3B	psi-mi:“MI:0915”(physical association)	0.980
GSK3B	AXIN1	psi-mi:“MI:0915”(physical association)	0.980
AXIN1	GSK3B	psi-mi:“MI:0403”(colocalization)	0.980
GSK3B	AXIN1	psi-mi:“MI:0914”(association)	0.980
GSK3B	CTNNB1	psi-mi:“MI:0915”(physical association)	0.950
GSK3B	CTNNB1	psi-mi:“MI:0217”(phosphorylation reaction)	0.950
CTNNB1	GSK3B	psi-mi:“MI:0217”(phosphorylation reaction)	0.950
CTNNB1	AXIN1	psi-mi:“MI:0914”(association)	0.940
AXIN1	CTNNB1	psi-mi:“MI:0914”(association)	0.940
AKT1	GSK3B	psi-mi:“MI:0407”(direct interaction)	0.830
AKT1	GSK3B	psi-mi:“MI:0914”(association)	0.830
FRAT1	GSK3B	psi-mi:“MI:0407”(direct interaction)	0.810
GSK3A	AXIN1	psi-mi:“MI:0914”(association)	0.800
PPP1CB	CCDC85C	psi-mi:“MI:0914”(association)	0.750
TRAF2	HTRA2	psi-mi:“MI:0914”(association)	0.750
GSK3B	GYS1	psi-mi:“MI:0217”(phosphorylation reaction)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710

BioGRID (1387): GSK3B (Biochemical Activity), GSK3B (Biochemical Activity), HDAC4 (Biochemical Activity), JUN (Biochemical Activity), GSK3B (Biochemical Activity), MAPT (Biochemical Activity), GSK3B (Affinity Capture-Western), GSK3B (Affinity Capture-Western), MAP3K4 (Biochemical Activity), GSK3B (Biochemical Activity), RICTOR (Biochemical Activity), MAPT (Biochemical Activity), KLF5 (Biochemical Activity), MAPT (Biochemical Activity), MAPT (Biochemical Activity)

ESM2 similar proteins: A0A8I3S724, A4IGM9, A4IIW7, A5GFW1, B0VXL7, B6A7Q3, C0RW22, D7UQM5, F4I4F2, O08605, O14965, O35495, O55099, O59790, O70126, O80673, O94921, P18266, P27466, P49841, P59241, P97477, Q00771, Q0VD22, Q13555, Q16566, Q2TA06, Q501Q9, Q58D94, Q5XIT0, Q66JF3, Q6BVA0, Q6C3J2, Q6CWQ4, Q6DE08, Q6DGS3, Q6GPL3, Q6Z8C8, Q755C4, Q7YRC6

Diamond homologs: A2X6X1, A2XFC8, A2XUW1, A2YCH5, A8WIP6, B0Y8W7, B3WFY8, G4N0Z0, G4NH08, G5EFV5, O04160, O23145, O42376, O42781, O80345, P16892, P18266, P20793, P20794, P21127, P23573, P24788, P27638, P38615, P39073, P43288, P43289, P43294, P46892, P47812, P49841, P51136, P51137, P51138, P51139, P54665, P54666, Q00532, Q00859, Q03957

SIGNOR signaling

200 interactions.

A	Effect	B	Mechanism
GSK3B	“down-regulates activity”	NOTCH2	phosphorylation
GSK3B	“down-regulates activity”	HNRNPD	phosphorylation
RPS6KA1	down-regulates	GSK3B	phosphorylation
GSK3B	down-regulates	HNRNPD	phosphorylation
GSK3B	“down-regulates activity”	CTNNB1	phosphorylation
GSK3B	down-regulates	CCNE1	phosphorylation
GSK3B	“down-regulates quantity by destabilization”	MYC	phosphorylation
CDC42	down-regulates	GSK3B	binding
PRKCZ	down-regulates	GSK3B	phosphorylation
STK11	down-regulates	GSK3B
GSK3B	down-regulates	NACA	phosphorylation
GSK3B	down-regulates	SNAI1	phosphorylation
GSK3B	up-regulates	BAX	phosphorylation
MAPK1	down-regulates	GSK3B	phosphorylation
MAPK3	down-regulates	GSK3B	phosphorylation
GSK3B	up-regulates	ESR1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 144 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Downregulation of TGF-beta receptor signaling	5	21.5×	9e-04
Transcriptional regulation by RUNX2	6	16.0×	8e-04
DDX58/IFIH1-mediated induction of interferon-alpha/beta	5	13.4×	4e-03
Toll Like Receptor 3 (TLR3) Cascade	5	10.2×	8e-03
mRNA Polyadenylation	11	10.2×	8e-06
TRIF (TICAM1)-mediated TLR4 signaling	5	10.0×	8e-03
MyD88-independent TLR4 cascade	5	9.7×	8e-03
Activation of NMDA receptors and postsynaptic events	5	9.7×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
canonical NF-kappaB signal transduction	5	15.7×	4e-03
circadian regulation of gene expression	6	12.0×	3e-03
MAPK cascade	8	10.5×	7e-04
cellular response to tumor necrosis factor	7	9.8×	3e-03
protein phosphorylation	9	5.2×	9e-03
DNA damage response	10	4.6×	9e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — STAD.

Clinical variants and AI predictions

ClinVar

76 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	32
Likely benign	2
Benign	22

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3897594	NM_001146156.2(GSK3B):c.472_473dup (p.Lys159fs)	Pathogenic
4267536	NM_001146156.2(GSK3B):c.499C>T (p.Arg167Ter)	Pathogenic
4057156	NM_001146156.2(GSK3B):c.916C>T (p.Arg306Ter)	Likely pathogenic

SpliceAI

4260 predictions. Top by Δscore:

Variant	Effect	Δscore
3:119843349:CAGTT:C	acceptor_gain	1.0000
3:119843351:GTT:G	acceptor_gain	1.0000
3:119843352:TT:T	acceptor_gain	1.0000
3:119843353:TCTAT:T	acceptor_loss	1.0000
3:119843354:C:CC	acceptor_gain	1.0000
3:119843354:CTATA:C	acceptor_loss	1.0000
3:119843355:T:C	acceptor_loss	1.0000
3:119863414:GTTAC:G	donor_loss	1.0000
3:119863415:TTAC:T	donor_loss	1.0000
3:119863416:TAC:T	donor_loss	1.0000
3:119863417:ACCTT:A	donor_loss	1.0000
3:119863418:C:CT	donor_loss	1.0000
3:119863601:AAGAC:A	acceptor_gain	1.0000
3:119863602:AGAC:A	acceptor_gain	1.0000
3:119863603:GAC:G	acceptor_gain	1.0000
3:119863604:AC:A	acceptor_gain	1.0000
3:119863605:CC:C	acceptor_gain	1.0000
3:119863606:C:CA	acceptor_loss	1.0000
3:119863606:C:CC	acceptor_gain	1.0000
3:119863606:C:T	acceptor_gain	1.0000
3:119863609:CAG:C	acceptor_gain	1.0000
3:119863610:A:T	acceptor_gain	1.0000
3:119863611:G:C	acceptor_gain	1.0000
3:119863611:G:GC	acceptor_gain	1.0000
3:119863614:C:CT	acceptor_gain	1.0000
3:119863615:A:T	acceptor_gain	1.0000
3:119866691:C:CT	acceptor_gain	1.0000
3:119866691:C:T	acceptor_gain	1.0000
3:119866692:A:T	acceptor_gain	1.0000
3:119866694:C:CT	acceptor_gain	1.0000

AlphaMissense

2700 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:119863548:A:C	Y323D	1.000
3:119863548:A:G	Y323H	1.000
3:119863553:A:G	L321P	1.000
3:119863568:A:G	L316P	1.000
3:119876421:A:G	W301R	1.000
3:119876421:A:T	W301R	1.000
3:119876435:A:C	I296S	1.000
3:119876435:A:G	I296T	1.000
3:119876435:A:T	I296N	1.000
3:119876442:G:A	P294S	1.000
3:119876443:G:C	F293L	1.000
3:119876443:G:T	F293L	1.000
3:119876444:A:C	F293C	1.000
3:119876444:A:G	F293S	1.000
3:119876445:A:G	F293L	1.000
3:119876449:A:C	F291L	1.000
3:119876449:A:T	F291L	1.000
3:119876451:A:G	F291L	1.000
3:119876467:G:C	N285K	1.000
3:119876467:G:T	N285K	1.000
3:119876469:T:C	N285D	1.000
3:119876470:C:A	M284I	1.000
3:119876470:C:G	M284I	1.000
3:119876470:C:T	M284I	1.000
3:119876471:A:C	M284R	1.000
3:119876471:A:G	M284T	1.000
3:119876471:A:T	M284K	1.000
3:119876480:A:T	I281N	1.000
3:119876495:G:C	P276R	1.000
3:119876495:G:T	P276Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000011870 (3:119985952 C>A), RS1000014717 (3:120083089 G>C), RS1000016683 (3:119859106 G>A), RS1000020021 (3:119954918 C>T), RS1000026929 (3:120040637 G>A), RS1000028023 (3:119992241 C>T), RS1000035422 (3:120040385 T>C), RS1000051976 (3:119856443 A>G), RS1000055379 (3:120080528 G>A,C), RS1000063761 (3:119996786 G>A), RS1000066786 (3:120068756 G>A), RS1000072807 (3:120089140 GAGA>G), RS1000098147 (3:120033819 A>C), RS1000105906 (3:119843790 T>C), RS1000106464 (3:119866326 C>T)

Disease associations

OMIM: gene MIM:605004 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Definitive	Autosomal dominant

Mondo (3): dilated cardiomyopathy (MONDO:0005021), intellectual disability (MONDO:0001071), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Dilated cardiomyopathy (Orphanet:217604), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001644	Dilated cardiomyopathy

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002223_34	HDL cholesterol	1.000000e-08
GCST004232_80	HDL cholesterol levels	4.000000e-08
GCST006993_4	Hippocampal volume in Alzheimer’s disease dementia	1.000000e-07
GCST010204_36	Low density lipoprotein cholesterol levels	1.000000e-08
GCST90002398_129	Neutrophil count	3.000000e-11
GCST90002401_121	Platelet distribution width	5.000000e-15
GCST90011900_23	Serum alkaline phosphatase levels	1.000000e-12
GCST90013406_224	Liver enzyme levels (alkaline phosphatase)	2.000000e-19

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0005035	hippocampal volume
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004833	neutrophil count
EFO:0007984	platelet component distribution width
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2095188 (PROTEIN FAMILY), CHEMBL262 (SINGLE PROTEIN), CHEMBL3883309 (PROTEIN-PROTEIN INTERACTION), CHEMBL6177905 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195601 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

67 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 445,201 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1448	NICLOSAMIDE	4	14,322
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL3301612	ENCORAFENIB	4	4,624
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL56337	EPALRESTAT	4	110
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL3318007	PIMODIVIR	3	144
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL50	QUERCETIN	3	74,559
CHEMBL85398	THIAZOLIDINEDIONE	3	54,290
CHEMBL140	CURCUMIN	3	93,882
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL3137331	DEFACTINIB	3	1,229
CHEMBL4297639	LORECIVIVINT	3	282
CHEMBL449317	HESPERIDIN	3	18,753
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL1276127	INDIRUBIN	2
CHEMBL14762	SELICICLIB	2
CHEMBL151	LUTEOLIN	2
CHEMBL31574	FISETIN	2
CHEMBL103667	DORAMAPIMOD	2
CHEMBL1230165	SILMITASERTIB	2
CHEMBL1614713	CC-401	2
CHEMBL1944698	ZOTIRACICLIB	2

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs334558	Efficacy	3	citalopram;fluoxetine	Major Depressive Disorder
rs334558	Efficacy	3	lithium	Bipolar Disorder
rs6438552	Efficacy	3	lithium	Bipolar Disorder

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs334558	GSK3B	3	2.50	2	citalopram;fluoxetine;lithium
rs3755557	GSK3B		0.00	0
rs6438552	GSK3B	3	1.25	1	lithium
rs3732361	GSK3B		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — GSK subfamily

Most potent curated ligand interactions (44 total), top 25:

Ligand	Action	Affinity	Parameter
CHIR-98014	Inhibition	9.24	pIC50
alsterpaullone 2-cyanoethyl	Inhibition	9.1	pIC50
LY2090314	Inhibition	8.96	pIC50
GSK-3β inhibitor 3 [PMID: 25845281]	Inhibition	8.96	pIC50
RGB-286638	Inhibition	8.52	pIC50
alsterpaullone	Inhibition	8.4	pIC50
AZD2858	Inhibition	8.31	pKi
GSK-3 inhibitor IX	Inhibition	8.3	pIC50
laduviglusib	Inhibition	8.17	pIC50
SB 216763	Inhibition	8.05	pIC50
GSK-3 inhibitor X	Inhibition	8.0	pIC50
GNF4877	Inhibition	7.8	pIC50
compound 2 [PMID: 22560567]	Inhibition	7.76	pIC50
1-azakenpaullone	Inhibition	7.74	pIC50
GSK-3 inhibitor XIII	Inhibition	7.66	pKi
indirubin-3’-monoxime	Inhibition	7.66	pIC50
kenpaullone	Inhibition	7.64	pIC50
GSK-3beta inhibitor XI	Inhibition	7.6	pKi
compound 52 [PMID: 9677190]	Inhibition	7.52	pIC50
TWS119	Inhibition	7.52	pIC50
AZD1080	Inhibition	7.51	pKi
GSK-3beta inhibitor VIII	Inhibition	7.42	pKi
SB-415286	Inhibition	7.42	pIC50
tideglusib	Irreversible inhibition	7.3	pKi
IM-12	Inhibition	7.28	pIC50

Binding affinities (BindingDB)

1666 measured of 3416 human assays (3482 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-amino-2,6-diphenyl-5-pyrimidinecarbonitrile	EC50	0.00117 nM
4-(4-fluorophenyl)-3,7,7-trimethyl-1,4,6,7,8,9-hexahydro-5H-pyrazolo[3,4-b]quinolin-5-one	EC50	0.0476 nM
3-amino-N-[4-(4-aminopiperidin-1-yl)-3-pyridinyl]-6-(2-fluorophenyl)pyrazine-2-carboxamide	IC50	0.1 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[4-(4-aminopiperidin-1-yl)-3-pyridinyl]-6-phenylpyrazine-2-carboxamide	IC50	0.2 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[4-(4-aminopiperidin-1-yl)-3-pyridinyl]-6-(4-methoxyphenyl)pyrazine-2-carboxamide	IC50	0.2 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-6-(2-fluorophenyl)-N-(4-piperazin-1-yl-3-pyridinyl)pyrazine-2-carboxamide	IC50	0.2 nM	US-9452998: Protein kinase C inhibitors and methods of their use
BDBM50375663	IC50	0.23 nM
N-(2-cycloheptyl-6-methylpyrimidin-4-yl)-5-fluoro-2H-pyrazolo[3,4-b]pyridin-3-amine	IC50	0.3 nM	US-8664219: Aminopyrimidines useful as inhibitors of protein kinases
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
4,7,7-trimethyl-4-phenyl-3-(trifluoromethyl)-2,4,6,7,8,9-hexahydro-5H-pyrazolo[3,4-b]quinolin-5-one (BRD1652)	IC50	0.4 nM
N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]-2-piperazin-1-ylpyridine-4-carboxamide	EC50	0.4 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[6-(1-methyltriazol-4-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	0.4 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-(2-cyclohexyl-6-methylpyrimidin-4-yl)-5-fluoro-2H-pyrazolo[3,4-b]pyridin-3-amine	IC50	0.5 nM	US-8664219: Aminopyrimidines useful as inhibitors of protein kinases
N-(4,5-dimethyl-6-phenyl-2-pyridinyl)-5-fluoro-2H-pyrazolo[3,4-b]pyridin-3-amine	IC50	0.6 nM	US-8735593: Aminopyridines useful as inhibitors of protein kinases
N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]-2-(4-propan-2-ylpiperazin-1-yl)pyridine-4-carboxamide	EC50	0.6 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-(2-hydroxyethyl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	0.6 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-(2-cyclohexyl-5,6-dimethylpyrimidin-4-yl)-5-fluoro-2H-pyrazolo[3,4-b]pyridin-3-amine	IC50	0.7 nM	US-8664219: Aminopyrimidines useful as inhibitors of protein kinases
2-(7-methyl-2,7-diazaspiro[3.5]nonan-2-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	0.7 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
2-(4-methylpiperazin-1-yl)-N-[6-(1,3,4-thiadiazol-2-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	0.7 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
2-(4-methylpiperazin-1-yl)-N-[6-(1H-pyrazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	0.8 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
2-(2,7-diazaspiro[3.5]nonan-2-yl)-N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	0.8 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
2-methyl-N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]-1,3-dihydroisoindole-5-carboxamide	EC50	0.8 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
6-(4-methylpiperazin-1-yl)-N-[6-(1,3,4-thiadiazol-2-yl)isoquinolin-3-yl]pyridine-3-carboxamide	EC50	0.8 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-methoxy-N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	0.8 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
3-(4-methylpiperazin-1-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]benzamide	EC50	0.9 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-(1-methylpiperidin-4-yl)oxy-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]benzamide	EC50	0.9 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
6-(4-methylpiperazin-1-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]pyridine-3-carboxamide	EC50	0.9 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]-2-(4-methylpiperazin-1-yl)pyridine-4-carboxamide	EC50	0.9 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
3-(1-methylpiperidin-4-yl)oxy-N-[6-(1,3-oxazol-5-yl)isoquinolin-3-yl]benzamide	EC50	0.9 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-(1-methylpiperidin-4-yl)oxy-N-[6-(1,3,4-thiadiazol-2-yl)isoquinolin-3-yl]benzamide	EC50	0.9 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]-1-(3,3,3-trifluoropropyl)piperidine-4-carboxamide	EC50	0.9 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-(hydroxymethyl)-N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	0.9 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-(dimethylamino)-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	0.9 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-(2-pyrrolidin-1-ylacetyl)-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	0.9 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[6-(4,4-difluorocyclohexyl)-2-methylpyrimidin-4-yl]-5-fluoro-2H-pyrazolo[3,4-b]pyridin-3-amine	IC50	1 nM	US-8664219: Aminopyrimidines useful as inhibitors of protein kinases
5-fluoro-N-[6-methyl-2-[(1S,2S)-2-methylcyclohexyl]pyrimidin-4-yl]-2H-pyrazolo[3,4-b]pyridin-3-amine	IC50	1 nM	US-8664219: Aminopyrimidines useful as inhibitors of protein kinases
3-amino-N-[2-(4-aminopiperidin-1-yl)phenyl]-6-phenylpyrazine-2-carboxamide	IC50	1 nM	US-9452998: Protein kinase C inhibitors and methods of their use
2-(4-methylpiperazin-1-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
2-(2,7-diazaspiro[3.5]nonan-2-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
6-(4-methylpiperazin-1-yl)-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]pyridine-3-carboxamide	EC50	1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
2-(4-methylpiperazin-1-yl)-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
2-cyano-N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	EC50	1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof
erk000537	KI	1 nM
erk000526	KI	1 nM
4-[(3-fluoroazetidin-1-yl)methyl]-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	1 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-(oxetan-3-yl)-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	1 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-[(4-{pyrazolo[1,5-a]pyridazin-3-yl}pyrimidin-2-yl)amino]benzonitrile	IC50	1 nM
N-(3,4-dichlorophenyl)-4-{pyrazolo[1,5-a]pyridazin-3-yl}pyrimidin-2-amine	IC50	1 nM
N-(3,5-difluorophenyl)-4-{pyrazolo[1,5-a]pyridazin-3-yl}pyrimidin-2-amine	IC50	1 nM
3-(1-methylpiperidin-4-yl)oxy-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]benzamide	EC50	1.1 nM	US-9951048: Isoquinolin-3-yl carboxamides and preparation and use thereof

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.89	IC50	0.013	nM	CHEMBL2386094
10.34	Kd	0.046	nM	CHEMBL4647659
10.30	Kd	0.05	nM	CHEMBL1232189
10.28	Kd	0.053	nM	CHEMBL1082152
10.22	IC50	0.06	nM	CHEMBL5290966
10.22	IC50	0.06	nM	CHEMBL1080901
10.15	IC50	0.07	nM	CHEMBL5409061
10.05	Ki	0.09	nM	CHEMBL461262
10.00	IC50	0.1	nM	CHEMBL3895998
10.00	IC50	0.1	nM	CHEMBL4084855
10.00	IC50	0.1	nM	CHEMBL5268011
9.85	IC50	0.14	nM	CHEMBL564450
9.82	IC50	0.15	nM	CHEMBL5278104
9.82	IC50	0.15	nM	CHEMBL5404581
9.82	IC50	0.15	nM	CHEMBL5413819
9.80	IC50	0.16	nM	CHEMBL5284020
9.74	IC50	0.18	nM	CHEMBL5418606
9.72	IC50	0.19	nM	CHEMBL5282887
9.70	IC50	0.2	nM	CHEMBL2386090
9.70	IC50	0.2	nM	CHEMBL3963605
9.70	IC50	0.2	nM	CHEMBL3942619
9.70	IC50	0.2	nM	CHEMBL3957649
9.70	IC50	0.2	nM	CHEMBL4077376
9.70	IC50	0.2	nM	CHEMBL4063206
9.70	IC50	0.2	nM	CHEMBL5270781
9.70	IC50	0.2	nM	CHEMBL5437994
9.70	IC50	0.2	nM	CHEMBL5416472
9.66	Ki	0.22	nM	CHEMBL2177173
9.66	IC50	0.22	nM	CHEMBL6176880
9.64	IC50	0.23	nM	CHEMBL3091542
9.64	IC50	0.23	nM	CHEMBL491647
9.62	IC50	0.24	nM	CHEMBL5440672
9.62	IC50	0.24	nM	CHEMBL6173985
9.62	IC50	0.24	nM	CHEMBL6177593
9.60	IC50	0.25	nM	CHEMBL4076186
9.60	IC50	0.25	nM	CHEMBL5283410
9.60	IC50	0.25	nM	CHEMBL5414726
9.60	IC50	0.25	nM	CHEMBL5407971
9.60	IC50	0.25	nM	CHEMBL5421040
9.59	IC50	0.26	nM	CHEMBL6175910
9.59	IC50	0.26	nM	CHEMBL6177214
9.57	IC50	0.27	nM	CHEMBL5419215
9.55	IC50	0.28	nM	CHEMBL5422776
9.55	IC50	0.28	nM	CHEMBL6174135
9.54	IC50	0.29	nM	CHEMBL3410091
9.52	IC50	0.3	nM	BISARYLMALEIMIDE 1
9.52	IC50	0.3	nM	CHEMBL6177098
9.51	IC50	0.31	nM	CHEMBL5436595
9.51	IC50	0.31	nM	CHEMBL5410665
9.51	IC50	0.31	nM	CHEMBL6177052

PubChem BioAssay actives

2554 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-amino-6-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]-N-pyridin-3-ylpyrazine-2-carboxamide	2017477: Inhibition of recombinant human GSK-3beta using YRRAAVPPSPSLSRHSSPHQ(pS)EDEE as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by Kinase-Glo luminescent kinase assay	ic50	<0.0001	uM
(3R)-1-[3-[[3-amino-6-(2-fluoro-5-propan-2-yloxyphenyl)pyrazine-2-carbonyl]amino]-4-pyridinyl]piperidine-3-carboxylic acid	1947698: Binding affinity to human GSK-3beta assessed as equilibrium dissociation constant measured upto 240 min by TR-FRET assay	kd	<0.0001	uM
3-[3-(2,3-dihydroxypropylamino)phenyl]-4-(5-fluoro-1-methylindol-3-yl)pyrrole-2,5-dione	465257: Inhibition of human recombinant GSK3-beta assessed as [gamma33]ATP transfer to biotinylated CREB-peptide substrate after 1 hr by scintillation counting	kd	0.0001	uM
2-(cyclopropanecarbonylamino)-N-[4-[(3S)-3-methylmorpholin-4-yl]-3-pyridinyl]pyridine-4-carboxamide	1937603: Inhibition of GSK-3beta (unknown origin) incubated for 1 hr by HTRF assay	ic50	0.0001	uM
2-(cyclopropanecarbonylamino)-N-[4-(3,3-dimethylmorpholin-4-yl)-3-pyridinyl]pyridine-4-carboxamide	1937603: Inhibition of GSK-3beta (unknown origin) incubated for 1 hr by HTRF assay	ic50	0.0001	uM
2-(cyclopropanecarbonylamino)-N-[4-(2-hydroxypropan-2-yl)-3-pyridinyl]pyridine-4-carboxamide	1937603: Inhibition of GSK-3beta (unknown origin) incubated for 1 hr by HTRF assay	ic50	0.0001	uM
2-(4-cyanoanilino)-N-(4-phenyl-3-pyridinyl)pyrimidine-4-carboxamide	1990476: Displacement of FL-KRREILSRRP[ps]ERYR-NH2 from human recombinant N-terminal His6-tagged GSK-3-beta (14 to 306 residues) H355L mutant expressed in baculovirus-infected Sf21 cells incubated for 20 hrs by fluorescence based analysis	ic50	0.0001	uM
2-(4-cyanoanilino)-N-[4-(2,2,2-trifluoroethoxy)-3-pyridinyl]pyrimidine-4-carboxamide	1990476: Displacement of FL-KRREILSRRP[ps]ERYR-NH2 from human recombinant N-terminal His6-tagged GSK-3-beta (14 to 306 residues) H355L mutant expressed in baculovirus-infected Sf21 cells incubated for 20 hrs by fluorescence based analysis	ic50	0.0001	uM
2-[(2R)-4-(4-methoxyphenyl)-2-methylpiperazin-1-yl]-3-methyl-6-pyrimidin-4-ylpyrimidin-4-one	1488461: Inhibition of human GSK-3beta using prephosphorylated-GS1 peptide as substrate after 1 hr in presence of [gamma-32P]ATP by liquid scintillation spectrometric analysis	ic50	0.0001	uM
3-(5-methoxy-1-benzofuran-7-yl)-4-[1-[2-(4-methylpiperazin-1-yl)ethyl]indol-3-yl]pyrrole-2,5-dione	419615: Inhibition of human GSK3-beta	ic50	0.0001	uM
3-amino-6-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]-N-[4-(pyrrolidin-1-ylmethyl)-3-pyridinyl]pyrazine-2-carboxamide	706596: Inhibition of human recombinant GSK3beta using biotin- AAEELDSRAGS(PO3H2)PQL as substrate and [gamma32P]ATP after 20 mins by scintillation proximity assay	ki	0.0002	uM
2-(cyclopropanecarbonylamino)-N-[4-(4,4-difluoropiperidin-1-yl)-3-pyridinyl]pyridine-4-carboxamide	1937603: Inhibition of GSK-3beta (unknown origin) incubated for 1 hr by HTRF assay	ic50	0.0002	uM
2-(3-chloro-4-cyanoanilino)-N-(4-phenyl-3-pyridinyl)pyrimidine-4-carboxamide	1990476: Displacement of FL-KRREILSRRP[ps]ERYR-NH2 from human recombinant N-terminal His6-tagged GSK-3-beta (14 to 306 residues) H355L mutant expressed in baculovirus-infected Sf21 cells incubated for 20 hrs by fluorescence based analysis	ic50	0.0002	uM
2-anilino-N-[4-(4,4-difluoropiperidin-1-yl)-3-pyridinyl]pyrimidine-4-carboxamide	1990476: Displacement of FL-KRREILSRRP[ps]ERYR-NH2 from human recombinant N-terminal His6-tagged GSK-3-beta (14 to 306 residues) H355L mutant expressed in baculovirus-infected Sf21 cells incubated for 20 hrs by fluorescence based analysis	ic50	0.0002	uM
2-(3-fluoro-4-methoxyanilino)-N-(4-phenyl-3-pyridinyl)pyrimidine-4-carboxamide	1990476: Displacement of FL-KRREILSRRP[ps]ERYR-NH2 from human recombinant N-terminal His6-tagged GSK-3-beta (14 to 306 residues) H355L mutant expressed in baculovirus-infected Sf21 cells incubated for 20 hrs by fluorescence based analysis	ic50	0.0002	uM
N-[4-(2-methylmorpholin-4-yl)-3-pyridinyl]-2-phenylimidazo[1,2-b]pyridazine-8-carboxamide	1934090: Inhibition of GSK3beta (unknown origin)	ic50	0.0002	uM
2-anilino-N-[4-(2,2,2-trifluoroethoxy)-3-pyridinyl]pyrimidine-4-carboxamide	1990476: Displacement of FL-KRREILSRRP[ps]ERYR-NH2 from human recombinant N-terminal His6-tagged GSK-3-beta (14 to 306 residues) H355L mutant expressed in baculovirus-infected Sf21 cells incubated for 20 hrs by fluorescence based analysis	ic50	0.0002	uM
2-[(3-chlorocyclobutanecarbonyl)amino]-N-[4-(4,4-difluoropiperidin-1-yl)-3-pyridinyl]pyridine-4-carboxamide	1937603: Inhibition of GSK-3beta (unknown origin) incubated for 1 hr by HTRF assay	ic50	0.0002	uM
2-[(2R)-4-(2-fluorophenyl)-2-methylpiperazin-1-yl]-3-methyl-6-pyrimidin-4-ylpyrimidin-4-one	1488461: Inhibition of human GSK-3beta using prephosphorylated-GS1 peptide as substrate after 1 hr in presence of [gamma-32P]ATP by liquid scintillation spectrometric analysis	ic50	0.0002	uM
2-[(2R)-4-(3-methoxyphenyl)-2-methylpiperazin-1-yl]-3-methyl-6-pyrimidin-4-ylpyrimidin-4-one	1488461: Inhibition of human GSK-3beta using prephosphorylated-GS1 peptide as substrate after 1 hr in presence of [gamma-32P]ATP by liquid scintillation spectrometric analysis	ic50	0.0002	uM
3-imidazo[1,2-b]pyridazin-3-yl-4-[10-(piperidine-1-carbonyl)-1,10-diazatricyclo[6.4.1.04,13]trideca-2,4,6,8(13)-tetraen-3-yl]pyrrole-2,5-dione	248695: Inhibitory concentration to inhibit Ser396 phosphorylation of tau, a natural substrate of GSK-3 in SY5Y cells	ic50	0.0003	uM
2-(cyclopropanecarbonylamino)-N-[4-(1-hydroxyethyl)-3-pyridinyl]pyridine-4-carboxamide	1937603: Inhibition of GSK-3beta (unknown origin) incubated for 1 hr by HTRF assay	ic50	0.0003	uM
2-[2-(cyclopropanecarbonylamino)-4-pyridinyl]-4-(cyclopropylmethoxy)-1,3-thiazole-5-carboxamide	1198904: Inhibition of GSK3beta (unknown origin) activity by competitive binding assay	ic50	0.0003	uM
2-(4-methylsulfonylanilino)-N-(4-phenyl-3-pyridinyl)pyrimidine-4-carboxamide	1990476: Displacement of FL-KRREILSRRP[ps]ERYR-NH2 from human recombinant N-terminal His6-tagged GSK-3-beta (14 to 306 residues) H355L mutant expressed in baculovirus-infected Sf21 cells incubated for 20 hrs by fluorescence based analysis	ic50	0.0003	uM
2-anilino-N-[4-(4-fluorophenyl)-3-pyridinyl]pyrimidine-4-carboxamide	1990476: Displacement of FL-KRREILSRRP[ps]ERYR-NH2 from human recombinant N-terminal His6-tagged GSK-3-beta (14 to 306 residues) H355L mutant expressed in baculovirus-infected Sf21 cells incubated for 20 hrs by fluorescence based analysis	ic50	0.0003	uM
2-(4-cyanoanilino)-N-[4-(4-fluorophenyl)-3-pyridinyl]pyrimidine-4-carboxamide	1990476: Displacement of FL-KRREILSRRP[ps]ERYR-NH2 from human recombinant N-terminal His6-tagged GSK-3-beta (14 to 306 residues) H355L mutant expressed in baculovirus-infected Sf21 cells incubated for 20 hrs by fluorescence based analysis	ic50	0.0003	uM
N-[4-(2,2,2-trifluoroethoxy)-3-pyridinyl]-2-[4-(trifluoromethyl)anilino]pyrimidine-4-carboxamide	1990476: Displacement of FL-KRREILSRRP[ps]ERYR-NH2 from human recombinant N-terminal His6-tagged GSK-3-beta (14 to 306 residues) H355L mutant expressed in baculovirus-infected Sf21 cells incubated for 20 hrs by fluorescence based analysis	ic50	0.0003	uM
2-(4-methylanilino)-N-(4-phenyl-3-pyridinyl)pyrimidine-4-carboxamide	1990476: Displacement of FL-KRREILSRRP[ps]ERYR-NH2 from human recombinant N-terminal His6-tagged GSK-3-beta (14 to 306 residues) H355L mutant expressed in baculovirus-infected Sf21 cells incubated for 20 hrs by fluorescence based analysis	ic50	0.0003	uM
2-[3-(4-fluoro-2-methoxyphenyl)piperazin-1-yl]-3-methyl-6-pyrimidin-4-ylpyrimidin-4-one;hydrochloride	1488483: Inhibition of recombinant human GSK-3beta using prephosphorylated GS-1 peptide as substrate after 1 hr in presence of [gamma-32P]ATP by liquid scintillation spectrometric method	ic50	0.0003	uM
N-[3-[4-[[(3,5-ditert-butyl-4-hydroxybenzoyl)amino]methyl]triazol-1-yl]propyl]-5-(3-iodo-4-methoxyphenyl)-1,3-oxazole-4-carboxamide	2017477: Inhibition of recombinant human GSK-3beta using YRRAAVPPSPSLSRHSSPHQ(pS)EDEE as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by Kinase-Glo luminescent kinase assay	ic50	0.0003	uM
5-(3-chloro-4-methoxyphenyl)-N-[3-[4-[[(E)-3-(3,5-ditert-butyl-4-hydroxyphenyl)prop-2-enoyl]amino]phenyl]propyl]-1,3-oxazole-4-carboxamide	2017477: Inhibition of recombinant human GSK-3beta using YRRAAVPPSPSLSRHSSPHQ(pS)EDEE as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by Kinase-Glo luminescent kinase assay	ic50	0.0003	uM
5-(3-chloro-4-methoxyphenyl)-N-[3-[4-[[3-(3,5-ditert-butyl-4-hydroxyphenyl)propanoylamino]methyl]triazol-1-yl]propyl]-1,3-oxazole-4-carboxamide	2017477: Inhibition of recombinant human GSK-3beta using YRRAAVPPSPSLSRHSSPHQ(pS)EDEE as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by Kinase-Glo luminescent kinase assay	ic50	0.0003	uM
N-[3-[4-[[[(E)-3-(3,5-ditert-butyl-4-hydroxyphenyl)prop-2-enoyl]amino]methyl]triazol-1-yl]propyl]-5-(3-iodo-4-methoxyphenyl)-1,3-oxazole-4-carboxamide	2017477: Inhibition of recombinant human GSK-3beta using YRRAAVPPSPSLSRHSSPHQ(pS)EDEE as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by Kinase-Glo luminescent kinase assay	ic50	0.0003	uM
3-amino-6-(4-piperidin-1-ylsulfonylphenyl)-N-pyridin-3-ylpyrazine-2-carboxamide	706596: Inhibition of human recombinant GSK3beta using biotin- AAEELDSRAGS(PO3H2)PQL as substrate and [gamma32P]ATP after 20 mins by scintillation proximity assay	ki	0.0004	uM
2-[2-(cyclopropanecarbonylamino)-4-pyridinyl]-4-propan-2-yloxy-1,3-thiazole-5-carboxamide	1198904: Inhibition of GSK3beta (unknown origin) activity by competitive binding assay	ic50	0.0004	uM
4-cyclobutyloxy-2-[2-(cyclopropanecarbonylamino)-4-pyridinyl]-1,3-thiazole-5-carboxamide	1198904: Inhibition of GSK3beta (unknown origin) activity by competitive binding assay	ic50	0.0004	uM
3-(5-chloro-1-methylindol-3-yl)-4-[3-(2,3-dihydroxypropylamino)phenyl]pyrrole-2,5-dione	465257: Inhibition of human recombinant GSK3-beta assessed as [gamma33]ATP transfer to biotinylated CREB-peptide substrate after 1 hr by scintillation counting	ic50	0.0004	uM
2-(4-methoxyanilino)-N-(4-phenyl-3-pyridinyl)pyrimidine-4-carboxamide	1990476: Displacement of FL-KRREILSRRP[ps]ERYR-NH2 from human recombinant N-terminal His6-tagged GSK-3-beta (14 to 306 residues) H355L mutant expressed in baculovirus-infected Sf21 cells incubated for 20 hrs by fluorescence based analysis	ic50	0.0004	uM
2-anilino-N-(4-phenyl-3-pyridinyl)pyrimidine-4-carboxamide	1990476: Displacement of FL-KRREILSRRP[ps]ERYR-NH2 from human recombinant N-terminal His6-tagged GSK-3-beta (14 to 306 residues) H355L mutant expressed in baculovirus-infected Sf21 cells incubated for 20 hrs by fluorescence based analysis	ic50	0.0004	uM
2-(4-cyano-2-methylanilino)-N-(4-phenyl-3-pyridinyl)pyrimidine-4-carboxamide	1990476: Displacement of FL-KRREILSRRP[ps]ERYR-NH2 from human recombinant N-terminal His6-tagged GSK-3-beta (14 to 306 residues) H355L mutant expressed in baculovirus-infected Sf21 cells incubated for 20 hrs by fluorescence based analysis	ic50	0.0004	uM
2-[4-(difluoromethoxy)anilino]-N-(4-phenyl-3-pyridinyl)pyrimidine-4-carboxamide	1990476: Displacement of FL-KRREILSRRP[ps]ERYR-NH2 from human recombinant N-terminal His6-tagged GSK-3-beta (14 to 306 residues) H355L mutant expressed in baculovirus-infected Sf21 cells incubated for 20 hrs by fluorescence based analysis	ic50	0.0004	uM
2-[4-(difluoromethoxy)anilino]-N-[4-(4-fluorophenyl)-3-pyridinyl]pyrimidine-4-carboxamide	1990476: Displacement of FL-KRREILSRRP[ps]ERYR-NH2 from human recombinant N-terminal His6-tagged GSK-3-beta (14 to 306 residues) H355L mutant expressed in baculovirus-infected Sf21 cells incubated for 20 hrs by fluorescence based analysis	ic50	0.0004	uM
4-[(3-chlorophenyl)diazenyl]-5-(3,4-dimethoxyphenyl)-1,2-dihydropyrazol-3-one	465436: Inhibition of GSK3-beta assessed as NADH level after 10 mins by pyruvate kinase/lactate dehydrogenase coupled spectrophotometric assay	ki	0.0004	uM
5-(3,4-dimethoxyphenyl)-4-[(3-methoxyphenyl)diazenyl]-1,2-dihydropyrazol-3-one	465436: Inhibition of GSK3-beta assessed as NADH level after 10 mins by pyruvate kinase/lactate dehydrogenase coupled spectrophotometric assay	ki	0.0004	uM
2-[3-(4-fluoro-2-methoxyphenyl)piperazin-1-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one;hydrochloride	1488483: Inhibition of recombinant human GSK-3beta using prephosphorylated GS-1 peptide as substrate after 1 hr in presence of [gamma-32P]ATP by liquid scintillation spectrometric method	ic50	0.0004	uM
3-(1-benzofuran-3-yl)-4-(5-fluoro-1-methylindol-3-yl)pyrrole-2,5-dione	1872903: Inhibition of GSK-3beta (unknown origin)	ic50	0.0004	uM
5-(3-chloro-4-methoxyphenyl)-N-[3-[[(E)-3-(3,5-ditert-butyl-4-hydroxyphenyl)prop-2-enoyl]amino]propyl]-1,3-oxazole-4-carboxamide	2017477: Inhibition of recombinant human GSK-3beta using YRRAAVPPSPSLSRHSSPHQ(pS)EDEE as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by Kinase-Glo luminescent kinase assay	ic50	0.0004	uM
2-[(2R)-4-(4-fluorophenyl)-2-methylpiperazin-1-yl]-3-methyl-6-pyrimidin-4-ylpyrimidin-4-one	1488461: Inhibition of human GSK-3beta using prephosphorylated-GS1 peptide as substrate after 1 hr in presence of [gamma-32P]ATP by liquid scintillation spectrometric analysis	ic50	0.0004	uM
3-amino-6-[2-methyl-4-(4-methylpiperazin-1-yl)sulfonylphenyl]-N-pyridin-3-ylpyrazine-2-carboxamide	706596: Inhibition of human recombinant GSK3beta using biotin- AAEELDSRAGS(PO3H2)PQL as substrate and [gamma32P]ATP after 20 mins by scintillation proximity assay	ki	0.0005	uM
3-amino-N-[4-[(dimethylamino)methyl]-3-pyridinyl]-6-(4-pyrrolidin-1-ylsulfonylphenyl)pyrazine-2-carboxamide	706596: Inhibition of human recombinant GSK3beta using biotin- AAEELDSRAGS(PO3H2)PQL as substrate and [gamma32P]ATP after 20 mins by scintillation proximity assay	ki	0.0005	uM

CTD chemical–gene interactions

342 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Lithium Chloride	affects reaction, decreases activity, decreases expression, decreases reaction, affects phosphorylation (+6 more)	24
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases expression, increases activity, affects cotreatment, decreases phosphorylation, increases abundance (+6 more)	21
sodium arsenite	increases phosphorylation, affects cotreatment, decreases phosphorylation, increases reaction, increases activity (+6 more)	17
Resveratrol	decreases activity, affects reaction, decreases expression, affects expression, affects phosphorylation (+9 more)	13
Arsenic Trioxide	increases phosphorylation, decreases phosphorylation, affects cotreatment, increases expression, increases activity (+6 more)	10
SB 216763	affects reaction, decreases reaction, increases expression, affects cotreatment, decreases response to substance (+4 more)	8
Wortmannin	affects reaction, increases expression, decreases activity, decreases reaction, increases phosphorylation (+2 more)	8
Metformin	decreases expression, decreases phosphorylation, decreases reaction, increases reaction, increases expression (+1 more)	8
cyanoginosin LR	decreases reaction, affects binding, increases reaction, decreases activity, increases phosphorylation (+2 more)	6
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases activity, increases phosphorylation	6
Cadmium Chloride	decreases phosphorylation, decreases reaction, increases abundance, increases expression, decreases activity (+1 more)	6
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases phosphorylation, increases response to substance	5
Acetylcysteine	increases phosphorylation, decreases phosphorylation, increases abundance, affects cotreatment, increases activity (+2 more)	5
Arsenic	increases abundance, increases phosphorylation, decreases expression, increases expression, affects cotreatment (+2 more)	5
Cadmium	decreases phosphorylation, decreases reaction, increases abundance, decreases expression, increases phosphorylation (+1 more)	5
Cisplatin	decreases phosphorylation, decreases reaction, decreases expression, increases expression, affects expression (+2 more)	5
Glucose	decreases reaction, affects cotreatment, decreases chemical synthesis, increases expression, increases phosphorylation (+1 more)	5
Quercetin	decreases phosphorylation, increases reaction, decreases activity, decreases expression	5
bisphenol A	affects binding, affects cotreatment, increases methylation, decreases methylation, increases expression (+1 more)	4
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	decreases phosphorylation, decreases reaction, affects reaction, increases phosphorylation, increases reaction (+1 more)	4
N-(4-methoxybenzyl)-N’-(5-nitro-1,3-thiazol-2-yl)urea	decreases activity, increases phosphorylation, decreases expression, increases response to substance, decreases response to substance (+3 more)	4
dorsomorphin	increases phosphorylation, decreases activity, affects cotreatment, decreases expression, decreases reaction	4
MK 2206	decreases reaction, increases expression, increases phosphorylation	4
Hydrogen Peroxide	affects reaction, increases phosphorylation, increases reaction, affects expression, decreases phosphorylation (+1 more)	4
Lithium	affects reaction, affects binding, decreases reaction, increases phosphorylation, increases reaction (+1 more)	4
Tretinoin	increases reaction, decreases reaction, increases phosphorylation, affects expression, affects cotreatment (+1 more)	4
1-Methyl-4-phenylpyridinium	increases cleavage, decreases phosphorylation, increases activity, increases expression, decreases reaction (+2 more)	4
Okadaic Acid	increases activity, decreases activity, increases phosphorylation, decreases phosphorylation, affects binding (+3 more)	4
baicalein	decreases reaction, increases phosphorylation, decreases phosphorylation	3
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	affects binding, decreases reaction, decreases expression, increases phosphorylation	3

ChEMBL screening assays

1871 unique, capped per target: 1839 binding, 18 functional, 12 admet, 2 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1032325	Binding	Inhibition of GSK3-mediated beta-casein phosphorylation in human SH-SY5Y cells in presence of MG132 by Western blot analysis	Soluble 3’,6-substituted indirubins with enhanced selectivity toward glycogen synthase kinase -3 alter circadian period. — J Med Chem
CHEMBL709400	Functional	Inhibition of glycogen synthesis in rat skeletal muscle L6 cells	Novel GSK-3 inhibitors with improved cellular activity. — Bioorg Med Chem Lett
CHEMBL4136607	ADMET	Inhibition of recombinant GSK3beta (unknown origin) using HSSPHQ(Sp)EDEEE as substrate by pyruvate kinase-lactate dehydrogenase coupled assay	Mtb PKNA/PKNB Dual Inhibition Provides Selectivity Advantages for Inhibitor Design To Minimize Host Kinase Interactions. — ACS Med Chem Lett

Cellosaurus cell lines

10 cell lines: 7 cancer cell line, 2 transformed cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8WF	Abcam MCF-7 GSK3B KO	Cancer cell line	Female
CVCL_B9JA	Abcam A-549 GSK3B KO	Cancer cell line	Male
CVCL_D7R3	Ubigene A-549 GSK3B KO	Cancer cell line	Male
CVCL_D8M7	Ubigene HCT 116 GSK3B KO	Cancer cell line	Male
CVCL_D9G0	Ubigene HEK293 GSK3B KO	Transformed cell line	Female
CVCL_E0E4	Ubigene HeLa GSK3B KO	Cancer cell line	Female
CVCL_E5GF	HEK293 GSK3B KO	Transformed cell line	Female
CVCL_RR02	MCF10A GSK3B (-/-)	Spontaneously immortalized cell line	Female
CVCL_SQ66	HAP1 GSK3B (-) 1	Cancer cell line	Male
CVCL_SQ67	HAP1 GSK3B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

496 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00629018	PHASE2	COMPLETED	Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
NCT00629096	PHASE2	COMPLETED	Intracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy
NCT00765518	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)
NCT00847964	PHASE2	COMPLETED	Safety and Feasibility of Algisyl-LVR™ as a Method of Left Ventricular Restoration in Patients With DCM Undergoing Open-heart Surgery
NCT01020968	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Catheter-based Cardiac Repair Cell [CRC]) Treatment in Patients With Heart Failure Due to Dilated Cardiomyopathy
NCT01302171	PHASE2	COMPLETED	Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy
NCT01350310	PHASE2	COMPLETED	Safety and Efficacy Study of Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy
NCT02133911	PHASE2	COMPLETED	A Pilot Trial of Ranolazine to Treat Patients With Dilated Cardiomyopathy
NCT03071653	PHASE2	SUSPENDED	Left Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study
NCT03572660	PHASE2	ACTIVE_NOT_RECRUITING	Use of Bone Marrow Derived Stem Cell and G-CSF With Circulatory Assistance in the Treatment of DCM