YWHAG

Summary

YWHAG (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma, HGNC:12852) is a protein-coding gene on chromosome 7q11.23, encoding 14-3-3 protein gamma (P61981). Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways.

This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 100% identical to the rat ortholog. It is induced by growth factors in human vascular smooth muscle cells, and is also highly expressed in skeletal and heart muscles, suggesting an important role for this protein in muscle tissue. It has been shown to interact with RAF1 and protein kinase C, proteins involved in various signal transduction pathways.

Source: NCBI Gene 7532 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 56 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 238 total — 21 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 63
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_012479

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12852
Approved symbol	YWHAG
Name	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Aliases	PPP1R170, 14-3-3GAMMA, 14-3-3γ
Ensembl gene	ENSG00000170027
Ensembl biotype	protein_coding
OMIM	605356
Entrez	7532

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000307630

RefSeq mRNA: 1 — MANE Select: NM_012479 NM_012479

CCDS: CCDS5584

Canonical transcript exons

ENST00000307630 — 2 exons

Exon	Start	End
ENSE00001127710	76326799	76330233
ENSE00001762086	76358722	76358991

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 99.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 110.1311 / max 973.0210, expressed in 1827 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84437	69.8471	1825
84438	24.8084	1816
84436	15.4756	1799

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	99.96	gold quality
pons	UBERON:0000988	99.93	gold quality
substantia nigra pars compacta	UBERON:0001965	99.93	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.92	gold quality
dorsal root ganglion	UBERON:0000044	99.91	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.88	gold quality
superior vestibular nucleus	UBERON:0007227	99.88	gold quality
endothelial cell	CL:0000115	99.87	gold quality
middle temporal gyrus	UBERON:0002771	99.87	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.87	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.86	gold quality
parietal lobe	UBERON:0001872	99.85	gold quality
postcentral gyrus	UBERON:0002581	99.84	gold quality
superior frontal gyrus	UBERON:0002661	99.82	gold quality
tibialis anterior	UBERON:0001385	99.79	gold quality
medulla oblongata	UBERON:0001896	99.79	gold quality
entorhinal cortex	UBERON:0002728	99.79	gold quality
ventral tegmental area	UBERON:0002691	99.75	gold quality
left ventricle myocardium	UBERON:0006566	99.75	gold quality
lateral globus pallidus	UBERON:0002476	99.73	gold quality
trigeminal ganglion	UBERON:0001675	99.68	gold quality
occipital lobe	UBERON:0002021	99.67	gold quality
deltoid	UBERON:0001476	99.66	gold quality
oviduct epithelium	UBERON:0004804	99.64	gold quality
primary visual cortex	UBERON:0002436	99.61	gold quality
cortical plate	UBERON:0005343	99.58	gold quality
vastus lateralis	UBERON:0001379	99.57	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.52	gold quality
ileal mucosa	UBERON:0000331	99.51	gold quality
quadriceps femoris	UBERON:0001377	99.50	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	56.95
E-ANND-3	yes	8.37
E-HCAD-25	yes	7.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CXXC1, TCF3, TP53

miRNA regulators (miRDB)

205 targeting YWHAG, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-651-3P	99.94	73.48	5177

Literature-anchored findings (GeneRIF, showing 40)

• Aberrant expression of signaling-related proteins 14-3-3 gamma and RACK1 in fetal Down syndrome brain (trisomy 21). (PMID:11824616)
• Results show that three 14-3-3 isoforms, beta, gamma and eta, are DAL-1/Protein 4.1B-binding proteins. (PMID:11996670)
• TSC2 associates with 14-3-3 in vivo (PMID:12364343)
• 14-3-3 binds to the IGF-1 receptor after IGF1R’s serine autophosphorylation (PMID:12482592)
• 14-3-3 suppresses importin alpha/beta-dependent nuclear localization of Thr157-phosphorylated p27, suggesting implications for cell cycle disorder in Akt-activated cancer cells. (PMID:15057270)
• multiple interactions of AICD with FE65 and 14-3-3gamma modulate FE65-dependent gene transactivation (PMID:16223726)
• Interaction of human 14-3-3gamma with the small heat shock protein Hsp20 was analyzed by means of size-exclusion chromatography and chemical crosslinking. (PMID:17109079)
• Both single marker and haplotype analyses were negative for the Ywhag gene association with smoking initiation and nicotine dependence. (PMID:17284169)
• our data indicate that 14-3-3gamma may contribute to tumorigenesis by promoting genomic instability. (PMID:17394238)
• Detection of only 2 (14-3-3 eta and gamma) out of 7 different isoforms in synovial fluid suggests they are specific to the site of joint inflammation (PMID:17611984)
• Report reduced expression of 14-3-3 gamma in uterine leiomyoma as identified by proteomics. (PMID:18054924)
• human 14-3-3gamma binds to the ERK1/2 molecular scaffold KSR1, which is mediated by the C-terminal stretch of 14-3-3gamma (PMID:18426801)
• These results suggest that the override of checkpoint observed in 14-3-3gamma knockdown cells is due to failure to inhibit cdc25C function. (PMID:18843201)
• This protein has been found differentially expressed in the temporal lobe from patients with schizophrenia. (PMID:19034380)
• changes in the expression of five 14-3-3 isoforms (beta, gamma, epsilon, tau, and zeta) during the apoptosis of JURL-MK1 and K562 cells. (PMID:19173300)
• 14-3-3beta, 14-3-3gamma, 14-3-3epsilon, 14-3-3eta and 14-3-3theta isoforms interact with the GPIb-IX complex in platelets (PMID:19558434)
• Abundant level of the phosphorylated FOXO1, its impaired nucleocytoplasmic shuttling, and the lowered expression of 14-3-3 protein in leiomyoma induces a shift in the cellular machinery toward a prosurvival execution program. (PMID:19772960)
• analysis of the interaction between 14-3-3 proteins, the N-terminal region of tyrosine hydroxylase, and negatively charged membranes (PMID:19801645)
• Zebrafish gene knockdowns imply roles for human YWHAG in infantile spasms and cardiomegaly. (PMID:20146355)
• This protein has been found differentially expressed in the anterior cingulate cortex from patients with schizophrenia (PMID:20381070)
• 14-3-3 eta, beta, gamma and sigma isoforms were negatively expressed in meningioma. (PMID:20388496)
• 14-3-3 protein gamma forms a complex with Checkpoint kinase 1 phosphorylated at Ser296, but not at ATR sites (Ser317 and Ser345). (PMID:20639859)
• Elevated expression of 14-3-3gamma in human hepatocellular carcinoma predicts extrahepatic metastasis and worse survival (PMID:20870266)
• data do not exclude the possibility that YWHAG loss of function is also sufficient to cause neurological phenotypes (PMID:21109226)
• a new role for 14-3-3gamma in protecting p21 from MDMX-mediated proteasomal turnover, which may partially account for DNA damage-induced elevation of p21 levels independent of p53. (PMID:21148311)
• Data indicate that gene analysis revealed an up-regulation of all four 14-3-3 isoforms beta, eta, gamma, and sigma. (PMID:21416292)
• results support that membrane binding involves the non-conserved, convex area of 14-3-3gamma, and that Trp residues do not intercalate in the bilayer. (PMID:21420405)
• Increased expression of 14-3-3 gamma in lung cancer coincides with loss of functional p53. (PMID:21867493)
• description of a protein complex that mediates carrier formation and contains budding and fission molecules, as well as other molecules, such as the adaptor protein 14-3-3gamma (PMID:22366688)
• miR-141/YWHAG and miR-520e/RAB11A are two potential miRNA/protein target pairs associated with severe obesity. (PMID:22537031)
• hypoxia can activate p53 through inactivation of MDMX by the ATR-Chk1-MDMX-14-3-3gamma pathway. (PMID:22556425)
• Increased expression of 14-3-3gamma in breast cancer is associated significantly with tumor progression and poor prognosis. (PMID:22658894)
• 14-3-3gamma protein binds strongly to long DNA targets and shows very strong preference for supercoiled DNA. (PMID:22856523)
• Using individual amino acid substitutions within the 14-3-3gamma VRII, we identified two residues required for and two contributing to the gamma-specific phenotypes. (PMID:23115241)
• The peripheral binding of 14-3-3gamma to membranes involves isoform-specific histidine residues. (PMID:23189152)
• high 14-3-3gamma expression is associated with poor survival in NPC patients. Thus, this study has identified that the 14-3-3gamma involves in the carcinogenesis of NPC. (PMID:23500129)
• Mitotic Plk1 activity is regulated not only by Plk1-Thr210 phosphorylation, but also by Plk1 binding to 14-3-3gamma following Plk1-Ser99 phosphorylation downstream of the PI3K-Akt signalling pathway. (PMID:23695676)
• 14-3-3gamma was induced in B cells by T-dependent and T-independent primary CSR-inducing stimuli in vitro. (PMID:23851690)
• physiological changes in phosphate anions concentration can modulate affinity and specificity of interaction of 14-3-3 with its multiple targets and therefore the actual phosphointeractome of 14-3-3. (PMID:23977325)
• The region surrounding pSer19 of Tyrosine hydroxylase adopts an extended conformation in the 14-3-3gamma-bound state, whereas adopts a bent conformation when free in solution. (PMID:24055376)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ywhag1	ENSDARG00000067626
danio_rerio	ywhag2	ENSDARG00000071658
mus_musculus	Ywhag	ENSMUSG00000051391
rattus_norvegicus	Ywhag	ENSRNOG00000001436
drosophila_melanogaster	14-3-3epsilon	FBGN0020238

Paralogs (6): YWHAE (ENSG00000108953), YWHAH (ENSG00000128245), YWHAQ (ENSG00000134308), YWHAZ (ENSG00000164924), YWHAB (ENSG00000166913), SFN (ENSG00000175793)

Protein

Protein identifiers

14-3-3 protein gamma — P61981 (reviewed: P61981)

Alternative names: Protein kinase C inhibitor protein 1

All UniProt accessions (1): P61981

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Promotes inactivation of WDR24 component of the GATOR2 complex by binding to phosphorylated WDR24. Participates in the positive regulation of NMDA glutamate receptor activity by promoting the L-glutamate secretion through interaction with BEST1. Reduces keratinocyte intercellular adhesion, via interacting with PKP1 and sequestering it in the cytoplasm, thereby reducing its incorporation into desmosomes. Plays a role in mitochondrial protein catabolic process (also named MALM) that promotes the degradation of damaged proteins inside mitochondria.

Subunit / interactions. Homodimer. Part of a complex that contains DSG3, PKP1, YAP1 and YWHAG; the complex is required for localization of DSG3 and YAP1 to the cell membrane in keratinocytes. Interacts with SAMSN1. Interacts with RAF1, SSH1 and CRTC2/TORC2. Interacts with ABL1 (phosphorylated form); the interaction retains it in the cytoplasm. Interacts with GAB2. Interacts with MDM4 (phosphorylated); negatively regulates MDM4 activity toward TP53. Interacts with PKA-phosphorylated AANAT and SIRT2. Interacts with the ‘Thr-369’ phosphorylated form of DAPK2. Interacts with PI4KB, TBC1D22A and TBC1D22B. Interacts with SLITRK1. Interacts with LRRK2; this interaction is dependent on LRRK2 phosphorylation. Interacts with MARK2 and MARK3. Interacts with MEFV. Interacts with ENDOG, TSC2 and PIK3C3; interaction with ENDOG weakens its interaction with TSC2 and PIK3C3. Interacts with (phosphorylated) WDR24. Interacts with BEST1; this interaction promotes L-glutamate channel activity leading to the positive regulation of NMDA glutamate receptor activity through the L-glutamate secretion. Interacts with PKP1 (when phosphorylated); the interaction results in translocation of PKP1 to the cytoplasm and loss of intercellular adhesion in keratinocytes. Interacts with SPATA18/MIEAP (isoforms 1 and 2); a protein that also plays a role in MALM.

Subcellular location. Cytoplasm. Cytosol. Mitochondrion matrix.

Tissue specificity. Highly expressed in brain, skeletal muscle, and heart.

Post-translational modifications. Phosphorylated by various PKC isozymes.

Disease relevance. Developmental and epileptic encephalopathy 56 (DEE56) [MIM:617665] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE56 is an autosomal dominant condition. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the 14-3-3 family.

RefSeq proteins (1): NP_036611* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000308	14-3-3	Family
IPR023409	14-3-3_CS	Conserved_site
IPR023410	14-3-3_domain	Domain
IPR036815	14-3-3_dom_sf	Homologous_superfamily

Pfam: PF00244

UniProt features (48 total): sequence conflict 12, helix 11, modified residue 9, sequence variant 5, turn 4, chain 2, region of interest 2, site 2, initiator methionine 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
6S9K	X-RAY DIFFRACTION	1.6
6ZBT	X-RAY DIFFRACTION	1.8
3UZD	X-RAY DIFFRACTION	1.86
6ZC9	X-RAY DIFFRACTION	1.9
6A5S	X-RAY DIFFRACTION	2.1
4E2E	X-RAY DIFFRACTION	2.25
7A6Y	X-RAY DIFFRACTION	2.5
2B05	X-RAY DIFFRACTION	2.55
6GKF	X-RAY DIFFRACTION	2.6
6BZD	X-RAY DIFFRACTION	2.67
7A6R	X-RAY DIFFRACTION	2.7
5D3E	X-RAY DIFFRACTION	2.75
6SAD	X-RAY DIFFRACTION	2.75
6FEL	X-RAY DIFFRACTION	2.84
6GKG	X-RAY DIFFRACTION	2.85
4O46	X-RAY DIFFRACTION	2.9
6BYJ	X-RAY DIFFRACTION	2.9
6Y4K	X-RAY DIFFRACTION	3
4J6S	X-RAY DIFFRACTION	3.08
6Y6B	X-RAY DIFFRACTION	3.08
6BYL	X-RAY DIFFRACTION	3.35
9CI3	ELECTRON MICROSCOPY	3.96

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61981-F1	94.57	0.90

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 (2): 57 (interaction with phosphoserine on interacting protein); 132 (interaction with phosphoserine on interacting protein)

Post-translational modifications (9): 71, 133, 145, 215, 234, 235, 1, 2, 2

Function

Pathways and Gene Ontology

Reactome pathways

54 pathways

ID	Pathway
R-HSA-111447	Activation of BAD and translocation to mitochondria
R-HSA-1445148	Translocation of SLC2A4 (GLUT4) to the plasma membrane
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-5625740	RHO GTPases activate PKNs
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-75035	Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex
R-HSA-8854518	AURKA Activation by TPX2
R-HSA-9614399	Regulation of localization of FOXO transcription factors
R-HSA-9735871	SARS-CoV-1 targets host intracellular signalling and regulatory pathways
R-HSA-9755779	SARS-CoV-2 targets host intracellular signalling and regulatory pathways
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity
R-HSA-9929491	SPOP-mediated proteasomal degradation of PD-L1(CD274)
R-HSA-109581	Apoptosis
R-HSA-109606	Intrinsic Pathway for Apoptosis
R-HSA-114452	Activation of BH3-only proteins
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-199991	Membrane Trafficking
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53

MSigDB gene sets: 545 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, GCM_MAP4K4, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, AP1_01, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, MODULE_151, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, AAGCCAT_MIR135A_MIR135B, GOBP_PROTEIN_TARGETING, PID_NFAT_3PATHWAY

GO Biological Process (28): positive regulation of T cell mediated immune response to tumor cell (GO:0002842), negative regulation of protein kinase activity (GO:0006469), protein targeting (GO:0006605), signal transduction (GO:0007165), intracellular protein localization (GO:0008104), regulation of signal transduction (GO:0009966), positive regulation of cell-cell adhesion (GO:0022409), cellular response to insulin stimulus (GO:0032869), regulation of protein localization (GO:0032880), cellular response to glucose starvation (GO:0042149), regulation of neuron differentiation (GO:0045664), regulation of synaptic plasticity (GO:0048167), positive regulation of T cell activation (GO:0050870), negative regulation of TORC1 signaling (GO:1904262), cytoplasmic translation (GO:0002181), negative regulation of T cell mediated immune response to tumor cell (GO:0002841), SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146), cellular response to nutrient levels (GO:0031669), cellular response to amino acid starvation (GO:0034198), TORC1 signaling (GO:0038202), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), negative regulation of translational initiation (GO:0045947), positive regulation of translational initiation (GO:0045948), protein stabilization (GO:0050821), negative regulation of T cell activation (GO:0050868), protein localization to lysosome (GO:0061462), protein K6-linked ubiquitination (GO:0085020), positive regulation of TORC1 signaling (GO:1904263)

GO Molecular Function (10): RNA binding (GO:0003723), protein kinase C binding (GO:0005080), insulin-like growth factor receptor binding (GO:0005159), protein kinase C inhibitor activity (GO:0008426), protein domain specific binding (GO:0019904), receptor tyrosine kinase binding (GO:0030971), identical protein binding (GO:0042802), phosphorylation-dependent protein binding (GO:0140031), protein sequestering activity (GO:0140311), protein binding (GO:0005515)

GO Cellular Component (11): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrial matrix (GO:0005759), cytosol (GO:0005829), focal adhesion (GO:0005925), membrane (GO:0016020), extracellular exosome (GO:0070062), presynapse (GO:0098793), mitochondrion (GO:0005739), vesicle (GO:0031982), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
G2/M Transition	2
Centrosome maturation	2
Activation of BH3-only proteins	1
Membrane Trafficking	1
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1
RHO GTPase Effectors	1
Transcriptional Regulation by TP53	1
G2/M DNA damage checkpoint	1
FOXO-mediated transcription	1
SARS-CoV-1-host interactions	1
SARS-CoV-2-host interactions	1
MITF-M-regulated melanocyte development	1
Regulation of PD-L1(CD274) Post-translational modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein binding	3
T cell mediated immune response to tumor cell	2
regulation of T cell mediated immune response to tumor cell	2
cellular response to stimulus	2
cellular response to starvation	2
signaling receptor binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
positive regulation of T cell mediated immunity	1
positive regulation of immune response to tumor cell	1
negative regulation of protein phosphorylation	1
protein kinase activity	1
negative regulation of kinase activity	1
regulation of protein kinase activity	1
establishment of protein localization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
macromolecule localization	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
regulation of cell-cell adhesion	1
positive regulation of cell adhesion	1
cell-cell adhesion	1
response to insulin	1
cellular response to peptide hormone stimulus	1
intracellular protein localization	1
regulation of localization	1
neuron differentiation	1
regulation of cell differentiation	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1
T cell activation	1
regulation of T cell activation	1
positive regulation of lymphocyte activation	1
positive regulation of leukocyte cell-cell adhesion	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

1300 interactions, top by confidence:

A	B	Type	Score
YWHAG	HDAC4	psi-mi:“MI:0915”(physical association)	0.950
HDAC4	YWHAG	psi-mi:“MI:0915”(physical association)	0.950
FAM53C	YWHAG	psi-mi:“MI:0915”(physical association)	0.880
YWHAG	FAM53C	psi-mi:“MI:0915”(physical association)	0.880
YWHAH	FAM83G	psi-mi:“MI:0914”(association)	0.710
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
TERF1	YWHAG	psi-mi:“MI:0915”(physical association)	0.550
YWHAG	TINF2	psi-mi:“MI:0915”(physical association)	0.510
ABL1	RPLP1	psi-mi:“MI:0914”(association)	0.350
ARAF	PPP6C	psi-mi:“MI:0914”(association)	0.350
ARAF	CALU	psi-mi:“MI:0914”(association)	0.350
TNK1	DDX5	psi-mi:“MI:0914”(association)	0.350
sspH2	AIP	psi-mi:“MI:0914”(association)	0.350
Cenpe	BBX	psi-mi:“MI:0914”(association)	0.350
RACGAP1	STX18	psi-mi:“MI:0914”(association)	0.350
YWHAZ	WDR62	psi-mi:“MI:0914”(association)	0.350
RBM7	ZC3H18	psi-mi:“MI:0914”(association)	0.350
MAP3K2	MAP3K3	psi-mi:“MI:0914”(association)	0.350
KIF23	MAP3K4	psi-mi:“MI:0914”(association)	0.350
CDC25B	CENPB	psi-mi:“MI:0914”(association)	0.350
WDR62	MAPKBP1	psi-mi:“MI:0914”(association)	0.350
KDR	AAR2	psi-mi:“MI:0914”(association)	0.350
Yap1	GEMIN2	psi-mi:“MI:0914”(association)	0.350
EPB41L3	YWHAG	psi-mi:“MI:0915”(physical association)	0.000
YWHAG	ANKS1A	psi-mi:“MI:0915”(physical association)	0.000
YWHAG	PNN	psi-mi:“MI:0915”(physical association)	0.000
YWHAG	SH3BP4	psi-mi:“MI:0915”(physical association)	0.000
YWHAG		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (2343): YWHAG (Affinity Capture-MS), YWHAG (Affinity Capture-Western), YWHAG (Affinity Capture-Western), DTL (Affinity Capture-Western), YWHAG (Affinity Capture-MS), HDAC4 (Two-hybrid), FAM53C (Two-hybrid), YWHAG (Affinity Capture-MS), YWHAG (Affinity Capture-MS), AKAP13 (Far Western), YWHAG (Reconstituted Complex), YWHAG (Affinity Capture-Western), YWHAG (Affinity Capture-MS), YWHAG (Affinity Capture-MS), YWHAG (Affinity Capture-MS)

ESM2 similar proteins: A4K2U9, P27348, P29309, P29310, P29361, P31946, P35213, P61981, P61982, P61983, P63101, P63102, P63103, P63104, P68250, P68252, P68254, P68255, P68509, P68510, P68511, Q04917, Q1HR36, Q20655, Q2F637, Q3SZI4, Q4R572, Q52M98, Q5F3W6, Q5PRD0, Q5R651, Q5RC20, Q5RFJ2, Q5XGC8, Q5XHK2, Q5ZKC9, Q5ZLQ6, Q5ZMD1, Q6NRY9, Q6P4Z5

Diamond homologs: A4K2U9, B8NLM9, O49995, O49998, O65352, O70456, O77642, P27348, P29309, P29310, P29311, P29361, P31946, P31947, P34730, P35213, P41932, P42643, P42644, P42652, P42653, P42654, P42656, P48348, P49106, P52908, P54632, P61981, P61982, P61983, P62258, P62259, P62260, P62261, P62262, P63101, P63102, P63103, P63104, P68250

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
LATS2	up-regulates	YWHAG	phosphorylation
YWHAG	“down-regulates activity”	NEFL	binding
YWHAG	“up-regulates quantity by stabilization”	GEM	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 184 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
Transport of Mature Transcript to Cytoplasm	9	25.4×	5e-09
mRNA Splicing	19	15.4×	2e-15
RNA Polymerase II Transcription Termination	9	14.6×	6e-07
mRNA 3’-end processing	9	13.1×	1e-06
Processing of Capped Intron-Containing Pre-mRNA	20	12.2×	3e-14
RHO GTPases Activate WASPs and WAVEs	5	11.8×	2e-03
mRNA Splicing - Major Pathway	29	11.7×	2e-20
mRNA Splicing - Minor Pathway	7	11.6×	8e-05

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	7	31.2×	4e-07
mRNA splice site recognition	6	28.0×	8e-06
regulation of mRNA splicing, via spliceosome	5	25.8×	1e-04
RNA splicing, via transesterification reactions	7	25.4×	1e-06
alternative mRNA splicing, via spliceosome	6	23.5×	2e-05
regulation of alternative mRNA splicing, via spliceosome	14	19.9×	3e-12
spliceosomal complex assembly	5	17.5×	8e-04
morphogenesis of an epithelium	6	12.0×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	8
Uncertain significance	88
Likely benign	98
Benign	7

Top pathogenic / likely-pathogenic (29)

Variant ID	HGVS	Classification
1180447	NM_012479.4(YWHAG):c.89dup (p.Thr31fs)	Pathogenic
1335673	NM_012479.4(YWHAG):c.398A>G (p.Tyr133Cys)	Pathogenic
1386883	NM_012479.4(YWHAG):c.60_61delinsGA (p.Tyr20_Asp21delinsTer)	Pathogenic
1416114	NM_012479.4(YWHAG):c.89del (p.Val30fs)	Pathogenic
2013349	NM_012479.4(YWHAG):c.518T>G (p.Leu173Ter)	Pathogenic
2034563	NM_012479.4(YWHAG):c.576dup (p.Ala193fs)	Pathogenic
2088488	NM_012479.4(YWHAG):c.462C>G (p.Tyr154Ter)	Pathogenic
2425823	NC_000007.13:g.(?75988019)(75988125_?)del	Pathogenic
2713430	NM_012479.4(YWHAG):c.648_671del (p.Tyr216_Gln224delinsTer)	Pathogenic
2747265	NM_012479.4(YWHAG):c.619G>A (p.Glu207Lys)	Pathogenic
2816056	NM_012479.4(YWHAG):c.529C>T (p.Leu177Phe)	Pathogenic
2827317	NM_012479.4(YWHAG):c.542T>C (p.Val181Ala)	Pathogenic
2845799	NM_012479.4(YWHAG):c.631del (p.Leu211fs)	Pathogenic
2867278	NM_012479.4(YWHAG):c.121del (p.Glu41fs)	Pathogenic
3651330	NM_012479.4(YWHAG):c.448del (p.Ser150fs)	Pathogenic
3657604	NM_012479.4(YWHAG):c.125G>A (p.Arg42Gln)	Pathogenic
3676386	NM_012479.4(YWHAG):c.202C>T (p.Gln68Ter)	Pathogenic
3725513	NM_012479.4(YWHAG):c.537C>G (p.Tyr179Ter)	Pathogenic
4084968	NM_012479.4(YWHAG):c.169C>G (p.Arg57Gly)	Pathogenic
659092	NM_012479.4(YWHAG):c.169C>T (p.Arg57Cys)	Pathogenic
802325	NM_012479.4(YWHAG):c.451G>T (p.Glu151Ter)	Pathogenic
1027791	NM_012479.4(YWHAG):c.683A>T (p.Asp228Val)	Likely pathogenic
1312189	NM_012479.4(YWHAG):c.682G>A (p.Asp228Asn)	Likely pathogenic
2056700	NM_012479.4(YWHAG):c.180G>A (p.Trp60Ter)	Likely pathogenic
2584359	NM_012479.4(YWHAG):c.628_642del (p.Thr210_Asp214del)	Likely pathogenic
2831365	NM_012479.4(YWHAG):c.-144_72del (p.Met1_Ala24del)	Likely pathogenic
3339914	NC_000007.13:g.(?75956115)(75988309_?)del	Likely pathogenic
3359022	NM_012479.4(YWHAG):c.532A>G (p.Asn178Asp)	Likely pathogenic
4073675	NM_012479.4(YWHAG):c.652_653insT (p.Asp218fs)	Likely pathogenic

SpliceAI

454 predictions. Top by Δscore:

Variant	Effect	Δscore
7:76330233:CCT:C	acceptor_loss	1.0000
7:76330234:C:G	acceptor_loss	1.0000
7:76330235:T:A	acceptor_loss	1.0000
7:76358718:TCA:T	donor_loss	1.0000
7:76358719:CACG:C	donor_loss	1.0000
7:76358720:A:AC	donor_gain	1.0000
7:76358720:ACG:A	donor_loss	1.0000
7:76358720:ACGTT:A	donor_gain	1.0000
7:76358721:C:CT	donor_gain	1.0000
7:76358721:CG:C	donor_gain	1.0000
7:76358721:CGT:C	donor_gain	1.0000
7:76358721:CGTT:C	donor_gain	1.0000
7:76358721:CGTTC:C	donor_gain	1.0000
7:76330230:TCAC:T	acceptor_gain	0.9900
7:76330231:CAC:C	acceptor_gain	0.9900
7:76330231:CACC:C	acceptor_gain	0.9900
7:76330232:AC:A	acceptor_gain	0.9900
7:76330233:CC:C	acceptor_gain	0.9900
7:76330234:C:CC	acceptor_gain	0.9900
7:76330238:C:CT	acceptor_gain	0.9900
7:76330239:A:T	acceptor_gain	0.9900
7:76358724:T:A	donor_gain	0.9900
7:76330230:TCACC:T	acceptor_gain	0.9800
7:76330232:ACCTG:A	acceptor_gain	0.9800
7:76330233:CCTGC:C	acceptor_gain	0.9800
7:76330234:CTGCC:C	acceptor_gain	0.9800
7:76330238:C:T	acceptor_gain	0.9800
7:76347453:G:C	donor_gain	0.9800
7:76358716:ACTC:A	donor_loss	0.9800
7:76330231:CACCT:C	acceptor_gain	0.9700

AlphaMissense

1639 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:76329622:C:A	W233C	1.000
7:76329622:C:G	W233C	1.000
7:76329623:C:G	W233S	1.000
7:76329624:A:G	W233R	1.000
7:76329624:A:T	W233R	1.000
7:76329626:A:G	L232P	1.000
7:76329626:A:T	L232H	1.000
7:76329632:A:G	L230P	1.000
7:76329632:A:T	L230H	1.000
7:76329633:G:A	L230F	1.000
7:76329634:G:C	N229K	1.000
7:76329634:G:T	N229K	1.000
7:76329635:T:A	N229I	1.000
7:76329636:T:A	N229Y	1.000
7:76329636:T:C	N229D	1.000
7:76329636:T:G	N229H	1.000
7:76329637:G:C	D228E	1.000
7:76329637:G:T	D228E	1.000
7:76329638:T:A	D228V	1.000
7:76329638:T:C	D228G	1.000
7:76329638:T:G	D228A	1.000
7:76329639:C:A	D228Y	1.000
7:76329639:C:G	D228H	1.000
7:76329639:C:T	D228N	1.000
7:76329641:C:A	R227L	1.000
7:76329641:C:G	R227P	1.000
7:76329642:G:A	R227C	1.000
7:76329642:G:T	R227S	1.000
7:76329644:A:C	L226R	1.000
7:76329644:A:G	L226P	1.000

dbSNP variants (sampled 300 via entrez): RS1000142507 (7:76358427 A>T), RS1000222353 (7:76351200 A>G), RS1000332025 (7:76327336 C>T), RS1000413621 (7:76343407 T>C), RS1000419932 (7:76348951 T>C,G), RS1000503838 (7:76359281 C>G), RS1000514387 (7:76343182 T>C), RS1000534167 (7:76357644 C>G), RS1000568129 (7:76343392 C>A), RS1000784127 (7:76353106 T>C), RS1000824473 (7:76352318 A>C,G), RS1000850099 (7:76337828 G>A), RS1000974756 (7:76331298 G>A), RS1001108356 (7:76358621 AC>A), RS1001128902 (7:76337880 A>T)

Disease associations

OMIM: gene MIM:605356 | disease phenotypes: MIM:617665

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 56	Definitive	Autosomal dominant
undetermined early-onset epileptic encephalopathy	Strong	Autosomal dominant

Mondo (6): developmental and epileptic encephalopathy, 56 (MONDO:0033365), specific learning disability (MONDO:0016225), intellectual disability (MONDO:0001071), microcephaly (MONDO:0001149), constipation disorder (MONDO:0002203), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (2): Specific learning disability (Orphanet:211047), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

63 total (30 of 63 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000348	High forehead
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001268	Mental deterioration
HP:0001273	Abnormal corpus callosum morphology
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001315	Reduced tendon reflexes
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001382	Joint hypermobility

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001096_1	Multiple sclerosis	8.000000e-06
GCST001096_2	Multiple sclerosis	6.000000e-06
GCST007201_10	Schizophrenia	5.000000e-07

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D003248	Constipation	C23.888.821.150
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D000067559	Specific Learning Disorder	C10.597.606.150.550.700; C23.888.592.604.150.550.700; F03.625.374.188.700; F03.625.562.700

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293296 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

Binding affinities (BindingDB)

14 measured of 52 human assays (52 total across all organisms); most potent 14 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
1-ethyl-2-([1,2,4]triazolo[4,3-a]pyridin-3-ylsulfanylmethyl)benzimidazole-5-carboxylic acid	IC50	853 nM
6-methyl-2-phenyl-1,2-dihydropyridine-3,3,4,4-tetracarbonitrile	IC50	3150 nM
2-(2-hydroxy-9-keto-5H-benzo[b][1,4]benzoxazepin-6-yl)benzoic acid	IC50	5020 nM
1-(ethylamino)-3-methyl-3H-naphtho[1,2,3-de]quinoline-2,7-dione	IC50	7290 nM
1-ethyl-4-keto-6-piperidinosulfonyl-N-(2-pyridylmethyl)quinoline-3-carboxamide	IC50	8920 nM
(4Z)-4-[[4-(dimethylamino)anilino]methylene]-2-phenyl-2-oxazolin-5-one	IC50	9680 nM
2-[[2-(4-methoxyphenyl)-5-methyl-1,3-oxazol-4-yl]methylsulfinyl]-N-(pyridin-2-ylmethyl)acetamide	IC50	10700 nM
5-Amino-2-pyrrolidin-1-yl-benzamide	IC50	18100 nM
2-(N-[2-(1-benzotriazolyl)-1-oxoethyl]-4-methoxyanilino)-N-(2-methoxyethyl)-2-pyridin-4-ylacetamide	IC50	24600 nM
MLS000119773	IC50	25600 nM
2,4-dimethyl-2,3-dihydrothieno[3,2-c]quinoline-8-carboxylic acid	IC50	25700 nM
(4-methoxy-7,7-dimethyl-6,8-dihydropyrimido[4,5-b][1,4]benzothiazin-9-yl)amine;hydrobromide	IC50	30000 nM
6-chloranyl-4-methyl-8-[(4-methylpiperidin-1-yl)methyl]-7-oxidanyl-chromen-2-one	IC50	45600 nM
5-[(2-methylbenzyl)sulfonylmethyl]-N-(2-pyridylmethyl)-2-furamide	IC50	50000 nM

ChEMBL bioactivities

15 potent at pChembl≥5 of 24 total, top 15 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.36	Kd	4.41	nM	CHEMBL3752910
8.35	ED50	4.485	nM	CHEMBL3752910
6.28	IC50	530	nM	MOLIBRESIB
6.17	Kd	668.8	nM	CHEMBL5653589
6.17	ED50	680.2	nM	CHEMBL5653589
6.07	IC50	852.7	nM	CHEMBL1502839
5.70	IC50	2000	nM	BLAPSIN A
5.60	IC50	2500	nM	BLAPSIN B
5.50	IC50	3147	nM	CHEMBL1598223
5.30	IC50	5022	nM	CHEMBL1385512
5.14	IC50	7294	nM	CHEMBL2003304
5.05	IC50	8917	nM	CHEMBL1544329
5.04	IC50	9200	nM	BLAPSIN A
5.01	IC50	9679	nM	CHEMBL2001481
5.00	IC50	1e+04	nM	BLAPSIN B

PubChem BioAssay actives

7 with measured affinity, of 16 total; 5 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149801: Binding affinity to human YWHAG incubated for 45 mins by Kinobead based pull down assay	kd	0.0044	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178979: Inhibition of YWHAG (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.5300	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149801: Binding affinity to human YWHAG incubated for 45 mins by Kinobead based pull down assay	kd	0.6688	uM
2-(3,4-dihydroxyphenyl)ethyl 2-(3,4-dihydroxyphenyl)acetate	662445: Inhibition of recombinant GST-tagged 14-3-3gamma interaction with TMR-pS259-Raf peptide after 30 mins by fluorescence polarization assay	ic50	2.0000	uM
1-(3,4-dihydroxyphenyl)-3,4-dihydro-1H-isochromene-6,7-diol	662445: Inhibition of recombinant GST-tagged 14-3-3gamma interaction with TMR-pS259-Raf peptide after 30 mins by fluorescence polarization assay	ic50	2.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
Smoke	decreases expression, increases abundance	3
bisphenol A	increases expression, decreases expression	2
Air Pollutants	increases abundance, decreases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Caffeine	increases expression, increases phosphorylation	2
Estradiol	affects expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
fumagillin	affects cotreatment, decreases activity, decreases metabolic processing	1
potassium chromate(VI)	affects cotreatment, increases expression	1
dibenzo(a,l)pyrene	decreases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
evodiamine	increases expression	1
microcystin RR	decreases expression	1
3,4,5-trihydroxy-2–methoxy-8,8-dimethyl-N-(hexahydro-2-oxo-6-(cyclohexylcarbonyl)oxy-2H-azepin-3-yl)non-6-enamide	affects cotreatment, decreases activity, decreases metabolic processing	1
bisphenol B	increases expression	1
bromovanin	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
eprenetapopt	increases expression, affects reaction	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1

ChEMBL screening assays

12 unique, capped per target: 11 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1614427	Functional	PUBCHEM_BIOASSAY: 14-3-3 protein interaction modulators Dose Response Confirmation. (Class of assay: confirmatory) [Related pubchem assays: 422 (Primary screen preceding this dose response confirmation assay.)]	PubChem BioAssay data set
CHEMBL2033506	Binding	Inhibition of recombinant GST-tagged 14-3-3gamma interaction with PRAS40 in Cos7 cell lysate by ELISA	Identification of blapsins A and B as potent small-molecule 14-3-3 inhibitors from the insect Blaps japanensis. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3LJ	Abcam HEK293T YWHAG KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT00149877	PHASE4	COMPLETED	Efficacy, Safety and Tolerability of Tegaserod in Patients With Chronic Constipation
NCT00153114	PHASE4	COMPLETED	PolyethyleneGlycol3350 Laxative vs Placebo in Constipated Children
NCT00153127	PHASE4	COMPLETED	Comparison of PolyethyleneGlycol and Placebo for Relief of Constipation From Constipating Medications
NCT00153140	PHASE4	COMPLETED	Polyethyleneglycol3350 vs Tegaserod in Treatment of Patients With Chronic Constipation
NCT00153153	PHASE4	COMPLETED	Extended Use of Polyethyleneglycol3350 Laxative in Constipated Patients
NCT00157638	PHASE4	COMPLETED	Integrating Family Medicine and Pharmacy to Advance Primary Care Therapeutics
NCT00164125	PHASE4	COMPLETED	An Open Label Study of Chronic Polyethyleneglycol3350 Use in Constipated Patients
NCT00171522	PHASE4	COMPLETED	Preference of Tegaserod vs. PEG 3350 in Patients With Constipation
NCT00256984	PHASE4	COMPLETED	Study of Stapled Transanal Rectal Resection (STARR) Surgery in Refractory Constipation Associated With Obstructive Defecation Syndrome (ODS)
NCT00276354	PHASE4	COMPLETED	Study of Long-term Use of Forlax® in Elderly Patients With Chronic Constipation
NCT00286520	PHASE4	COMPLETED	Treatment of Fecal Incontinence and Constipation in Patients With Spinal Cord Injury
NCT00319670	PHASE4	COMPLETED	A Pilot Study of a New MiraLax® Dose Formulation For Use in Constipated Children
NCT00348634	PHASE4	TERMINATED	Effect of Tegaserod on Orocecal Transit in Elderly Chronic Constipation Patients
NCT00452335	PHASE4	COMPLETED	Safety and Efficacy of Lubiprostone in Pediatric Patients With Constipation
NCT00521872	PHASE4	COMPLETED	Stapled Trans Anal Rectal Resection (STARR) for Outlet Obstruction: Functional and Morphological Outcome
NCT00583609	PHASE4	COMPLETED	A Pilot Study of a New PEG3350 Dose Formulation For Use in Constipated Children
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