YWHAE

Summary

YWHAE (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon, HGNC:12851) is a protein-coding gene on chromosome 17p13.3, encoding 14-3-3 protein epsilon (P62258). Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. It is a selective cancer dependency (DepMap: 33.6% of cell lines).

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 mouse ortholog. It interacts with CDC25 phosphatases, RAF1 and IRS1 proteins, suggesting its role in diverse biochemical activities related to signal transduction, such as cell division and regulation of insulin sensitivity. It has also been implicated in the pathogenesis of small cell lung cancer. Two transcript variants, one protein-coding and the other non-protein-coding, have been found for this gene.

Source: NCBI Gene 7531 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 101 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 33
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 33.6% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_006761

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12851
Approved symbol	YWHAE
Name	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon
Location	17p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ45465
Ensembl gene	ENSG00000108953
Ensembl biotype	protein_coding
OMIM	605066
Entrez	7531

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 11 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000264335, ENST00000466227, ENST00000469398, ENST00000486241, ENST00000489287, ENST00000496706, ENST00000498643, ENST00000571732, ENST00000572108, ENST00000573026, ENST00000573196, ENST00000575977, ENST00000576854, ENST00000928923, ENST00000928924, ENST00000928925, ENST00000928926, ENST00000928927, ENST00000946803

RefSeq mRNA: 1 — MANE Select: NM_006761 NM_006761

CCDS: CCDS11001

Canonical transcript exons

ENST00000264335 — 6 exons

Exon	Start	End
ENSE00001299180	1361092	1361298
ENSE00001858423	1344275	1345499
ENSE00002394042	1361902	1362008
ENSE00002683090	1400047	1400222
ENSE00003463905	1354211	1354347
ENSE00003621688	1364859	1365058

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 99.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 425.7423 / max 10564.2601, expressed in 1828 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163704	425.7423	1828

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superior frontal gyrus	UBERON:0002661	99.87	gold quality
ventricular zone	UBERON:0003053	99.85	gold quality
cortical plate	UBERON:0005343	99.82	gold quality
primary visual cortex	UBERON:0002436	99.81	gold quality
prefrontal cortex	UBERON:0000451	99.80	gold quality
ganglionic eminence	UBERON:0004023	99.78	gold quality
embryo	UBERON:0000922	99.77	gold quality
frontal cortex	UBERON:0001870	99.76	gold quality
frontal lobe	UBERON:0016525	99.76	gold quality
corpus callosum	UBERON:0002336	99.75	gold quality
cerebral cortex	UBERON:0000956	99.74	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.73	gold quality
temporal lobe	UBERON:0001871	99.72	gold quality
amygdala	UBERON:0001876	99.72	gold quality
telencephalon	UBERON:0001893	99.72	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.72	gold quality
anterior cingulate cortex	UBERON:0009835	99.71	gold quality
caudate nucleus	UBERON:0001873	99.70	gold quality
hypothalamus	UBERON:0001898	99.70	gold quality
Ammon’s horn	UBERON:0001954	99.70	gold quality
nucleus accumbens	UBERON:0001882	99.69	gold quality
right frontal lobe	UBERON:0002810	99.69	gold quality
brain	UBERON:0000955	99.68	gold quality
putamen	UBERON:0001874	99.68	gold quality
substantia nigra	UBERON:0002038	99.64	gold quality
spinal cord	UBERON:0002240	99.64	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.64	gold quality
cerebellum	UBERON:0002037	99.62	gold quality
cerebellar cortex	UBERON:0002129	99.62	gold quality
cerebellar hemisphere	UBERON:0002245	99.62	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	144.52
E-ENAD-21	no	1259.88
E-CURD-7	no	1252.09
E-GEOD-81608	no	1098.79
E-MTAB-5061	no	546.27
E-HCAD-10	no	37.17
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CEBPG, MYC, PPARD, PPARG

miRNA regulators (miRDB)

136 targeting YWHAE, 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-4668-3P	100.00	68.74	2635
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 33.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Identification of frequent G(2) checkpoint impairment and a homozygous deletion of 14-3-3epsilon at 17p13.3 in small cell lung cancers. (PMID:11782387)
• study suggests that the cleavage of 14-3-3 protein during apoptosis promotes cell death by releasing the associated Bad protein from the 14-3-3 protein and facilitates Bad translocation to the mitochondria and its interaction with Bcl-x(L) (PMID:12657644)
• HSF1 binding to 14-3-3 epsilon requires HSF1 phosphorylation on serines 303 and 307, the serine phosphorylation-dependent binding of HSF1 to 14-3-3 epsilon results in the transcriptional repression of HSF1 and its sequestration in the cytoplasm. (PMID:12917326)
• 14-3-3 adapter proteins may have a role in regulating CD81 signaling, possibly dependent on cellular redox (PMID:14966136)
• HSF1 associates with ERK1 and 14-3-3epsilon during heat shock to modulate the amplitude of the response and lead to efficient termination of HSP expression on resumption of growth conditions (PMID:15364926)
• there is a phosphorylation-regulated complex formation of Grb10 with 14-3-3 and Akt (PMID:15722337)
• 14-3-3 epsilon is a potential suicide susceptibility gene and implies that dysregulation of neurogenesis may be involved in suicide. (PMID:15838597)
• plasma membrane Na+/Ca2+ exchangers have inhibitory interactions with the 14-3-3 proteins (PMID:16679322)
• Upon co-expression with 14-3-3epsilon, mutant HERG channels still bound 14-3-3epsilon but did not respond with a hyperpolarizing shift in voltage dependence as seen in wild-type channels. (PMID:16923798)
• These results indicate that the epsilon isoform of 14-3-3 is a component of PrP amyloid deposits of GSS and suggest that this is the sole 14-3-3 isoform specifically involved in the neuropathologic changes associated with this disorder. (PMID:17278997)
• 14-3-3, a cruciform DNA binding protein, associates with yeast origins of replication and functions as an initiator of DNA replication (PMID:17430600)
• These results suggest that 14-3-3epsilon bound to MK5 inhibits cell migration by inhibiting the phosphorylation of HSP27 whose phosphorylation regulates F-actin polymerization, actin cytoskeleton organization and subsequent actinfilament dynamics. (PMID:17728103)
• 14-3-3epsilon and 14-3-3zeta are identified as Cby-binding partners. (PMID:18573912)
• YWHAE is a possible susceptibility gene that functions protectively in schizophrenia. (PMID:18658164)
• 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)
• Microdeletions on chromosome 17p13.3 present with growth retardaion, craniofacial dysmorphisms, structural abnormalities of the brain, and cognitive impairmant. (PMID:19584063)
• In one patient presenting with periventricular nodular heterotopias and pronounced corpus callosum hypoplasia, a small (400 kb) 17p13.3 deletion involving the YWHAE gene was identified. (PMID:19635726)
• Data suggest a novel mechanism in which PKA down-regulates Hedgehog signaling by promoting the interaction between 14-3-3 and Gli as well as proteolysis. (PMID:19996099)
• The 14-3-3 epsilon, zeta and theta may be involved in tumorigenesis of meningioma and be efficient markers for predicting the degree of malignancy in meningioma. (PMID:20388496)
• the identification of a novel splicing variant of human 14-3-3 epsilon (14-3-3 epsilon sv), derived from a novel exon 1’ insertion is reported. (PMID:20417184)
• For the first time, we found that TNF-alpha stimulation enhances the interactions between 14-3-3 epsilon and some key components in the mitogen-activated protein kinase (MAPK) signal module which is located at the immediate upstream of NF-kappaB. (PMID:20462248)
• Decreased expression of 14-3-3epsilon in contributes to the initiation and progression of laryngeal carcinoma by affecting apoptosis and invasion. (PMID:20565895)
• YWHAE does not play a major role in schizophrenia, major depressive disorder or bipolar disorder in the Han Chinese populatio (PMID:21184166)
• Results suggest that ERK and p38 MAPK regulate subcellular localization of Prdx6 by activation of 14-3-3epsilon as a chaperone protein, resulting in its translocation to acidic organelles. (PMID:21346153)
• Overexpression of 14-3-3epsilon predicts tumour metastasis and poor survival in hepatocellular carcinoma (PMID:21401702)
• Data suggest a regulatory circuitry involving Smad4 dependent up-regulation of KRT23 (directly or indirectly) which in turn modulates the interaction between KRT23 and 14-3-3epsilon leading to a cytoplasmic sequestration of 14-3-3epsilon. (PMID:21492476)
• Analyses show that high cytoplasmic levels of 14-3-3beta and epsilon independently correlate with poor disease-specific survival in vulvar squamous cell carcinoma cases. (PMID:21935479)
• Data present the high-resolution crystal structure of this binding motif [MLF1(29-42)pSer34] in complex with 14-3-3epsilon and analyse the interaction with isothermal titration calorimetry. (PMID:22151054)
• Fluorescence in situ hybridization analysis demonstrated absolute specificity of YWHAE-FAM22A/B genetic rearrangement for high-grade endometrial stromal sarcoma. (PMID:22223660)
• Collectively, these results identify a novel locus of apoptosomal regulation wherein MAPK signalling promotes Rsk-catalysed Apaf-1 phosphorylation and consequent binding of 14-3-3varepsilon, resulting in decreased cellular responsiveness to cytochrome c. (PMID:22246185)
• Tumors with YWHAE-FAM22 rearrangements constitute a distinct group of endometrial stromal sarcoma (ESS), which is associated with high-grade morphology and aggressive clinical behavior compared to JAZF1 ESS. (PMID:22456610)
• Data obtained, which have never previously been reported, were used to modify the published 14-3-3 crystal structure using molecular modeling. (PMID:22580067)
• 14-3-3epsilon is essential for the stable interaction of RIG-I with TRIM25, which facilitates RIG-I ubiquitination and initiation of innate immunity against hepatitis C virus and other pathogenic RNA viruses. (PMID:22607805)
• results indicate that the dosage effect of YWHAE varies from severe to very mild structural brain abnormalities, and suggest that the expression of YWHAE is associated with a complex mechanism of neuronal development (PMID:22887762)
• The ERK/MAPK pathway is involved in the pathogenesis of gastric cancer; RKIP and 14-3-3epsilon exert an opposite effect on this pathway and the cells possibly via both direct and indirect reactions with the elements in this pathway. (PMID:22899242)
• findings suggest that FAK expression is correlated with and upregulated by 14-3-3epsilon via activation of NFkappaB (PMID:22934705)
• When evaluating high-grade uterine sarcomas, cyclin D1 can be included in the immuno-histochemical panel as an indicator of YWHAE-FAM22endometrial stromal sarcoma. (PMID:22982899)
• These results showed that IgE is produced during malaria, and that the negative correlation between levels of IgE to 14-3-3 epsilon protein and parasitemia in asymptomatic malaria supports a role for these IgE molecules in defense mechanisms. (PMID:22984113)
• YWHAE gene contribute to the phenotype of small 17p13.3 chromosomal duplication in Miller-Dieker syndrome (PMID:23035971)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ywhae1	ENSDARG00000006399
mus_musculus	Ywhae	ENSMUSG00000020849
rattus_norvegicus	Ywhae	ENSRNOG00000005290
drosophila_melanogaster	14-3-3epsilon	FBGN0020238
caenorhabditis_elegans		WBGENE00010919

Paralogs (6): YWHAH (ENSG00000128245), YWHAQ (ENSG00000134308), YWHAZ (ENSG00000164924), YWHAB (ENSG00000166913), YWHAG (ENSG00000170027), SFN (ENSG00000175793)

Protein

Protein identifiers

14-3-3 protein epsilon — P62258 (reviewed: P62258)

All UniProt accessions (7): P62258, B4DJF2, I3L0W5, I3L3T1, K7EIT4, K7EM20, V9HW98

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. Positively regulates phosphorylated protein HSF1 nuclear export to the cytoplasm. Plays a positive role in the antiviral signaling pathway upstream of TBK1 via interaction with RIGI. Mechanistically, directs RIGI redistribution from the cytosol to mitochondrial associated membranes where it mediates MAVS-dependent innate immune signaling during viral infection. Plays a role in proliferation inhibition and cell cycle arrest by exporting HNRNPC from the nucleus to the cytoplasm to be degraded by ubiquitination.

Subunit / interactions. Homodimer. Heterodimerizes with YWHAZ. Interacts with PKA-phosphorylated AANAT. Interacts with ABL1 (phosphorylated form); the interaction retains it in the cytoplasm. Interacts with ARHGEF28. Interacts with BEX3. Weakly interacts with CDKN1B. Interacts with the ‘Thr-369’ phosphorylated form of DAPK2. Interacts with DENND1A. Interacts with GAB2. Interacts with phosphorylated GRB10. Interacts with KSR1. Interacts with NDEL1. Interacts with PI4KB, TBC1D22A and TBC1D22B. Interacts with the phosphorylated (by AKT1) form of SRPK2. Interacts with TIAM2. Interacts with the ‘Ser-1134’ and ‘Ser-1161’ phosphorylated form of SOS1. Interacts with ZFP36 (via phosphorylated form). Interacts with SLITRK1. Interacts with HSF1 (via phosphorylated form); this interaction promotes HSF1 sequestration in the cytoplasm in a ERK-dependent manner. Interacts with RIPOR2 isoform 2. Interacts with KLHL22; required for the nuclear localization of KLHL22 upon amino acid starvation. Interacts with CRTC1. Interacts with CRTC2 (probably when phosphorylated at ‘Ser-171’). Interacts with CRTC3 (probably when phosphorylated at ‘Ser-162’ and/or ‘Ser-273’). Interacts with ATP2B1 and ATP2B3; this interaction inhibits calcium-transporting ATPase activity. Interacts with MEFV. Interacts with RIGI. Interacts with TRIM25. Interacts with HNRNPC. Interacts with RNF115. Interacts with GPR15; this interaction promotes ER-to-Golgi transport of GPR15. (Microbial infection) Interacts with HCV core protein.

Subcellular location. Nucleus. Cytoplasm. Melanosome.

Post-translational modifications. (Microbial infection) Cleaved by poliovirus protease 3C, leading to disruption of the interaction with RIGI.

Miscellaneous. Unable to dimerize with YWHAZ.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P62258-1	1	yes
P62258-2	SV

RefSeq proteins (1): NP_006752* (*=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 (34 total): helix 11, modified residue 10, sequence conflict 3, site 3, chain 1, region of interest 1, cross-link 1, splice variant 1, mutagenesis site 1, strand 1, turn 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
2BR9	X-RAY DIFFRACTION	1.75
3UAL	X-RAY DIFFRACTION	1.8
7V9B	X-RAY DIFFRACTION	1.85
3UBW	X-RAY DIFFRACTION	1.9
6EIH	X-RAY DIFFRACTION	2.7
8DGP	X-RAY DIFFRACTION	2.7
8DP5	ELECTRON MICROSCOPY	3.1
7C8E	X-RAY DIFFRACTION	3.16
8DGN	X-RAY DIFFRACTION	3.16
8DGM	X-RAY DIFFRACTION	3.2
8Q1S	X-RAY DIFFRACTION	3.23

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62258-F1	92.90	0.86

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 (3): 57 (interaction with phosphoserine on interacting protein); 130 (interaction with phosphoserine on interacting protein); 236–237 ((microbial infection) cleavage; by poliovirus protease 3c)

Post-translational modifications (11): 123, 131, 137, 210, 232, 50, 1, 50, 65, 69, 118

Mutagenesis-validated functional residues (1):

Position	Phenotype
236	complete loss of cleavage by poliovirus protease 3c.

Function

Pathways and Gene Ontology

Reactome pathways

67 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-2028269	Signaling by Hippo
R-HSA-205025	NADE modulates death signalling
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-3371511	HSF1 activation
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-8862803	Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs
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-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-193704	p75 NTR receptor-mediated signalling

MSigDB gene sets: 593 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_POTASSIUM_ION_TRANSPORT, MODULE_52, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, TGCGCANK_UNKNOWN, PID_TELOMERASE_PATHWAY, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, KAAB_FAILED_HEART_ATRIUM_DN, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GCANCTGNY_MYOD_Q6, SP3_Q3, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_PROTEIN_TARGETING

GO Biological Process (32): MAPK cascade (GO:0000165), neuron migration (GO:0001764), cytoplasmic pattern recognition receptor signaling pathway (GO:0002753), regulation of heart rate by hormone (GO:0003064), protein targeting (GO:0006605), signal transduction (GO:0007165), regulation of mitotic cell cycle (GO:0007346), intracellular protein localization (GO:0008104), substantia nigra development (GO:0021762), hippocampus development (GO:0021766), cerebral cortex development (GO:0021987), intracellular potassium ion homeostasis (GO:0030007), negative regulation of toll-like receptor signaling pathway (GO:0034122), protein localization to nucleus (GO:0034504), cellular response to heat (GO:0034605), positive regulation of hippo signaling (GO:0035332), intracellular signal transduction (GO:0035556), positive regulation of protein export from nucleus (GO:0046827), regulation of cytosolic calcium ion concentration (GO:0051480), regulation of membrane repolarization (GO:0060306), protein localization to endoplasmic reticulum (GO:0070972), membrane repolarization during cardiac muscle cell action potential (GO:0086013), regulation of heart rate by cardiac conduction (GO:0086091), regulation of potassium ion transmembrane transport (GO:1901379), negative regulation of calcium ion export across plasma membrane (GO:1905913), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), Golgi to plasma membrane transport (GO:0006893), positive regulation of toll-like receptor signaling pathway (GO:0034123), toll-like receptor 4 signaling pathway (GO:0034142), hippo signaling (GO:0035329), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), protein K11-linked ubiquitination (GO:0070979)

GO Molecular Function (22): RNA binding (GO:0003723), protein phosphatase inhibitor activity (GO:0004864), calcium channel regulator activity (GO:0005246), potassium channel regulator activity (GO:0015459), calcium channel inhibitor activity (GO:0019855), enzyme binding (GO:0019899), protein phosphatase binding (GO:0019903), protein domain specific binding (GO:0019904), MHC class II protein complex binding (GO:0023026), ubiquitin protein ligase binding (GO:0031625), signaling adaptor activity (GO:0035591), identical protein binding (GO:0042802), histone deacetylase binding (GO:0042826), transmembrane transporter binding (GO:0044325), cadherin binding (GO:0045296), protein heterodimerization activity (GO:0046982), phosphoserine residue binding (GO:0050815), phosphoprotein binding (GO:0051219), scaffold protein binding (GO:0097110), protein sequestering activity (GO:0140311), protein binding (GO:0005515), molecular function inhibitor activity (GO:0140678)

GO Cellular Component (10): nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), focal adhesion (GO:0005925), membrane (GO:0016020), mitochondrial membrane (GO:0031966), melanosome (GO:0042470), extracellular exosome (GO:0070062), plasma membrane (GO:0005886)

Reactome top-level categories

Rollup of top-17 pathways:

Category	Pathways
G2/M Transition	2
Cellular response to heat stress	2
Centrosome maturation	2
Activation of BH3-only proteins	1
Membrane Trafficking	1
Signal Transduction	1
Cell death signalling via NRAGE, NRIF and NADE	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
Neurodegenerative Diseases	1
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	7
cellular anatomical structure	3
pallium development	2
anatomical structure development	2
intracellular anatomical structure	2
calcium channel activity	2
ion channel regulator activity	2
intracellular membrane-bounded organelle	2
cytoplasm	2
intracellular signaling cassette	1
cell migration	1
generation of neurons	1
positive regulation of cytokine production	1
pattern recognition receptor signaling pathway	1
intracellular receptor signaling pathway	1
regulation of heart rate by chemical signal	1
establishment of protein localization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
mitotic cell cycle	1
regulation of cell cycle	1
macromolecule localization	1
midbrain development	1
neural nucleus development	1
limbic system development	1
intracellular monoatomic cation homeostasis	1
potassium ion homeostasis	1
toll-like receptor signaling pathway	1
negative regulation of immune system process	1
negative regulation of signal transduction	1
regulation of toll-like receptor signaling pathway	1
protein localization to organelle	1
response to heat	1
cellular response to stress	1
hippo signaling	1
regulation of hippo signaling	1
positive regulation of intracellular signal transduction	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

1084 interactions, top by confidence:

A	B	Type	Score
MAP2K1	RAF1	psi-mi:“MI:0914”(association)	0.960
YWHAG	YWHAE	psi-mi:“MI:0407”(direct interaction)	0.940
BRAF	HRAS	psi-mi:“MI:0914”(association)	0.940
YWHAB	YWHAE	psi-mi:“MI:0407”(direct interaction)	0.930
YWHAE	YWHAQ	psi-mi:“MI:0407”(direct interaction)	0.920
YWHAE	RAF1	psi-mi:“MI:0915”(physical association)	0.920
PTPN3	YWHAQ	psi-mi:“MI:2364”(proximity)	0.850
ENTREP1	WWP2	psi-mi:“MI:0914”(association)	0.850
YAP1	YWHAE	psi-mi:“MI:0915”(physical association)	0.840
MARK3	YWHAE	psi-mi:“MI:0914”(association)	0.790
YWHAE	CDC25A	psi-mi:“MI:0915”(physical association)	0.760
CDC25B	YWHAE	psi-mi:“MI:0915”(physical association)	0.760
YWHAE	CDC25B	psi-mi:“MI:0915”(physical association)	0.760
YWHAE	RAB11FIP2	psi-mi:“MI:0915”(physical association)	0.740
MARK2	YWHAE	psi-mi:“MI:0914”(association)	0.730
INPP5E	PDE6D	psi-mi:“MI:0914”(association)	0.730
PARD6G	PRKCI	psi-mi:“MI:0914”(association)	0.720
YWHAH	FAM83G	psi-mi:“MI:0914”(association)	0.710
CGN	YWHAQ	psi-mi:“MI:0914”(association)	0.710
RAB3IP	TRAPPC3	psi-mi:“MI:0914”(association)	0.700
BRAF	KRAS	psi-mi:“MI:0914”(association)	0.680
SIK3	YWHAE	psi-mi:“MI:0914”(association)	0.670
SIK1	YWHAE	psi-mi:“MI:0914”(association)	0.670
YWHAE	YWHAE	psi-mi:“MI:0407”(direct interaction)	0.670
PTPN3	MCC	psi-mi:“MI:0914”(association)	0.660
MAST1	YWHAB	psi-mi:“MI:0914”(association)	0.640
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
PAK6	YWHAG	psi-mi:“MI:0914”(association)	0.640

BioGRID (2093): YWHAE (Affinity Capture-MS), YWHAE (Affinity Capture-Western), YWHAE (Reconstituted Complex), YWHAE (Affinity Capture-Western), GRB10 (Affinity Capture-Western), YWHAE (Two-hybrid), YWHAE (Affinity Capture-Western), DTL (Affinity Capture-Western), YWHAE (Affinity Capture-MS), YWHAE (Affinity Capture-MS), SORBS2 (Two-hybrid), FAM53C (Two-hybrid), Mdm4 (Reconstituted Complex), YWHAE (Affinity Capture-MS), YWHAE (Affinity Capture-MS)

ESM2 similar proteins: B8NLM9, O49995, O49996, O49998, O65352, P29307, P29309, P42644, P42648, P42653, P42654, P48347, P48348, P48349, P49106, P52908, P54632, P62258, P62259, P62260, P62261, P62262, P92177, P93206, P93207, P93208, P93210, P93212, P93214, P93259, P93342, Q01526, Q2F637, Q41246, Q41418, Q43470, Q43643, Q5XHK2, Q5ZMT0, Q6EUP4

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

6 interactions.

A	Effect	B	Mechanism
YWHAE	“up-regulates activity”	NDEL1	binding
YWHAE	“down-regulates activity”	NEFL	binding
ATG9A	“up-regulates activity”	YWHAE	binding
YWHAE	down-regulates	CDKN1B	binding
YWHAE	“up-regulates quantity by stabilization”	GRIN2C	binding
YWHAE	“up-regulates activity”	TBP	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 194 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
Activation of BAD and translocation to mitochondria	6	33.6×	7e-07
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	29.6×	1e-06
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	29.6×	1e-06
Signaling by high-kinase activity BRAF mutants	11	25.7×	2e-10
Signaling by RAS mutants	8	24.9×	6e-08
MAP2K and MAPK activation	11	23.1×	3e-10
Signaling by RAF1 mutants	11	22.5×	3e-10
Activation of BH3-only proteins	6	21.9×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
insulin-like growth factor receptor signaling pathway	6	17.2×	3e-04
positive regulation of fibroblast proliferation	7	12.0×	4e-04
ERK1 and ERK2 cascade	6	11.0×	2e-03
intrinsic apoptotic signaling pathway	5	10.4×	1e-02
MAPK cascade	11	9.7×	7e-06
positive regulation of protein localization to plasma membrane	6	9.4×	4e-03
insulin receptor signaling pathway	7	9.0×	2e-03
epidermal growth factor receptor signaling pathway	6	8.6×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	20
Likely benign	31
Benign	23

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
4813503	Single allele	Pathogenic
816551	GRCh37/hg19 17p13.3(chr17:1193546-1376587)x3	Pathogenic
152857	GRCh38/hg38 17p13.3(chr17:1348488-1358016)x3	Likely pathogenic
154956	GRCh38/hg38 17p13.3(chr17:1375174-1405502)x1	Likely pathogenic
2576581	NM_006761.5(YWHAE):c.179G>A (p.Trp60Ter)	Likely pathogenic

SpliceAI

1287 predictions. Top by Δscore:

Variant	Effect	Δscore
17:1345497:CAC:C	acceptor_gain	1.0000
17:1345498:ACCTG:A	acceptor_loss	1.0000
17:1345499:CCTG:C	acceptor_loss	1.0000
17:1345500:C:CC	acceptor_gain	1.0000
17:1345501:T:A	acceptor_loss	1.0000
17:1345503:T:TC	acceptor_gain	1.0000
17:1354205:GCTT:G	donor_loss	1.0000
17:1354206:CTT:C	donor_loss	1.0000
17:1354207:TTA:T	donor_loss	1.0000
17:1354208:T:TG	donor_loss	1.0000
17:1354209:A:AC	donor_gain	1.0000
17:1354209:A:AG	donor_loss	1.0000
17:1354210:C:CC	donor_gain	1.0000
17:1354210:CCG:C	donor_gain	1.0000
17:1354347:CCTA:C	acceptor_loss	1.0000
17:1355659:CAA:C	acceptor_gain	1.0000
17:1355660:A:T	acceptor_gain	1.0000
17:1355735:A:C	donor_gain	1.0000
17:1361088:TTA:T	donor_loss	1.0000
17:1361089:TACCT:T	donor_loss	1.0000
17:1361090:ACCT:A	donor_loss	1.0000
17:1361091:C:A	donor_loss	1.0000
17:1361294:CTTTC:C	acceptor_gain	1.0000
17:1361900:A:AC	donor_gain	1.0000
17:1361901:C:CC	donor_gain	1.0000
17:1361938:G:C	donor_gain	1.0000
17:1364853:TCTCA:T	donor_loss	1.0000
17:1364854:CTCA:C	donor_loss	1.0000
17:1364855:TCA:T	donor_loss	1.0000
17:1364856:CA:C	donor_loss	1.0000

AlphaMissense

1690 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:1354233:C:A	W231C	1.000
17:1354233:C:G	W231C	1.000
17:1354234:C:G	W231S	1.000
17:1354235:A:G	W231R	1.000
17:1354235:A:T	W231R	1.000
17:1354237:A:G	L230P	1.000
17:1354237:A:T	L230Q	1.000
17:1354243:A:G	L228P	1.000
17:1354243:A:T	L228Q	1.000
17:1354245:A:C	N227K	1.000
17:1354245:A:T	N227K	1.000
17:1354246:T:A	N227I	1.000
17:1354247:T:C	N227D	1.000
17:1354248:A:C	D226E	1.000
17:1354248:A:T	D226E	1.000
17:1354249:T:A	D226V	1.000
17:1354249:T:C	D226G	1.000
17:1354249:T:G	D226A	1.000
17:1354250:C:A	D226Y	1.000
17:1354250:C:G	D226H	1.000
17:1354250:C:T	D226N	1.000
17:1354252:C:G	R225P	1.000
17:1354253:G:T	R225S	1.000
17:1354254:T:A	L224F	1.000
17:1354254:T:G	L224F	1.000
17:1354255:A:G	L224S	1.000
17:1354257:C:A	L223F	1.000
17:1354257:C:G	L223F	1.000
17:1354258:A:C	L223W	1.000
17:1354258:A:G	L223S	1.000

dbSNP variants (sampled 300 via entrez): RS1000007499 (17:1349854 T>C), RS1000009360 (17:1394354 T>C,G), RS1000029832 (17:1397279 C>T), RS1000031424 (17:1374564 A>G), RS1000038646 (17:1347014 T>A), RS1000091122 (17:1366872 G>A), RS1000161835 (17:1368045 G>C), RS1000180929 (17:1401015 T>C), RS1000237850 (17:1386512 T>C), RS1000243935 (17:1370734 G>A), RS1000274566 (17:1393571 A>C), RS1000281090 (17:1370681 T>C), RS1000300240 (17:1357845 T>C,G), RS1000344170 (17:1395978 C>T), RS1000365843 (17:1374795 G>A)

Disease associations

OMIM: gene MIM:605066 | disease phenotypes: MIM:247200, MIM:142623

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant
complex neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (4): Miller-Dieker lissencephaly syndrome (MONDO:0009532), Hirschsprung disease (MONDO:0018309), complex neurodevelopmental disorder (MONDO:0100038), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Miller-Dieker syndrome (Orphanet:531), Hirschsprung disease (Orphanet:388)

HPO phenotypes

33 total (30 of 33 shown, HPO-id order):

HPO	Term
HP:0000023	Inguinal hernia
HP:0000098	Tall stature
HP:0000112	Nephropathy
HP:0000160	Narrow mouth
HP:0000177	Abnormal upper lip morphology
HP:0000218	High palate
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000445	Wide nose
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000494	Downslanted palpebral fissures
HP:0000960	Sacral dimple
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001339	Lissencephaly
HP:0001374	Congenital hip dislocation
HP:0001510	Growth delay
HP:0001539	Omphalocele
HP:0001561	Polyhydramnios
HP:0001626	Abnormality of the cardiovascular system
HP:0002007	Frontal bossing
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002120	Cerebral cortical atrophy
HP:0002353	EEG abnormality

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST004946_33	Schizophrenia	1.000000e-09
GCST006268_480	Reaction time	5.000000e-08
GCST006414_32	Atrial fibrillation	3.000000e-09
GCST007201_250	Schizophrenia	1.000000e-07
GCST010105_139	Nicotine dependence symptom count	8.000000e-06
GCST010105_196	Nicotine dependence symptom count	8.000000e-06
GCST011213_1	Left ventricular mass to end-diastolic volume ratio (MTAG)	4.000000e-06
GCST90002386_298	High light scatter reticulocyte percentage of red cells	1.000000e-09
GCST90002395_233	Mean platelet volume	4.000000e-13
GCST90002397_725	Mean spheric corpuscular volume	7.000000e-10
GCST90026611_1	Bevacizumab-induced composite toxicity (either hypertension or proteinuria)	2.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008393	reaction time measurement
EFO:0009262	nicotine dependence symptom count
EFO:0010556	Left ventricular mass to end-diastolic volume ratio
EFO:0005943	response to bevacizumab

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006627	Hirschsprung Disease	C06.198.439; C06.405.469.158.701.439; C16.131.314.439
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3329082 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.32	Kd	47.7	nM	CHEMBL5653589
7.32	ED50	47.7	nM	CHEMBL5653589
5.21	Kd	6152	nM	CHEMBL3752910
5.21	ED50	6152	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 10 total; 2 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149800: Binding affinity to human YWHAE incubated for 45 mins by Kinobead based pull down assay	kd	0.0477	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149800: Binding affinity to human YWHAE incubated for 45 mins by Kinobead based pull down assay	kd	6.1515	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, increases expression	5
Tobacco Smoke Pollution	affects expression, increases expression, increases metabolic processing	3
bisphenol F	decreases methylation, increases expression	2
sulindac sulfide	affects reaction, decreases expression, affects binding, increases reaction, increases localization	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
bisphenol S	decreases methylation, increases expression	2
Resveratrol	decreases expression, increases expression	2
Caffeine	decreases expression, decreases phosphorylation	2
Indomethacin	decreases expression, increases localization, affects reaction	2
Silicon Dioxide	affects expression, affects secretion	2
Dronabinol	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
methylselenic acid	decreases expression	1
titanium dioxide	increases phosphorylation	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
arsenite	affects binding, increases reaction	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sulforaphane	affects binding	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	increases abundance, affects methylation	1
cobaltous chloride	decreases expression	1
sulindac sulfone	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
nickel sulfate	increases expression	1
phenethyl isothiocyanate	affects binding	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide	decreases expression, increases localization, affects reaction	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid	increases expression, affects cotreatment	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3389100	Binding	Inhibition of recombinant 14-3-3epsilon protein (unknown origin) expression in Escherichia coli assessed as reduction in 14-3-3epsilon and histone H3 Ser10 interaction using human HT-29 cells lysates at 1 uM incubated for 1 hr by Western bl	Identification of 4’-O-β-D-glucosyl-5-O-methylvisamminol as a novel epigenetic suppressor of histone H3 phosphorylation at Ser10 and its interaction with 14-3-3ε. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8YC	Ubigene HCT 116 YWHAE KO	Cancer cell line	Male

Clinical trials (associated diseases)

257 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,
NCT02343562	PHASE4	UNKNOWN	Probiotics for Prophylaxis of Postoperative Hirschsprungs Associated Enterocolitis
NCT07186647	PHASE4	COMPLETED	Laparoscopic-Assisted Transanal Pull-Through for Hirschsprung Disease in Pediatric:Short and Intermediate Outcomes of Two Different Techniques
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
NCT03660176	PHASE3	UNKNOWN	Effects of Butyrate Enemas on Postoperative Intestinal Mobility Disorders in Hirschsprung’s Disease
NCT04904081	PHASE3	UNKNOWN	Feasibility of Use of Indocyanine Green in Pediatric Colorectal Surgery
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
NCT00630838	PHASE2	COMPLETED	Probiotic Prophylaxis of Hirschprung’s Disease Associated Enterocolitis (HAEC)
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers