YWHAE

tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon, the group of 14-3-3 phospho-serine/phospho-threonine binding proteins

Basic information

Region (hg38): 17:1344275-1400222

Links

ENSG00000108953 ∙ NCBI:7531 ∙ OMIM:605066 ∙ HGNC:12851 ∙ Uniprot:P62258 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the YWHAE gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the YWHAE gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				11		11
missense			3			3
nonsense		1				1
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				4	2	6
non coding			1	13	17	31
Total	0	1	5	24	17

Variants in YWHAE

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

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

Position	Type	Phenotype	Significance	ClinVar
17-1345289-TA-T			Benign (May 16, 2021)
17-1345289-T-TA			Benign (May 17, 2021)
17-1345289-T-TAA			Benign (May 17, 2021)
17-1345459-G-A		YWHAE-related disorder	Benign (Oct 17, 2022)
17-1345478-G-A			Uncertain significance (Mar 17, 2022)
17-1345511-GA-G			Benign (Jun 28, 2022)
17-1354198-C-T			Likely benign (Aug 30, 2023)
17-1354199-G-A			Likely benign (Apr 11, 2021)
17-1354236-T-C		YWHAE-related disorder	Likely benign (Dec 11, 2023)
17-1354252-C-T		not specified	Uncertain significance (Oct 25, 2024)
17-1354319-T-C			Uncertain significance (Nov 27, 2023)
17-1354356-A-G			Likely benign (Jun 21, 2021)
17-1360904-G-C			Benign (May 16, 2021)
17-1361027-G-A			Benign (May 17, 2021)
17-1361124-G-A		YWHAE-related disorder	Likely benign (Dec 28, 2023)
17-1361136-G-A		YWHAE-related disorder	Likely benign (Dec 22, 2023)
17-1361226-G-A		YWHAE-related disorder	Likely benign (Nov 01, 2023)
17-1361235-C-T			Likely benign (Aug 17, 2017)
17-1361250-G-A			Likely benign (Mar 03, 2023)
17-1361316-TTA-T			Likely benign (Apr 30, 2021)
17-1361317-T-A			Benign (Jan 11, 2024)
17-1361317-TA-T			Benign (Jan 11, 2024)
17-1361317-T-TA			Benign (Aug 04, 2023)
17-1361318-A-T			Likely benign (Dec 01, 2023)
17-1361770-A-C			Benign (May 16, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
YWHAE	protein_coding	protein_coding	ENST00000264335	6	56107

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.985	0.0152	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.83	49	145	0.338	0.00000783	1687
Missense in Polyphen		8	50.025	0.15992		677
Synonymous	-0.420	57	53.1	1.07	0.00000302	467
Loss of Function	3.30	0	12.7	0.00	5.38e-7	163

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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 (By similarity). Positively regulates phosphorylated protein HSF1 nuclear export to the cytoplasm (PubMed:12917326). {ECO:0000250|UniProtKB:P62261, ECO:0000269|PubMed:12917326}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Cell cycle - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Cell Cycle;Myometrial Relaxation and Contraction Pathways;VEGFA-VEGFR2 Signaling Pathway;Calcium Regulation in the Cardiac Cell;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer,s disease models;Neurodegenerative Diseases;Disease;Signal Transduction;Gene expression (Transcription);Vesicle-mediated transport;Membrane Trafficking;Generic Transcription Pathway;Regulation of HSF1-mediated heat shock response;Alpha6Beta4Integrin;Hedgehog;Fas;Cellular responses to stress;Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex;RNA Polymerase II Transcription;Activation of BAD and translocation to mitochondria ;G2/M DNA damage checkpoint;Activation of BH3-only proteins;G2/M Checkpoints;Intrinsic Pathway for Apoptosis;Cell Cycle Checkpoints;Apoptosis;FGF;Programmed Cell Death;insulin Mam;TP53 Regulates Metabolic Genes;RHO GTPases activate PKNs;Cellular responses to external stimuli;RHO GTPase Effectors;Signaling by Rho GTPases;Regulation of PLK1 Activity at G2/M Transition;Recruitment of mitotic centrosome proteins and complexes;Signaling events mediated by HDAC Class II;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;ErbB1 downstream signaling;AURKA Activation by TPX2;Rab regulation of trafficking;G2/M Transition;Mitotic G2-G2/M phases;NADE modulates death signalling;Cellular response to heat stress;Death Receptor Signalling;a6b1 and a6b4 Integrin signaling;p75 NTR receptor-mediated signalling;Transcriptional Regulation by TP53;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;M Phase;RAB GEFs exchange GTP for GDP on RABs;Signaling by Hippo;Cell Cycle;TNFalpha;Translocation of GLUT4 to the plasma membrane;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;EGF;Regulation of nuclear beta catenin signaling and target gene transcription;mTOR signaling pathway;Insulin-mediated glucose transport;Regulation of Telomerase;p75(NTR)-mediated signaling;Cell death signalling via NRAGE, NRIF and NADE;IGF1 pathway;p38 signaling mediated by MAPKAP kinases;FoxO family signaling;Role of Calcineurin-dependent NFAT signaling in lymphocytes;Class I PI3K signaling events mediated by Akt;Trk receptor signaling mediated by PI3K and PLC-gamma;PDGFR-beta signaling pathway;Lissencephaly gene (LIS1) in neuronal migration and development;TGF-beta receptor signaling;LKB1 signaling events;insulin;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Intolerance Scores

• loftool: 0.110
• rvis_EVS: -0.08
• rvis_percentile_EVS: 47.79

Haploinsufficiency Scores

• pHI: 0.811
• hipred: Y
• hipred_score: 0.783
• ghis: 0.496

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.995

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ywhae
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;MAPK cascade;regulation of heart rate by hormone;regulation of G2/M transition of mitotic cell cycle;viral process;substantia nigra development;protein localization to nucleus;cellular response to heat;hippo signaling;intracellular signal transduction;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;positive regulation of protein export from nucleus;regulation of cytosolic calcium ion concentration;regulation of membrane repolarization;membrane organization;membrane repolarization during cardiac muscle cell action potential;regulation of heart rate by cardiac conduction;ciliary basal body-plasma membrane docking;regulation of postsynaptic membrane neurotransmitter receptor levels;regulation of cellular response to heat;positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway;regulation of potassium ion transmembrane transporter activity;negative regulation of calcium ion transmembrane transporter activity;negative regulation of peptidyl-serine dephosphorylation;negative regulation of calcium ion export across plasma membrane
• Cellular component: nucleus;cytoplasm;mitochondrion;cytosol;kinesin complex;plasma membrane;focal adhesion;membrane;melanosome;extracellular exosome;central region of growth cone;glutamatergic synapse
• Molecular function: RNA binding;calcium channel regulator activity;protein binding;potassium channel regulator activity;Rab guanyl-nucleotide exchange factor activity;enzyme binding;protein domain specific binding;MHC class II protein complex binding;ubiquitin protein ligase binding;identical protein binding;histone deacetylase binding;ion channel binding;cadherin binding;protein heterodimerization activity;phosphoserine residue binding;phosphoprotein binding;scaffold protein binding