YWHAZ

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

Basic information

Region (hg38): 8:100916522-100953388

Previous symbols: [ "YWHAD" ]

Links

ENSG00000164924 ∙ NCBI:7534 ∙ OMIM:601288 ∙ HGNC:12855 ∙ Uniprot:P63104 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Popov-Chang syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	31024343

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the YWHAZ 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				6	3	9
missense			2			2
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding				6	3	9
Total	0	0	3	12	6

Variants in YWHAZ

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

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

Position	Type	Phenotype	Significance	ClinVar
8-100920726-G-A			Benign (Dec 09, 2023)
8-100920742-G-C		not specified • Reclassified - variant of unknown significance • See cases • Noonan-like disorder • YWHAZ-related neurodevelopmental syndrome	Conflicting classifications of pathogenicity (Sep 29, 2023)
8-100920742-G-GAT		Reclassified - variant of unknown significance	Uncertain significance (Dec 23, 2021)
8-100920763-A-G			Benign (Aug 10, 2023)
8-100920766-G-A			Likely benign (Oct 14, 2022)
8-100923937-A-C			Benign (Jan 22, 2024)
8-100923942-G-A			Likely benign (Sep 21, 2023)
8-100923978-GCATT-G			Uncertain significance (Jan 27, 2022)
8-100924018-T-G			Likely benign (Apr 07, 2023)
8-100924048-A-G			Likely benign (Dec 24, 2022)
8-100924055-G-A		YWHAZ-related disorder	Benign (Jan 31, 2024)
8-100924114-CG-C			Likely benign (Jun 06, 2023)
8-100924115-G-T			Benign (Jan 22, 2024)
8-100924147-A-C			Benign (Feb 01, 2023)
8-100924222-A-T			Likely benign (Aug 16, 2022)
8-100924283-G-A		Reclassified - variant of unknown significance	Uncertain significance (Dec 23, 2021)
8-100924943-C-T			Uncertain significance (Jan 26, 2022)
8-100924949-A-G			Likely benign (May 03, 2022)
8-100924965-T-G			Likely benign (Aug 10, 2018)
8-100925011-T-C			Uncertain significance (Feb 13, 2023)
8-100925053-G-A			Likely benign (Mar 31, 2023)
8-100948582-G-A			Likely benign (Jul 04, 2021)
8-100948585-T-C			Likely benign (Nov 27, 2023)
8-100948626-C-T			Likely benign (Nov 28, 2023)
8-100948629-C-T		YWHAZ-related disorder	Benign (Jan 29, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
YWHAZ	protein_coding	protein_coding	ENST00000395957	5	36864

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.940	0.0603	124788	0	1	124789	0.00000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.10	30	129	0.233	0.00000649	1594
Missense in Polyphen		2	41.16	0.048591		610
Synonymous	0.168	48	49.5	0.970	0.00000276	437
Loss of Function	3.13	1	13.3	0.0752	6.46e-7	169

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)	0.00000884	0.00000884
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. {ECO:0000269|PubMed:14578935, ECO:0000269|PubMed:15071501, ECO:0000269|PubMed:15644438, ECO:0000269|PubMed:16376338, ECO:0000269|PubMed:9360956}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Cell cycle - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Cell Cycle;Prolactin Signaling Pathway;Pathogenic Escherichia coli infection;JAK-STAT;Myometrial Relaxation and Contraction Pathways;Calcium Regulation in the Cardiac Cell;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Signaling by WNT;Signal Transduction;Gene expression (Transcription);Signaling by Interleukins;Vesicle-mediated transport;Membrane Trafficking;Generic Transcription Pathway;Prolactin;Cytokine Signaling in Immune system;Alpha6Beta4Integrin;Fas;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;TCR;Cell Cycle Checkpoints;Immune System;Apoptosis;Rap1 signalling;FGF;Programmed Cell Death;Adaptive Immune System;insulin Mam;GP1b-IX-V activation signalling;TP53 Regulates Metabolic Genes;RHO GTPases activate PKNs;Deactivation of the beta-catenin transactivating complex;Platelet activation, signaling and aggregation;RHO GTPase Effectors;Signaling by Rho GTPases;EGFR1;ErbB1 downstream signaling;Hemostasis;IL3;a6b1 and a6b4 Integrin signaling;Transcriptional Regulation by TP53;IL5;Cell Cycle;TNFalpha;Translocation of GLUT4 to the plasma membrane;EGF;Regulation of nuclear beta catenin signaling and target gene transcription;GMCSF-mediated signaling events;mTOR signaling pathway;Insulin-mediated glucose transport;TCF dependent signaling in response to WNT;IGF1 pathway;p38 signaling mediated by MAPKAP kinases;Alpha4 beta1 integrin signaling events;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;ATR signaling pathway;IL3-mediated signaling events;LKB1 signaling events;insulin;Interleukin-3, 5 and GM-CSF signaling (Consensus)

Recessive Scores

• pRec: 0.586

Intolerance Scores

• loftool: 0.410
• rvis_EVS: 0.08
• rvis_percentile_EVS: 59.43

Haploinsufficiency Scores

• pHI: 1.00
• hipred: Y
• hipred_score: 0.840
• ghis: 0.658

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.991

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ywhaz
• 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); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system 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); vision/eye phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: protein targeting;signal transduction;synaptic target recognition;cytokine-mediated signaling pathway;platelet activation;negative regulation of apoptotic process;regulation of mRNA stability;establishment of Golgi localization;membrane organization;regulation of synapse maturation;Golgi reassembly;positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
• Cellular component: extracellular space;nucleus;nucleoplasm;cytoplasm;mitochondrion;cytosol;focal adhesion;vesicle;melanosome;extracellular exosome;blood microparticle;hippocampal mossy fiber to CA3 synapse;glutamatergic synapse
• Molecular function: RNA binding;protein binding;transcription factor binding;protein kinase binding;protein domain specific binding;ubiquitin protein ligase binding;identical protein binding;ion channel binding;cadherin binding