YWHAG

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

Basic information

Region (hg38): 7:76326798-76358991

Links

ENSG00000170027 ∙ NCBI:7532 ∙ OMIM:605356 ∙ HGNC:12852 ∙ Uniprot:P61981 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 56 (Limited), mode of inheritance: AD
• developmental and epileptic encephalopathy, 56 (Strong), mode of inheritance: AD
• developmental and epileptic encephalopathy, 56 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 56	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	Musculoskeletal; Neurologic	28777935

ClinVar

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

• not provided (143 variants)
• Developmental and epileptic encephalopathy, 56 (17 variants)
• Inborn genetic diseases (3 variants)
• YWHAG-related condition (2 variants)
• not specified (1 variants)
• 8 conditions (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the YWHAG 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			1	70	7	78
missense	2	6	38	2	2	50
nonsense	2	1	7			10
start loss			1			1
frameshift	1		1			2
inframe indel		1	4			5
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding				7	1	8
Total	5	8	53	79	10

Variants in YWHAG

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

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

Position	Type	Phenotype	Significance	ClinVar
7-76329580-A-G			Likely benign (Feb 23, 2022)
7-76329585-T-C		See cases	Uncertain significance (Feb 25, 2020)
7-76329592-G-A			Likely benign (Jun 13, 2022)
7-76329595-G-A		Developmental and epileptic encephalopathy, 56	Benign/Likely benign (Feb 01, 2024)
7-76329599-T-C		Developmental and epileptic encephalopathy, 56	Likely benign (Feb 01, 2022)
7-76329600-C-T		Inborn genetic diseases	Uncertain significance (Oct 25, 2023)
7-76329601-G-A			Likely benign (Sep 26, 2023)
7-76329604-G-A			Likely benign (Nov 25, 2023)
7-76329610-C-T			Likely benign (Oct 10, 2023)
7-76329619-C-T			Likely benign (Oct 10, 2023)
7-76329625-G-A			Benign (Dec 11, 2023)
7-76329628-C-T			Benign (Jan 24, 2024)
7-76329634-G-A			Likely benign (Jul 27, 2022)
7-76329634-G-T			Uncertain significance (Sep 29, 2023)
7-76329637-G-A			Likely benign (Oct 10, 2021)
7-76329638-T-A		Developmental and epileptic encephalopathy, 56	Likely pathogenic (Jun 28, 2019)
7-76329639-C-T			Likely pathogenic (Jun 02, 2022)
7-76329640-G-A			Likely benign (Jan 14, 2024)
7-76329649-CTGCATGATGAGCGTGGAGTCCTTG-C			Uncertain significance (Jan 27, 2024)
7-76329658-G-A			Likely benign (Apr 29, 2022)
7-76329661-C-T			Likely benign (Sep 20, 2023)
7-76329673-G-T			Uncertain significance (Dec 26, 2019)
7-76329675-AGGAGTCCTCGTT-A			Uncertain significance (Apr 18, 2022)
7-76329676-G-A			Benign/Likely benign (Jan 21, 2024)
7-76329678-AGTCCTCGTTGAGGGT-A		Developmental and epileptic encephalopathy, 56	Likely pathogenic (Dec 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
YWHAG	protein_coding	protein_coding	ENST00000307630	2	32233

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.964	0.0359	125727	0	1	125728	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.95	54	159	0.341	0.0000108	1636
Missense in Polyphen		8	63.327	0.12633		675
Synonymous	-1.71	91	72.5	1.26	0.00000593	465
Loss of Function	2.98	0	10.3	0.00	6.44e-7	107

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000992	0.0000992
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. {ECO:0000269|PubMed:16511572}.
• Disease: DISEASE: Epileptic encephalopathy, early infantile, 56 (EIEE56) [MIM:617665]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood 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. EIEE56 is an autosomal dominant condition. {ECO:0000269|PubMed:28777935}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt 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;Prolactin Signaling Pathway;Myometrial Relaxation and Contraction Pathways;Calcium Regulation in the Cardiac Cell;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Signal Transduction;Gene expression (Transcription);Vesicle-mediated transport;Membrane Trafficking;Generic Transcription Pathway;Prolactin;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;Cell Cycle Checkpoints;Apoptosis;FGF;Programmed Cell Death;insulin Mam;TP53 Regulates Metabolic Genes;RHO GTPases activate PKNs;RHO GTPase Effectors;Signaling by Rho GTPases;Regulation of PLK1 Activity at G2/M Transition;Recruitment of mitotic centrosome proteins and complexes;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;G2/M Transition;Mitotic G2-G2/M phases;a6b1 and a6b4 Integrin signaling;Transcriptional Regulation by TP53;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;M Phase;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;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;IL3-mediated signaling events;LKB1 signaling events;insulin;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.533

Intolerance Scores

• rvis_EVS: -0.3
• rvis_percentile_EVS: 32.62

Haploinsufficiency Scores

• pHI: 0.989
• hipred: Y
• hipred_score: 0.783
• ghis: 0.638

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.897

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ywhag
• Phenotype: normal phenotype

Zebrafish Information Network

• Gene name: ywhag1
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: hypoplastic

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;negative regulation of protein kinase activity;protein targeting;regulation of signal transduction;regulation of G2/M transition of mitotic cell cycle;cellular response to insulin stimulus;regulation of neuron differentiation;regulation of synaptic plasticity;membrane organization;negative regulation of protein serine/threonine kinase activity;ciliary basal body-plasma membrane docking;positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
• Cellular component: mitochondrion;cytosol;focal adhesion;membrane;myelin sheath;extracellular exosome;presynapse
• Molecular function: RNA binding;protein kinase C binding;insulin-like growth factor receptor binding;protein binding;protein kinase C inhibitor activity;protein domain specific binding;receptor tyrosine kinase binding;identical protein binding