YWHAE

protein-coding

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

Gene summary

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. [provided by RefSeq, Aug 2008]

MANE transcript

NM_006761.5

Inheritance

ClinVar variants

P:1U:18B:13

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr17:1,344,275-1,400,222

External References & Databases

Ensembl (ENSG00000108953)

Transcript & Mutation Effects

hg38 • Region Span ~55.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to YWHAE variants in ClinVar

5 Conditions Cataloged

not providedTotal: 41

not specifiedTotal: 16

YWHAE-related disorderTotal: 10

Aganglionic megacolonTotal: 2

YWHAE-associated disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006761.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	12 clinvar	1 clinvar	14
missense			14 clinvar			14
nonsense		1 clinvar				1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	1	18	12	1	32

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006761.5	RefSeq	NP_006752.1	6	MANE Select
ENST00000264335.13	Ensembl	ENSP00000264335.8	6	MANE Select
ENST00000466227.6	Ensembl	ENSP00000464883.1	3	Standard
ENST00000496706.1	Ensembl	ENSP00000466324.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

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

Molecular Function

RNA binding
calcium channel regulator activity
protein binding
potassium channel regulator activity
Rab guanyl-nucleotide exchange factor activity

Cellular Component

nucleus
cytoplasm
mitochondrion
cytosol
kinesin complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264335
Coding exons: 6
Length: 56107
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.83	49	145	0.338	0.00000783	1687
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Intolerance Scores

LoFtool: 0.110
RVIS EVS: -0.08
RVIS percentile EVS: 47.79

Essentials

Essential (CRISPR): N
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.995

Gene Damage Prediction

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