YWHAB

protein-coding

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

Gene summary

This gene encodes a protein belonging to the 14-3-3 family of proteins, members of which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals. The encoded protein has been shown to interact with RAF1 and CDC25 phosphatases, suggesting that it may play a role in linking mitogenic signaling and the cell cycle machinery. Two transcript variants, which encode the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

YWHAA

MANE transcript

NM_139323.4

Inheritance

—

ClinVar variants

U:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr20:44,885,702-44,908,532

External References & Databases

Ensembl (ENSG00000166913)

Transcript & Mutation Effects

hg38 • Region Span ~22.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to YWHAB variants in ClinVar

1 Conditions Cataloged

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_139323.4. 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			2 clinvar			2
missense						0
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	2	0	0	2

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 67 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_139323.4	RefSeq	NP_647539.1	5	MANE Select
ENST00000353703.9	Ensembl	ENSP00000300161.4	5	MANE Select
NM_003404.5	RefSeq	NP_003395.1	5	Standard
ENST00000372839.7	Ensembl	ENSP00000361930.3	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ywhaba	Danio rerio	Structure: phagocytosis, engulfment Quality: decreased occurrence abnormal

Gene / Model

Organism

Observed Phenotype

ywhaba

Danio rerio

Structure: phagocytosis, engulfment

Quality: decreased occurrence

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

MAPK cascade
protein targeting
viral process
negative regulation of protein dephosphorylation
hippo signaling

Molecular Function

protein binding
protein C-terminus binding
enzyme binding
protein domain specific binding
identical protein binding

Cellular Component

nucleus
cytoplasm
mitochondrion
cytosol
focal adhesion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372839
Coding exons: 5
Length: 22857
Individuals with no LoFs: 125290
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125291
p: 0.00000399

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.89	75	137	0.546	0.00000737	1629
Missense (PolyPhen)		16	50.461	0.31708		621
Synonymous	0.324	48	50.9	0.942	0.00000288	440
Loss of Function	3.27	0	12.4	0.00	6.10e-7	150

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	0.000033	0.000033	rare
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. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2. Negative regulator of signaling cascades that mediate activation of MAP kinases via AKAP13. {ECO:0000269|PubMed:17717073, ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:21224381}.;

Recessive Scores

pRec: 0.707

Intolerance Scores

LoFtool: 0.176
RVIS EVS: 0.1
RVIS percentile EVS: 61.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.757

Gene Damage Prediction

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