YWHAH
protein-codingtyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta, 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 99% identical to the mouse, rat and bovine orthologs. This gene contains a 7 bp repeat sequence in its 5' UTR, and changes in the number of this repeat have been associated with early-onset schizophrenia and psychotic bipolar disorder. [provided by RefSeq, Jun 2009]
- YWHA1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.1 kbGenCC 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 YWHAH variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003405.4. 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 | 0 | |||||
| missense | 15 | 15 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 17 | 0 | 0 | 17 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003396.1 | 2 | MANE Select | |
| Ensembl | ENSP00000248975.5 | 2 | MANE Select | |
| Ensembl | ENSP00000380629.1 | 3 | Standard | |
| Ensembl | ENSP00000380629.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Cell cycle - Homo sapiens (human)
- Oocyte meiosis - Homo sapiens (human)
- Hippo signaling pathway - Homo sapiens (human)
- Viral carcinogenesis - Homo sapiens (human)
Biological Process
- regulation of sodium ion transport
- glucocorticoid catabolic process
- intracellular protein transport
- substantia nigra development
- glucocorticoid receptor signaling pathway
Molecular Function
- actin binding
- insulin-like growth factor receptor binding
- protein binding
- sodium channel regulator activity
- enzyme binding
Cellular Component
- cytoplasm
- mitochondrion
- cytosol
- plasma membrane
- intercalated disc
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000248975
- Coding exons
- 2
- Length
- 13144
- Individuals with no LoFs
- 125741
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125745
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.56 | 45 | 126 | 0.357 | 0.00000693 | 1618 |
| Missense (PolyPhen) | 8 | 55.881 | 0.14316 | 671 | ||
| Synonymous | -1.09 | 62 | 52.0 | 1.19 | 0.00000300 | 458 |
| Loss of Function | 2.54 | 1 | 9.42 | 0.106 | 6.35e-7 | 107 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| 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) | 0.000026 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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. Negatively regulates the kinase activity of PDPK1. {ECO:0000269|PubMed:12177059}.;
Recessive Scores
- pRec
- 0.546
Intolerance Scores
- LoFtool
- 0.106
- RVIS EVS
- -0.08
- RVIS percentile EVS
- 47.79
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.973
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Low | Low | Low |