YWHAH

Chr 22

tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta

Also known as: YWHA1

NCBI Gene: 7533ENSG00000128245UniProt: Q04917

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]

36
ClinVar variants
18
Pathogenic / LP
0.78
pLI score
0
Active trials
Clinical Summary— YWHAH
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.78) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 18 VUS of 36 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.50LOEUF
pLI 0.784
Z-score 2.54
OE 0.11 (0.04–0.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.56Z-score
OE missense 0.36 (0.28–0.46)
45 obs / 125.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.11 (0.04–0.50)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.36 (0.28–0.46)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.19
0≤1.21.6
LoF obs/exp: 1 / 9.4Missense obs/exp: 45 / 125.9Syn Z: -1.09

ClinVar Variant Classifications

36 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic1
VUS18
17
Pathogenic
1
Likely Pathogenic
18
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
1
0
1
VUS
0
15
3
0
18
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total01521036

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

YWHAH · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Extracellular vesicle-circEHD2 promotes the progression of renal cell carcinoma by activating cancer-associated fibroblasts.
He T et al.·Mol Cancer
2023
YWHAH‑driven autophagy via MAPK/ERK signaling enhances CRC cell migration and invasion.
Li Q et al.·Int J Mol Med
2025
AI-assisted multi-OMICS analysis reveals new markers for the prediction of AD.
Latifi-Navid H et al.·Biochim Biophys Acta Mol Basis Dis
2025
Inhibiting miR-33b-5p Enhances Chemoresistance in Lung Adenocarcinoma by Targeting YWHAH to Regulate Epithelial-mesenchymal Transition.
Liu B et al.·Anticancer Res
2023
YWHAH Genetic Variants are Associated with Increased Hypoxia Inducible Factor-1α/Vascular Endothelial Growth Factor in Egyptian Rheumatoid Arthritis Patients.
Fattah SA et al.·Biochem Genet
2022Cohort
Family-based association of YWHAH in psychotic bipolar disorder.
Grover D et al.·Am J Med Genet B Neuropsychiatr Genet
2009
KIF1C and new Huntingtin-interacting protein 1 binding proteins regulate rheumatoid arthritis fibroblast-like synoviocytes' phenotypes.
Laragione T et al.·Front Immunol
2024
Coordinating single-cell and bulk RNA-seq in deciphering the intratumoral immune landscape and prognostic stratification of prostate cancer patients.
Sun Z et al.·Environ Toxicol
2024Cohort
LncRNA NDUFA6-DT: A Comprehensive Analysis of a Potential LncRNA Biomarker and Its Regulatory Mechanisms in Gliomas.
Huang R et al.·Genes (Basel)
2024Functional
Genetic variants in cell cycle control pathway confer susceptibility to aggressive prostate carcinoma.
Kibel AS et al.·Prostate
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools