YWHAG
Chr 7ADtyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma
Also known as: 14-3-3GAMMA, DEE56, EIEE56, PPP1R170
The protein belongs to the 14-3-3 family and mediates signal transduction by binding to phosphoserine-containing proteins, with particular expression in muscle tissues and interactions with RAF1 and protein kinase C. Mutations cause developmental and epileptic encephalopathy 56 through an autosomal dominant inheritance pattern. The high pLI score (0.96) and low LOEUF score (0.29) indicate the gene is highly intolerant to loss-of-function variants, suggesting haploinsufficiency as the likely pathogenic mechanism.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
279 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 13 | 7 | 23 | 0 | 43 |
Likely Pathogenic | 3 | 8 | 4 | 0 | 15 |
VUS | 8 | 75 | 20 | 0 | 103 |
Likely Benign | 0 | 2 | 10 | 91 | 103 |
Benign | 0 | 1 | 2 | 5 | 8 |
Conflicting | — | 4 | |||
| Total | 24 | 93 | 59 | 96 | 276 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
YWHAG · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools