YWHAZ

Chr 8AD

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

Also known as: 14-3-3-zeta, HEL-S-3, HEL-S-93, HEL4, KCIP-1, POPCHAS, YWHAD

The encoded protein is a 14-3-3 family adapter protein that regulates diverse signaling pathways by binding to phosphoserine- and phosphothreonine-containing proteins, modulating their activity and subcellular localization. Mutations cause Popov-Chang syndrome with autosomal dominant inheritance. This gene is highly constrained against loss-of-function variants, reflecting its essential role in cellular signaling.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ADLOEUF 0.361 OMIM phenotype
Clinical SummaryYWHAZ
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.36LOEUF
pLI 0.940
Z-score 3.13
OE 0.08 (0.030.36)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.10Z-score
OE missense 0.23 (0.170.32)
30 obs / 128.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.08 (0.030.36)
00.351.4
Missense OE0.23 (0.170.32)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 1 / 13.3Missense obs/exp: 30 / 128.9Syn Z: 0.17

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

YWHAZ · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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