YWHAZ

Chr 8

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

NCBI Gene: 7534ENSG00000164924UniProt: P63104

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 sheep orthologs. The encoded protein interacts with IRS1 protein, suggesting a role in regulating insulin sensitivity. Several transcript variants that differ in the 5' UTR but that encode the same protein have been identified for this gene. [provided by RefSeq, Oct 2008]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPopov-Chang syndrome

Clinical highlights

Gene-disease validity (ClinGen)
complex neurodevelopmental disorder · ADModerateconsider for supplementary testing
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
87
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.36
LOEUF
—
Mechanism
📖
GeneReview available — YWHAZ
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.36LOEUF
pLI 0.940
Z-score 3.13
OE 0.08 (0.03–0.36)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
3.10Z-score
OE missense 0.23 (0.17–0.32)
30 obs / 128.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.08 (0.03–0.36)
0≤0.351.4
Missense OE?0.23 (0.17–0.32)
0≤0.61.4
Synonymous OE?0.97
0≤1.21.6
LoF obs/exp: 1 / 13.3Missense obs/exp: 30 / 128.9Syn Z: 0.17

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients