This report describes Popov-Chang syndrome a newly characterized autosomal dominant intellectual developemental disorder. This disorder is caused by a heterozygous missense mutation in the gene YWHAZ. YWHAZ encodes a member of the 14-3-3 family of highly conserved acidic 30 kDa homo/heterodimeric adapter proteins that bind and regulate protein activity. In Drosophila, there is one high-scoring ortholog, 14-3-3ζ, for which loss-of-function alleles, RNAi targeting constructs, a disease-implicated variant knock-in allele, and alleles caused by insertional mutagenesis have been generated.
The human gene Hsap\YWHAZ has been introduced into flies, but has not been analyzed in a human disease context.
Flies bearing the Dmel\14-3-3ζ K49N disease-implicated variant exhibit defects in short term aversive olfactory memory, and reduction in the size of the adult mushroom body gamma-lobes.
[updated May 2026 by FlyBase; FBrf0222196]
[POPOV-CHANG SYNDROME; POPCHAS](https://omim.org/entry/618428)
[TYROSINE 3-MONOOXYGENASE/TRYPTOPHAN 5-MONOOXYGENASE ACTIVATION PROTEIN, ZETA ISOFORM; YWHAZ](https://omim.org/entry/601288)
Popov-Chang syndrome (POPCHAS) is a neurodevelopmental disorder characterized by global developmental delay apparent from infancy. Affected individuals have impaired intellectual development and poor or absent speech, as well as behavioral abnormalities. Brain imaging may show simplified gyral pattern and small volume of the posterior cranial fossa. Some patients have small head circumference and facial dysmorphism, including coarse features, frontal bossing, and abnormal eye shape. Additional features are highly variable and can include seizures, short stature, feeding difficulties, and skin abnormalities (Popov et al., 2019, pubmed:31024343; Wan et al., 2023, pubmed:36001342). [from MIM:618428; 2026.05.01]
Seven individuals in three generations of the same family, with varying degrees of intellectual disability and global developmental delay, were studied. Brain MRI of several affected individuals showed simplified gyral pattern, smaller volume of posterior cranial fossa and decreased brainstem-tentorium angle. (Wan, et al., 2023, pubmed:36001342, FBrf0255504).
Popov-Chang syndrome (POPCHAS) is caused by heterozygous mutation in the YWHAZ gene on chromosome 8q22. [from MIM:618428; 2026.05.01]
A heterozygous missense variant of the gene YWHAZ was detected in each of the affected individuals. (Wan, et al., 2023, pubmed:36001342, FBrf0255504).
YWHAZ encodes Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Zeta, a protein belonging 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 the human 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. [provided by RefSeq, Oct 2008]
High-scoring ortholog of human YWHAZ and YWHAB; moderate scoring ortholog of YWHAG, YWHAH, SFN, YWHAQ, YWHAE (2 Drosophila to many human).
