ZNF423
Domain
Uses different DNA- and protein-binding zinc fingers to regulate the distinct BMP-Smad and Olf signaling pathways. C2H2-type zinc fingers 14-19 mediate the interaction with SMAD1 and SMAD4, while zinc fingers 28-30 mediate the interaction with EBF1. zinc fingers 2-8 bind the 5'-CCGCCC-3' DNA sequence in concert with EBF1, while zinc fingers 9-13 bind BMP target gene promoters in concert with SMADs.
Function
Transcription factor that can both act as an activator or a repressor depending on the context. Plays a central role in BMP signaling and olfactory neurogenesis. Associates with SMADs in response to BMP2 leading to activate transcription of BMP target genes. Acts as a transcriptional repressor via its interaction with EBF1, a transcription factor involved in terminal olfactory receptor neurons differentiation; this interaction preventing EBF1 to bind DNA and activate olfactory-specific genes. Involved in olfactory neurogenesis by participating in a developmental switch that regulates the transition from differentiation to maturation in olfactory receptor neurons. Controls proliferation and differentiation of neural precursors in cerebellar vermis formation.
Involvement in disease
Nephronophthisis 14
NPHP14
An autosomal recessive disorder manifesting as infantile-onset kidney disease, cerebellar vermis hypoplasia, and situs inversus. Nephronophthisis is a progressive tubulo-interstitial kidney disorder histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts.
None
The disease is caused by variants affecting the gene represented in this entry.
Joubert syndrome 19
JBTS19
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). JBTS19 patients have polycystic kidney disease, Leber congenital amaurosis, cerebellar vermis hypoplasia, and breathing abnormality.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the krueppel C2H2-type zinc-finger protein family.
Tissue Specificity
Expressed in brain, lung, skeletal muscle, heart, pancreas and kidney but not liver or placenta. Also expressed in aorta, ovary, pituitary, small intestine, fetal brain, fetal kidney and, within the adult brain, in the substantia nigra, medulla, amygdala, thalamus and cerebellum.
Cellular localization
- Nucleus
Alternative names
KIAA0760, NPHP14, OAZ, ZNF423, Zinc finger protein 423, Olf1/EBF-associated zinc finger protein, Smad- and Olf-interacting zinc finger protein, hOAZ