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FLASH GENE

Symbol

ZNF423

contributors: mct/ - updated : 22-05-2015

HGNC name	zinc finger protein 423
HGNC id	16762

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain hindbrain cerebellum     Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central

cell lineage	germinal zones
cell lines
fluid/secretion

at STAGE

physiological period

fetal

Text	brain, kidney

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a BMP-signaling module formed by two clusters of fingers
	30 Krüppel-like zinc fingers that are organized into discrete clusters

HOMOLOGY

Homologene

FAMILY

krueppel C2H2-type zinc-finger protein family

CATEGORY

DNA associated , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus

basic FUNCTION	transcriptionnally activating the homeobox regulator, that may have multiple roles in signal transduction during development
	can alter the intensity and duration of the BMP stimulus through SMAD6 and indicate that the tissue-specific expression of ZNF243 is a critical determinant of the cellular response to the BMP signal
	required for normal cerebellar development
	having a role as a SMAD cofactor in the context of mesodermal patterning
	component critically required for retinoic acid (RA)-induced differentiation
	multiple zinc-finger transcription factor involved in both OE/EBF and BMP-signaling pathways, and required for the proper formation of forebrain and hindbrain midline structures (may be having a pivotal role in CNS midline patterning)
	required for normal cerebellar development
	required for patterning the development of neuronal and glial precursors in the developing brain, particularly in midline structures
	has a key role in coordinating the expression of immature and mature stage-specific genes
	participates in a developmental switch regulating the transition from differentiation to maturation in olfactory-receptor neurons
	critical cofactor required for RAR/RXR function and is also crucial for RA-mediated growth arrest and differentiation in neuroblastoma cell lines
	acts to integrate BMP and Notch signaling, selectively promoting their convergence onto the HES5 gene promoter
	may help maintain a pool of HES5 positive neurogenic progenitors in the developing neural tube
	role as a cell-autonomous modifier of Notch signal transduction
	transcriptional activator of PPARG and inducer of adipogenic determination
	is the key transcription factor committing cells to the adipogenic lineage, with exceptionally dense CpG sites in its promoter
	regulates early adipogenic differentiation in fetal progenitor cells

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

signal transduction

BMP-SMAD and olf pathways

a component

forms a cytosolic complex with the peroxisome proliferator-activated receptor gamma (PPARG) transcriptional activator zinc finger protein 423 (ZNF423)

INTERACTION

DNA

binding

RNA

small molecule	metal binding,
	Zn2+

protein	SMADs (in response to bone morphogenetic protein-2 [BMP-2])
	binds to and negatively regulates EBF1, a basic helix-loop-helix transcription factor required for B-cell lineage commitment and olfactory epithelium development
	associates with the RARalpha/RXRalpha nuclear receptor complex and is essential for transactivation in response to retinoids
	interacts with the NOTCH1 intracellular domain in mammalian cell lines, to activate the expression of the NOTCH1 target HES5
	ZFP423 interacts with the HES5 promoter
	BMP4 was also able to increase ZFP423 gene activation, adding another layer of cross-talk in promoting adipogenic differentiation
	canonical WNT signaling inhibits adipogenic commitment and differentiation through WISP2, which retains ZNF423 in the cytosol
	appeared to be an estrogen-inducible BRCA1 transcription factor

cell & other

REGULATION

repressed by

ZNF521 that is the intrinsic repressor of ZNF423 and hence of adipocyte commitment during BMP-induced mesenchymal precursor differentiation

ASSOCIATED DISORDERS

corresponding disease(s)

NPHP14

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   by RNA interference in neuroblastoma cells results in a growth advantage and resistance to RA-induced differentiation with poor outcome tumoral     --low   with NF1, in neuroblastomas with poor outcome

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	Homozygous Zfp423 null mice are runted and ataxic, the cerebellum is underdeveloped, and the vermis is severely reduced
	Zfp423 null mice develop a profound hypoplasia of the cerebellar vermis, reminiscent of the Dandy-Walker malformation