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FLASH GENE

Symbol

ZIC1

contributors: mct/pgu - updated : 10-10-2015

HGNC name	Zic family member 1 (odd-paired homolog, Drosophila)
HGNC id	12872

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CRS12 craniosynostosis, syndromatic 12 DWS1 Dandy-Walker syndrome 1
Location	3q24      Physical location : 147.127.180 - 147.134.504
Synonym name	Zinc finger protein of the cerebellum 1
Synonym symbol(s)	ZIC, ZNF201

DNA

TYPE	functioning gene
STRUCTURE	7.33 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003412 3 - 5231 48 447 - 2007 17936758

EXPRESSION

Type	restricted

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   highly Visual eye retina       Homo sapiens Fetal

cell lineage	cellular granular cell lineage (potential marker)
cell lines
fluid/secretion

at STAGE

physiological period

embryo

Text	in embryonic retina

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

five C2H2 zinc finger in a domain homolog to Drosophila pair-rule gene Opa (odd paired)

HOMOLOGY

interspecies	homolog to murine Zic
	homolog to Drosophila pair-rule gene odd-paired

Homologene

FAMILY

ZIC family of C2H2-type zinc finger proteins

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus
text	ZIC1/ZIC2/ZIC3 proteins were translocated to the cytoplasmic compartment in the presence of MDFI

basic FUNCTION	transcription factor that can bind and transactivate the apolipoprotein E gene
	may be playing a role in cerebellar development
	candidate tumor suppressor gene downregulated through promoter hypermethylation in gastric cancer
	neural developmental transcription factor, plays an important role in shear flow mechanotransduction in osteocytes
	critical transcription factor for neuronal development
	its expression is essential for liposarcomagenesis
	ZIC1 and ZIC4 have both SHH-dependent and -independent roles during cerebellar development and that multiple developmental disruptions underlie ZIC1/4-related Dandy-Walker malformation
	ZIC1, ZIC2, ZIC3, are strongly expressed in immature retinal progenitor cells, and their roles in retinal differentiation and proliferation are suggested by gain-of-function analysis
	similar activities of ZIC1, ZIC2, and ZIC3, suggesting that Zics are redundant in terms of retinal cell differentiation
	ZIC1, and ZIC2 function in patterning hindbrain motor neurons through their regulation of embryonic retinoic acid signaling
	functions as a tumor suppressor in thyroid cancer through modulating PI3K/Akt and MAPK signaling pathways and transcription factor FOXO3
	ZIC1 and ZIC2 are required for coordinating mature neuronal gene expression patterns
	role for ZIC1 in early cranial suture development, potentially by regulating engrailed 1
	subsidiary role for ZIC1 in early patterning events in the coronal suture

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

development

text	cerebellum

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	transactivating the APOE promoter
	binding of the ZIC1/ZIC2/ZIC3 proteins to MDFIthrough their N-terminal regions
	neural crest specifier activity of GBX2 is dependent on the interaction with ZIC1 and the inhibition of preplacodal genes such as SIX1
	neural plate border specifier, ZIC1, is a critical factor in the control of FOXD3 expression at vagal and trunk levels

cell & other

REGULATION

Other

role for DNA methylation in the control of expression

ASSOCIATED DISORDERS

corresponding disease(s)

DWS1 , CRS12

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   through promoter hypermethylation in gastric cancer constitutional   deletion     of ZIC1 and ZIC4 in patient presented with mental retardation, epilepsy, and multiple congenital malformations including spina bifida, mild dysmorphic facial features and Dandy-Walker malformation ( tumoral     --over   in all five subtypes of liposarcoma compared with normal fat tumoral     --low   by hypermethylation may lead to promoter silencing of ZIC1 mRNA and associated with poor survival in hepatocellular carcinoma

Susceptibility

Variant & Polymorphism

Candidate gene	for DWS
Marker	ZIC1 promoter methylation may serve as a novel non-invasive plasma biomarker for the early detection of gastri cancer
Therapy target	potential marker for medulloblastoma
	System Type Disorder Pubmed cancer     targeting ZIC1 or its downstream targets might lead to novel therapy for liposarcoma cancer digestive stomach serves as a potential therapeutic target for gastric cancer

ANIMAL & CELL MODELS

loss of Zic1 gene in the mouse causes cerebellar hypoplasia and vertebral defects