ZIC2

Zinc finger protein ZIC2 is a protein that in humans is encoded by the ZIC2 gene.^[5][6] ZIC2 is a member of the Zinc finger of the cerebellum (ZIC) protein family.^[7]

ZIC2
Identifiers
Aliases	ZIC2, HPE5, Zic family member 2
External IDs	OMIM: 603073; MGI: 106679; HomoloGene: 5171; GeneCards: ZIC2; OMA:ZIC2 - orthologs
Gene location (Human) Chr. Chromosome 13 (human)[1] Band 13q32.3 Start 99,981,784 bp[1] End 99,986,765 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14 E5|14 65.97 cM Start 122,712,847 bp[2] End 122,717,264 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cerebellar cortex cerebellar hemisphere right hemisphere of cerebellum Pons cerebellar vermis ventricular zone trigeminal ganglion endothelial cell lateral nuclear group of thalamus ganglionic eminence Top expressed in cerebellar cortex neural groove neural fold stria vascularis epiblast lumbar subsegment of spinal cord ventricular zone tail of embryo urethra male urethra More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA-binding transcription factor activity DNA binding chromatin DNA binding metal ion binding nucleic acid binding DNA-binding transcription factor activity, RNA polymerase II-specific RNA polymerase II transcription regulatory region sequence-specific DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific Cellular component cytoplasm nucleus nuclear body Biological process positive regulation of transcription, DNA-templated multicellular organism development cell differentiation brain development positive regulation of DNA-binding transcription factor activity negative regulation of transcription, DNA-templated regulation of transcription, DNA-templated transcription, DNA-templated visual perception nervous system development regulation of transcription by RNA polymerase II positive regulation of transcription by RNA polymerase II central nervous system development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7546 22772 Ensembl ENSG00000043355 ENSMUSG00000061524 UniProt O95409 Q62520 RefSeq (mRNA) NM_007129 NM_009574 RefSeq (protein) NP_009060 NP_033600 Location (UCSC) Chr 13: 99.98 – 99.99 Mb Chr 14: 122.71 – 122.72 Mb PubMed search [3] [4]
Wikidata
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Function

ZIC2 is classified as a ZIC protein due to conservation of the five C2H2 zinc fingers, which enables the protein to interact with DNA and proteins.^[6]

Clinical significance

Correct function of these proteins is critical for early development, and as such mutations of the genes encoding these proteins is known to result in various congenital defects. For example, mutation of ZIC2 is known to result in holoprosencephaly due to defect in the function of the organizer region (node), which leads to a defective anterior notochord (ANC). The ANC provides a maintenance signal to the Prechordal plate (PCP), thus a defective ANC results in degradation of the PCP, which is normally responsible for sending a shh signal to the developing forebrain resulting in the formation of the two hemispheres.^[8] Holoprosencephaly is the most common structural anomaly of the human forebrain.

Recently ZIC2 has also been shown to be critical for establishment of the left-right axis, thus loss of ZIC2 function can result in defects in heart formation.^[9] Another member of the ZIC family, ZIC3, has previously been linked to establishment of the left-right axis.

A polyhistidine tract polymorphism in this gene may be associated with increased risk of neural tube defects (spina bifida). This gene is closely linked to a gene encoding ZIC5, a related family member on chromosome 13.^[6]

Interactions

ZIC2 has recently been found to interact with TCF7L2, enabling it to act as a Wnt/β-catenin signalling inhibitor.^[10] Such a role is of critical importance, as not only is correct Wnt signalling critical for early development,^[11] Wnt signalling has also been found to be upregulated to several cancers. ZIC2 has also been shown to interact with GLI3.^[12]