Description: Homo sapiens Zic family member 2 (ZIC2), mRNA. RefSeq Summary (NM_007129): This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. This protein functions as a transcriptional repressor and may regulate tissue specific expression of dopamine receptor D1. Expansion of an alanine repeat in the C-terminus of the encoded protein and other mutations in this gene cause holoprosencephaly type 5. Holoprosencephaly is the most common structural anomaly of the human brain. A polyhistidine tract polymorphism in this gene may be associated with increased risk of neural tube defects. This gene is closely linked to a gene encoding zinc finger protein of the cerebellum 5, a related family member on chromosome 13. [provided by RefSeq, Jul 2016]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Transcript (Including UTRs) Position: hg19 chr13:100,634,026-100,639,019 Size: 4,994 Total Exon Count: 3 Strand: + Coding Region Position: hg19 chr13:100,634,319-100,637,936 Size: 3,618 Coding Exon Count: 3
ID:ZIC2_HUMAN DESCRIPTION: RecName: Full=Zinc finger protein ZIC 2; AltName: Full=Zinc finger protein of the cerebellum 2; FUNCTION: Acts as a transcriptional activator or repressor. Plays important roles in the early stage of organogenesis of the CNS. Activates the transcription of the serotonin transporter SERT in uncrossed ipsilateral retinal ganglion cells (iRGCs) to refine eye-specific projections in primary visual targets. Its transcriptional activity is repressed by MDFIC. Involved in the formation of the ipsilateral retinal projection at the optic chiasm midline. Drives the expression of EPHB1 on ipsilaterally projecting growth cones. Binds to the minimal GLI-consensus sequence 5'-TGGGTGGTC-3'. Associates to the basal SERT promoter region from ventrotemporal retinal segments of retinal embryos. SUBUNIT: Interacts with RNF180. Interacts (via the C2H2-type domains 3, 4 and 5) with MDFIC (via the C2H2-type domains 3, 4 and 5); the interaction reduces its transcriptional activity. Interacts with DHX9 (By similarity). SUBCELLULAR LOCATION: Nucleus. Cytoplasm (By similarity). Note=Localizes in the cytoplasm in presence of MDFIC overexpression. Both phosphorylated and unphosphorylated forms are localized in the nucleus (By similarity). DOMAIN: The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation (By similarity). PTM: Phosphorylated. PTM: Ubiquitinated by RNF180, leading to its degradation. POLYMORPHISM: The poly-His region between amino acids 231-239 of ZIC2 is polymorphic and the number of His can vary from 8 to 12. DISEASE: Defects in ZIC2 are a cause of holoprosencephaly type 5 (HPE5) [MIM:609637]. A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. Although severe facial anomalies are common in HPE, patients with ZINC2 mutations have relatively normal faces. SIMILARITY: Belongs to the GLI C2H2-type zinc-finger protein family. SIMILARITY: Contains 5 C2H2-type zinc fingers. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ZIC2";
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Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): ZIC2 CDC HuGE Published Literature: ZIC2 Positive Disease Associations: Neural tube defects Related Studies:
Neural tube defects Brown LY et al. 2002, Possible association of NTDs with a polyhistidine tract polymorphism in the ZIC2 gene., American journal of medical genetics. 2002 Mar;108(2):128-31.
[PubMed 11857562]
Our sample was too small to reach definitive conclusions, but the evidence is sufficiently intriguing to encourage further research. If this association is confirmed, subtle alterations in ZIC2 activity may confer a risk of NTD.
neural tube defects Brown, L. Y. et al. 2002, Possible association of NTDs with a polyhistidine tract polymorphism in the ZIC2 gene., American journal of medical genetics. 2002 Mar;108(2):128-31.
[PubMed 11857562]
Our sample was too small to reach definitive conclusions, but the evidence is sufficiently intriguing to encourage further research. If this association is confirmed, subtle alterations in ZIC2 activity may confer a risk of NTD.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O95409
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0003676 nucleic acid binding GO:0003677 DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0031490 chromatin DNA binding GO:0046872 metal ion binding
Biological Process: GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0007275 multicellular organism development GO:0007399 nervous system development GO:0007420 brain development GO:0007601 visual perception GO:0030154 cell differentiation GO:0045892 negative regulation of transcription, DNA-templated GO:0045893 positive regulation of transcription, DNA-templated GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
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