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Aliases for ZIC2 Gene

Aliases for ZIC2 Gene

  • Zic Family Member 2 2 3 5
  • Zinc Finger Protein Of The Cerebellum 2 2 3 4
  • Zic Family Member 2 (Odd-Paired Homolog, Drosophila) 2 3
  • Zic Family Member 2 (Odd-Paired Drosophila Homolog) 2
  • Zinc Finger Protein ZIC 2 3
  • HPE5 3

External Ids for ZIC2 Gene

Previous GeneCards Identifiers for ZIC2 Gene

  • GC13P098994
  • GC13P095021
  • GC13P099470
  • GC13P098332
  • GC13P099432
  • GC13P100634
  • GC13P081227

Summaries for ZIC2 Gene

Entrez Gene Summary for ZIC2 Gene

  • 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]

GeneCards Summary for ZIC2 Gene

ZIC2 (Zic Family Member 2) is a Protein Coding gene. Diseases associated with ZIC2 include Holoprosencephaly 5 and Microform Holoprosencephaly. Among its related pathways are Mesodermal Commitment Pathway. Gene Ontology (GO) annotations related to this gene include DNA binding transcription factor activity and chromatin DNA binding. An important paralog of this gene is ZIC1.

UniProtKB/Swiss-Prot for ZIC2 Gene

  • 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.

Gene Wiki entry for ZIC2 Gene

Additional gene information for ZIC2 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ZIC2 Gene

Genomics for ZIC2 Gene

GeneHancer (GH) Regulatory Elements for ZIC2 Gene

Promoters and enhancers for ZIC2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH13J099978 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 657 +1.7 1745 10.8 HDGF ARNT SIN3A FEZF1 GLI4 ZNF2 BRCA1 YY1 ZNF121 GLIS2 ZIC2 LINC00554 ZIC5 CFL1P8 LINC01039 ARF4P3 RN7SKP9 LINC00411 UBAC2 GC13P099996
GH13J099967 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 652.2 -11.8 -11799 4.9 PKNOX1 ATF1 ARNT FEZF1 GLI4 ZNF2 YY1 ETS1 GLIS2 ZNF213 ZIC5 ZIC2 GC13M099970 PIR56949 LINC00554 CFL1P8 LINC01039 RN7SKP9 ARF4P3 LINC00411
GH13J099990 Enhancer 1.3 FANTOM5 ENCODE dbSUPER 11.1 +8.8 8753 0.8 ZSCAN5A SUZ12 ZSCAN4 KLF17 ZNF2 BCL11B RARA ZNF324 ZFHX2 GLIS2 ZIC5 ZIC2 GC13P099996
GH13J099991 Enhancer 1.2 FANTOM5 ENCODE dbSUPER 11 +11.2 11163 2.2 PKNOX1 INSM2 SIN3A FEZF1 ZNF384 ZNF2 ZNF324 ZNF335 CTBP1 POLR2A ZIC2 ZIC5 GC13P099996
GH13J099655 Enhancer 1.5 FANTOM5 Ensembl ENCODE dbSUPER 7.2 -323.9 -323875 5.3 PKNOX1 FOXA2 ZSCAN4 SIN3A ZNF2 RAD21 RARA RFX5 YY1 ETS1 ZIC5 CLYBL ZIC2 LINC00449 MIR4306 GC13P099679
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ZIC2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the ZIC2 gene promoter:
  • Sox9
  • HNF-4alpha2
  • HNF-4alpha1
  • COUP-TF1
  • COUP-TF
  • COUP
  • MyoD
  • E2F-4
  • E2F-3a

Genomic Locations for ZIC2 Gene

Genomic Locations for ZIC2 Gene
chr13:99,981,772-99,986,773
(GRCh38/hg38)
Size:
5,002 bases
Orientation:
Plus strand
chr13:100,634,026-100,639,019
(GRCh37/hg19)
Size:
4,994 bases
Orientation:
Plus strand

Genomic View for ZIC2 Gene

Genes around ZIC2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ZIC2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ZIC2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ZIC2 Gene

Proteins for ZIC2 Gene

  • Protein details for ZIC2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95409-ZIC2_HUMAN
    Recommended name:
    Zinc finger protein ZIC 2
    Protein Accession:
    O95409
    Secondary Accessions:
    • Q5VYA9
    • Q9H309

    Protein attributes for ZIC2 Gene

    Size:
    532 amino acids
    Molecular mass:
    55006 Da
    Quaternary structure:
    • 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 GLI1 and GLI2 (By similarity). Interacts (via C2H2-type domain 3) with DHX9 (PubMed:17251188).

neXtProt entry for ZIC2 Gene

Post-translational modifications for ZIC2 Gene

Other Protein References for ZIC2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for ZIC2 Gene

Domains & Families for ZIC2 Gene

Gene Families for ZIC2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for ZIC2 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for ZIC2 Gene

Graphical View of Domain Structure for InterPro Entry

O95409

UniProtKB/Swiss-Prot:

ZIC2_HUMAN :
  • The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation.
  • Belongs to the GLI C2H2-type zinc-finger protein family.
Domain:
  • The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation.
Family:
  • Belongs to the GLI C2H2-type zinc-finger protein family.
genes like me logo Genes that share domains with ZIC2: view

Function for ZIC2 Gene

Molecular function for ZIC2 Gene

UniProtKB/Swiss-Prot 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.
GENATLAS Biochemistry:
zinc finger protein 2,expressed in dorsal neural tube,eye and distal limb during development and later only in cerebellum,homolog to mouse Zic2 and Drosophila odd-paired (Opa) gene,putative regulator of the kinetics of regulation,located in the critical region of 13q32 deletion

Phenotypes From GWAS Catalog for ZIC2 Gene

Gene Ontology (GO) - Molecular Function for ZIC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding NAS 19274049
GO:0003676 nucleic acid binding IEA --
GO:0003677 DNA binding ISS --
GO:0003700 DNA binding transcription factor activity ISS --
GO:0031490 chromatin DNA binding ISS --
genes like me logo Genes that share ontologies with ZIC2: view
genes like me logo Genes that share phenotypes with ZIC2: view

Human Phenotype Ontology for ZIC2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

Transcription Factor Targets for ZIC2 Gene

Selected GeneGlobe predicted Target genes for ZIC2

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ZIC2

No data available for Enzyme Numbers (IUBMB) , Animal Models and HOMER Transcription for ZIC2 Gene

Localization for ZIC2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ZIC2 Gene

Nucleus. Cytoplasm. Note=Localizes in the cytoplasm in presence of MDFIC overexpression. Both phosphorylated and unphosphorylated forms are localized in the nucleus (By similarity). {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ZIC2 gene
Compartment Confidence
nucleus 5

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear bodies (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ZIC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA,ISS --
GO:0005737 cytoplasm ISS --
GO:0016604 nuclear body IDA --
genes like me logo Genes that share ontologies with ZIC2: view

Pathways & Interactions for ZIC2 Gene

SuperPathway Contained pathways
1 Mesodermal Commitment Pathway
genes like me logo Genes that share pathways with ZIC2: view

Pathways by source for ZIC2 Gene

1 BioSystems pathway for ZIC2 Gene

Gene Ontology (GO) - Biological Process for ZIC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006357 regulation of transcription by RNA polymerase II IEA --
GO:0007275 multicellular organism development IEA --
GO:0007399 nervous system development IEA --
genes like me logo Genes that share ontologies with ZIC2: view

No data available for SIGNOR curated interactions for ZIC2 Gene

Drugs & Compounds for ZIC2 Gene

(2) Drugs for ZIC2 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with ZIC2: view

Transcripts for ZIC2 Gene

mRNA/cDNA for ZIC2 Gene

Unigene Clusters for ZIC2 Gene

Zic family member 2:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ZIC2

Alternative Splicing Database (ASD) splice patterns (SP) for ZIC2 Gene

No ASD Table

Relevant External Links for ZIC2 Gene

GeneLoc Exon Structure for
ZIC2
ECgene alternative splicing isoforms for
ZIC2

Expression for ZIC2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for ZIC2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ZIC2 Gene

This gene is overexpressed in Brain - Cerebellar Hemisphere (x22.9) and Brain - Cerebellum (x20.3).

Protein differential expression in normal tissues from HIPED for ZIC2 Gene

This gene is overexpressed in Monocytes (68.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ZIC2 Gene



Protein tissue co-expression partners for ZIC2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of ZIC2 Gene:

ZIC2

SOURCE GeneReport for Unigene cluster for ZIC2 Gene:

Hs.653700

Evidence on tissue expression from TISSUES for ZIC2 Gene

  • Nervous system(4.7)

Phenotype-based relationships between genes and organs from Gene ORGANizer for ZIC2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • endocrine
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cerebellum
  • cerebrospinal fluid
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • meninges
  • mouth
  • nose
  • pharynx
  • pituitary gland
  • skull
  • tooth
General:
  • hair
  • skin
genes like me logo Genes that share expression patterns with ZIC2: view

No data available for mRNA Expression by UniProt/SwissProt for ZIC2 Gene

Orthologs for ZIC2 Gene

This gene was present in the common ancestor of animals.

Orthologs for ZIC2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ZIC2 34 33
  • 99.56 (n)
OneToOne
dog
(Canis familiaris)
Mammalia ZIC2 34 33
  • 95.63 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia ZIC2 34
  • 94 (a)
OneToOne
cow
(Bos Taurus)
Mammalia ZIC2 34 33
  • 91.05 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Zic2 16 34 33
  • 90.74 (n)
rat
(Rattus norvegicus)
Mammalia Zic2 33
  • 90.23 (n)
chicken
(Gallus gallus)
Aves ZIC2 34 33
  • 88.42 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia ZIC2 34
  • 82 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia zic2 33
  • 76.27 (n)
zebrafish
(Danio rerio)
Actinopterygii zic2b 34
  • 77 (a)
OneToMany
zic2a 34 33
  • 76.2 (n)
OneToMany
zic2 33
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.10414 33
fruit fly
(Drosophila melanogaster)
Insecta lmd 35
  • 43 (a)
opa 34 35
  • 35 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 37 (a)
ManyToMany
Cin.14192 33
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.14192 33
Species where no ortholog for ZIC2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for ZIC2 Gene

ENSEMBL:
Gene Tree for ZIC2 (if available)
TreeFam:
Gene Tree for ZIC2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ZIC2: view image

Paralogs for ZIC2 Gene

Paralogs for ZIC2 Gene

(6) SIMAP similar genes for ZIC2 Gene using alignment to 1 proteins:

  • ZIC2_HUMAN
genes like me logo Genes that share paralogs with ZIC2: view

Variants for ZIC2 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for ZIC2 Gene

ZIC2_HUMAN-O95409
The poly-His region between amino acids 231-239 of ZIC2 is polymorphic and the number of His can vary from 8 to 12.

Sequence variations from dbSNP and Humsavar for ZIC2 Gene

SNP ID Clin Chr 13 pos Variation AA Info Type
rs1060499562 pathogenic, Holoprosencephaly 5 99,984,962(+) GTGTG/GTG coding_sequence_variant, inframe_indel, stop_gained
rs1060499563 pathogenic, Holoprosencephaly 5 99,982,857(+) C/T coding_sequence_variant, stop_gained
rs1060499564 likely-pathogenic, Holoprosencephaly 5 99,984,966(+) GAG/G coding_sequence_variant, frameshift
rs182192729 benign, not specified, Holoprosencephaly 5 99,985,409(+) C/T 3_prime_UTR_variant, coding_sequence_variant, synonymous_variant
rs397515364 pathogenic, Holoprosencephaly 5 99,985,401(+) C/CC 3_prime_UTR_variant, coding_sequence_variant, frameshift

Structural Variations from Database of Genomic Variants (DGV) for ZIC2 Gene

Variant ID Type Subtype PubMed ID
dgv345n67 CNV gain 20364138
dgv346n67 CNV gain 20364138
dgv347n67 CNV gain 20364138
esv24692 CNV gain 19812545
esv2672999 CNV deletion 23128226
esv2747875 CNV deletion 23290073
nsv1070192 CNV deletion 25765185
nsv1146 CNV deletion 18451855
nsv456093 CNV loss 19166990
nsv510622 CNV deletion 20534489
nsv562953 CNV loss 21841781
nsv562954 CNV loss 21841781
nsv826757 CNV loss 20364138
nsv826766 CNV gain 20364138
nsv832697 CNV loss 17160897

Variation tolerance for ZIC2 Gene

Residual Variation Intolerance Score: 20.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.12; 61.28% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ZIC2 Gene

Human Gene Mutation Database (HGMD)
ZIC2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ZIC2

SNP Genotyping and Copy Number Assay Products

Disorders for ZIC2 Gene

MalaCards: The human disease database

(16) MalaCards diseases for ZIC2 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search ZIC2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

ZIC2_HUMAN
  • Holoprosencephaly 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. {ECO:0000269 PubMed:11285244, ECO:0000269 PubMed:15221788, ECO:0000269 PubMed:15590697, ECO:0000269 PubMed:19177455, ECO:0000269 PubMed:9771712}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for ZIC2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with ZIC2: view

No data available for Genatlas for ZIC2 Gene

Publications for ZIC2 Gene

  1. The full spectrum of holoprosencephaly-associated mutations within the ZIC2 gene in humans predicts loss-of-function as the predominant disease mechanism. (PMID: 19177455) Roessler E … Muenke M (Human mutation 2009) 3 4 22 58
  2. ZIC2-dependent transcriptional regulation is mediated by DNA-dependent protein kinase, poly(ADP-ribose) polymerase, and RNA helicase A. (PMID: 17251188) Ishiguro A … Aruga J (The Journal of biological chemistry 2007) 3 4 22 58
  3. Genetic variants in ZIC1, ZIC2, and ZIC3 are not major risk factors for neural tube defects in humans. (PMID: 14679585) Klootwijk R … Franke B (American journal of medical genetics. Part A 2004) 3 22 44 58
  4. Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: Mutation review and genotype-phenotype correlations. (PMID: 15221788) Dubourg C … David V (Human mutation 2004) 3 4 22 58
  5. Possible association of NTDs with a polyhistidine tract polymorphism in the ZIC2 gene. (PMID: 11857562) Brown LY … Brown S (American journal of medical genetics 2002) 3 22 44 58

Products for ZIC2 Gene

Sources for ZIC2 Gene

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