Human Gene ZIC3 (ENST00000287538.10) from GENCODE V43
  Description: Homo sapiens Zic family member 3 (ZIC3), transcript variant 1, mRNA. (from RefSeq NM_003413)
RefSeq Summary (NM_003413): This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. This nuclear protein probably functions as a transcription factor in early stages of left-right body axis formation. Mutations in this gene cause X-linked visceral heterotaxy, which includes congenital heart disease and left-right axis defects in organs. [provided by RefSeq, Jul 2008].
Gencode Transcript: ENST00000287538.10
Gencode Gene: ENSG00000156925.12
Transcript (Including UTRs)
   Position: hg38 chrX:137,566,127-137,572,102 Size: 5,976 Total Exon Count: 3 Strand: +
Coding Region
   Position: hg38 chrX:137,566,692-137,570,070 Size: 3,379 Coding Exon Count: 3 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-02-17 13:02:02

-  Sequence and Links to Tools and Databases
Genomic Sequence (chrX:137,566,127-137,572,102)mRNA (may differ from genome)Protein (467 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSCGAPEnsemblEntrez GeneExonPrimer

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Zinc finger protein ZIC 3; AltName: Full=Zinc finger protein 203; AltName: Full=Zinc finger protein of the cerebellum 3;
FUNCTION: Acts as transcriptional activator. Required in the earliest stages in both axial midline development and left-right (LR) asymmetry specification. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC-3'.
SUBUNIT: 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 (By similarity). Interacts with KPNA1 and KPNA6. Interacts (via C2H2-type domains 3, 4 and 5) with GLI3; the interaction enhances its transcriptional activity.
SUBCELLULAR LOCATION: Nucleus. Cytoplasm (By similarity). Note=Localizes in the cytoplasm in presence of MDFIC overexpression (By similarity). Translocation to the nucleus requires KPNA1 or KPNA6.
DOMAIN: The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation (By similarity).
DISEASE: Defects in ZIC3 are the cause of visceral heterotaxy X- linked type 1 (HTX1) [MIM:306955]. A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. It results in an abnormal arrangement of visceral organs, and a wide variety of congenital defects. Clinical features of visceral heterotaxy X- linked type 1 include dextrocardia, corrected transposition of great arteries, ventricular septal defect, patent ductus arteriosus, pulmonic stenosis, situs inversus viscerum, and asplenia and/or polysplenia.
DISEASE: Defects in ZIC3 are a cause of VACTERL association X- linked with or without hydrocephalus (VACTERLX) [MIM:314390]. A syndrome characterized by vertebral anomalies, anal atresia, cardiac malformations, tracheoesophageal fistula, renal anomalies (urethral atresia with hydronephrosis), and limb anomalies (hexadactyly, humeral hypoplasia, radial aplasia, and proximally placed thumb). Some patients may have hydrocephalus. Some cases of VACTERL-H are associated with increased chromosome breakage and rearrangement.
SIMILARITY: Belongs to the GLI C2H2-type zinc-finger protein family.
SIMILARITY: Contains 5 C2H2-type zinc fingers.
WEB RESOURCE: Name=GeneReviews; URL="";

-  Primer design for this transcript

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3

-  MalaCards Disease Associations
  MalaCards Gene Search: ZIC3
Diseases sorted by gene-association score: vacterl association, x-linked* (1329), heterotaxy, visceral, 1, x-linked* (1231), vacterl association with hydrocephaly, x-linked* (400), zic3-related visceral heterotaxy* (100), heterotaxy* (80), vacterl association (43), visceral heterotaxy* (30), isolated congenitally uncorrected transposition of the great arteries* (25), heart disease (19), transposition of the great arteries (17), hydrocephalus (11), thyroid crisis (11), tracheoesophageal fistula (9), toxic myocarditis (9), tricuspid valve insufficiency (8), vater/vacterl association (8), parotid gland cancer (7), cerebral degeneration (7), hemopneumothorax (7), opportunistic bacterial infectious disease (7), nocardiosis (7), dextro-looped transposition of the great arteries (6), tricuspid valve disease (6), pulmonic stenosis (6), omphalocele (6), hydronephrosis (5), neural tube defects (4)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 11.60 RPKM in Brain - Cerebellum
Total median expression: 28.41 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -204.10565-0.361 Picture PostScript Text
3' UTR -451.202032-0.222 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR007087 - Znf_C2H2
IPR015880 - Znf_C2H2-like
IPR013087 - Znf_C2H2/integrase_DNA-bd

Pfam Domains:
PF00096 - Zinc finger, C2H2 type

Protein Data Bank (PDB) 3-D Structure
MuPIT help

ModBase Predicted Comparative 3D Structure on O60481
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein SequenceProtein Sequence   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0003676 nucleic acid binding
GO:0003677 DNA binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0005515 protein binding
GO:0043565 sequence-specific DNA binding
GO:0046872 metal ion binding

Biological Process:
GO:0001947 heart looping
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006366 transcription from RNA polymerase II promoter
GO:0007275 multicellular organism development
GO:0007368 determination of left/right symmetry
GO:0007389 pattern specification process
GO:0007399 nervous system development
GO:0009952 anterior/posterior pattern specification
GO:0030154 cell differentiation
GO:0030324 lung development
GO:0035019 somatic stem cell population maintenance
GO:0035469 determination of pancreatic left/right asymmetry
GO:0035545 determination of left/right asymmetry in nervous system
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0071907 determination of digestive tract left/right asymmetry
GO:0071910 determination of liver left/right asymmetry

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm

-  Descriptions from all associated GenBank mRNAs
  LF211493 - JP 2014500723-A/18996: Polycomb-Associated Non-Coding RNAs.
MA447070 - JP 2018138019-A/18996: Polycomb-Associated Non-Coding RNAs.
AF028706 - Homo sapiens zinc-finger protein of the cerebellum 3 (ZIC3) mRNA, complete cds.
JD191982 - Sequence 173006 from Patent EP1572962.
JD141709 - Sequence 122733 from Patent EP1572962.
JD343157 - Sequence 324181 from Patent EP1572962.
JD318014 - Sequence 299038 from Patent EP1572962.
JD560379 - Sequence 541403 from Patent EP1572962.
JD461811 - Sequence 442835 from Patent EP1572962.
JD298884 - Sequence 279908 from Patent EP1572962.
JD392947 - Sequence 373971 from Patent EP1572962.
JD519522 - Sequence 500546 from Patent EP1572962.
JD261818 - Sequence 242842 from Patent EP1572962.
EU532020 - Homo sapiens clone IMAGE: 664181 Zic family member 3 heterotaxy 1 (ZIC3) mRNA, complete cds.
BC113393 - Homo sapiens Zic family member 3 (odd-paired homolog, Drosophila), mRNA (cDNA clone MGC:141953 IMAGE:8322445), complete cds.
BC113395 - Homo sapiens Zic family member 3 (odd-paired homolog, Drosophila), mRNA (cDNA clone MGC:141955 IMAGE:8322447), complete cds.
AB464363 - Synthetic construct DNA, clone: pF1KB7199, Homo sapiens ZIC3 gene for Zic family member 3 heterotaxy 1, without stop codon, in Flexi system.
BC111854 - Synthetic construct Homo sapiens clone IMAGE:40080845, MGC:133399 ZIC3 protein (ZIC3) mRNA, encodes complete protein.
HQ258447 - Synthetic construct Homo sapiens clone IMAGE:100072876 Zic family member 3 (odd-paired homolog, Drosophila) (ZIC3) gene, encodes complete protein.
KJ892399 - Synthetic construct Homo sapiens clone ccsbBroadEn_01793 ZIC3 gene, encodes complete protein.
JD458522 - Sequence 439546 from Patent EP1572962.
LF380450 - JP 2014500723-A/187953: Polycomb-Associated Non-Coding RNAs.
MA616027 - JP 2018138019-A/187953: Polycomb-Associated Non-Coding RNAs.
LF380453 - JP 2014500723-A/187956: Polycomb-Associated Non-Coding RNAs.
MA616030 - JP 2018138019-A/187956: Polycomb-Associated Non-Coding RNAs.
JD179583 - Sequence 160607 from Patent EP1572962.
JD075544 - Sequence 56568 from Patent EP1572962.
JD242158 - Sequence 223182 from Patent EP1572962.
JD119470 - Sequence 100494 from Patent EP1572962.
JD524836 - Sequence 505860 from Patent EP1572962.
JD556734 - Sequence 537758 from Patent EP1572962.
JD037373 - Sequence 18397 from Patent EP1572962.
LF380455 - JP 2014500723-A/187958: Polycomb-Associated Non-Coding RNAs.
MA616032 - JP 2018138019-A/187958: Polycomb-Associated Non-Coding RNAs.
LF380456 - JP 2014500723-A/187959: Polycomb-Associated Non-Coding RNAs.
MA616033 - JP 2018138019-A/187959: Polycomb-Associated Non-Coding RNAs.
LF380457 - JP 2014500723-A/187960: Polycomb-Associated Non-Coding RNAs.
MA616034 - JP 2018138019-A/187960: Polycomb-Associated Non-Coding RNAs.
LF380458 - JP 2014500723-A/187961: Polycomb-Associated Non-Coding RNAs.
MA616035 - JP 2018138019-A/187961: Polycomb-Associated Non-Coding RNAs.
JD037986 - Sequence 19010 from Patent EP1572962.
JD071778 - Sequence 52802 from Patent EP1572962.
LF380459 - JP 2014500723-A/187962: Polycomb-Associated Non-Coding RNAs.
MA616036 - JP 2018138019-A/187962: Polycomb-Associated Non-Coding RNAs.
JD207152 - Sequence 188176 from Patent EP1572962.
JD352308 - Sequence 333332 from Patent EP1572962.
LF380460 - JP 2014500723-A/187963: Polycomb-Associated Non-Coding RNAs.
MA616037 - JP 2018138019-A/187963: Polycomb-Associated Non-Coding RNAs.
JD429776 - Sequence 410800 from Patent EP1572962.
LF380461 - JP 2014500723-A/187964: Polycomb-Associated Non-Coding RNAs.
MA616038 - JP 2018138019-A/187964: Polycomb-Associated Non-Coding RNAs.
JD551098 - Sequence 532122 from Patent EP1572962.
LF380462 - JP 2014500723-A/187965: Polycomb-Associated Non-Coding RNAs.
MA616039 - JP 2018138019-A/187965: Polycomb-Associated Non-Coding RNAs.
LF380463 - JP 2014500723-A/187966: Polycomb-Associated Non-Coding RNAs.
MA616040 - JP 2018138019-A/187966: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein O60481 (Reactome details) participates in the following event(s):

R-HSA-2892247 POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
R-HSA-452723 Transcriptional regulation of pluripotent stem cells
R-HSA-1266738 Developmental Biology

-  Other Names for This Gene
  Alternate Gene Symbols: B2CNW4, ENST00000287538.1, ENST00000287538.2, ENST00000287538.3, ENST00000287538.4, ENST00000287538.5, ENST00000287538.6, ENST00000287538.7, ENST00000287538.8, ENST00000287538.9, NM_003413, O60481, Q14DE5, Q5JY75, uc004fak.1, uc004fak.2, uc004fak.3, uc004fak.4, uc004fak.5, ZIC3_HUMAN, ZNF203
UCSC ID: ENST00000287538.10
RefSeq Accession: NM_003413
Protein: O60481 (aka ZIC3_HUMAN)
CCDS: CCDS14663.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.