ZIC3 Zic family member 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ZIC3provided by HGNC
Official Full Name: Zic family member 3provided by HGNC
Primary source: HGNC:HGNC:12874
See related: Ensembl:ENSG00000156925 MIM:300265; AllianceGenome:HGNC:12874
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HTX; HTX1; ZNF203; VACTERLX
Summary: 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]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: Xq26.3

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (137566127..137577691)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (135876075..135887645)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (136648286..136659850)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

ZIC2 and ZIC3 promote SWI/SNF recruitment to safeguard progression towards human primed pluripotency.
Title: ZIC2 and ZIC3 promote SWI/SNF recruitment to safeguard progression towards human primed pluripotency.
Zic family member 3 attenuates oxidative stress-induced vascular smooth muscle cell apoptosis in patients with chronic kidney disease.
Title: Zic family member 3 attenuates oxidative stress-induced vascular smooth muscle cell apoptosis in patients with chronic kidney disease.
A novel ZIC3 mutation in a Chinese family with heterotaxy and multiple types of congenital heart defect.
Title: A novel ZIC3 mutation in a Chinese family with heterotaxy and multiple types of congenital heart defect.
Description of a family with X-linked oculo-auriculo-vertebral spectrum associated with polyalanine tract expansion in ZIC3.
Title: Description of a family with X-linked oculo-auriculo-vertebral spectrum associated with polyalanine tract expansion in ZIC3.
This study characterized cis-regulatory elements required for Zic3 expression.
Title: An Evolutionarily Conserved Mesodermal Enhancer in Vertebrate Zic3.
The results of functional indicated that this ZIC3 mutation decreases transcriptional activity, affects the affinity of the GLI-binding site and results in aberrant cellular localization in transfected cells.
Title: A novel ZIC3 gene mutation identified in patients with heterotaxy and congenital heart disease.
miR-155-5p inhibits the viability of vascular smooth muscle cell via targeting FOS and ZIC3 to promote aneurysm formation
Title: miR-155-5p inhibits the viability of vascular smooth muscle cell via targeting FOS and ZIC3 to promote aneurysm formation.
current understanding of ZIC3 function and describe the potential role ZIC3 plays in important signalling pathways and their links to heterotaxy.
Title: ZIC3 in Heterotaxy.
Six novel pathogenic variants were identified in either male patients with heterotaxy or a female patient with multiple male deaths due to heterotaxy in the family. Truncating variants showed abnormal trafficking of mutated ZIC3 proteins.
Title: Rare novel variants in the ZIC3 gene cause X-linked heterotaxy.
Targeted Resequencing of 29 Candidate Genes and Mouse Expression Studies Implicate ZIC3 and FOXF1 in Human VATER/VACTERL Association
Title: Targeted Resequencing of 29 Candidate Genes and Mouse Expression Studies Implicate ZIC3 and FOXF1 in Human VATER/VACTERL Association.

Submit: New GeneRIF Correction See all GeneRIFs (28)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Heterotaxy, visceral, 1, X-linked MedGen: C1844020 OMIM: 306955 GeneReviews: Not available	not available
VACTERL association, X-linked, with or without hydrocephalus MedGen: C2931228 OMIM: 314390 GeneReviews: Not available	not available

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2020-12-02) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2020-12-02) ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

stSG20553 (e-PCR)
- UniSTS:181779

ZIC3 (e-PCR)
- UniSTS:506650

NoName (e-PCR)
- UniSTS:483411

ZIC3_2181 (e-PCR)
- UniSTS:281085

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables transcription coactivator activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in atrial cardiac muscle tissue development	IEA Inferred from Electronic Annotation more info
involved_in axial mesoderm development	IEA Inferred from Electronic Annotation more info
involved_in central nervous system development	IBA Inferred from Biological aspect of Ancestor more info
involved_in central nervous system segmentation	IEA Inferred from Electronic Annotation more info
involved_in cranial skeletal system development	IEA Inferred from Electronic Annotation more info
involved_in determination of digestive tract left/right asymmetry	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in determination of left/right asymmetry in nervous system	IEA Inferred from Electronic Annotation more info
involved_in determination of left/right symmetry	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in determination of liver left/right asymmetry	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in determination of pancreatic left/right asymmetry	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in embryonic pattern specification	IEA Inferred from Electronic Annotation more info
involved_in face development	IEA Inferred from Electronic Annotation more info
involved_in germ-line stem cell population maintenance	IEA Inferred from Electronic Annotation more info
involved_in heart looping	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in hippocampus development	IEA Inferred from Electronic Annotation more info
involved_in left/right axis specification	IEA Inferred from Electronic Annotation more info
involved_in limb morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in lung development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mRNA transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in neural plate development	IEA Inferred from Electronic Annotation more info
involved_in neuron differentiation	IEA Inferred from Electronic Annotation more info
involved_in olfactory bulb development	IEA Inferred from Electronic Annotation more info
involved_in outer ear morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in paraxial mesoderm development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in primitive streak formation	IEA Inferred from Electronic Annotation more info
involved_in skeletal system development	IEA Inferred from Electronic Annotation more info
involved_in smoothened signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in stem cell differentiation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: zinc finger protein ZIC 3

Names: Zic family member 3 (odd-paired homolog, Drosophila); heterotaxy 1; zinc finger protein 203; zinc finger protein of the cerebellum 3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008115.2 RefSeqGene

Range

5001..10976

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001330661.1 → NP_001317590.1 zinc finger protein ZIC 3 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2, also known as ZIC3-B) uses an alternate 3'-terminal exon, compared to variant 1. The encoded isoform (2) has a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

AL035443

Consensus CDS

CCDS83494.1

UniProtKB/Swiss-Prot

O60481

Related

ENSP00000359638.3, ENST00000370606.3
NM_003413.4 → NP_003404.1 zinc finger protein ZIC 3 isoform 1

See identical proteins and their annotated locations for NP_003404.1

Status: REVIEWED

Description

Transcript Variant: This variant (1, also known as ZIC3-A) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AL035443

Consensus CDS

CCDS14663.1

UniProtKB/Swiss-Prot

B2CNW4, O60481, Q14DE5, Q5JY75

Related

ENSP00000287538.5, ENST00000287538.10

Conserved Domains (2) summary

COG5189
Location:324 → 408

SFP1; Putative transcriptional repressor regulating G2/M transition [Transcription / Cell division and chromosome partitioning]

sd00017
Location:302 → 322

ZF_C2H2; C2H2 Zn finger [structural motif]