ZIC4 Zic family member 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ZIC4provided by HGNC
Official Full Name: Zic family member 4provided by HGNC
Primary source: HGNC:HGNC:20393
See related: Ensembl:ENSG00000174963 MIM:608948; AllianceGenome:HGNC:20393
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
Summary: This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. Members of this family are important during development, and have been associated with X-linked visceral heterotaxy and holoprosencephaly type 5. This gene is closely linked to the gene encoding zinc finger protein of the cerebellum 1, a related family member on chromosome 3. Heterozygous deletion of these linked genes is involved in Dandy-Walker malformation, which is a congenital cerebellar malformation. Multiple transcript variants have been identified for this gene. [provided by RefSeq, Dec 2009]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 3q24

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (147386046..147406543, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (150141298..150161796, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (147103833..147124330, complement)

Chromosome 3 - NC_000003.12 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
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?

Epigenetic silencing of ZIC4 unveils a potential tumor suppressor role in pediatric choroid plexus carcinoma.
Title: Epigenetic silencing of ZIC4 unveils a potential tumor suppressor role in pediatric choroid plexus carcinoma.
Common Variants Near ZIC1 and ZIC4 in Autopsy-Confirmed Multiple System Atrophy.
Title: Common Variants Near ZIC1 and ZIC4 in Autopsy-Confirmed Multiple System Atrophy.
Transcriptional expression of ZICs as an independent indicator of survival in gliomas.
Title: Transcriptional expression of ZICs as an independent indicator of survival in gliomas.
Epigenetic silencing of ZIC4 contributes to cancer progression in hepatocellular carcinoma.
Title: Epigenetic silencing of ZIC4 contributes to cancer progression in hepatocellular carcinoma.
The rate of methylation of ZIC1, ZIC4, HHIP, and DACT2 in tumors was very high, while methylation of CXXC4 was low to moderate in OSCC and LSCC.
Title: Prognostic significance of the methylation of Wnt pathway antagonists-CXXC4, DACT2, and the inhibitors of sonic hedgehog signaling-ZIC1, ZIC4, and HHIP in head and neck squamous cell carcinomas.
ZIC4 CPG island methylation predicts progression in bladder cancer.
Title: Genome-wide analysis of CpG island methylation in bladder cancer identified TBX2, TBX3, GATA2, and ZIC4 as pTa-specific prognostic markers.
Dandy-Walker malformation associated with heterozygous ZIC1 and ZIC4 deletion.
Title: Dandy-Walker malformation associated with heterozygous ZIC1 and ZIC4 deletion: Report of a new patient.
Through physical mapping of 3q2 interstitial deletions in several individuals with Dandy-Walker malformation (DWM), we defined the first critical region associated with DWM, encompassing two adjacent Zinc finger in cerebellum genes, ZIC1 and ZIC4.
Title: Heterozygous deletion of the linked genes ZIC1 and ZIC4 is involved in Dandy-Walker malformation.

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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

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2021-08-25) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2021-08-25) ClinGen Genome Curation Page

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

RH91704 (e-PCR)
- UniSTS:83715

D3S3991 (e-PCR)
- UniSTS:1296

G33011 (e-PCR)
- UniSTS:117588

D3S2841E (e-PCR)
- UniSTS:150869

SHGC-31137 (e-PCR)
- UniSTS:64627

A009Z14 (e-PCR)
- UniSTS:51329

SGC30596 (e-PCR)
- UniSTS:46763

NoName (e-PCR)
- UniSTS:490425

SHGC-77439 (e-PCR)
- UniSTS:57849

ZIC4_2201 (e-PCR)
- UniSTS:281086

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	ISS Inferred from Sequence or Structural Similarity more info
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 metal ion binding	IEA Inferred from Electronic Annotation more info
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in central nervous system development	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
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 4

Names: zinc family member 4 protein HZIC4; zinc finger protein of the cerebellum 4

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_009242.1 RefSeqGene

Range

5078..25575

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001168378.1 → NP_001161850.1 zinc finger protein ZIC 4 isoform 1

See identical proteins and their annotated locations for NP_001161850.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AK124600, AK294831, DA066220

Consensus CDS

CCDS54652.1

UniProtKB/Swiss-Prot

Q8N9L1

Related

ENSP00000435509.2, ENST00000525172.6

Conserved Domains (4) summary

COG5048
Location:192 → 338

COG5048; FOG: Zn-finger [General function prediction only]

sd00017
Location:228 → 248

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00096
Location:314 → 338

zf-C2H2; Zinc finger, C2H2 type

pfam13465
Location:270 → 297

zf-H2C2_2; Zinc-finger double domain
NM_001168379.2 → NP_001161851.1 zinc finger protein ZIC 4 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and 5' coding region, compared to variant 1, resulting in an isoform (2) with a distinct and shorter N-terminus, compared to isoform 1.

Source sequence(s)

AC092959, AK124600, AK293981, DA066220

Consensus CDS

CCDS54653.1

UniProtKB/Swiss-Prot

Q8N9L1

Related

ENSP00000397695.3, ENST00000425731.7

Conserved Domains (4) summary

COG5048
Location:180 → 326

COG5048; FOG: Zn-finger [General function prediction only]

sd00017
Location:216 → 236

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00096
Location:302 → 326

zf-C2H2; Zinc finger, C2H2 type

pfam13465
Location:258 → 285

zf-H2C2_2; Zinc-finger double domain
NM_001243256.2 → NP_001230185.1 zinc finger protein ZIC 4 isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (6) differs in the 5' UTR and has multiple differences in the coding region but maintains the reading frame, compared to variant 1. The encoded isoform (4) is shorter than isoform 1.

Source sequence(s)

AC092959, AK124600, DA218617, DA759114

Consensus CDS

CCDS58857.1

UniProtKB/Swiss-Prot

Q8N9L1

Related

ENSP00000418277.1, ENST00000491672.5

Conserved Domains (2) summary

COG5189
Location:20 → 80

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

sd00017
Location:30 → 52

ZF_C2H2; C2H2 Zn finger [structural motif]
NM_032153.6 → NP_115529.2 zinc finger protein ZIC 4 isoform 3

See identical proteins and their annotated locations for NP_115529.2

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and uses a downstream, in-frame start codon, compared to variant 1. The resulting isoform (3) has a shorter N-terminus, compared to isoform 1.

Source sequence(s)

AC092959, AK056262, AK124600

Consensus CDS

CCDS43160.1

UniProtKB/Swiss-Prot

A0AVA2, B2RMQ8, B4DF89, B7Z2L2, C9J7D5, J3KQG1, Q4G157, Q8N9L1, Q9BZ94

Related

ENSP00000372553.3, ENST00000383075.8

Conserved Domains (4) summary

COG5048
Location:142 → 288

COG5048; FOG: Zn-finger [General function prediction only]

sd00017
Location:178 → 198

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00096
Location:264 → 288

zf-C2H2; Zinc finger, C2H2 type

pfam13465
Location:220 → 247

zf-H2C2_2; Zinc-finger double domain

RNA

NR_033118.3 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks three 5' exons but includes an alternate 5' exon, compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region, including the translational start codon, found in variant 1.

Source sequence(s)

AC092959, AK124600, AK127733, DA106797

Related

ENST00000472749.6
NR_033119.3 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks three 5' exons but includes an alternate 5' exon, compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region, including the translational start codon, found in variant 1.

Source sequence(s)

AC092959, AK124600, AK127733, DA314072, DA416382
NR_040762.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (7) lacks three 5' exons but includes an alternate 5' exon, compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region, including the translational start codon, found in variant 1.

Source sequence(s)

AC092959, AK124600, DA121447, DA411998