CXXC4 CXXC finger protein 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CXXC4provided by HGNC
Official Full Name: CXXC finger protein 4provided by HGNC
Primary source: HGNC:HGNC:24593
See related: Ensembl:ENSG00000168772 MIM:611645; AllianceGenome:HGNC:24593
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: IDAX
Summary: This gene encodes a CXXC-type zinc finger domain-containing protein that functions as an antagonist of the canonical wingless/integrated signaling pathway. The encoded protein negatively regulates wingless/integrated signaling through interaction with the post synaptic density protein/ Drosophila disc large tumor suppressor/ zonula occludens-1 protein domain of Dishevelled, a scaffolding protein required for the stabilization of the transcriptional co-activator beta-catenin. In addition, the CXXC domain of this protein has been shown to bind unmethylated CpG dinucleotides, localize to promoters and CpG islands, and interact with the catalytic domain of methylcytosine dioxygenase ten-eleven-translocation 2, an iron and alpha-ketoglutarate-dependent dioxygenase that modifies the methylation status of DNA. In humans, a mutation in this gene has been associated with development of malignant renal cell carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]
Expression: Broad expression in brain (RPKM 4.6), thyroid (RPKM 1.9) and 20 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4q24

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (104468308..104494894, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (107779515..107806100, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (105389465..105416051, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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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?

Malignant Transformation Involving CXXC4 Mutations Identified in a Leukemic Progression Model of Severe Congenital Neutropenia.
Title: Malignant Transformation Involving CXXC4 Mutations Identified in a Leukemic Progression Model of Severe Congenital Neutropenia.
SPZ1 promotes glioma aggravation via targeting CXXC4.
Title: SPZ1 promotes glioma aggravation via targeting CXXC4.
CXXC finger protein 4 inhibits the CDK18-ERK1/2 axis to suppress the immune escape of gastric cancer cells with involvement of ELK1/MIR100HG pathway.
Title: CXXC finger protein 4 inhibits the CDK18-ERK1/2 axis to suppress the immune escape of gastric cancer cells with involvement of ELK1/MIR100HG pathway.
LUCAT1 Epigenetically Downregulates the Tumor Suppressor Genes CXXC4 and SFRP2 in Gastric Cancer.
Title: LUCAT1 Epigenetically Downregulates the Tumor Suppressor Genes CXXC4 and SFRP2 in Gastric Cancer.
The results presented here suggest that miR-629-5p functions as a tumor promoter by improving proliferation and migration and repressing apoptosis and 5-FU sensitivity in colorectal cancer progression by directly down-regulating CXXC4.
Title: MiR-629-5p promotes colorectal cancer progression through targetting CXXC finger protein 4.
The findings indicate that BMI1-mediated IDAX epigenetic suppression is crucial for enhancement of colon carcinogenesis.
Title: BMI1 activates WNT signaling in colon cancer by negatively regulating the WNT antagonist IDAX.
Age of patients and levels of CXXC4 mRNA, hemoglobin, and marrow blast associated with survival of Myelodysplastic syndrome patients.
Title: CXXC4 mRNA levels are associated with clinicopathological parameters and survival of myelodysplastic syndrome patients.
EZH2 can activate MAPK signaling by inhibiting CXXC4 expression.
Title: New tumor suppressor CXXC finger protein 4 inactivates mitogen activated protein kinase signaling.
CXXC4 is a novel potential tumor suppressor directly regulated by EZH2, and its expression is a significant prognosis factor for patients with early stages of gastric cancer.
Title: Enhancer of zeste homolog 2 activates wnt signaling through downregulating CXXC finger protein 4.
IDAX expression results in caspase activation and TET2 protein downregulation, in a manner that depends on DNA binding through the IDAX CXXC domain, suggesting that IDAX recruits TET2 to DNA before degradation
Title: Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX.

Submit: New GeneRIF Correction See all GeneRIFs (12)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of CXXC finger protein 4 (CXXC4; IDAX) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH102703 (e-PCR)
- UniSTS:97037

D4S2678 (e-PCR)
- UniSTS:61086

RH35803 (e-PCR)
- UniSTS:25812

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables PDZ domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables methyl-CpG binding	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in zygotic specification of dorsal/ventral axis	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: CXXC-type zinc finger protein 4

Names: CXXC finger 4; Dvl-binding protein IDAX (inhibition of the Dvl and Axin complex); inhibition of the Dvl and axin complex protein

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.

mRNA and Protein(s)

NM_025212.4 → NP_079488.2 CXXC-type zinc finger protein 4

See identical proteins and their annotated locations for NP_079488.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the protein.

Source sequence(s)

AA708035, AC093628, AK125395, CB068467, DA804531

Consensus CDS

CCDS3665.2

UniProtKB/TrEMBL

J9JIF5

Related

ENSP00000378248.2, ENST00000394767.3

Conserved Domains (1) summary

pfam02008
Location:301 → 341

zf-CXXC; CXXC zinc finger domain

RNA

NR_132741.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate internal exon and lacks another alternate internal 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)

AA708035, AC093628, AK125395, CB068467, CR627201, DA397981

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

104468308..104494894 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011532284.3 → XP_011530586.1 CXXC-type zinc finger protein 4 isoform X1

See identical proteins and their annotated locations for XP_011530586.1

UniProtKB/TrEMBL

J9JIF5

Conserved Domains (1) summary

pfam02008
Location:301 → 341

zf-CXXC; CXXC zinc finger domain

Alternate T2T-CHM13v2.0

Genomic

NC_060928.1 Alternate T2T-CHM13v2.0

Range

107779515..107806100 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054350899.1 → XP_054206874.1 CXXC-type zinc finger protein 4 isoform X1

UniProtKB/TrEMBL

J9JIF5
XM_054350898.1 → XP_054206873.1 CXXC-type zinc finger protein 4 isoform X2

UniProtKB/TrEMBL

A0A8V8TLX0
XM_054350896.1 → XP_054206871.1 CXXC-type zinc finger protein 4 isoform X2

UniProtKB/TrEMBL

A0A8V8TLX0
XM_054350897.1 → XP_054206872.1 CXXC-type zinc finger protein 4 isoform X2

UniProtKB/TrEMBL

A0A8V8TLX0