CXXC5: A Key Regulator of Wnt/β-Catenin Signaling and Cellular Differentiation
Comprehensive genomic and functional analysis of the CXXC5 gene, its role in development, disease, and potential as a therapeutic target.
Gene Information Card
| Symbol | CXXC5 |
|---|---|
| Full Name | CXXC finger protein 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q31.2 |
| NCBI Gene ID | 51523 ncbi.nlm.nih.gov/gene/51523 |
| Ensembl ID | ENSG00000113522 |
| UniProt ID | Q7LFL8 |
| OMIM ID | 611251 |
| HGNC ID | 26943 |
| Aliases | CF5, HSPC195, RINF, WID |
Description
CXXC5 (CXXC finger protein 5) is a protein-coding gene located on chromosome 5q31.2. It encodes a zinc finger protein that contains a CXXC-type zinc finger domain, which is involved in DNA binding and chromatin regulation. CXXC5 functions as a key regulator of the Wnt/β-catenin signaling pathway by interacting with Dishevelled (DVL) proteins and modulating β-catenin stability. It also plays roles in retinoic acid signaling, cell differentiation, and apoptosis. CXXC5 is expressed in various tissues, with high levels in the brain, and is implicated in neural development, cancer, and other diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute Myeloid Leukemia (AML) | CXXC5 is a retinoic acid target gene; its downregulation may contribute to leukemogenesis by impairing differentiation. | PMID: 20015956 |
| Colorectal Cancer | CXXC5 acts as a tumor suppressor by inhibiting Wnt/β-catenin signaling; loss of expression promotes tumor growth. | PMID: 23994610 |
| Gastric Cancer | Reduced CXXC5 expression correlates with poor prognosis; epigenetic silencing via promoter methylation. | PMID: 25695636 |
| Hepatocellular Carcinoma | CXXC5 suppresses Wnt signaling; decreased expression is associated with metastasis and recurrence. | PMID: 25944712 |
| Neural Tube Defects | CXXC5 regulates neural tube closure via Wnt/planar cell polarity (PCP) pathway; mutations may contribute to defects. | PMID: 23714752 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.2 | Low |
| Thyroid | 7.1 | Low |
| Lung | 6.0 | Low |
| Liver | 4.5 | Low |
| Kidney | 4.0 | Low |
| Heart | 3.8 | Low |
| Spleen | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 10.2 | Embryonic kidney cells; moderate expression |
| K562 | 8.5 | Leukemia cells; low expression |
| HepG2 | 6.8 | Hepatocellular carcinoma cells; low expression |
| SH-SY5Y | 15.3 | Neuroblastoma cells; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon; likely loss of function |
| c.100C>T (p.Arg34Trp) | Missense | <0.01% | Alters CXXC domain; may affect DNA binding |
| c.200_201del (p.Glu67fs) | Frameshift | Very rare | Truncating; loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein, leading to loss of CXXC domain and impaired Wnt signaling inhibition.
Gain of Function (GOF)
Not reported; no activating mutations documented in COSMIC or ClinVar.
Dominant Negative (DN)
Not reported; no evidence for dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • zinc ion binding |
| • protein binding | • regulation of Wnt signaling pathway |
| • negative regulation of transcription by RNA polymerase II | • cell differentiation |
| • apoptotic process | • neural tube closure |
Pathways
• Wnt signaling pathway
• Retinoic acid signaling pathway
• Planar cell polarity pathway
Protein Summary
The CXXC5 protein (UniProt Q7LFL8) is a 322-amino acid zinc finger protein containing a CXXC-type domain (residues 1-60) that binds unmethylated CpG DNA. It localizes to the nucleus and cytoplasm. CXXC5 interacts with Dishevelled (DVL) proteins to inhibit Wnt/β-catenin signaling by promoting β-catenin degradation. It also interacts with retinoic acid receptors to regulate gene expression during differentiation. The protein is involved in neural development, hematopoiesis, and tumor suppression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CXXC5 Knockout HEK293 Cell Line | EDJ-KQ1133 | Human | 51523 | Details Get a Quote |
| CXXC5 Knockout A-549 Cell Line | EDJ-KQ20343 | Human | 51523 | Details Get a Quote |
| CXXC5 Knockout HCT 116 Cell Line | EDJ-KQ20344 | Human | 51523 | Details Get a Quote |
| CXXC5 Knockout HeLa Cell Line | EDJ-KQ20345 | Human | 51523 | Details Get a Quote |
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