CUX1 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the CUX1 gene, its protein product, associated diseases, and implications in cancer and development.
Gene Information Card
| Symbol | CUX1 |
|---|---|
| Full Name | Cut Like Homeobox 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q22.1 |
| NCBI Gene ID | 1523 ncbi.nlm.nih.gov/gene/1523 |
| Ensembl ID | ENSG00000157992 |
| UniProt ID | P39880 |
| OMIM ID | 116896 |
| HGNC ID | 2557 |
| Aliases | CDP, CUTL1, Gp95, CASP, CUTL1, CUX1, CUX |
Description
The CUX1 gene encodes a transcription factor that belongs to the homeodomain family. It is involved in the regulation of gene expression during development, cell cycle progression, and DNA damage response. CUX1 is widely expressed in various tissues and plays a role in cell differentiation and proliferation. Alterations in CUX1 have been associated with several cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Myelodysplastic syndrome (MDS) | Loss-of-function mutations leading to haploinsufficiency or altered transcriptional regulation | COSMIC, ClinVar |
| Acute myeloid leukemia (AML) | Somatic mutations and deletions causing reduced CUX1 activity, contributing to leukemogenesis | COSMIC, ClinVar |
| Breast cancer | Overexpression or aberrant splicing leading to constitutive activation of CUX1, promoting cell proliferation | COSMIC, PubMed |
| Colorectal cancer | CUX1 overexpression associated with poor prognosis and increased invasiveness | COSMIC, PubMed |
| Lung cancer | CUX1 amplification or overexpression linked to tumor progression | COSMIC, PubMed |
| Developmental delay and intellectual disability | Germline mutations in CUX1 causing haploinsufficiency | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Liver | 8.2 | Low |
| Lung | 6.4 | Low |
| Brain | 5.1 | Low |
| Breast | 4.8 | Low |
| Colon | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.3 | High expression |
| HeLa | 10.2 | Moderate expression |
| MCF7 | 8.7 | Moderate expression |
| A549 | 6.5 | Low expression |
| K562 | 4.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Ter) | Nonsense | Rare (0.01%) | Loss of function, premature truncation |
| c.567_568del (p.Glu190fs) | Frameshift | Somatic in AML | Loss of function, protein truncation |
| c.890A>G (p.Asn297Ser) | Missense | Somatic in MDS | Altered DNA binding affinity |
| c.1024G>A (p.Gly342Arg) | Missense | Somatic in breast cancer | Potential gain-of-function, increased transcriptional activity |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations, including nonsense, frameshift, and deletions, lead to reduced CUX1 protein levels or activity. This haploinsufficiency is associated with myelodysplastic syndrome and acute myeloid leukemia, where CUX1 acts as a tumor suppressor.
Gain of Function (GOF)
Gain-of-function mutations or overexpression of CUX1, particularly the p75 isoform, can promote cell proliferation and survival, contributing to oncogenesis in solid tumors like breast and lung cancer.
Dominant Negative (DN)
Some missense mutations may produce a dominant-negative effect by interfering with wild-type CUX1 function, though this is less well characterized. Further studies are needed to confirm such mechanisms.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • chromatin binding | • protein dimerization activity |
| • regulation of transcription by RNA polymerase II | • cell cycle regulation |
| • DNA damage response | • cell differentiation |
Pathways
• Cell cycle - G1/S transition
• p53 signaling pathway
• TGF-beta signaling pathway
• Wnt signaling pathway
• DNA damage response
• Transcriptional regulation by CUX1
Protein Summary
The CUX1 protein is a large transcription factor with multiple isoforms generated by alternative splicing and proteolytic processing. The full-length protein (p200) is involved in cell cycle regulation and differentiation, while the N-terminal truncated isoform (p110) and the C-terminal isoform (p75) have distinct functions. CUX1 binds to DNA via its homeodomain and cut repeats, regulating genes involved in proliferation, apoptosis, and DNA repair. Its activity is modulated by phosphorylation and interaction with other proteins.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CUX1 Knockout HEK293 Cell Line | EDJ-KQ3664 | Human | 1523 | Details Get a Quote |
| CUX1 Knockout A-549 Cell Line | EDJ-KQ26921 | Human | 1523 | Details Get a Quote |
| CUX1 Knockout HCT 116 Cell Line | EDJ-KQ26923 | Human | 1523 | Details Get a Quote |
| CUX1 Knockout HeLa Cell Line | EDJ-KQ26924 | Human | 1523 | Details Get a Quote |
