TRIP4 Gene (Thyroid Hormone Receptor Interactor 4): Function, Disease Associations, and Expression
Comprehensive biomedical overview of TRIP4, including genomic context, protein function, tissue expression, and clinical significance.
Gene Information Card
| Symbol | TRIP4 |
|---|---|
| Full Name | Thyroid Hormone Receptor Interactor 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q22.31 |
| NCBI Gene ID | 9325 ncbi.nlm.nih.gov/gene/9325 |
| Ensembl ID | ENSG00000103671 |
| UniProt ID | Q15650 |
| OMIM ID | 604501 |
| HGNC ID | 12311 |
| Aliases | ASC1, FLJ10901, MGC126562, MGC126564, ZFP67 |
Description
TRIP4 (Thyroid Hormone Receptor Interactor 4) encodes a protein that functions as a transcriptional coactivator. It is a core subunit of the ASC-1 (Activating Signal Cointegrator 1) complex, which is involved in chromatin remodeling and transcriptional regulation. TRIP4 interacts with nuclear receptors, including thyroid hormone receptor, and other transcription factors to modulate gene expression. The protein contains a C4-type zinc finger domain and is involved in various cellular processes, including development and cellular differentiation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | TRIP4 is part of the ASC-1 complex, which can act as a coactivator for β-catenin/TCF-mediated transcription, potentially promoting tumorigenesis. Overexpression may enhance Wnt signaling. | COSMIC: Mutations and copy number alterations observed in colorectal cancer samples. PubMed: Functional studies show ASC-1 complex enhances β-catenin transcriptional activity. |
| Prostate Cancer | TRIP4/ASC-1 complex can coactivate androgen receptor (AR) signaling, potentially contributing to prostate cancer progression. | PubMed: Studies demonstrate ASC-1 enhances AR-mediated transcription in prostate cancer cell lines. |
| Breast Cancer | TRIP4 may act as a coactivator for estrogen receptor (ER) and other transcription factors, potentially influencing tumor growth and hormone resistance. | PubMed: Expression analysis shows TRIP4 upregulation in some breast cancer subtypes; functional studies link it to ER-mediated transcription. |
| Developmental Disorders | While specific germline mutations are rare, TRIP4's role in transcriptional regulation suggests potential involvement in developmental processes. However, no definitive monogenic disorder is established. | ClinVar: No pathogenic germline variants for a specific Mendelian disorder are listed. OMIM: No disease association is curated. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 25.3 | High |
| Thyroid | 18.7 | Medium |
| Adrenal Gland | 15.2 | Medium |
| Small Intestine | 12.8 | Medium |
| Colon | 11.5 | Medium |
| Kidney | 10.1 | Medium |
| Liver | 8.4 | Low |
| Brain | 6.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 22.5 | High expression; used in functional studies of ASC-1 complex. |
| HepG2 (liver cancer) | 15.3 | Moderate expression; relevant for metabolic studies. |
| A549 (lung cancer) | 12.1 | Moderate expression; used in cancer biology research. |
| MCF7 (breast cancer) | 18.9 | High expression; relevant for ER signaling studies. |
| K562 (leukemia) | 8.7 | Low expression; used in hematopoiesis research. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Trp) | Missense | Rare (<0.01%) | Located in the C-terminal domain; functional impact unknown, may affect protein stability or interactions. |
| c.1546A>G (p.Ile516Val) | Missense | Rare (<0.01%) | In the coiled-coil region; predicted to be benign by in silico tools. |
| c.2017_2018insA (p.Thr673AsnfsTer19) | Frameshift | Very rare | Predicted to cause loss of function via nonsense-mediated decay; observed in cancer samples. |
| c.2345T>C (p.Leu782Pro) | Missense | Rare (<0.01%) | In the C-terminal region; may disrupt protein-protein interactions. |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that lead to premature stop codons are predicted to cause loss of function through nonsense-mediated mRNA decay, resulting in haploinsufficiency. This could impair ASC-1 complex function and transcriptional regulation.
Gain of Function (GOF)
No clear gain-of-function mutations have been characterized for TRIP4. Missense mutations in cancer may potentially alter coactivator activity, but evidence is limited.
Dominant Negative (DN)
No dominant-negative mutations have been reported. Given TRIP4 is a core subunit of a multimeric complex, some missense mutations could theoretically exert a dominant-negative effect by disrupting complex assembly, but this remains speculative.
View complete mutation data：
Gene Ontology (GO)
| • transcription coactivator activity | • zinc ion binding |
| • protein binding | • nucleus |
| • nucleoplasm | • ASC-1 complex |
| • regulation of transcription by RNA polymerase II | • chromatin remodeling |
| • cell differentiation | • response to hormone |
Pathways
• Wnt signaling pathway (β-catenin/TCF)
• Androgen receptor signaling pathway
• Estrogen receptor signaling pathway
• Thyroid hormone signaling pathway
• Chromatin organization
Protein Summary
The TRIP4 protein, also known as ASC-1, is a 645-amino acid nuclear protein that serves as a core component of the ASC-1 complex. This complex possesses histone acetyltransferase (HAT) activity and facilitates transcriptional activation by bridging sequence-specific transcription factors to the basal transcriptional machinery. TRIP4 contains a C4-type zinc finger domain that mediates protein-protein interactions. It plays a critical role in regulating gene expression in response to various hormonal and developmental signals. Its function is essential for proper cellular differentiation and proliferation, and dysregulation has been implicated in several cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRIP4 Knockout HEK293 Cell Line | EDJ-KQ6548 | Human | 9325 | Details Get a Quote |
| TRIP4 Knockout HeLa Cell Line | EDJ-KQ17941 | Human | 9325 | Details Get a Quote |
| TRIP4 Knockout A-549 Cell Line | EDJ-KQ30737 | Human | 9325 | Details Get a Quote |
| TRIP4 Knockout HCT 116 Cell Line | EDJ-KQ30738 | Human | 9325 | Details Get a Quote |
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