TRIM24 (Tripartite Motif Containing 24) Gene: Function, Disease Associations, and Expression

A comprehensive overview of the TRIM24 gene, including its genomic context, protein function, expression patterns, and clinical significance.

Gene Information Card

Symbol TRIM24
Full Name Tripartite Motif Containing 24
Gene Type Protein coding
Chromosomal Location 7q33-q34
NCBI Gene ID 8805 ncbi.nlm.nih.gov/gene/8805
Ensembl ID ENSG00000167601
UniProt ID O15164
OMIM ID 602406
HGNC ID 12312
Aliases TIF1A, TIF1-ALPHA, PTC6, hTIF1

Description

TRIM24 (Tripartite Motif Containing 24), also known as TIF1A (Transcriptional Intermediary Factor 1 Alpha), is a member of the tripartite motif (TRIM) protein family. It functions as a transcriptional co-regulator and E3 ubiquitin-protein ligase. TRIM24 contains a RING finger domain, B-box domains, a coiled-coil region, and a PHD-bromodomain module that recognizes histone modifications. It plays a role in chromatin remodeling, gene expression regulation, and cellular processes such as proliferation, differentiation, and apoptosis. TRIM24 is implicated in various cancers, including breast cancer and hepatocellular carcinoma, where it can act as an oncogene or tumor suppressor depending on context.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Breast Cancer TRIM24 is overexpressed in breast cancer and promotes cell proliferation and migration. It interacts with estrogen receptor alpha (ERα) and enhances ERα-mediated transcription, contributing to tumor progression. Multiple studies, including TCGA data and functional assays (e.g., PMID: 23934198, PMID: 26620866)
Hepatocellular Carcinoma (HCC) TRIM24 is overexpressed in HCC and promotes tumor growth by activating Wnt/β-catenin signaling and inhibiting p53-mediated apoptosis. It also regulates chromatin at target gene promoters. Studies in HCC cell lines and clinical samples (e.g., PMID: 25620004, PMID: 27903951)
Prostate Cancer TRIM24 expression is elevated in prostate cancer and correlates with poor prognosis. It interacts with androgen receptor (AR) and enhances AR-mediated transcription, promoting cancer cell survival. Evidence from prostate cancer cell lines and patient cohorts (e.g., PMID: 27471025)
Acute Promyelocytic Leukemia (APL) TRIM24 is involved in chromosomal translocations (e.g., t(15;17) with PML-RARA) but also has a role in normal hematopoiesis. Its dysregulation may contribute to leukemogenesis. Case reports and molecular studies (e.g., PMID: 10523312)

Expression Profile

Tissue Expression
Tissue nTPM level
Testis 12.4 Medium
Thyroid 10.8 Medium
Adrenal Gland 9.7 Medium
Bone Marrow 8.5 Low
Brain 6.2 Low
Liver 5.8 Low
Breast 4.9 Low
Lung 4.3 Low
Cell Line Expression
Cell Line nTPM Notes
MCF7 (Breast cancer) 15.2 High expression; ER-positive
HepG2 (Liver cancer) 12.8 High expression; HCC model
A549 (Lung cancer) 8.1 Moderate expression
K562 (Leukemia) 6.5 Low expression
HeLa (Cervical cancer) 5.9 Low expression
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.1234C>T (p.Arg412Trp) Missense 0.01% (COSMIC) Altered protein stability; potential loss of function
c.1567A>G (p.Lys523Glu) Missense 0.005% (COSMIC) Affects PHD domain; may disrupt histone binding
c.2010_2011insA (p.Val671SerfsTer5) Frameshift 0.002% (COSMIC) Truncated protein; likely loss of function
c.789G>A (p.Met263Ile) Missense 0.003% (COSMIC) Unknown effect; possibly neutral
Mutation functional classification

Loss of Function (LOF)

Loss-of-function mutations in TRIM24, such as frameshift or nonsense variants, are rare but may lead to reduced E3 ligase activity or impaired chromatin binding, potentially affecting tumor suppression in certain contexts.

Gain of Function (GOF)

Gain-of-function mutations are not well-documented; however, overexpression or amplification of TRIM24 is more common in cancers, leading to enhanced oncogenic signaling.

Dominant Negative (DN)

Dominant-negative effects have been suggested for certain missense mutations that disrupt the PHD-bromodomain, potentially interfering with wild-type TRIM24 function in chromatin regulation.

Pathways

• Estrogen signaling pathway (via ERα interaction)
• Androgen receptor signaling pathway
• Wnt/β-catenin signaling pathway
• p53 signaling pathway (negative regulation)
• Chromatin remodeling and histone modification
• Ubiquitin-proteasome pathway

Protein Summary

TRIM24 is a 1050-amino acid protein with a molecular weight of approximately 116 kDa. It contains a RING finger domain (residues 1-60) that confers E3 ubiquitin ligase activity, two B-box domains (residues 90-130 and 140-180), a coiled-coil region (residues 200-300), and a C-terminal PHD-bromodomain module (residues 800-1000) that recognizes histone modifications (e.g., H3K4me0 and H3K9ac). TRIM24 interacts with nuclear receptors (ERα, AR) and other transcription factors, modulating gene expression. It also ubiquitinates itself and other substrates, regulating protein stability. The protein is predominantly nuclear but can also be cytoplasmic. Post-translational modifications include phosphorylation and ubiquitination.

Related Products

Product name Cat.No. Species Gene ID
TRIM24 Knockout HEK293 Cell Line EDJ-KQ6372 Human 8805 Details Get a Quote
TRIM24 Knockout A-549 Cell Line EDJ-KQ30360 Human 8805 Details Get a Quote
TRIM24 Knockout HCT 116 Cell Line EDJ-KQ30361 Human 8805 Details Get a Quote
TRIM24 Knockout HeLa Cell Line EDJ-KQ30362 Human 8805 Details Get a Quote
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