TRRAP Gene: Transformation/Transcription Domain-Associated Protein
A key scaffold in chromatin modification complexes, linking transcription factors to histone acetyltransferase activity.
Gene Information Card
| Symbol | TRRAP |
|---|---|
| Full Name | Transformation/Transcription Domain-Associated Protein |
| Gene Type | Protein coding |
| Chromosomal Location | 7q22.1 |
| NCBI Gene ID | 8295 ncbi.nlm.nih.gov/gene/8295 |
| Ensembl ID | ENSG00000196367 |
| UniProt ID | Q9Y4A5 |
| OMIM ID | 603015 |
| HGNC ID | 12347 |
| Aliases | PAF400, STAF40, TR-AP, Tra1 |
Description
TRRAP encodes a large protein (approximately 400 kDa) that serves as a scaffold component of several histone acetyltransferase (HAT) complexes, including SAGA, ATAC, and NuA4. It directly interacts with transcription factors such as MYC and E2F to recruit HAT activity, thereby regulating chromatin structure and gene expression. TRRAP is essential for cell cycle progression, differentiation, and DNA repair.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types, e.g., colorectal, breast, lung) | TRRAP mutations or amplification alter HAT complex recruitment, leading to dysregulated transcription of oncogenes and tumor suppressors. | COSMIC; ClinVar |
| Intellectual disability / developmental delay | De novo missense variants in TRRAP impair chromatin remodeling during neurodevelopment. | ClinVar; OMIM |
| Glioblastoma | TRRAP overexpression correlates with poor prognosis; promotes tumor growth via MYC pathway activation. | NCBI Gene; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 35.2 | High |
| Brain (cerebellum) | 18.7 | Medium |
| Heart | 12.4 | Medium |
| Liver | 8.1 | Low |
| Pancreas | 6.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 22.3 | Embryonic kidney; high expression |
| HeLa | 19.8 | Cervical carcinoma; moderate |
| K562 | 15.6 | Leukemia; moderate |
| HepG2 | 10.2 | Hepatocellular carcinoma; low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.6325C>T (p.Arg2109Cys) | Missense | <0.1% | Alters SAGA complex binding; associated with neurodevelopmental disorders (ClinVar) |
| c.7582G>A (p.Glu2528Lys) | Missense | <0.1% | Reduced HAT activity; linked to intellectual disability (ClinVar) |
| Amplification (7q22.1) | Copy number gain | ~5% in breast cancer | Increased TRRAP expression; drives MYC-dependent transcription (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants (e.g., p.Arg2109Cys) reduce TRRAP stability or disrupt HAT complex assembly, impairing chromatin acetylation and gene activation.
Gain of Function (GOF)
Gene amplification or overexpression enhances recruitment of HAT complexes to oncogenic transcription factors (e.g., MYC), promoting uncontrolled proliferation.
Dominant Negative (DN)
Not well documented; some missense variants may compete with wild-type TRRAP for complex incorporation, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• MYC pathway (PID: MYC_ACTIVPATHWAY)
• E2F transcription factor network (Reactome: R-HSA-9006925)
• Chromatin modifying enzymes (Reactome: R-HSA-3244100)
• p53 pathway (Reactome: R-HSA-3700989)
Protein Summary
TRRAP is a large, evolutionarily conserved scaffold protein that does not possess intrinsic enzymatic activity but is indispensable for the assembly and function of multiple HAT complexes. It acts as a bridge between sequence-specific transcription factors (e.g., MYC, E2F, p53) and the acetylation machinery, thereby regulating chromatin accessibility and gene expression. TRRAP is ubiquitously expressed, with highest levels in testis and brain. Its dysregulation—through mutation, amplification, or altered expression—is implicated in cancer and neurodevelopmental disorders.
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