TBL1XR1 Gene: TBL1X Receptor 1
A key transcriptional regulator involved in nuclear receptor signaling, development, and oncogenesis.
Gene Information Card
| Symbol | TBL1XR1 |
|---|---|
| Full Name | Transducin Beta Like 1 X-Linked Receptor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q26.32 |
| NCBI Gene ID | 79718 ncbi.nlm.nih.gov/gene/79718 |
| Ensembl ID | ENSG00000177565 |
| UniProt ID | Q9BZK7 |
| OMIM ID | 608628 |
| HGNC ID | 29529 |
| Aliases | TBLR1, IRA1, DC42, C21, F-box-like protein 1 |
Description
TBL1XR1 (Transducin Beta Like 1 X-Linked Receptor 1) encodes a protein that functions as a component of the NCoR/SMRT transcriptional co-repressor complex. It mediates the exchange of co-repressor for co-activator complexes upon nuclear receptor activation, playing a critical role in transcriptional regulation. The gene is involved in development, cell differentiation, and is implicated in various cancers and neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pierpont syndrome | Missense mutations in TBL1XR1 disrupt transcriptional co-repressor function, leading to developmental abnormalities. | OMIM #602342; ClinVar |
| Intellectual disability, autosomal dominant 41 | De novo loss-of-function mutations impair NCoR/SMRT complex activity, affecting neuronal gene expression. | OMIM #616944; ClinVar |
| Hematologic malignancies (e.g., acute lymphoblastic leukemia) | Recurrent deletions and mutations in TBL1XR1 alter transcriptional regulation of oncogenic pathways. | COSMIC; NCBI PubMed |
| Prostate cancer | TBL1XR1 overexpression or mutation modulates androgen receptor signaling and tumor progression. | COSMIC; NCBI PubMed |
| Breast cancer | Altered TBL1XR1 expression affects estrogen receptor-mediated transcription and cell proliferation. | COSMIC; NCBI PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 15.2 | Medium |
| Heart | 10.8 | Medium |
| Liver | 8.5 | Low |
| Kidney | 12.3 | Medium |
| Testis | 18.7 | Medium |
| Lung | 9.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 20.5 | Embryonic kidney; high expression |
| HeLa | 14.2 | Cervical carcinoma; moderate expression |
| K562 | 11.8 | Leukemia; moderate expression |
| MCF7 | 16.3 | Breast cancer; moderate-high expression |
| SH-SY5Y | 22.1 | Neuroblastoma; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Tyr446Cys | Missense | Rare (0.01%) | Disrupts WD40 domain; associated with Pierpont syndrome |
| p.Arg386Trp | Missense | Rare (0.005%) | Impairs co-repressor complex interaction; intellectual disability |
| p.Gln397* | Nonsense | Very rare | Loss of function; truncation; developmental delay |
| c.1135_1136del | Frameshift deletion | Rare | Loss of function; associated with leukemia |
| p.Ser361Phe | Missense | Rare (0.008%) | Altered protein stability; reported in breast cancer |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and some missense mutations (e.g., p.Gln397*) that truncate or destabilize the protein, reducing co-repressor complex activity.
Gain of Function (GOF)
Not well characterized; some missense variants (e.g., p.Tyr446Cys) may alter substrate specificity or enhance oncogenic signaling.
Dominant Negative (DN)
Missense mutations in the WD40 domain (e.g., p.Arg386Trp) that disrupt complex assembly but retain partial function, interfering with wild-type activity.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Nuclear Receptor Transcription Pathway (NCoR/SMRT complex)
• Notch Signaling Pathway
• Wnt Signaling Pathway
• PI3K-Akt Signaling Pathway
Protein Summary
The TBL1XR1 protein (UniProt Q9BZK7) is a 529-amino acid F-box-like protein containing WD40 repeats that mediate protein-protein interactions. It is a core component of the NCoR/SMRT transcriptional co-repressor complex, where it facilitates the exchange of co-repressor for co-activator complexes in response to nuclear receptor signaling. The protein is localized to the nucleus and is involved in regulating gene expression during development, cell cycle, and differentiation. Mutations in TBL1XR1 are linked to neurodevelopmental disorders and multiple cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TBL1XR1 Knockout HEK293 Cell Line | EDJ-KQ336 | Human | 79718 | Details Get a Quote |
| TBL1XR1 Knockout A-549 Cell Line | EDJ-KQ18505 | Human | 79718 | Details Get a Quote |
| TBL1XR1 Knockout HCT 116 Cell Line | EDJ-KQ18506 | Human | 79718 | Details Get a Quote |
| TBL1XR1 Knockout HeLa Cell Line | EDJ-KQ18507 | Human | 79718 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
