TBL1XR1

F-box-like/WD repeat-containing protein TBL1XR1 is a protein that in humans is encoded by the TBL1XR1 gene.^[5][6][7] The protein encoded by this gene has sequence similarity with members of the WD40 repeat-containing protein family. The WD40 group is a large family of proteins that appear to have a regulatory function. It is believed that the WD40 repeats mediate protein–protein interactions, and members of the family are involved in signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly and may play a role in the control of cytotypic differentiation.^[7]

TBL1XR1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4LG9
Identifiers
Aliases	TBL1XR1, C21, DC42, IRA1, TBLR1, MRD41, transducin (beta)-like 1 X-linked receptor 1, transducin beta like 1 X-linked receptor 1, TBL1X receptor 1
External IDs	OMIM: 608628; MGI: 2441730; HomoloGene: 69382; GeneCards: TBL1XR1; OMA:TBL1XR1 - orthologs
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q26.32 Start 177,019,340 bp[1] End 177,228,000 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3|3 A3 Start 22,130,816 bp[2] End 22,270,758 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon nipple tibia corpus callosum lactiferous duct visceral pleura Brodmann area 23 parietal pleura germinal epithelium pylorus Top expressed in granulocyte blood zygote calvaria tibiofemoral joint ankle cumulus cell extensor digitorum longus muscle thymus lymph node More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding beta-catenin binding transcription corepressor activity protein N-terminus binding histone binding protein binding Cellular component histone deacetylase complex transcription repressor complex nucleoplasm spindle microtubule nucleus mitotic spindle Biological process fat pad development response to dietary excess regulation of transcription, DNA-templated multicellular organism growth negative regulation of transcription by RNA polymerase II transcription, DNA-templated positive regulation of transcription, DNA-templated lipid catabolic process regulation of triglyceride metabolic process white fat cell differentiation regulation of gene expression adipose tissue development negative regulation of transcription, DNA-templated histone deacetylation positive regulation of transcription by RNA polymerase II proteasome-mediated ubiquitin-dependent protein catabolic process regulation of lipid metabolic process positive regulation of canonical Wnt signaling pathway chromatin organization blastocyst hatching regulation of transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 79718 81004 Ensembl ENSG00000177565 ENSMUSG00000027630 UniProt Q9BZK7 Q8BHJ5 RefSeq (mRNA) NM_024665 NM_001321193 NM_001321194 NM_001321195 NM_001374327 NM_001374328 NM_001374329 NM_001374330 NM_030732 RefSeq (protein) NP_001308122 NP_001308123 NP_001308124 NP_078941 NP_001361256 NP_001361257 NP_001361258 NP_001361259 NP_109657 Location (UCSC) Chr 3: 177.02 – 177.23 Mb Chr 3: 22.13 – 22.27 Mb PubMed search [3] [4]
Wikidata
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Clinical significance

Mutations in TBL1XR1 cause Pierpont syndrome, which involves intellectual disability, a characteristic facial appearance and limb abnormalities.^[8]

Mutations in TBL1XR1 have been identified in lymphomas, including MYD88 wild-type Waldenstrom's macroglobulinemia.^[9]

In prostate cancer, somatic copy-number gains (CNA) in TBL1XR1 are present in around 15% of patients with localised disease, co-occurring with adjacent megagene NAALADL2.^[10] The frequency of CNA gains in these genes associate with a number of clinical features of aggressive prostate cancer including high Gleason grade, tumour stage, positive surgical margins and cancer which has spread to the lymph nodes.^[10] The frequency of copy-number gains in this genetic region also increase in castrate resistant and neuroendocrine prostate cancer.^[10]

The region surrounding TBL1XR1 is rich in oncogenes.^[11] Copy-number gains in TBL1XR1 often co-occur with neighbouring oncogenes including: BCL6, ATR and PI3K family members. Copy-number gains at the DNA level associate with mRNA expression changes in more than 450 known oncogenes, suggesting this region may be important in driving aggressive prostate cancer.^[10] TBL1XR1 is a co-activator of the androgen receptor, a major hormone receptor driving prostate cancer development.^[12] Of the genes whose expression was altered between patients with and without gains, 506 (14.09%) of the genes were androgen-regulated or contained an AR binding site.^[10]

Interactions

TBL1XR1 has been shown to interact with nuclear receptor co-repressor 1.^[6][13][14]