TBL1XR1

Summary

TBL1XR1 (TBL1X/Y related 1, HGNC:29529) is a protein-coding gene on chromosome 3q26.32, encoding F-box-like/WD repeat-containing protein TBL1XR1 (Q9BZK7). F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units. It is a selective cancer dependency (DepMap: 30.8% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene is a member of the WD40 repeat-containing gene family and shares sequence similarity with transducin (beta)-like 1X-linked (TBL1X). The protein encoded by this gene is thought to be a component of both nuclear receptor corepressor (N-CoR) and histone deacetylase 3 (HDAC 3) complexes, and is required for transcriptional activation by a variety of transcription factors. Mutations in these gene have been associated with some autism spectrum disorders, and one finding suggests that haploinsufficiency of this gene may be a cause of intellectual disability with dysmorphism. Mutations in this gene as well as recurrent translocations involving this gene have also been observed in some tumors.

Source: NCBI Gene 79718 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 27
• Clinical variants (ClinVar): 632 total — 33 pathogenic, 53 likely-pathogenic
• Phenotypes (HPO): 121
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 7 cancer types
• Cancer dependency (DepMap): dependent in 30.8% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity little evidence
• MANE Select transcript: NM_024665

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29529
Approved symbol	TBL1XR1
Name	TBL1X/Y related 1
Location	3q26.32
Locus type	gene with protein product
Status	Approved
Aliases	IRA1, FLJ12894, TBLR1, C21, DC42
Ensembl gene	ENSG00000177565
Ensembl biotype	protein_coding
OMIM	608628
Entrez	79718

Gene structure

Transcript identifiers

Ensembl transcripts: 83 — 66 protein_coding, 13 protein_coding_CDS_not_defined, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000352800, ENST00000413084, ENST00000422066, ENST00000422442, ENST00000424913, ENST00000427349, ENST00000428970, ENST00000430069, ENST00000431421, ENST00000431674, ENST00000437738, ENST00000443315, ENST00000450267, ENST00000457928, ENST00000474363, ENST00000491623, ENST00000626758, ENST00000627825, ENST00000630796, ENST00000630833, ENST00000631253, ENST00000635757, ENST00000635794, ENST00000636187, ENST00000636348, ENST00000636478, ENST00000636864, ENST00000636912, ENST00000637123, ENST00000637137, ENST00000637544, ENST00000637659, ENST00000637681, ENST00000637755, ENST00000638074, ENST00000673974, ENST00000704383, ENST00000704384, ENST00000704385, ENST00000883460, ENST00000883461, ENST00000883462, ENST00000883463, ENST00000883464, ENST00000883465, ENST00000883466, ENST00000883467, ENST00000883468, ENST00000883469, ENST00000883470, ENST00000883471, ENST00000883472, ENST00000883473, ENST00000883474, ENST00000883475, ENST00000883476, ENST00000883477, ENST00000883478, ENST00000883479, ENST00000883480, ENST00000883481, ENST00000883482, ENST00000883483, ENST00000883484, ENST00000925106, ENST00000925107, ENST00000925108, ENST00000925109, ENST00000925110, ENST00000925111, ENST00000925112, ENST00000971505, ENST00000971506, ENST00000971507, ENST00000971508, ENST00000971509, ENST00000971510, ENST00000971511, ENST00000971512, ENST00000971513, ENST00000971514, ENST00000971515, ENST00000971516

RefSeq mRNA: 8 — MANE Select: NM_024665 NM_001321193, NM_001321194, NM_001321195, NM_001374327, NM_001374328, NM_001374329, NM_001374330, NM_024665

CCDS: CCDS46961, CCDS93428

Canonical transcript exons

ENST00000457928 — 16 exons

Exon	Start	End
ENSE00000780554	177034198	177034325
ENSE00000780555	177038098	177038172
ENSE00000780558	177038313	177038434
ENSE00000780560	177047300	177047397
ENSE00000780562	177047486	177047549
ENSE00000780564	177049997	177050138
ENSE00000780565	177050478	177050610
ENSE00000826275	177032971	177033136
ENSE00001072449	177064920	177065022
ENSE00001209510	177098466	177098541
ENSE00001399748	177026373	177026474
ENSE00001623070	177197121	177197482
ENSE00001636486	177046129	177046189
ENSE00001821501	177019344	177025524
ENSE00003546628	177051504	177051726
ENSE00003762186	177053773	177053918

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 99.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.4435 / max 473.6693, expressed in 1821 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45683	28.2432	1810
45686	4.9300	1629
45684	4.2414	1621
45679	3.2943	1379
45682	2.3317	1217
45675	2.1081	1118
45676	1.3010	835
45685	0.5458	303
45680	0.4327	211
45687	0.4302	203

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.20	gold quality
nipple	UBERON:0002030	98.84	gold quality
tibia	UBERON:0000979	98.72	gold quality
adrenal tissue	UBERON:0018303	98.68	gold quality
corpus callosum	UBERON:0002336	98.56	gold quality
mammary duct	UBERON:0001765	98.51	gold quality
visceral pleura	UBERON:0002401	98.51	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.47	gold quality
parietal pleura	UBERON:0002400	98.35	gold quality
pylorus	UBERON:0001166	98.33	gold quality
germinal epithelium of ovary	UBERON:0001304	98.33	gold quality
trabecular bone tissue	UBERON:0002483	98.29	gold quality
endothelial cell	CL:0000115	98.25	gold quality
colonic epithelium	UBERON:0000397	98.23	gold quality
skin of hip	UBERON:0001554	98.22	gold quality
upper leg skin	UBERON:0004262	98.19	gold quality
postcentral gyrus	UBERON:0002581	98.17	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.11	gold quality
parietal lobe	UBERON:0001872	98.07	gold quality
caput epididymis	UBERON:0004358	98.02	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.00	gold quality
entorhinal cortex	UBERON:0002728	97.97	gold quality
urethra	UBERON:0000057	97.81	gold quality
colonic mucosa	UBERON:0000317	97.80	gold quality
parotid gland	UBERON:0001831	97.76	gold quality
medial globus pallidus	UBERON:0002477	97.76	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.75	gold quality
epithelium of nasopharynx	UBERON:0001951	97.67	gold quality
superficial temporal artery	UBERON:0001614	97.62	gold quality
pleura	UBERON:0000977	97.61	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-112	no	2.44
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
SMAD7

Upstream regulators (CollecTRI, top): AR, NCOR1, NCOR2

miRNA regulators (miRDB)

421 targeting TBL1XR1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-186-5P	99.99	70.83	3707

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 1 (little evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 30.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• TBL1 and TBLR1 are functionally redundant and essential for transcriptional repression by unliganded thyroid hormone receptors (TR) but not essential for transcriptional activation by liganded TR (PMID:15601853)
• TBLR1 is a multifunctional co-repressor of transcription (PMID:16893456)
• A cDNA library consisting of 220 upregulated genes in tumour tissue was established and named as LSCC. Differential expression was confirmed in five of these genes, including IGFBP5, SQLE, RAP2B, CLDN1, and TBL1XR1. (PMID:17316888)
• Wnt signalling induced the interaction between beta-catenin and TBL1-TBLR1, as well as their binding to Wnt target genes. Importantly, the recruitment of TBL1-TBLR1 and beta-catenin to Wnt target-gene promoters was mutually dependent on each other. (PMID:18193033)
• the TBL1XR1 gene was significantly under-expressed in acute lymphoblastic leukemia. (PMID:18767146)
• TBL1XR1/TP63: a novel recurrent gene fusion in B-cell non-Hodgkin lymphoma. (PMID:22496164)
• Our study provides new insights into the molecular tumorigenesis of PCNSL and identifies novel genetic alterations in this disease, especially MYD88 and TBL1XR1 mutations activating the NF-kappaB signaling pathway. (PMID:22837180)
• Stable ectopic expression of TBLR1 leads to androgen-dependent growth suppression of prostate cancer cells by selective activation of androgen-regulated genes associated with differentiation and growth suppression but not cell proliferation. (PMID:24243687)
• results demonstrated that TBL1XR1 induced lymphangiogenesis and lymphatic metastasis in esophageal squamous cell carcinoma via upregulation of VEGF-C, and may represent a novel prognostic biomarker and therapeutic target for patients with ESCC. (PMID:24667177)
• The TBLR1 protein may be a prognostic marker in cervical cancer and play an important role in the invasion and metastasis of human cervical cancer (PMID:24874481)
• data indicate that loss of TBL1XR1 is a novel driver of glucocorticoid resistance in ALL and that epigenetic therapy may have future application in restoring drug sensitivity at relapse. (PMID:24895125)
• Patient with TBL1XR1 mutation [c.209 G>A (p.Gly70Asp)] leading to West syndrome with Rett-like features, together with autistic features was reported. (PMID:25102098)
• Results show that upregulation of TBL1XR1 induces Nasopharyngeal Carcinoma cells resistance to cisplatin by activating the NF-kappaB pathway. (PMID:25145705)
• TBLR1 plays a key role in the development and progression of breast cancer cells via cyclin D1-transactivation and activation of the beta-catenin signaling pathway. (PMID:25341494)
• that TBL1XR1 haploinsufficiency can cause intellectual disability with a recognizable dysmorphism, without necessarily causing autistic behavior. (PMID:25425123)
• These finding suggested that TBLR1 is likely to be a potential prognostic indicator and therapeutic target for HCC and that TBLR1 may be implicated in EMT of HCC cells. (PMID:26386862)
• in splenic hemangioma with t(3;6)(q26;p21), the entire coding region of HMGA1 comes under the control of the TBL1XR1 promoter, bringing about dysregulation of HMGA1 (PMID:26708416)
• Integrating population variation and protein structural analysis is harnessed to improve clinical interpretation of missense mutations in WD40 domain-containing TBLR1 protein for the prognosis of developmental disabilities. (PMID:26740553)
• This study identifies a specific TBL1XR1 mutation as the cause of Pierpont syndrome. Deletions and other mutations in TBL1XR1 can cause autism. The marked differences between Pierpont patients with the p.Tyr446Cys mutation and individuals with other mutations and whole gene deletions indicate a specific, but as yet unknown, disease mechanism of the TBL1XR1 p.Tyr446Cys mutation. (PMID:26769062)
• TBLR1 has a role in reducing apoptosis in prostate cancer under androgen deprivation (PMID:27127173)
• Targeted SUMOylation of TBL1 and TBLR1 may be a useful strategy for therapeutic treatment of androgen-independent prostate cancer. (PMID:27129164)
• the twins described by Fitzsimmons had heterozygous mutations in the SACS gene, the gene responsible for autosomal recessive spastic ataxia of Charlevoix Saguenay as well as a heterozygous mutation in the TRPS1, the gene responsible in Trichorhinophalangeal syndrome type 1A TBL1XR1 mutation was identified in the patient described in 2009 as contributing to his cognitive impairment and autistic features.. (PMID:27133561)
• TBL1XR1 contributes to GC tumorigenesis and progression through the activation of the beta-catenin/MMP7/EGFR/ERK signalling pathway and may act as a new therapeutic target for GC. (PMID:27694893)
• emonstrated that TBL1XR1 can regulate the expression of vascular endothelial growth factor C and epithelial-mesenchymal transition proteins (PMID:28127799)
• In targeted sequencing, a disruptive mutation of TNFAIP3 was the most common alteration (54%), followed by mutations of TBL1XR1 (18%) and cAMP response element binding proteins (CREBBP) (17%). (PMID:28152507)
• High TBL1XR1 expression indicates poor disease-free survival of stage I-III colorectal cancer patients; beta-catenin signaling is critical for TBL1XR1-mediated colorectal cancer cells oncogenicity. (PMID:28295012)
• High expressions of TBL1XR1 is associated with liver metastasis for early stage colorectal cancer. (PMID:28317580)
• TBL1XR1 overexpression may be an unfavorable prognostic factor for Epithelial Ovarian Cancer. (PMID:28344213)
• TBL1XR1-microduplication syndrome is an intellectual disability/learning disability syndrome with associated incomplete penetrance autism spectrum disorders, hearing loss, and delay of puberty. Its phenotypic overlap indicates that it is a genomic sister-disorder to the 3q26.32 microdeletion syndrome (PMID:28574232)
• These results suggest that a de novo TBL1XR1 point mutation could alter Wnt/beta-catenin signaling activity. Further studies are required to clarify the involvement of TBL1XR1 mutations in neuropsychiatric conditions. (PMID:28588275)
• The patient with Tyr446Cys mutation presents with a submucous cleft palate and hydronephrosis in addition to severe delays, hypotonia, dysmorphic findings and emerging scoliosis, consistent with previous reports. (PMID:28687524)
• miR-130a-3p suppressed aggressive phenotype of Gastric Cancer cells partially by direct targeting and decreasing TBL1XR1 and subsequent epithelial-mesenchymal transition process. (PMID:29091326)
• TBL1XR1 mutation is not associated with Rett syndrome. (PMID:29777588)
• Over-expression of miR-199 in gastric carcinoma is associated with the decreased ability of proliferation and migration of gastric carcinoma cells by targeting the 3’ untranslated region of TBL1XR1. (PMID:30193607)
• Taken together, our results provide new evidence that TBL1XR1 overexpression induces cancer stem cell-like phenotypes and tumorigenic capability of osteosarcoma and might represent a novel therapeutic target for its treatment. (PMID:30529193)
• TBL1XR1 is involved in c-Met-mediated tumorigenesis of human nonsmall cell lung cancer. (PMID:31243347)
• Exosomal miR-103a-3p ameliorates lipopolysaccharide-induced immune response in BEAS-2B cells via NF-kappaB pathway by targeting transducin beta-like 1X related protein 1. (PMID:31876003)
• TBL1XR1 Mutations in Primary Marginal Zone Lymphomas of Ocular Adnexa are Associated with Unique Morphometric Phenotypes. (PMID:32339039)
• TBLR1 and CREBBP as potential novel prognostic immunohistochemical biomarkers in diffuse large B-cell lymphoma. (PMID:32546039)
• TBL1XR1 induces cell proliferation and inhibit cell apoptosis by the PI3K/AKT pathway in pancreatic ductal adenocarcinoma. (PMID:32742128)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbl1xr1b	ENSDARG00000008966
danio_rerio	tbl1xr1a	ENSDARG00000058696
mus_musculus	Tbl1xr1	ENSMUSG00000027630
rattus_norvegicus	Tbl1xr1	ENSRNOG00000011216
drosophila_melanogaster	ebi	FBGN0263933

Paralogs (2): TBL1Y (ENSG00000092377), TBL1X (ENSG00000101849)

Protein

Protein identifiers

F-box-like/WD repeat-containing protein TBL1XR1 — Q9BZK7 (reviewed: Q9BZK7)

Alternative names: Nuclear receptor corepressor/HDAC3 complex subunit TBLR1, TBL1-related protein 1, Transducin beta-like 1X-related protein 1

All UniProt accessions (17): A0A0D9SEW5, A0A0D9SF25, A0A0D9SF63, A0A0D9SFI2, A0A1B0GUU2, A0A1B0GVH3, C9IYU9, C9J3H2, Q9BZK7, C9J7E1, C9J903, C9JBN1, C9JCK0, C9JCW4, C9JEC9, C9JLJ1, C9JTW8

UniProt curated annotations — full annotation on UniProt →

Function. F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units. Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of the N-Cor corepressor complex that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of N-Cor complex, thereby allowing cofactor exchange, and transcription activation.

Subunit / interactions. Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1XR1, CORO2A and GPS2. Probable component of some E3 ubiquitin ligase complex. Interacts with histones H2B and H4. Interacts with MECP2; bridges interaction between MECP2 and NCOR1. Interacts with USP44.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed including the pituitary, hypothalamus, white and brown adipose tissue, muscle and liver.

Disease relevance. Pierpont syndrome (PRPTS) [MIM:602342] An autosomal dominant syndrome characterized by multiple congenital anomalies, global developmental delay, learning disability, palmar and plantar fat pads, and distinctive facial characteristics, especially when smiling. The disease is caused by variants affecting the gene represented in this entry. Intellectual developmental disorder, autosomal dominant 41 (MRD41) [MIM:616944] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD41 patients manifest delayed psychomotor development, variable severity of intellectual disability, and delayed language. Non-specific dysmorphic features and autistic behavior is observed in some patients. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The F-box-like domain is related to the F-box domain, and apparently displays the same function as component of ubiquitin E3 ligase complexes.

Similarity. Belongs to the WD repeat EBI family.

RefSeq proteins (8): NP_001308122, NP_001308123, NP_001308124, NP_001361256, NP_001361257, NP_001361258, NP_001361259, NP_078941* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR006594	LisH	Conserved_site
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR045183	Ebi-like	Family

Pfam: PF00400, PF08513

UniProt features (64 total): strand 32, repeat 8, sequence variant 7, modified residue 3, sequence conflict 3, turn 3, domain 2, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, cross-link 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4LG9	X-RAY DIFFRACTION	2.28

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZK7-F1	88.81	0.74

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 2, 102, 119, 277

Function

Pathways and Gene Ontology

Reactome pathways

61 pathways

ID	Pathway
R-HSA-1368108	BMAL1:CLOCK,NPAS2 activates circadian expression
R-HSA-1989781	PPARA activates gene expression
R-HSA-2122947	NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
R-HSA-2426168	Activation of gene expression by SREBF (SREBP)
R-HSA-2644606	Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-3214815	HDACs deacetylate histones
R-HSA-350054	Notch-HLH transcription pathway
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-9022537	Loss of MECP2 binding ability to the NCoR/SMRT complex
R-HSA-9022692	Regulation of MECP2 expression and activity
R-HSA-9029569	NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux
R-HSA-9609690	HCMV Early Events
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-9707616	Heme signaling
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis
R-HSA-9931509	Expression of BMAL (ARNTL), CLOCK, and NPAS2
R-HSA-9933387	RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)
R-HSA-1266738	Developmental Biology
R-HSA-1368082
R-HSA-1430728	Metabolism
R-HSA-157118	Signaling by NOTCH
R-HSA-1592230	Mitochondrial biogenesis
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-1655829	Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-1852241	Organelle biogenesis and maintenance

MSigDB gene sets: 763 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, REACTOME_SIGNALING_BY_NOTCH, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_REGULATION_OF_TRIGLYCERIDE_METABOLIC_PROCESS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_RESPONSE_TO_DIETARY_EXCESS, TTTGTAG_MIR520D, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH, GOBP_WHITE_FAT_CELL_DIFFERENTIATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, TGACCTY_ERR1_Q2

GO Biological Process (17): negative regulation of transcription by RNA polymerase II (GO:0000122), blastocyst hatching (GO:0001835), response to dietary excess (GO:0002021), chromatin organization (GO:0006325), regulation of transcription by RNA polymerase II (GO:0006357), lipid catabolic process (GO:0016042), multicellular organism growth (GO:0035264), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), white fat cell differentiation (GO:0050872), fat pad development (GO:0060613), regulation of triglyceride metabolic process (GO:0090207), positive regulation of canonical Wnt signaling pathway (GO:0090263), regulation of gene expression (GO:0010468), negative regulation of DNA-templated transcription (GO:0045892), adipose tissue development (GO:0060612)

GO Molecular Function (6): transcription cis-regulatory region binding (GO:0000976), transcription corepressor activity (GO:0003714), beta-catenin binding (GO:0008013), histone binding (GO:0042393), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (5): histone deacetylase complex (GO:0000118), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription repressor complex (GO:0017053), mitotic spindle (GO:0072686)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
Circadian clock	3
Regulation of lipid metabolism by PPARalpha	1
Signaling by NOTCH1	1
Mitochondrial biogenesis	1
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1
Chromatin modifying enzymes	1
Generic Transcription Pathway	1
Adipogenesis	1
Metabolism of lipids	1
Loss of function of MECP2 in Rett syndrome	1
Transcriptional Regulation by MECP2	1
NR1H2 and NR1H3-mediated signaling	1
HCMV Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
regulation of transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
DNA-templated transcription	2
protein binding	2
blastocyst development	1
hatching	1
response to nutrient levels	1
energy homeostasis	1
cellular component organization	1
lipid metabolic process	1
catabolic process	1
multicellular organismal process	1
developmental growth	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
fat cell differentiation	1
adipose tissue development	1
triglyceride metabolic process	1
regulation of lipid metabolic process	1
positive regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
gene expression	1
regulation of macromolecule biosynthetic process	1
negative regulation of RNA biosynthetic process	1
animal organ development	1
connective tissue development	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
transcription coregulator activity	1
nucleic acid binding	1
binding	1
nucleoplasm	1
nuclear protein-containing complex	1
catalytic complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3274 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBL1XR1	NCOR1	O75376	996
TBL1XR1	GPS2	Q13227	996
TBL1XR1	HDAC3	O15379	991
TBL1XR1	TBL1Y	Q9BQ87	987
TBL1XR1	TBL1X	O60907	987
TBL1XR1	NCOR2	Q9Y618	965
TBL1XR1	CTNNB1	P35222	958
TBL1XR1	CTBP1	Q13363	713
TBL1XR1	HDAC1	Q13547	649
TBL1XR1	BARX2	Q9UMQ3	643
TBL1XR1	MECP2	P51608	630
TBL1XR1	SKP1	P34991	615
TBL1XR1	BCL6	P41182	596
TBL1XR1	AGRN	O00468	593
TBL1XR1	PDE6B	P35913	587

IntAct

131 interactions, top by confidence:

A	B	Type	Score
GPS2	HDAC3	psi-mi:“MI:0914”(association)	0.900
HDAC3	TBL1X	psi-mi:“MI:0914”(association)	0.760
ATXN1	TBL1XR1	psi-mi:“MI:0915”(physical association)	0.700
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
TBL1XR1	ARL2	psi-mi:“MI:0915”(physical association)	0.670
ARL2	TBL1XR1	psi-mi:“MI:0915”(physical association)	0.670
HDAC3	KDM1A	psi-mi:“MI:0914”(association)	0.650
QPRT	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
TBL1XR1	HDAC3	psi-mi:“MI:0914”(association)	0.640
KSR2	MAP2K2	psi-mi:“MI:0914”(association)	0.640
IRS4	PIK3R2	psi-mi:“MI:0914”(association)	0.640
DNALI1	TBL1XR1	psi-mi:“MI:0915”(physical association)	0.560
KLF11	TBL1XR1	psi-mi:“MI:0915”(physical association)	0.560
SOD1	TBL1XR1	psi-mi:“MI:0915”(physical association)	0.560
MECP2	HDAC3	psi-mi:“MI:0914”(association)	0.530
HAO2	EIF4G3	psi-mi:“MI:0914”(association)	0.530

BioGRID (661): TBL1XR1 (Two-hybrid), TBL1XR1 (Affinity Capture-MS), TBL1XR1 (Affinity Capture-MS), TBL1XR1 (Affinity Capture-MS), TBL1XR1 (Affinity Capture-MS), TBL1XR1 (Affinity Capture-MS), TBL1XR1 (Affinity Capture-MS), TBL1XR1 (Affinity Capture-MS), TBL1XR1 (Co-fractionation), TBL1XR1 (Co-fractionation), TBL1XR1 (Co-fractionation), TBL1XR1 (Co-fractionation), TBL1XR1 (Co-fractionation), TBL1XR1 (Co-fractionation), TBL1XR1 (Co-fractionation)

ESM2 similar proteins: A7YY75, C1BK83, O60907, O89050, P17427, P18484, P61962, P61963, P97834, Q05048, Q08211, Q1JP79, Q28141, Q28D01, Q4FZW5, Q4R8H1, Q58E77, Q5BJQ6, Q5R874, Q5R8K2, Q5RAN6, Q5RB35, Q5U4Y8, Q5ZHN3, Q5ZMV7, Q640J6, Q6GL39, Q6GNF1, Q6GPC6, Q6NV31, Q6TGU2, Q6UXN9, Q7SZM9, Q8BFQ4, Q8BHJ5, Q8C6G8, Q8R2U0, Q92747, Q96EE3, Q99LC2

Diamond homologs: A1CQL6, A1D3I2, A2QPW4, A4R7U3, A4REK3, A5D7H2, A6RT32, A7EZJ5, A7RWD2, A7TLU2, A8IZG4, A9VDW7, B0XAF3, B0XQ15, B3MC74, B3NQR5, B3RNR8, B4GDM7, B4HRQ6, B4JW81, B4KTK4, B4LJT7, B4MY77, B4P7Q3, B4QFZ8, B5X212, B5X9P2, B6K1G6, B7QKS1, F1LTR1, O16519, O43815, O55106, O60907, O76071, O80990, P58404, P70483, Q13033, Q17GR9

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
TBL1XR1	down-regulates	BCL3	ubiquitination
TBL1XR1	up-regulates	AR	binding
PRKCD	“up-regulates activity”	TBL1XR1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 138 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Notch-HLH transcription pathway	10	40.0×	2e-11
Downregulation of SMAD2/3:SMAD4 transcriptional activity	7	25.3×	7e-07
Regulation of MECP2 expression and activity	7	25.3×	7e-07
NOTCH1 Intracellular Domain Regulates Transcription	10	23.3×	2e-09
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	6	21.7×	2e-05
Constitutive Signaling by NOTCH1 PEST Domain Mutants	10	19.3×	1e-08
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	10	19.3×	1e-08
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	6	18.2×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of miRNA transcription	5	25.6×	4e-04
epigenetic regulation of gene expression	5	15.7×	2e-03
negative regulation of osteoblast differentiation	6	14.5×	8e-04
positive regulation of miRNA transcription	6	14.3×	8e-04
epidermal growth factor receptor signaling pathway	6	12.2×	1e-03
phosphatidylinositol 3-kinase/protein kinase B signal transduction	6	10.4×	3e-03
transcription by RNA polymerase II	10	5.8×	1e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 7 cancer types — ALL, BL, BRCA, DLBCLNOS, MLYM, NHL, PLMESO.

Clinical variants and AI predictions

ClinVar

632 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	33
Likely pathogenic	53
Uncertain significance	230
Likely benign	221
Benign	37

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1164048	NM_024665.7(TBL1XR1):c.597_600del (p.Ser199fs)	Pathogenic
1220231	NM_024665.7(TBL1XR1):c.1333G>C (p.Val445Leu)	Pathogenic
1327306	NM_024665.7(TBL1XR1):c.58+2T>C	Pathogenic
1330245	NM_024665.7(TBL1XR1):c.419dup (p.Ile141fs)	Pathogenic
1452089	NM_024665.7(TBL1XR1):c.41del (p.Arg14fs)	Pathogenic
1453577	NM_024665.7(TBL1XR1):c.1195T>A (p.Trp399Arg)	Pathogenic
1686249	NM_024665.7(TBL1XR1):c.1340G>A (p.Ser447Asn)	Pathogenic
1710357	NM_024665.7(TBL1XR1):c.64dup (p.Ser22fs)	Pathogenic
225872	NM_024665.7(TBL1XR1):c.1189del (p.Ile397fs)	Pathogenic
225874	NM_024665.7(TBL1XR1):c.1337A>G (p.Tyr446Cys)	Pathogenic
2443985	NM_024665.7(TBL1XR1):c.697T>A (p.Trp233Arg)	Pathogenic
2498943	NM_024665.7(TBL1XR1):c.646C>T (p.Arg216Ter)	Pathogenic
2572833	NM_024665.7(TBL1XR1):c.724A>C (p.Thr242Pro)	Pathogenic
2581100	NM_024665.7(TBL1XR1):c.420dup (p.Ile141fs)	Pathogenic
2685097	GRCh37/hg19 3q26.32(chr3:176670986-176807882)x1	Pathogenic
2760511	NM_024665.7(TBL1XR1):c.776_780dup (p.Thr261fs)	Pathogenic
2854416	NM_024665.7(TBL1XR1):c.830_831del (p.Lys277fs)	Pathogenic
3254814	NM_024665.7(TBL1XR1):c.1331C>T (p.Pro444Leu)	Pathogenic
3340594	NM_024665.7(TBL1XR1):c.557C>T (p.Ser186Leu)	Pathogenic
3640472	NM_024665.7(TBL1XR1):c.377dup (p.Asn126fs)	Pathogenic
4072012	NM_024665.7(TBL1XR1):c.1195T>C (p.Trp399Arg)	Pathogenic
4085931	NM_024665.7(TBL1XR1):c.1251-1G>A	Pathogenic
4181127	NM_024665.7(TBL1XR1):c.1177_1180del (p.Glu393fs)	Pathogenic
422081	NM_024665.7(TBL1XR1):c.754T>C (p.Trp252Arg)	Pathogenic
4279428	GRCh37/hg19 3q26.32(chr3:176679236-176894269)x1	Pathogenic
4535957	NM_024665.7(TBL1XR1):c.160C>T (p.Gln54Ter)	Pathogenic
4689811	NM_024665.7(TBL1XR1):c.820T>A (p.Trp274Arg)	Pathogenic
4820315	NM_024665.7(TBL1XR1):c.1372_1387dup (p.Asp463delinsGlyLysTrpPhePheTer)	Pathogenic
559571	NM_024665.7(TBL1XR1):c.1336T>G (p.Tyr446Asp)	Pathogenic
807509	NM_024665.7(TBL1XR1):c.799G>T (p.Gly267Cys)	Pathogenic

SpliceAI

5100 predictions. Top by Δscore:

Variant	Effect	Δscore
3:177026363:CTATA:C	donor_gain	1.0000
3:177026367:ACTT:A	donor_loss	1.0000
3:177026368:CTTA:C	donor_gain	1.0000
3:177026369:TTA:T	donor_loss	1.0000
3:177026370:TACT:T	donor_loss	1.0000
3:177026371:A:AC	donor_gain	1.0000
3:177026372:C:CA	donor_gain	1.0000
3:177026372:CT:C	donor_gain	1.0000
3:177026372:CTG:C	donor_gain	1.0000
3:177026372:CTGA:C	donor_gain	1.0000
3:177026372:CTGAA:C	donor_gain	1.0000
3:177026471:CTGT:C	acceptor_gain	1.0000
3:177026472:TGT:T	acceptor_gain	1.0000
3:177026473:GT:G	acceptor_gain	1.0000
3:177026475:C:CC	acceptor_gain	1.0000
3:177026476:T:A	acceptor_loss	1.0000
3:177033133:TGCA:T	acceptor_gain	1.0000
3:177033135:CA:C	acceptor_gain	1.0000
3:177033137:C:CC	acceptor_gain	1.0000
3:177034192:TATCA:T	donor_loss	1.0000
3:177034195:CA:C	donor_loss	1.0000
3:177034196:A:C	donor_loss	1.0000
3:177034230:AGTC:A	donor_gain	1.0000
3:177034325:TCTAA:T	acceptor_loss	1.0000
3:177034326:C:CC	acceptor_gain	1.0000
3:177034326:C:T	acceptor_loss	1.0000
3:177034327:T:A	acceptor_loss	1.0000
3:177038309:TTAC:T	donor_loss	1.0000
3:177038310:TACC:T	donor_loss	1.0000
3:177038311:A:AC	donor_gain	1.0000

AlphaMissense

3423 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:177026377:C:T	G505D	1.000
3:177026388:A:C	S501R	1.000
3:177026388:A:T	S501R	1.000
3:177026390:T:G	S501R	1.000
3:177026392:G:T	A500D	1.000
3:177026395:C:T	G499E	1.000
3:177026396:C:G	G499R	1.000
3:177026396:C:T	G499R	1.000
3:177026398:A:T	V498D	1.000
3:177026418:C:A	W491C	1.000
3:177026418:C:G	W491C	1.000
3:177026419:C:G	W491S	1.000
3:177026420:A:G	W491R	1.000
3:177026420:A:T	W491R	1.000
3:177026428:T:A	E488V	1.000
3:177026429:C:T	E488K	1.000
3:177026430:A:C	F487L	1.000
3:177026430:A:T	F487L	1.000
3:177026431:A:C	F487C	1.000
3:177026431:A:G	F487S	1.000
3:177026432:A:C	F487V	1.000
3:177026432:A:G	F487L	1.000
3:177026432:A:T	F487I	1.000
3:177026434:A:C	I486R	1.000
3:177026434:A:T	I486K	1.000
3:177026437:C:T	G485E	1.000
3:177026438:C:G	G485R	1.000
3:177026438:C:T	G485R	1.000
3:177032980:C:A	W469C	1.000
3:177032980:C:G	W469C	1.000

dbSNP variants (sampled 300 via entrez): RS1000005519 (3:177202514 A>G), RS1000071708 (3:177106079 A>G), RS1000094933 (3:177168475 T>C,G), RS1000096951 (3:177121972 C>G), RS1000107422 (3:177159245 TC>T), RS1000113879 (3:177061523 G>A,C), RS1000141004 (3:177024116 T>A,C), RS1000142002 (3:177170612 T>C), RS1000142472 (3:177174227 T>C), RS1000146850 (3:177019377 G>A), RS1000149863 (3:177135909 G>A), RS1000152714 (3:177172709 G>A,C), RS1000164676 (3:177073622 T>C), RS1000181543 (3:177110091 G>A), RS1000182785 (3:177062864 G>A,T)

Disease associations

OMIM: gene MIM:608628 | disease phenotypes: MIM:602342, MIM:616944, MIM:217095

GenCC curated gene-disease

Disease	Classification	Inheritance
Pierpont syndrome	Definitive	Autosomal dominant
intellectual disability, autosomal dominant 41	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

Mondo (7): Pierpont syndrome (MONDO:0011213), intellectual disability, autosomal dominant 41 (MONDO:0014842), neurodevelopmental disorder (MONDO:0700092), diffuse large B-cell lymphoma (MONDO:0018905), complex neurodevelopmental disorder (MONDO:0100038), intellectual disability (MONDO:0001071), conotruncal heart malformations (MONDO:0016581)

Orphanet (8): Pierpont syndrome (Orphanet:487825), OBSOLETE: Paraplegia-brachydactyly-cone-shaped epiphysis syndrome (Orphanet:2823), Diffuse large B-cell lymphoma (Orphanet:544), Non-specific syndromic intellectual disability (Orphanet:528084), Conotruncal heart malformations (Orphanet:2445), Common arterial trunk (Orphanet:3384), Double outlet right ventricle (Orphanet:3426), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

121 total (30 of 121 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000212	Gingival overgrowth
HP:0000219	Thin upper lip vermilion
HP:0000225	Gingival bleeding
HP:0000232	Everted lower lip vermilion
HP:0000233	Thin vermilion border
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000283	Broad face
HP:0000289	Broad philtrum
HP:0000293	Full cheeks
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000400	Macrotia
HP:0000421	Epistaxis
HP:0000445	Wide nose
HP:0000455	Broad nasal tip
HP:0000470	Short neck
HP:0000482	Microcornea
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000506	Telecanthus
HP:0000568	Microphthalmia
HP:0000574	Thick eyebrow

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST001089_4	Esophageal cancer	3.000000e-07
GCST001806_4	Corneal structure	1.000000e-08
GCST002740_20	Inflammatory skin disease	4.000000e-08
GCST003989_37	Chin dimples	7.000000e-11
GCST005667_4	Central corneal thickness	4.000000e-11
GCST006626_20	Pulse pressure	3.000000e-09
GCST007576_112	Chronotype	1.000000e-10
GCST007798_57	Asthma	9.000000e-14
GCST007798_58	Asthma	5.000000e-15
GCST007799_14	Asthma (adult onset)	6.000000e-06
GCST007800_95	Asthma (childhood onset)	4.000000e-11
GCST007941_27	Medication use (adrenergics, inhalants)	1.000000e-08
GCST008916_37	Asthma	2.000000e-12
GCST009414_4	Central corneal thickness	4.000000e-09
GCST009798_14	Asthma	6.000000e-11
GCST010042_127	Asthma	5.000000e-15
GCST010043_118	Asthma	4.000000e-15
GCST010220_5	Attention deficit hyperactivity disorder (hyperactivity-impulsivity symptoms)	9.000000e-06
GCST011793_10	Early chronic obstructive pulmonary disease in never smokers	9.000000e-06
GCST012017_2	Mastocytosis (KIT D816V positive)	2.000000e-09
GCST90000654_14	Central corneal thickness	4.000000e-16
GCST90002390_298	Mean corpuscular hemoglobin	9.000000e-12
GCST90002392_319	Mean corpuscular volume	6.000000e-21
GCST90002396_258	Mean reticulocyte volume	1.000000e-13
GCST90002397_87	Mean spheric corpuscular volume	5.000000e-36
GCST90002404_68	Red cell distribution width	3.000000e-15
GCST90014325_40	Asthma	6.000000e-10

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004345	corneal topography
EFO:0005213	central corneal thickness
EFO:0005763	pulse pressure measurement
EFO:0008328	chronotype measurement
EFO:1002011	adult onset asthma
EFO:0009941	Inhalant adrenergic use measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0009188	Red cell distribution width

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D016403	Lymphoma, Large B-Cell, Diffuse	C04.557.386.480.150.585; C15.604.515.569.480.150.585; C20.683.515.761.480.150.585
D065886	Neurodevelopmental Disorders	F03.625
C566559	Plantar Lipomatosis, Unusual Facies, and Developmental Delay (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523746 (PROTEIN-PROTEIN INTERACTION), CHEMBL6067529 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs57449396	Efficacy	3	allopurinol

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.27	Kd	5.327	nM	CHEMBL5653589
8.27	ED50	5.327	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 3 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149557: Binding affinity to human TBL1XR1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0053	uM

CTD chemical–gene interactions

63 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	8
bisphenol A	increases methylation, increases expression, affects cotreatment	3
trichostatin A	affects cotreatment, decreases expression	3
(+)-JQ1 compound	affects expression, increases reaction, decreases expression	3
sodium arsenite	increases abundance, decreases expression, affects cotreatment	2
Acetaminophen	decreases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Cisplatin	decreases expression	2
Hydrogen Peroxide	affects expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
tert-Butylhydroperoxide	decreases methylation, affects expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
sodium arsenate	decreases expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CD 437	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
torcetrapib	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4349425	Binding	Protac activity at TBLR1/BCL6 in human OCI-LY1 cells assessed as BCL6 degradation at 1 uM after 1 to 72 hrs relative to control	Small molecule PROTACs in targeted therapy: An emerging strategy to induce protein degradation. — Eur J Med Chem

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_2127	MOTN-1	Cancer cell line	Female
CVCL_D1QV	Abcam K-562 TBL1XR1 KO	Cancer cell line	Female
CVCL_D2MG	Abcam Raji TBL1XR1 KO	Cancer cell line	Male
CVCL_D9TZ	Ubigene HEK293 TBL1XR1 KO	Transformed cell line	Female
CVCL_WQ64	Abcam Jurkat TBL1XR1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

202 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
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