TBL1X

transducin beta like 1 X-linked, the group of WD repeat domain containing|NCoR/SMRT transcriptional repression complex subunits

Basic information

Region (hg38): X:9463320-9741037

Previous symbols: [ "TBL1" ]

Links

ENSG00000101849 ∙ NCBI:6907 ∙ OMIM:300196 ∙ HGNC:11585 ∙ Uniprot:O60907 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypothyroidism, congenital, nongoitrous, 8 (Limited), mode of inheritance: Unknown
• hypothyroidism, congenital, nongoitrous, 8 (Strong), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypothyroidism, congenital, nongoitrous, 8	XL	Audiologic/Otolaryngologic; Endocrine	Individuals may have hearing loss, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals have been described with hypothyroidism, and awareness may allow management (eg, with thyroid hormone replacement)	Audiologic/Otolaryngologic; Endocrine	27603907; 30591955

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TBL1X gene.

• Inborn_genetic_diseases (43 variants)
• not_provided (36 variants)
• Hypothyroidism,_congenital,_nongoitrous,_8 (8 variants)
• TBL1X-related_disorder (5 variants)
• not_specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBL1X gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005647.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6	3	9
missense		1	69	2	1	73
nonsense		1	1			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	2	70	8	4

Highest pathogenic variant AF is 9.118904e-7

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBL1X	protein_coding	protein_coding	ENST00000217964	15	256446

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.979	0.0205	125741	2	3	125746	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.48	138	248	0.557	0.0000211	3774
Missense in Polyphen		17	68.15	0.24945		1129
Synonymous	-0.338	118	113	1.04	0.0000115	1113
Loss of Function	4.09	3	25.1	0.119	0.00000216	362

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000369	0.0000369
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000740	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000367	0.0000264
Middle Eastern	0.0000740	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units (PubMed:14980219). Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of corepressor complexes that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of transcription repressor complexes, thereby allowing cofactor exchange (PubMed:21240272). {ECO:0000269|PubMed:14980219, ECO:0000269|PubMed:21240272}.
• Pathway: Wnt signaling pathway - Homo sapiens (human);Ectoderm Differentiation;Disease;Signal Transduction;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);Metabolism of lipids;HDACs deacetylate histones;Chromatin modifying enzymes;Metabolism;Signaling by NOTCH1;Signaling by NOTCH;Chromatin organization;Constitutive Signaling by NOTCH1 PEST Domain Mutants;Signaling by NOTCH1 PEST Domain Mutants in Cancer;Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants;Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer;Signaling by NOTCH1 in Cancer;Regulation of nuclear beta catenin signaling and target gene transcription;Diseases of signal transduction;NOTCH1 Intracellular Domain Regulates Transcription (Consensus)

Recessive Scores

• pRec: 0.368

Intolerance Scores

• loftool: 0.0803
• rvis_EVS: -0.82
• rvis_percentile_EVS: 11.77

Haploinsufficiency Scores

• pHI: 0.372
• hipred: Y
• hipred_score: 0.677
• ghis: 0.536

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.943

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tbl1x

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;regulation of transcription by RNA polymerase II;proteolysis;sensory perception of sound;histone deacetylation;regulation of lipid metabolic process;proteasome-mediated ubiquitin-dependent protein catabolic process;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;protein stabilization;positive regulation of canonical Wnt signaling pathway
• Cellular component: histone deacetylase complex;nucleus;nucleoplasm;transcriptional repressor complex;mitotic spindle
• Molecular function: transcription corepressor activity;protein binding;beta-catenin binding;protein C-terminus binding;transcription factor binding;protein domain specific binding;histone binding;transcription regulatory region DNA binding