TBL1XR1

TBL1X/Y related 1, the group of WD repeat domain containing|NCoR/SMRT transcriptional repression complex subunits

Basic information

Region (hg38): 3:177019340-177228000

Links

ENSG00000177565 ∙ NCBI:79718 ∙ OMIM:608628 ∙ HGNC:29529 ∙ Uniprot:Q9BZK7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Pierpont syndrome (Definitive), mode of inheritance: AD
• intellectual disability, autosomal dominant 41 (Moderate), mode of inheritance: AD
• Pierpont syndrome (Moderate), mode of inheritance: AD
• Pierpont syndrome (Strong), mode of inheritance: AD
• intellectual disability, autosomal dominant 41 (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
• intellectual disability, autosomal dominant 41 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 41; Pierpont syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	9450851; 16007632; 22495309; 23160955; 24891185; 25102098; 26769062

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TBL1XR1 gene.

• Pierpont_syndrome (418 variants)
• not_provided (171 variants)
• Intellectual_disability,_autosomal_dominant_41 (61 variants)
• Inborn_genetic_diseases (43 variants)
• TBL1XR1-related_disorder (22 variants)
• not_specified (14 variants)
• Intellectual_disability (6 variants)
• TBL1XR1-related_neurodevelopmental_disorder (3 variants)
• Neurodevelopmental_disorder (2 variants)
• Malignant_lymphoma,_large_B-cell,_diffuse (2 variants)
• Conotruncal_heart_malformations (1 variants)
• Cleft_lip/palate (1 variants)
• See_cases (1 variants)
• TBL1XR1-related_neurodevelopmental_disorders,_including_Pierpont_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBL1XR1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024665.7. 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			4	113	1	118
missense	17	59	176	7		259
nonsense	2	5				7
start loss						0
frameshift	14	5	2			21
splice donor/acceptor (+/-2bp)	3	7	3			13
Total	36	76	185	120	1

Highest pathogenic variant AF is 0.0000014399906

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBL1XR1	protein_coding	protein_coding	ENST00000430069	14	178119

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000491	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.20	69	260	0.266	0.0000120	3404
Missense in Polyphen		5	74.44	0.067168		1045
Synonymous	-0.375	94	89.5	1.05	0.00000443	942
Loss of Function	4.91	0	28.1	0.00	0.00000144	335

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
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. 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. {ECO:0000269|PubMed:14980219}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:26769062}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Mental retardation, autosomal dominant 41 (MRD41) [MIM:616944]: A form of mental retardation, 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. {ECO:0000269|PubMed:22495309, ECO:0000269|PubMed:23160955, ECO:0000269|PubMed:25102098, ECO:0000269|PubMed:27133561}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Wnt signaling pathway - Homo sapiens (human);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: 0.254

Intolerance Scores

• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.25

Haploinsufficiency Scores

• pHI: 0.930
• hipred: Y
• hipred_score: 0.783
• ghis: 0.686

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.937

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tbl1xr1
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); liver/biliary system phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;blastocyst hatching;response to dietary excess;regulation of transcription by RNA polymerase II;lipid catabolic process;histone deacetylation;regulation of lipid metabolic process;multicellular organism growth;proteasome-mediated ubiquitin-dependent protein catabolic process;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;white fat cell differentiation;fat pad development;regulation of triglyceride metabolic process;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;histone binding;transcription regulatory region DNA binding;protein N-terminus binding