TNRC6B

trinucleotide repeat containing adaptor 6B, the group of Armadillo like helical domain containing|TNRC6 adaptor family

Basic information

Region (hg38): 22:40044817-40335808

Links

ENSG00000100354 ∙ NCBI:23112 ∙ OMIM:610740 ∙ HGNC:29190 ∙ Uniprot:Q9UPQ9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic intellectual disability (Supportive), mode of inheritance: AD
• global developmental delay with speech and behavioral abnormalities (Moderate), mode of inheritance: AD
• global developmental delay with speech and behavioral abnormalities (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
• global developmental delay with speech and behavioral abnormalities (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Global developmental delay with speech and behavioral abnormalities	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	29463886; 32152250

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TNRC6B gene.

• not_provided (218 variants)
• Inborn_genetic_diseases (200 variants)
• Global_developmental_delay_with_speech_and_behavioral_abnormalities (89 variants)
• TNRC6B-related_disorder (58 variants)
• not_specified (13 variants)
• Global_developmental_delay (3 variants)
• Neurodevelopmental_disorder (2 variants)
• Autism_spectrum_disorder (2 variants)
• Neurodevelopmental_delay (2 variants)
• Atypical_behavior (2 variants)
• Autistic_behavior (2 variants)
• TNRC6B-related_complex_neurodevelopmental_disorder (1 variants)
• See_cases (1 variants)
• EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
• Neurodevelopmental_disorder_with_dysmorphic_facies_and_distal_limb_anomalies (1 variants)
• Developmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNRC6B gene is commonly pathogenic or not. These statistics are base on transcript: NM_001162501.2. 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			7	42	1	50
missense	1	1	342	59	3	406
nonsense	16	10	9			35
start loss			1			1
frameshift	13	13	4			30
splice donor/acceptor (+/-2bp)	2	3	2			7
Total	32	27	365	101	4

Highest pathogenic variant AF is 0.0000020526406

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNRC6B	protein_coding	protein_coding	ENST00000454349	23	290992

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	9.12e-9	124654	0	23	124677	0.0000922

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.87	733	987	0.743	0.0000522	11944
Missense in Polyphen		238	383.7	0.62028		4603
Synonymous	-0.216	390	385	1.01	0.0000228	3617
Loss of Function	7.95	9	90.7	0.0992	0.00000485	928

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00146	0.000874
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000555	0.0000555
Finnish	0.000141	0.000139
European (Non-Finnish)	0.0000470	0.0000354
Middle Eastern	0.0000555	0.0000555
South Asian	0.00	0.00
Other	0.000167	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs). Required for miRNA-dependent translational repression and siRNA-dependent endonucleolytic cleavage of complementary mRNAs by argonaute family proteins. As scaffoldng protein associates with argonaute proteins bound to partially complementary mRNAs and simultaneously can recruit CCR4-NOT and PAN deadenylase complexes. {ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:19167051, ECO:0000269|PubMed:19304925, ECO:0000269|PubMed:21981923}.
• Pathway: Competing endogenous RNAs (ceRNAs) regulate PTEN translation;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;Oncogene Induced Senescence;Oxidative Stress Induced Senescence;Cellular Senescence;Cellular responses to stress;RNA Polymerase II Transcription;Pre-NOTCH Transcription and Translation;Pre-NOTCH Expression and Processing;Signaling by NOTCH;TP53 Regulates Metabolic Genes;Cellular responses to external stimuli;Regulation of PTEN mRNA translation;PTEN Regulation;PIP3 activates AKT signaling;Signaling by Nuclear Receptors;Transcriptional Regulation by TP53;Regulation of RUNX1 Expression and Activity;Estrogen-dependent gene expression;ESR-mediated signaling;Intracellular signaling by second messengers;Transcriptional regulation by RUNX1;Post-transcriptional silencing by small RNAs;Gene Silencing by RNA (Consensus)

Recessive Scores

• pRec: 0.119

Intolerance Scores

• loftool: 0.377
• rvis_EVS: -1.81
• rvis_percentile_EVS: 2.2

Haploinsufficiency Scores

• pHI: 0.518
• hipred: Y
• hipred_score: 0.785
• ghis: 0.563

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.867

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tnrc6b
• Phenotype: growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype

Gene ontology

• Biological process: Wnt signaling pathway, calcium modulating pathway;positive regulation of gene expression;negative regulation of gene expression;gene silencing by RNA;posttranscriptional gene silencing by RNA;gene silencing by miRNA;miRNA mediated inhibition of translation;regulation of megakaryocyte differentiation;positive regulation of nuclear-transcribed mRNA poly(A) tail shortening;positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
• Cellular component: P-body;nucleoplasm;cytosol;micro-ribonucleoprotein complex
• Molecular function: RNA binding;protein binding