TNRC6A

protein-coding

trinucleotide repeat containing adaptor 6A, the group of TNRC6 adaptor family

Gene summary

This gene encodes a member of the trinucleotide repeat containing 6 protein family. The protein functions in post-transcriptional gene silencing through the RNA interference (RNAi) and microRNA pathways. The protein associates with messenger RNAs and Argonaute proteins in cytoplasmic bodies known as GW-bodies or P-bodies. Inhibiting expression of this gene delocalizes other GW-body proteins and impairs RNAi and microRNA-induced gene silencing. [provided by RefSeq, Jul 2008]

Previous symbols:

TNRC6

MANE transcript

NM_014494.4

Inheritance

ClinVar variants

U:289B:33

Top phenotype

Epilepsy, familial adult myoclonic, 6

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr16:24,610,209-24,827,632

External References & Databases

Ensembl (ENSG00000090905)

Transcript & Mutation Effects

hg38 • Region Span ~217.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

epilepsy, familial adult myoclonic, 6LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0054846

Submitter: Labcorp Genetics (formerly Invitae)

epilepsy, familial adult myoclonic, 6LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0054846

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Epilepsy, familial adult myoclonic, 6AD

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 29507423

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TNRC6A variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 291

not providedTotal: 25

Epilepsy, familial adult myoclonic, 6Total: 4

Familial meningiomaTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014494.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	14 clinvar	3 clinvar	21
missense			272 clinvar	13 clinvar	3 clinvar	288
nonsense			2 clinvar			2
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	289	27	6	322

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 80 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014494.4	RefSeq	NP_055309.2	25	MANE Select
ENST00000395799.8	Ensembl	ENSP00000379144.3	25	MANE Select
NM_001330520.3	RefSeq	NP_001317449.1	24	Standard
NM_001351850.2	RefSeq	NP_001338779.1	23	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Competing endogenous RNAs (ceRNAs) regulate PTEN translation
Signal Transduction
Gene expression (Transcription)
Generic Transcription Pathway
Oncogene Induced Senescence

Biological Process

Wnt signaling pathway, calcium modulating pathway
cellular response to starvation
positive regulation of gene expression
negative regulation of gene expression
posttranscriptional gene silencing by RNA

Molecular Function

RNA binding
protein binding

Cellular Component

P-body
nucleoplasm
Golgi apparatus
cytosol
micro-ribonucleoprotein complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000395799
Coding exons: 25
Length: 97938
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125748
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.13	951	1.05e+3	0.902	0.0000558	12885
Missense (PolyPhen)		249	333.56	0.74649		3869
Synonymous	-0.711	398	380	1.05	0.0000212	3786
Loss of Function	8.38	9	98.9	0.0910	0.00000502	1050

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00018	rare
Latino/Admixed American	0.00015	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000048	0.000046	rare
European (Non-Finnish)	0.000080	0.000070	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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 repression of translation and for siRNA- dependent endonucleolytic cleavage of complementary mRNAs by argonaute family proteins. As a scaffolding protein, associates with argonaute proteins bound to partially complementary mRNAs, and can simultaneously recruit CCR4-NOT and PAN deadenylase complexes. {ECO:0000269|PubMed:16284622, ECO:0000269|PubMed:16284623, ECO:0000269|PubMed:17596515, ECO:0000269|PubMed:17671087, ECO:0000269|PubMed:19056672, ECO:0000269|PubMed:19304925}.;

Recessive Scores

pRec: 0.114

Intolerance Scores

LoFtool: 0.231
RVIS EVS: -1.02
RVIS percentile EVS: 7.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.871

Gene Damage Prediction

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