Curation FAME6 TNRC6A

Gene TNRC6A

Disease FAME6

Inheritance AD

Score

2.5 + 0.2 = 2.7 / 18

Genetic + experimental = total

Classification

Limited

Refuted

Moderate

Definitive

Last Updated 08/14/2025

Pubs Reviewed 1

Publication Span –

Publication Interval –

Curator(s) Macayla Weiner, Laurel Hiatt, Harriet Dashnow

Description

FAME6/BAFME6 is an autosomal dominant familial adult myoclonic epilepsy phenotype associated with noncoding TTTCA and TTTTA repeat expansions in TNRC6A. PMID:29507423 identified TNRC6A expansions in one BAFME family (F9283), confirmed the repeat configuration by RP-PCR and Southern blot, and reported co-segregation in five affected individuals and one unaffected individual. TTTCA-repeat expansions in TNRC6A were absent from 1,000 control subjects, while TTTTA-only expansions were observed rarely in controls, supporting the TTTCA-containing expanded allele as the disease-relevant motif.

All criTRia Curations Locus Page

Genetic evidence

Total: 2.5

Per page

Category	Type	Citation	Score	Details
Singular Evidence	Probands	PMID:29507423	1.5	One unrelated BAFME6 family (F9283) with five affected individuals carried TNRC6A TTTCA/TTTTA repeat expansions; the expanded allele was validated by RP-PCR and Southern blot and co-segregated with disease.
Collective Evidence	Allele	PMID:29507423	1	TNRC6A TTTCA-repeat expansions were absent in 1,000 controls and in patients with SAMD12 expansions; TTTTA-only expansions occurred rarely in controls, supporting the TTTCA-containing expanded motif as disease-relevant.

Experimental evidence

Total: 0.2

Per page

Category	Type	Citation	Score	Details
Function	Regulatory impact	PMID:29507423	0.2	In the supplementary materials of pmid:29507423 RNA-seq data from control brains show that TNRC6A is transcribed with spliced transcripts flanking the repeat, and RT-PCR confirms expression in brain and other tissues; however, no differential expression or regulatory effect of the repeat expansion is demonstrated. Downgraded score to 0.2 as the evidence does not assess the impact of the expansion on gene function.

Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.