Mitochondrial disorders

Gene: SUPV3L1

Green List (high evidence)

Comment on publications: PMID: 39596606 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.

Created: 25 Mar 2025, 2:07 p.m. | Last Modified: 25 Mar 2025, 2:07 p.m.

Panel Version: 8.16

Three SUPV3L1 variants have been reported in two unrelated cases with a syndrome that includes ataxia, spasticity, optic atrophy and skin hypopigmentation (ASOASH) and also intellectual disability (PMID: 35023579;39596606).
The homozygous terminating SUPV3L1 variant (NM_003171.3: c.2215C>T, p.Gln739*) reported in the siblings in PMID: 35023579, was shown to results in reduced expression of the truncated protein in the proband's fibroblasts, resulting in a reduction of the mature ND6 mRNA species and also the accumulation of double-stranded RNA. This effect was partly restored using full-length SUPV3L1 cDNA (PMID: 35023579). This variant and the compound heterozygous SUPV3L1 variants (NM_003171.5: c.272-2A>G and c.1924A>C; p.(Ser642Arg) reported in PMID: 39596606 were each inherited from the parents of the proband (PMID: 35023579;39596606). Supportive functional studies were presented in PMID: 35023579 and 39596606.
Sources: Literature

Created: 25 Mar 2025, 2:03 p.m. | Last Modified: 25 Mar 2025, 2:09 p.m.

Panel Version: 8.16

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial RNA Helicase SUPV3L1-Associated neurodegenerative syndrome

Publications

• 35023579
• 39596606