Likely inborn error of metabolism

Gene: SUPV3L1

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 12 Mar 2026, 10:16 a.m. | Last Modified: 12 Mar 2026, 10:16 a.m.

Panel Version: 8.94

SUPV3L1 is currently being recommended for promotion to green rating on Mitochondrial disorders panel (https://panelapp.genomicsengland.co.uk/panels/112/gene/SUPV3L1/) Hence, this gene can also be promoted to green rating on this panel in the next GMS update.

Created: 10 Jun 2025, 9:29 a.m. | Last Modified: 10 Jun 2025, 9:29 a.m.

Panel Version: 8.49

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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