Retinal disorders

Gene: STX3

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 5:49 p.m. | Last Modified: 24 Feb 2025, 5:49 p.m.

Panel Version: 7.8

Comment on list classification: There is sufficient evidence available (six unrelated families and functional studies) for the promotion of this gene to green rating in the next GMS update.

Created: 19 Sep 2024, 9:33 a.m. | Last Modified: 19 Sep 2024, 9:33 a.m.

Panel Version: 6.5

PMID:33974130 assembled a cohort of ten individuals from eight families with microvillus inclusion disease (MVID), which included follow up of five previously reported individuals and five new individuals. All of them had homozygous loss-of-function nonsense variants in STX3 gene. Eight of them presented with a novel syndrome consisting of MVID and early-onset severe retinal dystrophy (EOSRD). All six different variants identified in individuals with MVID and EOSRD are located in exons shared between the STX3A and the STX3B transcripts, while the single variant (p.Arg247Ter) present in other two individuals with MVID only is located in exon 9A and it spares STX3B transcript.

Functional studies showed that STX3B transcript is highly expressed in human retina and that the protein is enriched in the inner and outer segments of photoreceptors and in ribbon synapses of the human retina. The study also showed that the inactivation of Stx3 in murine rod photoreceptors leads to a progressive degeneration of photoreceptors, corroborating a recently published study that used a different Stx3 knockout mouse line.

In summary, biallelic variants affecting both STX3A and STX3B transcripts cause MVID and EOSRD, while variants affecting only STX3A transcript cause MVID.

This gene has been associated with both phenotypes in OMIM (MIMs #619445 & #619446), but not yet in Gene2Phenotype.
Sources: Literature

Created: 19 Sep 2024, 9:30 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Retinal dystrophy and microvillus inclusion disease, OMIM:619446

Publications

• 33974130