SNORA31

Inheritance Pattern: AD

Disease ID:MONDO:0030313

Submitter: PanelApp Australia

Inheritance Pattern: AD

Disease ID:MONDO:0030313

Submitter: ClinGen

The *SNORA31* gene is located on chromosome 13 at 13q14.13 and encodes Small Nucleolar RNA, H/ACA Box 31, a noncoding RNA gene. The gene is predicted to be a guide RNA responsible for pseudouridylation of 18S ribosomal RNA and small nuclear RNA (Kiss *et al*., 2004, PMID: 15199136). *SNORA31* was first reported in relation to autosomal dominant susceptibility to herpes simplex encephalitis in 2019 (Lafaille *et al*., 2019 PMID: 31806906). Authors identified five individuals in a cohort with herpes simplex encephalitis that carried rare variants in *SNORA31*. Two variants across three of these probands are included in this curation. Both variants have supporting functional evidence indicating that these variants reduce transcript expression, suggesting a loss-of-function mechanism. Because *SNORA31* is located within the fifth intron of *TPT1*, associated variants are currently listed under the *TPT1* transcript. The appropriate HGVS nomenclature for these entries is undergoing internal review. This gene-disease relationship is also supported by experimental evidence (functional alteration and model systems), specifically in vitro functional assays showing that patient cells and cell culture models have an increased susceptibility to HSV-1 (PMID: 31806906). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Syndromic Disorders GCEP on the meeting date March 4, 2026 (SOP Version 12).