RNU7-1

Inheritance Pattern: AR

Disease ID:MONDO:0030362

Submitter: PanelApp Australia

Inheritance Pattern: AR

Disease ID:MONDO:0030362

Submitter: Illumina

Inheritance Pattern: AR

Disease ID:MONDO:0700263

Submitter: ClinGen

The *RNU7-1* gene is located on chromosome 12 at 12p13.31 and encodes RNA, U7 small nuclear 1, a noncoding RNA gene. This gene has been shown to have a role in post-transcriptional modification of replication dependent histone pre-mRNA. Binding of *RNU7-1* to the 3 prime UTR of histone pre mRNA prevents polyadenylation and allows careful regulation of histone translation. *RNU7-1* was first reported in association with Aicardi Goutieres syndrome 9 in 2020 (Uggenti et al., PMID: 33230297) with biallelic variants resulting in neurological regression in affected individuals, as well as CNS imaging consistent with hallmarks of Aicardi Goutieres syndrome. Variants were proposed to be loss of function. However, all individuals had compound heterozygous variants, with authors proposing one severe and mild allele being causative of disease and homozygosity of a severe allele likely incompatible with life and homozygosity of a mild allele resulting in no disease. Evidence supporting this gene disease relationship includes case-level data and experimental evidence (functional alteration in patient and non-patient cells). 12 variants from 20 probands from 15 families across 3 publications are included in this curation (PMID: 33230297, 35320431, 39748568). This gene-disease relationship is also supported by biochemical and functional alteration evidence (PMID: 33230297,35320431). It was demonstrated that loss of function of *RNU7-1* results in misprocessing of replication dependent histone RNA transcripts with alteration in expression including reduction of linker histone H1-4. It was subsequently shown that alterations in histone expression resulted in activation of interferon signalling via the cGAS/STING pathway. Analysis of interferon signalling gene expression in patient cells demonstrated a significant increase compared to controls. Lentivirus knockdown of H1-4 in a human monocytic cell line resulted in induction of interferon signalling gene expression (PMID: 33230297). This gene-disease relationship was limited on the basis of the calculated classification; however, it was upgraded to moderate by expert panel opinion weighing up all available evidence. This classification was approved by the ClinGen Syndromic Disorders GCEP on the meeting date February 4, 2026 (SOP Version 12).

Inheritance Pattern: AR

Disease ID:MONDO:0030362

Submitter: Labcorp Genetics (formerly Invitae)