This report describes intellectual disability, syndromic, autosomal recessive 82, a newly identified neurodevelopmental disorder associated with rare variants in the human NSUN6 gene. NSUN6 encodes a cytoplasmic methyltransferase that has a role in both tRNA and mRNA post-transcriptional targeted modification. There is a single ortholgous gene in Drosophila, Nsun6, for which a limited number of genetic reagents has been generated, including RNAi targeting constructs, alleles caused by insertional mutagenesis, and a CRISPR/Cas9-based LOF construct.
The human NSUN6 gene has not been introduced into flies.
Animals homozygous for a severe loss-of-function mutation of Dmel\Nsun6 survive to adulthood and appear morphologically normal; they exhibit locomotor and learning defects.
[updated Mar. 2025 by FlyBase; FBrf0222196]
Intellectual disability is characterized by impairments in intellectual functioning and adaptive behavior; symptoms must be present before a child becomes 18 years old (http://medical-dictionary.thefreedictionary.com/mental+retardation; 2016.01.19).
Intellectual disability can be subdivided into syndromic forms, characterized by cognitive impairment accompanied by dysmorphic features, malformations or neurological abnormalities, and nonsyndromic forms, characterized by cognitive impairment without additional features (Basel-Vanagaite, 2008; DOI: 10.1002/9780470015902.a0021454).
[INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 82; MRT82](https://omim.org/entry/620779)
[NOP2/SUN RNA METHYLTRANSFERASE FAMILY, MEMBER 6; NSUN6](https://omim.org/entry/617199)
Autosomal recessive intellectual developmental disorder-82 (MRT82) is characterized by global developmental delay with motor and speech delay, variably impaired intellectual development, and behavioral abnormalities (Mattioli et al., 2023; pubmed:37226891). [from MIM:620779; 2024.05.21]
A neurodevelopmental disorder of variable severity, typically characterized by intellectual disability, global developmental delay, motor delay, and behavioral anomalies (eg, aggressiveness or attention-deficit/hyperactivity disorder) (Mattioli, et al., 2023; pubmed:37226891; FBrf0257531).
Autosomal recessive intellectual developmental disorder-82 (MRT82) is caused by homozygous mutation in the NSUN6 gene. [from MIM:620779; 2024.05.21]
The 3 characterized individuals carry homozygous deleterious variants in the NSUN6 gene; the predicted deleterious impact of the respective variants appears to correlate with the severity of the disease phenotype (Mattioli, et al., 2023; pubmed:37226891; FBrf0257531).
NSUN6 encodes a cytoplasmic methyltransferase involved in tRNA C5-cytosine methylation. [Gene Cards, NSUN6; 23.10.13]
NSUN6 acts as a methyltransferase targeting mRNA, potentially as part of a quality control mechanism involved in translation termination fidelity (Selmi et al., 2020; pubmed:33330931).
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human NSUN6 (1 Drosophila to 1 human).
