This report describes intellectual disability, autosomal recessive 5; an alternative designation of this disease is 'mental retardation, autosomal recessive 5' (MRT5). The human gene implicated in this disease is NSUN2, a methyltransferase that effects methylation of a number of tRNA species. There is a single Drosophila ortholog Dmel\Nsun2, for which multiple genetic reagents have been generated including amorphic mutations, RNAi-targeting constructs, and over-expression constructs.
Multiple UAS constructs of the human Hsap\NSUN2 gene have been introduced into flies, including wild-type and a variant implicated in this disease. See the 'Disease-Implicated Variants' table below. Heterologous rescue (functional complementation) of the Dmel\Nsun2 increased social space behavioral phenotype has been demonstrated using the wild-type human gene.
Animals homozygous for an amorphic allele of the Dmel\Nsun2 gene are viable, but exhibit a memory defective phenotype. In assessment of behaviors correlated with autism, animals homozygous for a CRISPR-generated knockout mutation exhibit an increased social space behavioral phenotype.
[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 5; MRT5](https://omim.org/entry/611091)
[NOP2/SUN RNA METHYLTRANSFERASE FAMILY, MEMBER 2; NSUN2](https://omim.org/entry/610916)
In addition to moderate to severe cognitive impairment, MRT5 is often associated with multiple dysmorphic features, delayed psychomotor development, and other abnormalities. [from MIM:611091; 2016.01.25]
MRT5 is caused by homozygous mutation in the NOP2/Sun RNA methyltransferase gene NSUN2, exhibiting an autosomal-recessive mode of inheritance. [from MIM:611091; 2016.01.25]
NSUN2 encodes a methyltransferase that catalyzes the intron-dependent methylation of the first position of the anti-codon of several tRNA species, a modification necessary to stabilize anticodon-codon pairing. [from MIM:610916; 2016.01.25]
One to one: 1 human to 1 Drosophila.
Ortholog of human gene NSUN2 (1 Drosophila to 1 human). Dmel\Nsun2 shares 42% identity and 57% similarity with the human gene.
