Molecular characteristics
The DALR anticodon binding domain containing 3 (DALRD3) gene is located on chromosome 3p21.31 of the human genome. The encoded DALRD3 protein forms a complex with the METTL2 methyltransferase to generate the 3-methylcytosine (m3C) modification in specific arginine tRNAs.
Mutations and pathophysiology
Biallelic nonsense and missense variants in DALRD3 have been shown to cause developmental delay and early-onset epileptic encephalopathy. Pathogenic variants in DALRD3 are rare and inherited in an autosomal recessive manner. All known pathogenic variants in DALRD3 cause loss of function with patient cells exhibiting deficiency in the m3C modification in arginine tRNAs.
Diagnosis/testing
Variants in DALRD3 can be identified using exome/genome sequencing. The pathogenic effects of the variant on DALRD3 function can be validated using molecular biology approaches with patient-derived cells or in vitro assays.
DALRD3