Asn40Asp

Asn40Asp is a shorthand notation used in protein and genetic contexts to describe a missense substitution in which asparagine (N) at position 40 of a protein is replaced by aspartic acid (D). The same change may be written as N40D or N40→D. The impact of such a substitution is highly dependent on the specific protein and its structural and functional context.

Asparagine is a neutral, polar amino acid, while aspartic acid carries a negative charge at physiological pH. Introducing a charge and potential size difference at position 40 can alter local interactions, including hydrogen bonds, salt bridges, and the geometry of nearby functional or binding sites. If Asn40 participates in an N-linked glycosylation motif (N-X-S/T), replacing it with Asp would disrupt that motif and could affect protein folding, stability, trafficking, or surface expression.

Assessing the consequence of an Asn40Asp change typically involves multiple lines of evidence. Sequence conservation at position 40 across related proteins suggests functional importance; in silico tools (for example, SIFT or PolyPhen-2) provide predictions of potential deleterious effects; structural modeling can reveal perturbations in 3D contacts; and experimental assays can measure effects on activity, stability, or interactions. Population data from databases such as gnomAD help interpret rarity and potential pathogenicity, while clinical correlation in affected individuals informs disease relevance.

Overall, Asn40Asp is a context-dependent variant. Its significance varies with the gene and protein involved, and no universal conclusion about pathogenicity can be drawn without specific molecular and phenotypic information.