ANGDelMut – a web-based tool for predicting and analyzing functional loss mechanisms of amyotrophic lateral sclerosis-associated angiogenin mutations

Abstract

ANGDelMut is a web-based tool for predicting the functional consequences of missense mutations in the angiogenin (ANG) protein, which is associated with amyotrophic lateral sclerosis (ALS). Missense mutations in ANG result in loss of either ribonucleolytic activity or nuclear translocation activity or both of these functions, and in turn cause ALS. However, no web-based tools are available to predict whether a newly identified ANG mutation will possibly lead to ALS. More importantly, no web-implemented method is currently available to predict the mechanisms of loss-of-function(s) of ANG mutants. In light of this observation, we developed the ANGDelMut web-based tool, which predicts whether an ANG mutation is deleterious or benign. The user selects certain attributes from the input panel, which serves as a query to infer whether a mutant will exhibit loss of ribonucleolytic activity or nuclear translocation activity or whether the overall stability will be affected. The output states whether the mutation is deleterious or benign, and if it is deleterious, gives the possible mechanism(s) of loss-of-function. This web-based tool, freely available at http://bioschool.iitd.ernet.in/DelMut/, is the first of its kind to provide a platform for researchers and clinicians, to infer the functional consequences of ANG mutations and correlate their possible association with ALS ahead of experimental findings.

Insights into the role of d‐amino acid oxidase mutations in amyotrophic lateral sclerosis

“…Since the initial discovery of SOD1 mutations in patients with ALS that account for one‐fifth of the familial cases, a number of other genetic factors have been subsequently discovered. Among them, mutations in TARDBP , FUS , VAPB , ANG , FIG4 , OPTN , VCP , SETX , and hexanucleotide repeat expansion in the C9ORF72 are primarily driven in ALS . However, as most reported cases of ALS are sporadic and known genes account for only approximately 30%‐35% of familial ALS, there is a need to study the other gene mutations thoroughly.…”

“…Among them, mutations in TARDBP, FUS, VAPB, ANG, FIG4, OPTN, VCP, SETX, and hexanucleotide repeat expansion in the C9ORF72 are primarily driven in ALS. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] However, as most reported cases of ALS are sporadic and known genes account for only approximately 30%-35% of familial ALS, there is a need to study the other gene mutations thoroughly.…”