In silico study of missense variants of FANCA, FANCC and FANCG genes reveals high risk deleterious alleles predisposing to Fanconi anemia pathogenesis.
Gene
; 812: 146104, 2022 Feb 20.
Article
in En
| MEDLINE
| ID: mdl-34864095
ABSTRACT
Among the 22 Fanconi anemia (FA) reported genes, 90% of mutational spectra were found in three genes, namely FANCA (64%), FANCC (12%) and FANCG (8%). Therefore, this study aimed to identify the high-risk deleterious variants in three selected genes (FANCA, FANCC, and FANCG) through various computational approaches. The missense variant datasets retrieved from the UCSC genome browser were analyzed for their pathogenicity, stability, and phylogenetic conservancy. A total of 23 alterations, of which 16 in FANCA, 6 in FANCC and one variant in FANCG, were found to be highly deleterious. The native and mutant structures were generated, which demonstrated a profound impact on the respective proteins. Besides, their pathway analysis predicted many other pathways in addition to the Fanconi anemia pathway, homologous recombination, and mismatch repair pathways. Hence, this is the first comprehensive study that can be useful for understanding the genetic signatures in the development of FA.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Computational Biology
/
Mutation, Missense
/
Fanconi Anemia Complementation Group A Protein
/
Fanconi Anemia Complementation Group C Protein
/
Fanconi Anemia Complementation Group G Protein
/
Fanconi Anemia
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Gene
Year:
2022
Document type:
Article
Affiliation country:
Malaysia