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FB2026_01
,
released March 12, 2026
Initially identified in an analysis of two genome-wide association studies (FBrf0223922), the human gene FERMT2 is proposed as a candidate susceptibility locus for Alzheimer disease. FERMT2 encodes a scaffolding protein necessary for assembly of focal adhesions and cell adhesion onto the extracellular matrix. There are two Drosophila members of this family of genes, Fit1 and Fit2; RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for both Drosophila genes. There are two additional fermitin genes in human, FERMT1 and FERMT3.
A UAS construct of the wild-type human Hsap\FERMT2 gene has been introduced into flies, but has not been characterized.
Both the fly orthologs, Fit1 and Fit2, were tested for genetic interaction with a transgenically introduced mutational variant of the human tau gene (Hsap\MAPT): RNAi-mediated reduction in the expression of either enhances the phenotype associated with tau toxicity; overexpression in the eye reduces the tau toxicity phenotype. Fit1 and Fit2 are observed to interact with each other, both genetically and physically; see below and in the gene reports for Fit1 and Fit2.
[updated Apr. 2020 by FlyBase; FBrf0222196]
Alzheimer disease (AD) is the most common form of progressive dementia in the elderly. [from MIM:104300; 2016.01.08]
Memory loss is the most common sign of Alzheimer disease. As the disorder progresses, some people with AD experience personality and behavioral changes; other common symptoms include agitation, restlessness, withdrawal, and loss of language skills. Total care is usually required during the advanced stages of the disease. Affected individuals usually survive 8 to 10 years after the appearance of symptoms, but the course of the disease can range from 1 to 25 years. Death usually results from pneumonia, malnutrition, or general body wasting. [from Genetics Home Reference, Alzheimer disease; 2016.01.08]
Alzheimer disease can be classified as early-onset or late-onset. The signs and symptoms of the early-onset form appear before age 65, while the late-onset form appears after age 65. The early-onset form is much less common than the late-onset form, accounting for less than 5 percent of all cases of Alzheimer disease. [from Genetics Home Reference, Alzheimer disease; 2016.01.08]
Locus identified as showing significant association with susceptibility to Alzheimer disease in an analysis of two genome-wide association studies (GWAS).
FERMT2 is associated with late-onset Alzheimer disease in a GWAS study (see GWAS Catalog, below in 'External links').
A large genome-wide association meta-analysis of clinically diagnosed late-onset Alzheimer's disease (94,437 individuals) supports previous studies implicating FERMT2 as a susceptibility locus for AD (Kunkle et al., 2019; pubmed:30820047).
FERMT2 is one of several proteins in humans described as fermitins or kindlins; these are scaffolding proteins that are required for assembly of focal adhesions and have a role in integrin-mediated cell adhesion onto the extracellular matrix. [from Gene Cards, FERMT2; 2016.06.02]
Many to many: 3 human to 2 Drosophila; additional high-scoring human orthologs are FERMT1 and FERMT3.
One of two Drosophila orthologs of human genes FERMT2, FERMT1, FERMT3 (2 Drosophila to 3 human). Dmel\Fit1 shares 40-46% identity and 60-64% similarity with the human genes.
One of two Drosophila orthologs of human genes FERMT2, FERMT1, FERMT3 (2 Drosophila to 3 human). Dmel\Fit2 shares 41-44% identity and 60-64% similarity with the human genes.