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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 PTPRD is proposed as a candidate susceptibility locus for Alzheimer disease. PTPRD encodes a transmembrane receptor-type protein tyrosine phosphatase signaling molecule. There is a single fly ortholog, Lar, for which classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\Lar is orthologous to two additional human genes, PTPRF and PTPRS.
The PTPRD gene has not been introduced into flies.
The fly ortholog Lar was tested for genetic interaction with a transgenically introduced mutational variant of the human tau gene (Hsap\MAPT): RNAi-mediated reduction in the expression of Lar was observed to enhance the phenotype associated with tau toxicity; over-expression in the eye reduces the tau toxicity phenotype. Animals homozygous for amorphic alleles of Dmel\Lar are semi-lethal; larvae exhibit neural defects. Physical and genetic interactions of Dmel\Lar have been characterized; see below and in the gene report for Lar.
[updated June 2016 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).
PTPRD (protein tyrosine phosphatase, receptor type D) contains an extracellular region, a single transmembrane segment and two tandem intracytoplasmic catalytic domains. It may play a role in promoting neurite growth and regulating axon guidance. [from Gene Cards, PTPRD; 2016.06.01]
Many to one: 3 human to 1 Drosophila; the fly gene Lar is orthologous to PTPRD, PTPRF and PTPRS in human.
High-scoring ortholog of human genes PTPRD, PTPRF and PTPRS (1 Drosophila to 3 human). Dmel\Lar shares 46-48% identity and 61-63% similarity with the human genes.