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FB2026_01
,
released March 12, 2026
Wolfram syndrome 1 is a rare and severe autosomal recessive neurodegenerative disease characterized by diabetes mellitus, optic atrophy, diabetes insipidus, and deafness. The human gene implicated is WFS1, which encodes the Wolframin ER tranmembrane glycoprotein. This gene is associated with several diseases with an overlapping array of phenotypes of which WFS1 is the most severe; see the human disease model report 'WFS1-related disorders' (FBhh0000806). There is one high-scoring fly ortholog, Dmel\wfs1, for which multiple genetic reagents, including amorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis, have been generated.
The human WFS1 gene has not been introduced into flies.
Flies bearing knockout alleles of Dmel\wfs1 weigh less than wild-type flies at 30 days of age, suggestive of weight loss exhibited by patients with type 1 diabetes mellitus. These flies also exhibit increased hemolymph glucose and triglycerol levels, lower levels of Ilp2 mRNA and ILP2 protein, and impaired calcium homeostasis. Disrupted endoplasmic calcium efflux and diabetes-like symptoms associated with the loss of Dmel\wfs1 could be rescued by ubiquitous overexpression of Dmel\wfs1 or by overexpression of Dmel\Cisd, the ortholog of the human gene associated with Wolfram syndrome 2 (MIM:604928; FBhh0001638).
[updated June 2024 by FlyBase; FBrf0222196]
[WOLFRAM SYNDROME 1; WFS1](https://omim.org/entry/222300)
[WOLFRAMIN ER TRANSMEMBRANE GLYCOPROTEIN; WFS1](https://omim.org/entry/606201)
Wolfram syndrome-1 (WFS1) is a rare and severe autosomal recessive neurodegenerative disease characterized by diabetes mellitus, optic atrophy, diabetes insipidus, and deafness (DIDMOAD). Additional clinical features may include renal abnormalities, ataxia, dementia or impaired intellectual development, and diverse psychiatric illnesses. The minimal diagnostic criteria for Wolfram syndrome are optic atrophy and diabetes mellitus of juvenile onset. Hearing impairment in Wolfram syndrome is typically progressive and mainly affects the higher frequencies, but a small fraction of affected individuals have congenital deafness (summary by Rendtorff et al., 2011, pubmed:21538838). [from MIM:222300; 2025.06.11]
Wolfram syndrome is a progressive neurodegenerative disorder characterized by onset of diabetes mellitus and optic atrophy before age 16 years, and typically associated with sensorineural hearing loss, progressive neurologic abnormalities (cerebellar ataxia, peripheral neuropathy, dementia, psychiatric illness, and urinary tract atony), and other endocrine abnormalities. [Gene Reviews, WFS1-Related Disorders; 2018.05.14]
Wolfram syndrome-1 (WFS1) is caused by homozygous or compound heterozygous mutation in the gene encoding wolframin on chromosome 4p16. [from MIM:222300; 2025.06.11]
The WFS1 encodes a transmembrane glycoprotein that localizes primarily in the endoplasmic reticulum (ER). [from MIM:606201; 2018.05.14]
One to one (1 human to 1 Drosophila); WFS1 has one high-scoring Drosophila ortholog, wfs1.
High-scoring ortholog of human WFS1 (1 Drosophila to 1 human).