This report describes arrhythmogenic right ventricular dysplasia 5 (ARVD5), an autosomal dominant form of familial cardiomyopathy. The human gene implicated in this disease is TMEM43, which encodes a transmembrane protein associated with the nuclear membrane. There is a single orthologous gene in Drosophila, Dmel\Tmem43, for which multiple genetic reagents, including RNAi targeting constructs, an overexpression construct, and a CRISPR/Cas9-mediated knockout construct, have been generated. A mutation in the fly gene analogous to a variant implicated in ARVD5 has been characterized.
The human TMEM43 gene has not been introduced into flies.
Dmel\Tmem43 is expressed in all stages; it is observed to localize to the ER, as well as to the nuclear membrane. However, animals homozygous for amorphic mutations of Dmel\Tmem43 are viable and fertile, and exhibit normal cardiac performance. A mutation in the fly gene analogous to a variant implicated in human disease has been characterized; overexpression of this mutation causes growth defects, loss of body weight, cardiac arrhythmias, and premature death. See the 'Disease-Implicated Variants' table below. Using this disease model, the role of impaired lipid metabolism has been investigated.
[updated Aug. 2022 by FlyBase; FBrf0222196]
[ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 5; ARVD5](https://omim.org/entry/604400)
[TRANSMEMBRANE PROTEIN 43; TMEM43](https://omim.org/entry/612048)
Arrhythmogenic right ventricular dysplasia (ARVD) is a clinical and pathologic entity for which the diagnosis rests on electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular free wall. It is inherited in an autosomal dominant manner with reduced penetrance and is one of the major genetic causes of juvenile sudden death. [from MIM:107970; 2022.08.23]
Familial arrhythmogenic right ventricular dysplasia-5 (ARVD5) is caused by heterozygous mutation in the TMEM43 gene. [from MIM:604400; 2022.08.23]
The transmembrane protein encoded by TMEM43 is postulated to have a role in maintaining nuclear envelope structure by organizing protein complexes at the inner nuclear membrane. [Gene Cards, TMEM43; 2022.08.23]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human TMEM43 (1 Drosophila to 1 human).
