The human gene WDR81 is implicated in the development of several neurodevelopmental disorders (see MIM:614218) which exhibit autosomal recessive inheritance. Variants corresponding to nonsense mutations in WDR81 were recently identified in five families with associated progressive microcephaly and reduced brain gyrations (lissencephaly), potentially defining a new disease associated with this gene. This newly defined disorder also exhibits autosomal recessive inheritance. The WDR81 gene encodes a multi-domain transmembrane protein which is predominantly expressed in the brain and is thought to play a role in endolysosomal trafficking. There is a single orthologous gene in Drosophila, Wdr81, for which RNAi constructs have been generated.
The human WDR81 gene has not been introduced into flies.
Dmel\Wdr81 has not been well characterized genetically. RNAi-mediated knockdown of Wdr81 in neural stem cells results in an increased mitotic index in those cells, with delayed mitotic progression; this recapitulates the phenotype observed in patient-derived fibroblast cells.
[updated Jul. 2021 by FlyBase; FBrf0222196]
In addition to cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2 (CAMRQ2; MIM:610185), WDR81 has been identified in several WES analyses of profound neurological syndromes that include hydrocephalus or microcephaly with lissencephaly (Shaheen et al., 2017, pubmed:28556411; Cappuccio et al., 2017, pubmed:28972664).
In the cases identified thus far, autosomal recessive inheritance is observed. [CAMRQ2, MIM:610185, Shaheen et al., 2017, pubmed:28556411; Cappuccio et al., 2017, pubmed:28972664
The WDR81 gene encodes a multi-domain transmembrane protein which is predominantly expressed in the brain and is thought to play a role in endolysosomal trafficking. [Gene Cards, WDR81; 2016.07.02]
One to one: 1 human to 1 Drosophila.
High-scoring ortholog of human WDR81 (1 Drosophila to 1 human). Dmel\CG6734 shares 31% identity and 45% similarity with the human gene.
