This report describes neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities, a neurological disorder that exhibits autosomal recessive inheritance. The human gene implicated is GEMIN4, which encodes gem nuclear organelle associated protein 4, a component of the SMN complex.
There is no predicted fly ortholog of GEMIN4, however Dmel\Glos has been proposed as a structural ortholog (FBrf237151). Several RNAi-targeting constructs have been generated for Dmel\Glos.
Human GEMIN4 has not been introduced into flies.
Mifepristone-induced ubiquitous RNAi knockdown of Dmel\Glos at larval stages results in complete pupal lethality. Affected larvae also exhibit neuromuscular junction morphology defects, with a significant decrease in the number of mature synaptic boutons, and an increase in satellite boutons. Mifepristone-induced ubiquitous RNAi knockdown of Dmel\Glos at adult stages results in a decreased lifespan and decreased climbing ability.
[updated July 2024 by FlyBase; FBrf0222196]
[NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, CATARACTS, AND RENAL ABNORMALITIES; NEDMCR](https://omim.org/entry/617913)
[GEM NUCLEAR ORGANELLE-ASSOCIATED PROTEIN 4; GEMIN4](https://omim.org/entry/606969)
Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities (NEDMCR) is an autosomal recessive neurodevelopmental disorder characterized by global developmental delay, microcephaly, congenital cataracts, brain abnormalities, and renal abnormalities (Alazami et al., 2015, pubmed:25558065). [from MIM:617913; 2024.07.05]
NEDMCR is caused by homozygous mutation in the GEMIN4 gene on chromosome 17p13. [from MIM:617913; 2024.07.05]
The GEMIN4 gene encodes a protein that is part of a large complex localized to the cytoplasm, nucleoli, and to discrete nuclear bodies called Gemini bodies (gems). The complex functions in spliceosomal snRNP assembly in the cytoplasm, and regenerates spliceosomes required for pre-mRNA splicing in the nucleus. The encoded protein directly interacts with a DEAD box protein and several spliceosome core proteins. [provided by RefSeq, Jul 2008]
GEMIN4 is part of a high molecular mass multiprotein complex that also contains SMN, GEMIN2, and GEMIN3. In the cytoplasm, this complex is associated with small nuclear ribonucleoproteins (snRNPs) (Charroux et al., 2000. pubmed:10725331). [from MIM:606969; 2024.07.05]
Based on conserved secondary structure, the human gene GEMIN4 appears to be orthologous to Dmel\Glos (FBrf237151).
Dmel\Glos has been proposed as a putative ortholog to human GEMIN4; structural prediction reveals a high degree of overlap between Dmel\Glos and human Gemin4 sequences throughout the entire length of the protein. Further, Glos protein coimmuopreciptates with the Drosophila SMN complex. However, no orthology prediction algorithms identify Dmel\Glos as an ortholog of human GEMIN4 (see DIOPT, below).
