This report describes microcephaly, epilepsy, and diabetes syndrome 1. The human gene implicated is IER3IP1, which encodes immediate early response 3 interacting protein 1. There is one high-scoring fly ortholog, Dmel\Insep, for which multiple genetic reagents, including classical alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
Multiple UAS constructs of the human Hsap\IER3IP1 gene have been introduced into flies, including wild-type IER3IP1 and genes carrying mutational lesions implicated in MEDS1. See the 'Disease-Implicated Variants' table below. Functional complementation (heterologous rescue) of null mutations in Dmel\Insep by expression of the human construct has been demonstrated.
Pan-neuronal RNAi knockdown of Dmel\Insep results in developmental delay and larval lethality with a small brain phenotype. Flies bearing a null allele or a conditional knockout of Dmel\Insep exhibit similar phenotypes. Ubiquitous expression of wild-type Insep or of Hsap\IER3IP1 rescues these phenotypes, while expression of mutant Hsap\IER3IP1 does not. Neuroblasts in larvae mutant for Dmel\Insep fail to complete cytokinesis.
[updated Aug. 2026 by FlyBase; FBrf0222196]
[MICROCEPHALY, EPILEPSY, AND DIABETES SYNDROME 1; MEDS1](https://omim.org/entry/614231)
[IMMEDIATE-EARLY RESPONSE 3-INTERACTING PROTEIN 1; IER3IP1](https://omim.org/entry/609382)
Microcephaly, epilepsy, and diabetes syndrome-1 (MEDS1) is an autosomal recessive neurodevelopmental disorder characterized by microcephaly, simplified gyral pattern, severe epilepsy, and infantile diabetes (summary by Poulton et al., 2011, pubmed:21835305). [from MIM:614231; 2026.08.07]
Microcephaly, epilepsy, and diabetes syndrome-1 (MEDS1) is caused by homozygous or compound heterozygous mutation in the IER3IP1 gene on chromosome 18q21. [from MIM:614231; 2026.08.07]
IER3IP1 encodes an endoplasmic reticulum membrane protein that is localized to the endoplasmic reticulum and cytoplasmic vesicles. It is named for its interaction with immediate early response 3 and is linked to negative regulation of apoptotic process and negative regulation of cell population proliferation (GeneCards).
One to one (1 human to 1 Drosophila); IER3IP1 has one high-scoring Drosophila ortholog, Insep.
High-scoring ortholog of human IER3IP1 (1 Drosophila to 1 human).
