This report describes intellectual disability, autosomal recessive 3. The human gene implicated in this diseases is CC2D1A, a transcriptional repressor active in neuronal cells. There is a single orthologous gene in Drosophila, l(2)gd1, for which multiple genetic reagents have been generated, including classical loss-of-function mutations, an RNAi-targeting construct, and alleles caused by insertional mutagenesis. Dmel\l(2)gd1 is also orthologous to the human gene CC2D1B.
UAS constructs of the human Hsap\CC2D1A have been introduced into flies, both wild-type and a variant implicated in this disease. See the 'Disease-Implicated Variants' table below. For the wild-type human gene, partial heterologous rescue (functional complementation) of the l(2)gd1 lethal phenotype has been demonstrated; the disease-implicated variant fails to rescue.
Animals homozygous for loss-of-function mutations for l(2)gd1 typically die in the late larval stage or during the pupal stage; over-proliferation of imaginal discs is observed. Both Hsap\CC2D1A and Hsap\CC2D1B have been tested for ability to rescue the l(2)gd1 lethal phenotype. Hsap\CC2D1B is more effective: one copy of Hsap\CC2D1B results in complete rescue, producing normal adult animals; two copies of Hsap\CC2D1A effect partial rescue, producing normally differentiated flies that fail to eclose (FBrf0230521).
[updated Jun. 2025 by FlyBase; FBrf0222196]
Intellectual disability is characterized by impairments in intellectual functioning and adaptive behavior; symptoms must be present before a child becomes 18 years old (http://medical-dictionary.thefreedictionary.com/mental+retardation; 2016.01.19).
Intellectual disability can be subdivided into syndromic forms, characterized by cognitive impairment accompanied by dysmorphic features, malformations or neurological abnormalities, and nonsyndromic forms, characterized by cognitive impairment without additional features (Basel-Vanagaite, 2008; DOI: 10.1002/9780470015902.a0021454).
[INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 3; MRT3](https://omim.org/entry/608443)
[COILED-COIL AND C2 DOMAINS-CONTAINING PROTEIN 1A; CC2D1A](https://omim.org/entry/610055)
MRT3 is a non-syndromic form of severe intellectual disability with psychomotor developmental delay (Basel-Vanagaite et al, 2003; pubmed:14569116). [from MIM:608443; 2025.06.03]
Autosomal recessive intellectual developmental disorder 3 (MRT3) is caused by homozygous mutation in the CC2D1A gene. [from MIM:608443; 2025.06.03]
CC2D1A encodes a transcription factor that binds specifically to the DRE (dual repressor element) and represses HTR1A gene transcription in neuronal cells.
Many to one: 2 human genes to 1 Drosophila gene.
High-scoring ortholog of human CC2D1A and CC2D1B (1 Drosophila to 2 human).
