- Tools
- Downloads
- Links
- Community
- About
- Help
FB2026_01
,
released March 12, 2026
This report describes Kleefstra syndrome 2 (KLEFS2), which is a subtype of Kleefstra syndrome; KLEFS2 exhibits an autosomal dominant pattern of inheritance. The human gene implicated in this disease is KMT2C, a lysine-specific histone methyltransferase. There are two orthologous genes in Drosophila, trr and Lpt, for which classical loss-of-function alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated. Of the two fly genes, Dmel\trr is more closely related to KMT2C; there is also a second orthologous gene in human, KMT2D.
The human KMT2C gene has not been introduced into flies. Missense mutations of KMT2C have been implicated in autism and/or intellectual disability, without other phenotypes of KLEFS2 (see ClinVar, https://www.ncbi.nlm.nih.gov/clinvar/?term=KMT2C%5Bgene%5D).
Animals homozygous for an amorphic mutation of Dmel\trr die during the embryonic stages. RNAi-mediated knockdown of trr in the mushroom body of the adult brain results in a defect in short-term memory. Dmel\trr and Dmel\Lpt have been observed to interact genetically and physically; they also share multiple interacting partners. Additional genetic and physical interactions have been described for both genes; see below and in the trr and Lpt gene reports.
[updated Apr. 2021 by FlyBase; FBrf0222196]
Kleefstra syndrome is characterized by developmental delay and variable intellectual disability, with other symptoms characteristic of the specific subtype.
[KLEEFSTRA SYNDROME 2; KLEFS2](https://omim.org/entry/617768)
[LYSINE-SPECIFIC METHYLTRANSFERASE 2C; KMT2C](https://omim.org/entry/606833)
Clinical phenotypes observed in common are intellectual disability, ranging from mild to severe; language and motor delay; and autism or Pervasive Developmental Disorder (PDD), a condition in the autistic spectrum. Additional recurrent clinical features are short stature, microcephaly, childhood hypotonia, kyphosis/scoliosis and recurrent respiratory infections. Kleefstra-like facial dysmorphisms, including flattened midface, prominent eyebrows, everted lower lip, and thick ear helices, were observed in several individuals. (Koemans et al., 2017; pubmed:29069077)
Kleefstra syndrome 2 is an autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development, variable intellectual disability, and mild dysmorphic features. (summary by Koemans et al., 2017; pubmed:29069077). [from MIM:617768; 2018.02.02]
Kleefstra syndrome-2 (KLEFS2) is caused by heterozygous mutation in the KMT2C gene. [from MIM:617768; 2018.02.02]
The lysine-specific methyltransferase 2C (KMT2C) gene encodes a histone methyltransferase that regulates gene transcription by modifying chromatin structure. KMT2C mediates mono- and tri-methylation of histone H3 at lysine 4 (H3K4me1 and H3K4me3) (summary by Koemans et al., 2017; pubmed:29069077). [from MIM:606833; 2018.02.02]
Many to many: 2 human to 2 Drosophila; the second human gene is KMT2D.
Moderate-scoring ortholog of human KMT2C and KMT2D (2 Drosophila to 2 human); Dmel\trr shares 25-26% identity and 38% similarity with the human genes; 52-54% identity and 69% similarity within the conserved carboxy terminal regions.