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FB2026_03
,
released September 17, 2026
This report describes Pitt-Hopkins-like syndrome 1 (PTHSL1), also called cortical dysplasia-focal epilepsy syndrome; PTHSL1 exhibits autosomal recessive inheritance. The human gene implicated in this disease is CNTNAP2 (contactin associated protein like 2), a neuronal transmembrane protein member of the neurexin superfamily involved in neural-glia interactions and clustering of potassium channels in myelinated axons. There is a single high-scoring ortholog in Drosophila, Nrx-IV, for which classical amorphic alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated.
CNTNAP2 is also implicated is susceptibility to autism (AUTS15, MIM:612100). Dmel\Nrx-IV is orthologous to multiple other related genes in human, including CNTNAP1. CNTNAP1 is implicated in several neurological diseases (see MIM:602346).
The human CNTNAP2 gene has not been introduced into flies.
Animals homozygous for loss-of-function mutations of Dmel\Nrx-IV typically die before the embryonic or larval stage. In larvae, neuroanatomy defects and defects of septate junctions are observed. Neuronal overexpression results in increased bouton number in larval neuromuscular junctions. Physical interactions for Dmel\Nrx-IV have been described; see below and in the Nrx-IV gene report.
[updated Apr. 2019 by FlyBase; FBrf0222196]
[PITT-HOPKINS-LIKE SYNDROME 1; PTHSL1](https://omim.org/entry/610042)
[CONTACTIN-ASSOCIATED PROTEIN-LIKE 2; CNTNAP2](https://omim.org/entry/604569)
PTHSL1 is an autosomal recessive neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, severe speech impairment or regression, and behavioral abnormalities. Most patients have onset of seizures within the first years of life. Some patients may have cortical dysplasia on brain imaging (summary by Smogavec et al., 2016; pubmed:27439707). [from MIM:610042; 2019.02.27]
Pitt-Hopkins-like syndrome-1 (PTHSL1) is caused by homozygous or compound heterozygous mutation in the CNTNAP2 gene. [from MIM:610042; 2019.02.27]
The CNTNAP2 gene encodes a neuronal transmembrane protein member of the neurexin superfamily involved in neural-glia interactions and clustering of potassium channels in myelinated axons. [from MIM:604569; 2019.02.27]
Many to one: 6 human to 1 Drosophila. The other human genes are CNTNAP1, CNTNAP3, CNTNAP3B, CNTNAP4, and CNTNAP5.
High-scoring ortholog of human CNTNAP1, CNTNAP2, CNTNAP3, CNTNAP3B, CNTNAP4, and CNTNAP5 (1 Drosophila to 6 human). Dmel\Nrx-IV shares 30-33% identity and 47-51% similarity with the human genes.