LAT is one of nine genes that reside within a 220-kb region of the 16p11.2 locus in which deletions are associated with a highly penetrant form of isolated severe early-onset obesity, as well as obesity with developmental delay (chromosome 16p11.2 deletion syndrome, 220kb; OMIM 613444). Two of the six patients with 200 kb 16p11.2 deletions for which detailed clinical information was available in Bachmann-Gagescu et al., 2010 presented with autism in additional to developmental delay. Lovilgio et al., 2017 demonstrated that overexpression of LAT in zebrafish resulted in reduced cellular proliferation in the brain and microcephaly, whereas suppression of the zebrafish ortholog of LAT resulted in increased cellular proliferation in the brain and macrocephaly. Furthermore, LAT was found to interact genetically with genes within the 600 kb 16p11.2 CNV region (including the ASD candidate gene KCTD13) in co-injected zebrafish embryos to elicit increased microcephaly, mirroring the increased severity of phenotypes observed in human patients with 1.7 Mb 16p11.2 CNVs containing both the 220 kb and the 600 kb loci.
Molecular Function
The protein encoded by this gene is phosphorylated by ZAP-70/Syk protein tyrosine kinases following activation of the T-cell antigen receptor (TCR) signal transduction pathway. This transmembrane protein localizes to lipid rafts and acts as a docking site for SH2 domain-containing proteins. Upon phosphorylation, this protein recruits multiple adaptor proteins and downstream signaling molecules into multimolecular signaling complexes located near the site of TCR engagement.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
The Immune Signaling Adaptor LAT Contributes to the Neuroanatomical Phenotype of 16p11.2 BP2-BP3 CNVs.
Overexpression of LAT induced a reduction of brain proliferating cells and concomitant microcephaly. Suppression of the zebrafish ortholog of LAT induced an increase of proliferation and macrocephaly.
References
Type
Title
Author, Year
Primary
The Immune Signaling Adaptor LAT Contributes to the Neuroanatomical Phenotype of 16p11.2 BP2-BP3 CNVs.
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
LAT and ATP2A1 human transcripts were over-expressed by injection into wildtype zebrafish embryos at the 1- to 2-cell stage.
Allele Type: Overexpression
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source: 28965845
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
LAT and ATXN2L human transcripts were over-expressed by injection into wildtype zebrafish embryos at the 1- to 2-cell stage.
Allele Type: Overexpression
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source: 28965845
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
LAT and CD19 human transcripts were over-expressed by injection into wildtype zebrafish embryos at the 1- to 2-cell stage.
Allele Type: Overexpression
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source: 28965845
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
100pg LAT human transcripts were over-expressed by injection into wildtype zebrafish embryos at the 1- to 2-cell stage.
Allele Type: Overexpression
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source: 28965845
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
150pg LAT human transcripts were over-expressed by injection into wildtype zebrafish embryos at the 1- to 2-cell stage.
Allele Type: Overexpression
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source: 28965845
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
50pg LAT human transcripts were over-expressed by injection into wildtype zebrafish embryos at the 1- to 2-cell stage.
Allele Type: Overexpression
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source: 28965845
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
LAT and MVP human transcripts were over-expressed by injection into wildtype zebrafish embryos at the 1- to 2-cell stage.
Allele Type: Overexpression
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source: 28965845
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
LAT and NFATC2IP human transcripts were over-expressed by injection into wildtype zebrafish embryos at the 1- to 2-cell stage.
Allele Type: Overexpression
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source: 28965845
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
RABEP2 human transcript was over-expressed by injection into wildtype zebrafish embryos at the 1- to 2-cell stage.
Allele Type: Overexpression
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source: 28965845
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
LAT and SH2B1 human transcripts were over-expressed by injection into wildtype zebrafish embryos at the 1- to 2-cell stage.
Allele Type: Overexpression
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source: 28965845
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
LAT and SPNS1 human transcripts were over-expressed by injection into wildtype zebrafish embryos at the 1- to 2-cell stage.
Allele Type: Overexpression
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source: 28965845
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
LAT and TUFM human transcripts were over-expressed by injection into wildtype zebrafish embryos at the 1- to 2-cell stage.
Allele Type: Overexpression
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source: 28965845
Description: Injection of Lat mRNA resulted in a significant decrease in the number of proliferating brain cells compared to controls. The decrease was specific to the cell counts in the brain and not the eyes.
Description: Injection of Lat mRNA resulted in a significant decrease in the number of axon tracks projecting from the optic tecta compared to controls.
