Adaptor-Related Protein Complex 3, Beta-2 Subunit

Alternative Names

  • AP3B2
  • Adaptor-Related Protein Complex 3B, Neuron-Specific, Beta-3B
  • AP3B, Beta-3B
  • Neuronal Adaptin-Like Protein, Beta Subunit
  • NAPTB
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OMIM Number

602166

Gene Map Locus
15q25.2

Description

The AP3B2 gene encodes a neuron-specific subunit of the heterotetrameric Adaptor protein-3 (AP3) vesicle-coat protein complex. The complex is required for intracellular protein transport, particularly post-Golgi vesicle-mediated transport and anterograde synaptic vesicle transport. It has been found that the interaction of neuronal AP3 with vesicles regulates vesicle neurotransmitter content. 

The gene is associated with Epileptic Encephalopathy, Early Infantile, 48 (EIEE48), a severe neurologic disorder characterized by intellectual disability, global developmental delay, seizures, microcephaly and absent speech. 

Molecular Genetics

The AP3B2 gene is located on the long arm of chromosome 15 at position 15q25.2. The gene spans a length of 50.6 kb of DNA and its coding sequence is spread across 28 exons. The protein product encoded by AP3B2 has a molecular mass of 119 kDa and is made up of 1082 amino acids. Alternative splicing results in multiple transcript variants that encode different isoforms of the AP3B2 protein. Expression of this gene is specific to the nervous system and is seen in Purkinje cells, cortical neurons, neuroectodermal tumors and cerebral cortex. Homozygous or compound heterozygous mutations in the AP3B2 gene are associated with EIEE48. These include splice site, nonsense and frameshift mutations that generally have a loss-of-function effect of the AP3B2 enzyme.

Epidemiology in the Arab World

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Other Reports

Saudi Arabia

Anazi et al. (2016) reported a higher diagnostic yield for genomic testing in Intellectual Disability (ID) cases compared to standard clinical evaluations. The authors carried out exome sequencing to uncover mutations in the AP3B2 gene of two consanguineous families. In the first family, a nine year old girl and her 2.5 year old brother carried a homozygous c.1837del (p.Glu613Serfs*182) mutation. The patients suffered from global developmental delay, seizures and white matter changes. In the second family, a 15-month-old girl was found to have the same mutation. She suffered from global developmental delay, seizures, mild Dandy-Walker malformation, gastro-eosophageal reflux, microcephaly, hypotonia, hyporeflexia, and type 1 diabetes. In both families, positional mapping established a single locus spanning AP3B2. It was also noted that Ap3b2 knockout mice exhibit marked neurobehavioral abnormalities and epilepsy. Furthermore, the mutation was a loss-of function variant, had a minor allele frequency <0.001 based on 1500 Saudi exomes, fully segregated with the phenotype and there were no other candidate variants.   

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