Molecular characteristics

Molecular characteristics
The AP1B1 (Adaptor-Related Protein Complex 1, Beta-1 Subunit) geneis located at 22q12.2 andencodes the large β1 subunit of the adaptor-related protein complex 1 (AP-1), which functions with clathrin in mediating the trafficking of transmembrane proteins from the trans-Golgi network and endosomes to the plasma membrane. Two important copper transporters, ATP7A and ATP7B, depend on AP-1 complex for their trafficking.

Mutations and pathophysiology
Functional studies suggest that deficiency of the β1 of AP-1 complex leads to abnormal trafficking of ATP7A. Homozygous and compound heterozygous pathogenic variants in AP1B1 have been reported to cause KIDAR.

The following are two selected examples of pathogenic variants in AP1B1:

  • Alsaif et al. (2019) reported homozygosity for c.38-1G>A splicing variant in intron 2 of AP1B1 (NM_001127) leading to a premature termination codon (p.Glu14Argfs*5) predicted to cause loss of function. The affected individual is a 4.5-year-old Saudi boy with ichthyosis, erythroderma, palmoplantar hyperkeratosis, deafness, global developmental delay and sparse hair.
  • Boyden et al. (2019) reported a compound heterozygous variant (NM_001127.3: c.430T>C (p.Cys144Arg); c.2335del (p.Leu779Serfs*26)) in a 33-year-old man with congenital ichthyosis, erythroderma, palmoplantar keratoderma, deafness, corneal and scarring.