HERC1

Molecular characteristics

The HERC1 gene encodes the Hect Domain and RCC1-like Domain 1 protein that acts as an E3-ubiquitine ligase targeting proteins for degradation and plays a putative role in intracellular membrane trafficking. HERC1 is expressed ubiquitously in all human tissues examined, with highest levels in brain and testis. Mutations in HERC1 cause syndromic intellectual disability, most likely due to the decreased production as well as loss of function of the aberrant protein.

Genetic testing
Mutations in HERC1 can be identified using molecular genetic testing, either directly by targeted sequencing of the HERC1 gene or by exome/genome sequencing.

Molecular characteristics
So far, three homozygous loss of functions variants (nonsense, frameshift and splice-site) and a compound heterozygous variant (one is nonsense and another one is missense) of HERC1 have been reported in the scientific literature. All these mutations are presumed to result in loss of function of the protein.