Molecular characteristics

Molecular Characteristics
UFC1 (Ubiquitin-Fold Modifier-Conjugating Enzyme 1) encodes for an E2-like enzyme which plays an essential role (along with E1 activating enzymes and E3 ligases) in ufmylation, the post-translational modification of proteins through addition of UFM1. It accepts the ubiquitin-like modifier UFM1 from the E1 enzyme UBA5 and forms an intermediate with UFM1 by thioester linkage. Ufmylation is notably involved in reticulopahgy in response to endoplasmic reticulum stress. The gene has low regional specificity and is expressed in most tissues.

Mutations and pathophysiology
Mutations in UFC1 lead to impaired thioester binding and intermediate formation with UFM1. Dysfunction at one of levels of the ufmylation process (UFC1 mutations, UFM1 mutations, UBA5 mutations) have been shown to lead to neurodevelopmental defects.

Nahorski et al. (2018) reported two homozygous truncating variants in UFC1 (NM_016406.3):
c.317C4T p.(Thr106Ile)) homozygous variant in 7 individuals from 3 Saudi families
c.68G4A:p.(Arg23Gln) in a 4 year-old boy with Swiss ancestry.