The role of HCFC1 in syndromic and non-syndromic intellectual disability

Abstract

Mutations in the HCFC1 gene are associated with cases of syndromic (cblX) and non-syndromic intellectual disability. Syndromic individuals present with severe neurological defects including intractable epilepsy, facial dysmorphia, and intellectual disability. Non-syndromic individuals have also been described and implicate a role for HCFC1 during brain development. The penetrance of phenotypes and the presence of an overall syndrome is associated with the location of the mutation within the HCFC1 protein. Thus, one could hypothesize that the positioning of HCFC1 mutations lead to different neurological phenotypes that include but are not restricted to intellectual disability. The HCFC1 protein is comprised of multiple domains that function in cellular proliferation/metabolism. Several reports of HCFC1 disease variants have been identified, but a comprehensive review of each variant and its associated phenotypes has not yet been compiled. Here we perform a detailed review of HCFC1 function, model systems, variant location, and accompanying phenotypes to highlight current knowledge and the future status of the field.

LPCAT1 enhances the invasion and migration in gastric cancer: Based on computational biology methods and in vitro experiments

“…RBBP5 encodes a ubiquitously expressed nuclear protein which belongs to a highly conserved subfamily of WD‐repeat proteins, and it leads a progression in multiple malignancies especially in prostate cancer 46,47 . HCFC1 is a member of the host cell factor family, and it is also active in many diseases and exerts its transcriptional regulatory role 48,49 . For the first time, we found that RBBP5 and HCFC1 can boost the expression of LPCAT1 to accelerate tumor progression in GC.…”

Missense and nonsense mutations of the zebrafishhcfc1agene result in contrasting mTor and radial glial phenotypes

“…We do not fully understand how individual mutations can cause such different overall disorders. Literature has suggested that location of each mutation in the protein may play a significant role (Castro and Quintana, 2020) However, our results suggest that this is much more complex than the location of the mutation because we studied two different types of mutations in the same exon and protein domain each with contrasting phenotypes. Thus, suggesting that subtypes of cblX may exist with different mTor signatures.…”

Neurodevelopmental defects in a mouse model of O-GlcNAc transferase intellectual disability

“…OGT is composed of a catalytic domain and an N-terminal tetratricopeptide repeat (TPR) domain consisting of 13.5 TPRs that is responsible for substrate binding and protein-protein interactions ( Hart et al, 2011 ). In addition to installing O- GlcNAc on proteins, OGT is involved in the proteolytic processing and activation of host cell factor 1 (HCF1) ( Capotosti et al, 2011 ), which is encoded by a known ID gene ( Castro and Quintana, 2020 ), and possesses non-catalytic functions implicated in cellular proliferation ( Levinea et al, 2021 ). To date, 17 OGT-CDG missense variants have been reported in OGT , with missense and exon-skipping variants in the TPR and catalytic domains giving rise to similar clinical features.…”