Alt. symbols: TTC7 | KIAA1140

Approved name: tetratricopeptide repeat domain 7A
Alt. names: tetratricopeptide repeat domain 7

Location: 2p21: 46915869 - 47076137 (+)
Gene type: protein_coding, 22 transcripts.

Scores: LoFtool: 0.832000 | pLI: 0.00000000 | LOEUF: 1.285

HGNC: 19750

NCBI: 57217, RefSeq: NG_034143.2

Ensembl: ENSG00000068724.18

LRG_1323 | Status: public

OMIM: 609332

Expression | ProteinAtlas

This protein is a component of a complex required to bind, shuttle, and tether phosphatidylinositol 4-kinase (PI4K) to the plasma membrane, where PI4K catalyzes the conversion of PI to PI4P. Synthesis of PI4P is an important regulatory step in the phosphatidyl inositol–phosphate (PIP) pathway, which is important for survival and intestinal epithelial cell polarity. TTC7A plays an important role in maintaining intestinal homeostasis (Jardine et al. 2019).

Biallelic mutations leading to TTC7A deficiency cause an autosomal recessive condition known as Gastrointestinal defects and immunodeficiency syndrome (GIDID) [MIM:243150]. To date, more than 50 patients with more than 20 distinct hypomorphic and truncating disease-causing mutations in TTC7A have been reported. Truncating mutations are associated with more severe phenotypes and are predicted to cause a complete loss of protein function. TTC7A deficiency shows heterogeneous intestinal and immunol ogic disease manifestations, including but not limited to multiple intestinal atresias, very early onset inflammatory bowel disease, loss of intestinal architecture, apoptotic enterocolitis, combined immunodeficiency, and various extra-intestinal features related to the skin and/or hair. Loss of TTC7A function in intestinal epithelial cells results in reduced PI4P production, which causes loss of cell polarity and pseudo-stratification, eventually leading to increased cell apoptosis. TTC7A deficiency is also correlated with increased phosphorylation of myosin light chain, which initiates actomyosin contraction and can therefore disturb junction and integrin adhesion proteins and promote cell lifting. Increased intestinal epithelial cell apoptosis, actomyosin contraction, and cell lifting disrupts epithelial barrier function. A weakened intestinal barrier results in the translocation of luminal bacteria into the lamina propria, which can trigger an inflammatory response (Jardine et al. 2019). [Load More]