Species Human Entrez 57217 | Human Mouse Ensembl ENSG00000068724 | |
Aliases TTC7A, MINAT, TTC7, GIDID, tetratricopeptide repeat domain 7A External IDs MGI: 1920999 HomoloGene: 12515 GeneCards: TTC7A | ||
Tetratricopeptide repeat domain 7A (TTC7A) is a protein that in humans is encoded by the TTC7A gene.
Contents
Function
TPR domain-containing proteins, such as TTC7A, have diverse functions in cell cycle control, protein transport, phosphate turnover, and protein trafficking or secretion, and they can act as chaperones or scaffolding proteins.
Clinical significance
TTC7A deficiency is extremely rare with less than 30 cases reported to date. TTC7A deficiency disrupts epithelial intestinal cell growth thereby promoting multiple intestinal atresia (MIA), a rare type of bowel obstruction. Not all patients with TTC7A Deficiency exhibit the same symptoms. Although quality of life is generally very poor for most children with very few surviving beyond the first year or two of life, there is a broad spectrum of severity of symptoms varying from individual to individual with some forms of TTC7A Deficiency being less severe with survival being many years or even decades.
Mutations in this gene are known to cause hereditary multiple intestinal atresia (MIA), severe infantile or very early onset inflammatory bowel disease, extensive enteropathy, combined immunodeficiencies (CID), thyroid dysfunction, and alopecia. Some TTC7A Deficiency patients have also been shown to develop lung disease
There is no standard treatment for TTC7A Deficiency at this time. Management of TTC7A deficiency currently entails bowel resection for any atresias, possibly hematopoietic stem cell transplantation to correct the immunodeficiencies, and immunosuppression to help alleviate bowel disease and immune disregulation. Hematopoietic stem cell transplantation may be ineffective.Small bowel transplant has proven successful in at least one case.
Research indicates that TTC7A deficiency results in "increased Rho kinase activity which disrupts polarity, growth, and differentiation of intestinal epithelial cells, and which impairs immune cell homeostasis, thereby promoting MIA-CID development." Based on this research, it has been proposed that Rho kinase inhibitors may be a therapeutic option, although no specific rho kinase inhibitors are currently available for patient use with the exception of Fasudil which is only available in Japan. It has been shown that statins such as Lipitor are useful as Rho kinase inhibitors. Therefore, statins may be helpful for the treatment of TTC7A deficiency, although this has yet to be proven.