TTC7A

Tetratricopeptide repeat domain 7A (TTC7A) is a protein that in humans is encoded by the TTC7A gene.^[5]

TTC7A
Identifiers
Aliases	TTC7A, MINAT, TTC7, GIDID, tetratricopeptide repeat domain 7A
External IDs	OMIM: 609332; MGI: 1920999; HomoloGene: 12515; GeneCards: TTC7A; OMA:TTC7A - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2p21 Start 46,916,157 bp[1] End 47,076,137 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 E4 Start 87,590,314 bp[2] End 87,689,197 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sperm right testis left testis tendon of biceps brachii monocyte granulocyte thymus pancreatic ductal cell left adrenal cortex right adrenal gland Top expressed in granulocyte lip otolith organ lumbar spinal ganglion utricle mesenteric lymph nodes duodenum jejunum right kidney spermatid More reference expression data BioGPS n/a
Orthologs Species Human Mouse Entrez 57217 225049 Ensembl ENSG00000068724 ENSMUSG00000036918 UniProt Q9ULT0 Q8BGB2 RefSeq (mRNA) NM_001288951 NM_001288953 NM_001288955 NM_020458 NM_028639 RefSeq (protein) NP_001275880 NP_001275882 NP_001275884 NP_065191 NP_082915 NP_001391016 NP_001391017 Location (UCSC) Chr 2: 46.92 – 47.08 Mb Chr 17: 87.59 – 87.69 Mb PubMed search [3] [4]
Wikidata
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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 disrupts epithelial cell differentiation and polarization in the intestinal tract, thymus, and lungs. ^[6] TTC7A deficiency is very rare with less than 80 cases described in the literature to date.

Mutations in this gene are known to cause intestinal atresia, severe infantile or very early onset inflammatory bowel disease, extensive enteropathy, combined immunodeficiencies, thyroid dysfunction, alopecia, and lung disease. ^{[7][8][9][10][11][12][13]}

There is a broad spectrum of severity and variety of symptoms, although quality of life is generally very poor for these children with few surviving beyond the first year or two of life. ^[14]

Treatment

There is no standard treatment for TTC7A Deficiency at this time. Management of TTC7A deficiency currently entails bowel resection for any atresias, hematopoietic stem cell transplantation to correct the immunodeficiencies and immunosuppression to help alleviate bowel disease and immune disregulation. However, Hematopoietic stem cell transplantation is ineffective for resolving the intestinal disease ^[15] Small bowel transplant has proven successful in at least one case.^[16]

Rho Kinase Inhibitors

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."^[17] 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.^[18] Therefore, statins may be helpful for the treatment of TTC7A deficiency, although this has yet to be proven.

Recent research suggests that rho kinase inhibitors may be ineffective in treating TTC7A Deficiency. ^[19]

Leflunomide As Potential Treatment

Recent research shows that Leflunomide reduces intestinal tract narrowing, restores gut motility, and increases intestinal cell survival in Zebrafish with TTC7A Deficiency. The researchers concluded that Leflunomide "might be repurposed for treatment of TTC7A deficiency."^[20]