Recombinant Human Chymotrypsin-C (CTRC)

1. CTRC variants, including p.Gly60Gly (c.180C>T) variant are significant chronic pancreatitis risk factors in pediatric patients. Screening for CTRC variants should be always considered in routine molecular diagnostics in early onset chronic pancreatitis. PMID: 28968289
2. Our preliminary results show that the CTRC polymorphism p.G60= (c.180C>T) is frequent in patients with pancreatic cancer. However, further research is needed to verify our findings. PMID: 29154238
3. Gene mutations were present in PRSS1 in 26 patients with acute recurrent and chronic pancreatitis, SPINK1 in 23, CTRC in 3, and CPA1 in 5. In the 31 patients with mutations in SPINK1, CTRC, or CPA1, 16 (51.6%) had homozygous or heterozygous mutations with other mutations. PMID: 27409067
4. Early-onset pancreatitis is associated strongly with PRSS1 or CTRC mutations and family history of pancreatitis. PMID: 28502372
5. CTRC polymorphism increases the risk of an acute pancreatitis occurrence and together with the SPINK 1 mutation, may be responsible for a more severe course of the disease. PMID: 28095786
6. One patient carried a heterozygous CTRC p.P249L pathogenic variant, which is a known high-risk variant for pancreatitis. PMID: 27578509
7. Human anionic trypsinogen is controlled by CTRC in a manner that individual natural mutations are unlikely to increase stability enough to promote intra-pancreatic activation. PMID: 27129265
8. Letter: CTRC intron mutations associated with acute or chronic pancreatitis. PMID: 26166474
9. In Israel, pediatric as well as adult recurrent acute pancreatitis and chronic pancreatitis are often associated with cationic trypsinogen, serine protease inhibitor Kazal type 1, CTRC, or Cystic Fibrosis Transmembrane Conductance Regulator mutations. PMID: 25383785
10. Mutations in SPINK 1, CFTR and CTRC were detected in 6.3%, 2.3% and 1.8% of patients with acute pancreatitis versus 3.2%, 3.8% and 1.2% of controls. No relationship was found between the detected mutations and severity of pancreatitis. PMID: 26100556
11. Loss-of-function mutations in CTRC increase the risk for chronic pancreatitis. Describe functional analysis of eight previously uncharacterized natural CTRC variants tested for potential defects in secretion, proteolytic stability, and catalytic activity. PMID: 26013824
12. Expression of endoplasmic reticulum stress associated CTRC mutants reduces the levels of acetylated tubulin by increasing both the levels and phosphorylation of the deacetylase SIRT2. PMID: 26022124
13. None of the selected 121 pancreatic cancer samples showed a pancreatitis-predisposing mutation in the CTRC gene. PMID: 25003218
14. Rare CTRC genotypes contributed to the development of idiopathic chronic pancreatitis in 4.3% of cases. PMID: 23951356
15. Chymotrypsin C variants reveals distinct loss-of-function mechanisms associated with chronic pancreatitis risk. PMID: 22942235
16. This study on a large cohort of tropical calcific pancreatitis patients provides evidence of allelic heterogeneity and confirms that CTRC variants play a significant role in its pathogenesis. PMID: 22580415
17. long-range electrostatic attraction toward substrates of concentrated negative charge governs substrate discrimination, which explains CTRC selectivity in regulating active digestive enzyme levels PMID: 23430245
18. Frequencies of CFTR variants p.R75Q, p.I148T, 5T-allele and p.E528E were comparable in patients and controls. We identified 103 CFTR variants, which represents a 2.7-fold risk increase (p<0.0001). PMID: 22427236
19. In Japanese, 5 novel missense variants in heterozygous form were found in CTRC. PMID: 23135764
20. hereditary pancreatitis is caused by CTRC-dependent dysregulation of cationic trypsinogen autoactivation, which results in elevated trypsin levels in the pancreas. PMID: 22539344
21. Review: summarize the functional defects associated with CTRC mutations in chronic pancreatitis. PMID: 21631589
22. speculated that chymotrypsin C might regulate pancreatic cancer cell migration in relation to cytokeratin 18 expression PMID: 21460362
23. CTRC (p.R254W) mutation might contribute to the panel of mutations that have been reported to elevate pancreatitis susceptibility in primary hyperparathyroidism. PMID: 20625975
24. review of its association with chronic pancreatitis in the Asia Pacific region PMID: 21323990
25. Chymotrypsin C is a co-activator of human pancreatic procarboxypeptidases A1 and A2. PMID: 21098023
26. The contribution of CTRC variants to tropical calcific pancreatitis (TCP) is relatively small, but the identification of novel loss-of-function variants (p.G61R) underscores the importance of the trypsinogen pathway in causing TCP. PMID: 19404200
27. A key regulator of activation and degradation of cationic trypsin; facilitates trypsinogen activation in the duodenum, and promotes trypsin degradation in the lower intestines as a function of decreasing luminal calcium ion concentrations. PMID: 17592142
28. Study analyzed the gene encoding the trypsin-degrading enzyme chymotrypsin C in German subjects with idiopathic or hereditary chronic pancreatitis; 2 alterations in this gene were significantly overrepresented in the pancreatitis group. PMID: 18059268
29. Novel CTRC gene variations and single nucleotide polymorphisms are associated with chymotrypsin C in a Chinese population. PMID: 19407484

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HGNC: 2523

OMIM: 167800

KEGG: hsa:11330

STRING: 9606.ENSP00000365116

UniGene: Hs.631869