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SPINK1

Friday 14 November 2003

WKP

Definition: SPINK1 codes for a trypsin inhibitor. Pancreatic secretory trypsin inhibitor (PSTI) also known as serine protease inhibitor Kazal-type 1 (SPINK1) or tumor-associated trypsin inhibitor (TATI) is a protein that in humans is encoded by the SPINK1 gene.

Mutations in SPINK1 has been associated with hereditary pancreatitis.

Trypsinogen is normally created and stored an inactive zymogen of trypsin in the pancreas, but occasionally will autoactivate itself. PSTI serves to cleave prematurely activated trypsin to prevent the enzyme from causing cellular damage to the organ. Without the function of PSTI, the pancreas is subject to repeated episodes of damage.

It has also been associated with prostate cancer.

The endogenous pancreatic trypsin inhibitor, SPINK, is believed to limit enzyme activity in the pancreas and reduce the risk of pancreatitis.

Pathology

- Mutations in the SPINK1 gene

  • Mutations in the SPINK1 gene have been associated with development of both acute and chronic pancreatitis.
  • In most patients with SPINK1 mutations, the genetic variants do not cause the disease independently, but may act in concert with other genetic or environmental factors.
  • Recent studies, using mice in which the trypsin inhibitor gene has been deleted or overexpressed, provide novel insights into the role of SPINK in pancreatic development and pancreatitis.

- SPINK1 variants

- Loss of SPINK1 expression is associated with unfavorable outcomes in urothelial carcinoma of the bladder after radical cystectomy. (22944196)

See also

- SPINKs

Paywall References

- Liddle RA. Pathophysiology of SPINK mutations in pancreatic development and disease. Endocrinol Metab Clin North Am. 2006 Jun;35(2):345-56, x. PMID: 16632097