SPINK1 (Serine Peptidase Inhibitor, Kazal Type 1)

2014-12-01   Hannu Koistinen , Outi Itkonen , Ulf-Hakan Stenman 

Department of Clinical Chemistry, University of Helsinki (HK,OI, UHS),, Laboratory Division HUSLAB, Helsinki University Central Hospital (OI), Helsinki, Finland hannu.k.koistinen@helsinki.fi; outi.itkonen@hus.fi; ulf-hakan.stenman@helsinki.fi




Review on SPINK1, with data on DNA, on the protein encoded, and where the gene is implicated.



Some other SPINK family members are similar in size, are encoded for by 4 exons and contain a single Kazal type serine protease inhibitor domain.
Atlas Image
Chromosomal location and gene structure of SPINK1 gene (extracted from Ensembl database release 73). Some putative regulatory elements are also shown (Ohmachi et al., 1993; Yasuda et al., 1993; Yasuda et al., 1998; Boulling et al., 2011). After the translation-initiating codon (ATG) exons of the major transcript are shown in black. One splicing variant also contains parts outside of these exons. *, CAATCAATAAC, potential pancreas-specific regulatory element; IL6RE, interleukin-6 responsive element; AP-1, activator protein-1 element; HNF1, hepatic nuclear factor; PTF1, pancreas-specific transcription factor 1.


Maps to chromosomal region 5q32: 147,204,131-147,211,349 on reverse (minus) strand (7,219 bp). Gene consists of 4 exons (Horii et al., 1987). Region between 3.8 and 4.0 kb upstream from the translation initiation codon contains an interleukin-6 responsive element (IL6RE) and two potential AP-1 binding sites (Ohmachi et al., 1993; Yasuda et al., 1993). CAATCAATAAC sequence (-149 to -139) is a potential pancreas-specific regulatory element (Yasuda et al., 1998). This region in the SPINK1 promoter has been subsequently identified as a binding site for hepatic nuclear factor (HNF1) (Boulling et al., 2011). A putative binding site for pancreas-specific transcription factor 1 (PTF1) has also been identified within the SPINK1 promoter (Boulling et al., 2011).


SPINK1 mRNA (NCBI Reference Sequence: NM_003122.3) has 454 bp (Yamamoto et al., 1985). Expression, at least in some cell lines, is regulated by IL-6 (Yasuda et al., 1993). Three differentially spliced mRNA forms have been described (Ensembl, release 73). Two of these have been classified as protein encoding.



In the literature, SPINK1 is widely referred to as TATI (tumor-associated trypsin inhibitor) and PSTI (pancreatic secretory trypsin inhibitor).
Atlas Image
Ribbon diagram of recombinant SPINK1 variant (RSCB Protein Data Bank code 1HPT (Hecht et al., 1991)). Protein Workshop program (Moreland et al., 2005) with the surfaces feature (Xu and Zhang, 2009) was used for visualization. Cysteines, forming three disulfide bonds, are shown as balls and sticks. The atoms of asparagine-34 (N34) residue, mutation in which is associated with chronic pancreatitis, and reactive site lysine (K41) are shown as balls without side-chains. Alpha-helix is shown in blue and beta-sheets in yellow.


SPINK1(NCBI Reference Sequence: NP_003113.2 ; UniProtKB/Swiss-Prot: ISK1_HUMAN, P00995; PDB: 1cgj; 1cgi; 1hpt) is a 6242 Da secreted protein, containing 79 amino acids. Mature SPINK1 contains 56 amino acids and three disulfide bonds. It has a Kazal-type serine protease inhibitor domain and belongs to the SPINK (serine peptidase inhibitor, Kazal-type) family. SPINK1 has been reported to inhibit several proteases, including human trypsin-1 and -2 (cationic and anionic trypsins), acrosin and granzyme A (Pubols et al., 1974; Huhtala et al., 1984; Turpeinen et al., 1988; Tsuzuki et al., 2003).


SPINK1 was first characterized in bovine pancreas (Kazal et al. 1948) and pancreatic juice (Greene 1966), and later from human pancreatic juice (Fritz et al 1967). SPINK1 is mainly expressed in the pancreas, but to a lesser extent also in several other tissues, e.g., in the gastrointestinal tract, including the liver, duodenum, small intestine, gall bladder, colon, appendix, stomach, and in the genitourinary tract, e.g., prostate and urothelium (Paju and Stenman, 2006; Itkonen and Stenman, 2014). Expression has been found also in kidney, lung, breast, brain, spleen and ovary. SPINK1 is often strongly expressed in ETS-rearrangement-negative prostate cancers (Tomlins et al., 2008). A putative bipartite pancreas-specific transcription factor 1 (PTF1)-binding sequence has been identified (Boulling et al., 2011) in the SPINK1 gene. Outside the pancreas, SPINK1 has been considered an inflammatory pleiotropic cytokine, which is regulated by immune and inflammatory responses. In some cell lines, the expression is regulated by IL-6 (Yasuda et al., 1993). In cultured prostate cancer cells, SPINK1 expression has been shown to be regulated by androgens (Paju et al., 2007). In mouse, the synthesis of Spink3 (mouse orthologue of SPINK1) is dependent upon testicular androgens in the sex accessory tissues, but not in the pancreas (Mills et al., 1987). Very high serum and urine concentrations occur in patients with pancreatitis (Ogawa, 1988). Serum levels of SPINK1 may also be elevated in several cancers, including prostate cancer, ovarian cancer and benign cysts, renal-cell carcinoma, bladder carcinoma, and colorectal cancer (Paju and Stenman, 2006; Itkonen and Stenman, 2014). Severe inflammation, tissue destruction and major trauma leads to an acute phase reaction causing increased circulating SPINK1 concentrations.
Atlas Image
Relative mRNA expression levels of SPINK1 in different tissues. The data is from the IST4 database containing gene expression data in ~10 000 samples (http://ist.medisapiens.com/) (Kilpinen et al., 2008).


SPINK1 is highly expressed in the pancreas (Kazal et al., 1948). It has been localized to the zymogen granules of pancreatic acinar cells, where it protects the pancreas from premature activation of trypsinogens. SPINK1 is secreted into the pancreatic fluid along with digestive enzymes. Many cancers secrete SPINK1 causing elevated serum concentrations (Paju and Stenman, 2006; Itkonen and Stenman, 2014).


SPINK1 is a protease inhibitor and has been reported to inhibit human trypsin-1 and -2 (cationic and anionic trypsins), but not trypsin-3 (mesotrypsin)(Sahin-Tóth, 2005). SPINK1 also inhibits granzyme A (Tsuzuki et al., 2003), plasmin, urokinase, tissue plasminogen activator (Turpeinen et al., 1988) and acrosin (Huhtala et al., 1984). SPINK1 has been reported to exert growth stimulation of cultured cells (Niinobu et al., 1990) and to activate the EGF-receptor (Ozaki 2009; Ateeq et al., 2011). However, growth stimulation by mechanisms other than via EGF receptor cannot be ruled out. It has been suggested that SPINK1 mediates tumor growth, differentiation, and angiogenesis via stimulation of the EGF-receptor or by suppression of serine-protease- or caspase-dependent apoptosis (Ateeq et al., 2011; Gouyer et al., 2008). There is evidence that SPINK1 plays a role in tissue differentiation (Ohmuraya et al., 2005) and repair (Marchbank et al., 1996), reproduction (Huhtala, 1984) and regulation of apoptosis (Lu et al., 2011). Over-expression of SPINK1 in cancer could block cancer cell apoptosis resulting in suppression of the immune response and escape of cancer cells from immune surveillance (Lamontagne et al., 2010).


SPINK1 contains a Kazal-type serine protease inhibitor domain, found in many other proteins and especially in members of SPINK family. Apart from this domain, SPINKs do not share high sequence similarity. Apart from SPINK5, SPINKs are of similar size and most genes contain the same number of exons. Some of the family members lack functional annotatation. A functional SPINK1 orthologue, Spink3 (NP_033284.1), has been found in mouse. The rat has two orthologues, Spink1 (NP_690919.1) and Spink3 (NP_036806.1) (HomoloGene, Release 67). Orhologues have been found also in common chimpanzee (XP_001160275.1), rhesus macaque (XP_001102888.1), grey wolf (XP_850557.1) and cattle (NP_001020519.1). Sequence similarity between SPINK1 and EGF has been reported (Hunt et al., 1974).



NCBI SNP database (http://www.ncbi.nlm.nih.gov/SNP/) reports 631 SPINK1 SNPs (Homo sapiens, December 29., 2014). At least 15 missense mutations have been described in the mature polypeptide and three in the signal peptide (Chen and Férec, 2009). Association of mutations with familial pancreatitis and other diseases has been described (see below).

Implicated in

Entity name
Liver cancer
Up-regulation of SPINK1 in tissue has been shown to distinguish hepatocellular carcinoma (HCC) from benign liver disease and normal liver (Marshall A 2013). Elevated serum concentrations of SPINK1 are associated with adverse prognosis of hepatocellular cancer (Lyytinen et al., 2013). Serum SPINK1 is also a useful marker for distinguishing between patients with or without liver metastasis of colorectal and breast cancer (Taccone W 1991; Gaber A 2010).
HCC is the fifth most frequently diagnosed cancer and the second most common cause of cancer death worldwide in men (Jemal et al., 2011). In females the rate is about half of that of men. Half of the cases occur in China and liver cancer is less common in Western countries. HCC is the most common type of liver cancer. It may be caused by viral infections, like hepatitis B and C, or cirrhosis. Most tumors in the liver are not primary liver cancers, but metastases of other cancers.
Plasma SPINK1 concentration is elevated in HCC patients and it correlates with tumor size (Ohmachi et al., 1993). Overexpression of SPINK1 mRNA is a stage-independent prognostic factor and a predictor of early tumor recurrence in HCC (Lee et al., 2007) and in cholangiocarcinoma (Tonouchi et al., 2006). Serum SPINK1 has been shown to predict adverse prognosis in HCC (Lyytinen I 2013).
Entity name
Prostate cancer
SPINK1 is often overexpressed in ETS-rearrangement-negative prostate cancers (Tomlins et al., 2008).
Prostate cancer is a considerable health care problem with 342 000 new cases and about 71 000 deaths annually in the EU countries, it is the most frequently diagnosed cancer in men and the third most common cause of cancer death (data from GLOBOCAN 2008). Prostate cancer can be diagnosed by screening at an early stage, when most patients can be cured by radical prostatectomy or radiotherapy. However, about one third of the tumors relapse. Most of these cases can be treated by androgen ablation, but within 3 - 5 years the tumor usually becomes castration-resistant.
High SPINK1 expression has been associated with adverse prognosis in prostate cancer in some (Tomlins et al., 2008; Paju et al., 2007), but not all studies (Leinonen et al., 2013; Grupp et al., 2013; Lippolis et al., 2013). The differences may be related to the type of treatment, e.g., surgery or androgen ablation (Leinonen et al., 2013).
Entity name
Breast cancer
Breast cancer is the most common cancer among women worldwide, accounting for 23% of all cases (Jemal et al., 2011). Although the prognosis has improved due to early diagnosis and therapies, breast cancer remains a major cause of death among women (14% of the cancer deaths). Most neoplasms of the breast originate from the ductal epithelium, while a minority originates from the lobular epithelium. A family history of breast cancer is associated with a 2-3-fold higher risk of the disease.
SPINK1 expression is associated with poor prognosis in estrogen receptor-positive breast cancer (Soon et al., 2011).
Entity name
Colorectal cancer
Elevated serum SPINK1 has been observed in some patients with colorectal cancer. (Solakidi et al., 2004; Pasanen et al., 1995)
Colorectal cancer is the third most commonly diagnosed cancer in males and the second in females (Jemal et al., 2011). It originates from colon or rectum, but, based on genetic studies, these are the same tumor. When locally confined, colorectal cancer is often curable by surgery.
High expression of SPINK1 has been associated with adverse prognosis and liver metastases (Gaber et al., 2010; Gaber at al., 2009)
Entity name
Bladder cancer
Urinary SPINK1 is a useful marker for high-grade bladder cancer (Kelloniemi et al., 2003; Shariat et al., 2005; Gkialas et al., 2008, Patschan et al., 2012).
Bladder cancer is more common in males than in females and there is great geographic variation in incidence (Jemal et al., 2011). The highest incidence rates are found in Europe, North America and Northern Africa. Smoking, occupational exposures and chronic infection with Schistosoma hematobium are major risk factors. Most bladder cancers originate from the epithelial lining of the urinary bladder. Transitional cell carcinoma is the most common type of bladder cancer.
Serum SPINK1 has been shown to be an independent prognostic factor for bladder cancer (Kelloniemi et al., 2003) and for prediction of the response to chemotherapy (Pectasides et al., 1996). SPINK1 expression is stronger in noninvasive than in invasive tumors and decreases with advancing tumor stage (Hotakainen et al., 2006; Patschan et al., 2012).
Entity name
Ovarian cancer
The association of SPINK1 (TATI) and cancer was first observed in a patients with ovarian cancer (Stenman et al. 1982)
Ovarian cancer is the leading cause of death from gynecologic cancer. Most cases are diagnosed at advanced stages and, thus have relatively poor prognosis. The vast majority of ovarian cancers are epithelial. Cancer of the fallopian tubes is similar to ovarian cancer.
Increased SPINK1 expression is associated with adverse outcome in epithelial ovarian cancer (Huhtala et al., 1983; Paju et al., 2004). Elevated serum SPINK1 is an independent prognostic factor (Venesmaa et al., 1994; Venesmaa et al., 1998; Paju et al., 2004).
Entity name
Gastric cancer
SPINK1 is detected in the normal gastric mucosa.
Gastric cancers account for 8% of all cancer cases and 10% of the deaths (Jamal et al., 2011). Over 70% of new cases and deaths occur in developing countries and rates are higher in males than in females. Helicobacter pylori infection is the main risk factor, but smoking also increases the risk of gastric cancer.
The prognosis of gastric cancer is generally poor and metastases develop frequently. High tissue expression of SPINK1 is a sign of favorable outcome and loss of SPINK1 immunoreactivity in tumor tissue is associated with adverse prognosis (Wiksten et al., 2008). Serum SPINK1 is elevated in 50% of patients with gastric cancer (Solakidi et al., 2004).
Entity name
Renal cell carcinoma
Renal cancer comprises five distinct histological types. Within each type, there is considerable variation in clinical course and survival. Presently, many tumors are detected at an early stage by sonography performed for various reasons.
Prognosis of metastatatic and advanced disease is poor, but surgical treatment of localized disease is often curative. There are no specific serum markers for RCC. Elevated serum SPINK1 has been shown to be an independent prognostic factor in renal cell carcinoma (Meria et al., 1995; Paju et al., 2001).
Entity name
Pancreatitis, hereditary (Online Mendelian Inheritance in Man (OMIM): 167800)
SPINK1 polymorphisms are found more frequently in patients with hereditary and idiopatic chronic pancreatitis (23%) than in healthy controls (0.4%) (Witt et al., 2000; Chen and Férec, 2009). Several mutations of SPINK1 cause loss-of-function by splicing, frameshift, deletion or initiation codon mutation. Some missense mutations have been suggested to affect polypeptide folding, leading to intracellular retention and degradation of the mutated polypeptide (Boulling et al., 2012). These mutations are suggested to cause pancreatitis because of SPINK1 deficiency. The most common mutation worldwide is a 101A>G transition within exon 3 resulting in the substitution of Asp by Ser at codon 34 (N34S) (Witt et al., 2000). The frequency of the N34S mutation in pancreatitis patients is 9-29 % as compared to 0.5-2.5 % in the general population. In functional studies no differences in SPINK1 expression, trypsin inhibitory activity or binding to trypsin have been found between wild-type and N34S-SPINK1. The mutations D50E, Y54H and R67C result in marked reduction or complete loss of SPINK1 secretion, and are classified as disease-causing mutations although trypsin inhibitory activity of the mutated proteins was retained (Király et al., 2007). The P55S mutation of SPINK1 is found in healthy controls as well as in pancreatitis patients with an incidence of 0.5-1.3 % and 0.9-7 %, respectively (Witt et al., 2000; Pfutzer et al., 2000). The role of this mutation in pancreatitis remains unclear.
Elevated serum and urine concentrations are caused by pancreatitis, i.e., inflammation of pancreas. Some hereditary mutations of the SPINK1 gene, increase the risk of pancreatitis. These cases are characterized by recurrent episodes of pancreatitis starting at young age. These episodes often lead to tissue damage and loss of pancreatic function, including insulin production. This also increases the risk of pancreatic cancer.
The life expectancy of the pancreatitis patients is close to normal. However, patients have an increased risk of developing pancreatic cancer (Weiss, 2014).
Entity name
Tropical calcific pancreatitis
SPINK1 mutations, especially the N34S mutation has been reported to associate with tropical calcific pancreatitis (Bhatia et al., 2002).
Tropical calcific pancreatitis (OMIM: 608189) is a special type of chronic pancreatitis that occurs only in tropical countries.
Patients usually present at young age with recurrent abdominal pain and nutritional deficiencies. The disease often leads to beta-cell deficiency and diabetes requiring insulin before the age of 30. Prognosis is dismal and many patients succumb to complications caused by malnutrition.


Pubmed IDLast YearTitleAuthors
213682222011Therapeutic targeting of SPINK1-positive prostate cancer.Ateeq B et al
123604632002Tropical calcific pancreatitis: strong association with SPINK1 trypsin inhibitor mutations.Bhatia E et al
223439812012Functional analysis of eight missense mutations in the SPINK1 gene.Boulling A et al
194532522009Chronic pancreatitis: genetics and pathogenesis.Chen JM et al
42316551967[On protease inhibitors, V. On the chemistry and physiology of the specific trypsin inhibitors from the ox, dog, pig and human pancreas].Fritz H et al
193843002009High expression of tumour-associated trypsin inhibitor correlates with liver metastasis and poor prognosis in colorectal cancer.Gaber A et al
208495962010Increased serum levels of tumour-associated trypsin inhibitor independently predict a poor prognosis in colorectal cancer patients.Gaber A et al
185147702008Evaluation of urine tumor-associated trypsin inhibitor, CYFRA 21-1, and urinary bladder cancer antigen for detection of high-grade bladder carcinoma.Gkialas I et al
59282001966Trypsin inhibitor from bovine pancreatic juice.Greene LJ et al
238431462013SPINK1 expression is tightly linked to 6q15- and 5q21-deleted ERG-fusion negative prostate cancers but unrelated to PSA recurrence.Grupp K et al
18701271991Three-dimensional structure of the complexes between bovine chymotrypsinogen A and two recombinant variants of human pancreatic secretory trypsin inhibitor (Kazal-type).Hecht HJ et al
35012891987Primary structure of human pancreatic secretory trypsin inhibitor (PSTI) gene.Horii A et al
163279842006Differential expression of trypsinogen and tumor-associated trypsin inhibitor (TATI) in bladder cancer.Hotakainen K et al
63840121984Demonstration of a new acrosin inhibitor in human seminal plasma.Huhtala ML et al
61907631983Excretion of a tumor-associated trypsin inhibitor (TATI) in urine of patients with gynecological malignancy.Huhtala ML et al
44295571974Epidermal growth factor: internal duplication and probable relationship to pancreatic secretory trypsin inhibitor.Hunt LT et al
245832262014TATI as a biomarker.Itkonen O et al
212968552011Global cancer statistics.Jemal A et al
188825361948Isolation of a crystalline trypsin inhibitor-anticoagulant protein from pancreas.KAZAL LA et al
128933282003Tumor-associated trypsin inhibitor as a prognostic factor during follow-up of bladder cancer.Kelloniemi E et al
188038402008Systematic bioinformatic analysis of expression levels of 17,330 human genes across 9,783 samples from 175 types of healthy and pathological tissues.Kilpinen S et al
175250912007Missense mutations in pancreatic secretory trypsin inhibitor (SPINK1) cause intracellular retention and degradation.Király O et al
225262742012Do genetic variants in the SPINK1 gene affect the level of serum PSTI?Kume K et al
198643832010Hepatitis B and hepatitis C virus replication upregulates serine protease inhibitor Kazal, resulting in cellular resistance to serine protease-dependent apoptosis.Lamontagne J et al
172672022007Overexpression of tumour-associated trypsin inhibitor (TATI) enhances tumour growth and is associated with portal vein invasion, early recurrence and a stage-independent prognostic factor of hepatocellular carcinoma.Lee YC et al
240839952013Loss of PTEN is associated with aggressive behavior in ERG-positive prostate cancer.Leinonen KA et al
234590952013A high-density tissue microarray from patients with clinically localized prostate cancer reveals ERG and TATI exclusivity in tumor cells.Lippolis G et al
220439412011Role of the inflammatory protein serine protease inhibitor Kazal in preventing cytolytic granule granzyme A-mediated apoptosis.Lu F et al
238891872013Prognostic significance of tumor-associated trypsin inhibitor (TATI) and human chorionic gonadotropin-β (hCGβ) in patients with hepatocellular carcinoma.Lyytinen I et al
87741271996Distribution and expression of pancreatic secretory trypsin inhibitor and its possible role in epithelial restitution.Marchbank T et al
235271992013Global gene expression profiling reveals SPINK1 as a potential hepatocellular carcinoma marker.Marshall A et al
76011861995Tumour-associated trypsin inhibitor and renal cell carcinoma.Meria P et al
34282721987A secretory protease inhibitor requires androgens for its expression in male sex accessory tissues but is expressed constitutively in pancreas.Mills JS et al
156940092005The Molecular Biology Toolkit (MBT): a modular platform for developing molecular visualization applications.Moreland JL et al
21705601990Identification and characterization of receptors specific for human pancreatic secretory trypsin inhibitor.Niinobu T et al
24499861988Pancreatic secretory trypsin inhibitor as an acute phase reactant.Ogawa M et al
82445681993Specific expression of the pancreatic-secretory-trypsin-inhibitor (PSTI) gene in hepatocellular carcinoma.Ohmachi Y et al
160837222005Autophagic cell death of pancreatic acinar cells in serine protease inhibitor Kazal type 3-deficient mice.Ohmuraya M et al
197379652009Serine protease inhibitor Kazal type 1 promotes proliferation of pancreatic cancer cells through the epidermal growth factor receptor.Ozaki N et al
173064432007Increased expression of tumor-associated trypsin inhibitor, TATI, in prostate cancer and in androgen-independent 22Rv1 cells.Paju A et al
111765222001Tumor associated trypsin inhibitor as a prognostic factor in renal cell carcinoma.Paju A et al
165174202006Biochemistry and clinical role of trypsinogens and pancreatic secretory trypsin inhibitor.Paju A et al
152691502004Expression of trypsinogen-1, trypsinogen-2, and tumor-associated trypsin inhibitor in ovarian cancer: prognostic study on tissue and serum.Paju A et al
76676041995Tumour-associated trypsin inhibitor (TATI) in patients with colorectal cancer: a comparison with CEA, CA 50 and CA 242.Pasanen P et al
217391202012Association of tumor-associated trypsin inhibitor (TATI) expression with molecular markers, pathologic features and clinical outcomes of urothelial carcinoma of the urinary bladder.Patschan O et al
109827532000SPINK1/PSTI polymorphisms act as disease modifiers in familial and idiopathic chronic pancreatitis.Pfützer RH et al
48188321974Trypsin inhibitor from human pancreas and pancreatic juice.Pubols MH et al
160291582005Human mesotrypsin defies natural trypsin inhibitors: from passive resistance to active destruction.Sahin-Tóth M et al
159636282005Urinary levels of tumor-associated trypsin inhibitor (TATI) in the detection of transitional cell carcinoma of the urinary bladder.Shariat SF et al
146755632004Tumour-associated trypsin inhibitor, carcinoembryonic antigen and acute-phase reactant proteins CRP and alpha1-antitrypsin in patients with gastrointestinal malignancies.Solakidi S et al
216566872011Combined genomic and phenotype screening reveals secretory factor SPINK1 as an invasion and survival factor associated with patient prognosis in breast cancer.Soon WW et al
32029761988Characterization of a tumor-associated serine protease.Stenman UH et al
17806861991Evaluation of TATI and other markers in solid tumors.Taccone W et al
185387352008The role of SPINK1 in ETS rearrangement-negative prostate cancers.Tomlins SA et al
168635672006Relationship between pancreatic secretory trypsin inhibitor and early recurrence of intrahepatic cholangiocarcinoma following surgical resection.Tonouchi A et al
125906502003Purification and identification of a binding protein for pancreatic secretory trypsin inhibitor: a novel role of the inhibitor as an anti-granzyme A.Tsuzuki S et al
24617021988Reaction of a tumour-associated trypsin inhibitor with serine proteinases associated with coagulation and tumour invasion.Turpeinen U et al
96371191998Pre-operative serum level of tumour-associated trypsin inhibitor and residual tumour size as prognostic indicators in Stage III epithelial ovarian cancer.Venesmaa P et al
246004092014Pancreatic cancer risk in hereditary pancreatitis.Weiss FU et al
187514072008Comparison of the prognostic value of a panel of tissue tumor markers and established clinicopathological factors in patients with gastric cancer.Wiksten JP et al
108356402000Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis.Witt H et al
199565772009Generating triangulated macromolecular surfaces by Euclidean Distance Transform.Xu D et al
38775081985Molecular cloning and nucleotide sequence of human pancreatic secretory trypsin inhibitor (PSTI) cDNA.Yamamoto T et al
76916871993Identification of the IL-6-responsive element in an acute-phase-responsive human pancreatic secretory trypsin inhibitor-encoding gene.Yasuda T et al
98521081998Identification of novel pancreas-specific regulatory sequences in the promoter region of human pancreatic secretory trypsin inhibitor gene.Yasuda T et al

Other Information

Locus ID:

NCBI: 6690
MIM: 167790
HGNC: 11244
Ensembl: ENSG00000164266


dbSNP: 6690
ClinVar: 6690
TCGA: ENSG00000164266


Gene IDTranscript IDUniprot

Expression (GTEx)


Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
193723762009Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans.299
185387352008The role of SPINK1 in ETS rearrangement-negative prostate cancers.108
213682222011Therapeutic targeting of SPINK1-positive prostate cancer.54
224272362013CFTR, SPINK1, CTRC and PRSS1 variants in chronic pancreatitis: is the role of mutated CFTR overestimated?53
204423002010Association of SPINK1 expression and TMPRSS2:ERG fusion with prognosis in endocrine-treated prostate cancer.44
209779042011Combined bicarbonate conductance-impairing variants in CFTR and SPINK1 variants are associated with chronic pancreatitis in patients without cystic fibrosis.41
209779042011Combined bicarbonate conductance-impairing variants in CFTR and SPINK1 variants are associated with chronic pancreatitis in patients without cystic fibrosis.41
119508152002The N34S mutation of SPINK1 (PSTI) is associated with a familial pattern of idiopathic chronic pancreatitis but does not cause the disease.38
119508152002The N34S mutation of SPINK1 (PSTI) is associated with a familial pattern of idiopathic chronic pancreatitis but does not cause the disease.38
184146732008Pathways to injury in chronic pancreatitis: decoding the role of the high-risk SPINK1 N34S haplotype using meta-analysis.37


Hannu Koistinen ; Outi Itkonen ; Ulf-Hakan Stenman

SPINK1 (Serine Peptidase Inhibitor, Kazal Type 1)

Atlas Genet Cytogenet Oncol Haematol. 2014-12-01

Online version: http://atlasgeneticsoncology.org/gene/42375/spink1-(serine-peptidase-inhibitor-kazal-type-1)