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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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SPINK1
serine peptidase inhibitor Kazal type 1
Chromosome 5 Β· 5q32
NCBI Gene: 6690Ensembl: ENSG00000164266.11HGNC: HGNC:11244UniProt: P00995
261PubMed Papers
22Diseases
0Drugs
15Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingextracellular exosomeendopeptidase inhibitor activityGO:0005615chronic pancreatitishereditary chronic pancreatitisacute pancreatitispancreas disease
✦AI Summary

SPINK1 is a serine protease inhibitor with dual roles in normal physiology and disease. In pancreatic tissue, SPINK1 functions as pancreatic secretory trypsin inhibitor, protecting the pancreas by inhibiting prematurely activated trypsin 1. SPINK1 is synthesized primarily in pancreatic acinar cells and acts as an acute-phase reactant 2. SPINK1 is implicated in multiple diseases. Genetic variantsβ€”including c.-4141G > T, c.194 + 2T > C, and Alu insertionsβ€”are causative of chr5 pancreatitis, with common CFTR haplotypes modulating disease susceptibility in SPINK1 mutation carriers 13. SPINK1 mutations represent likely etiological factors in tropical calcific pancreatitis, prevalent in southern India 4. Beyond pancreatic disease, SPINK1 demonstrates oncogenic functions across multiple cancers. SPINK1 is a molecular subtype classifier in prostate cancer 5. In hepatocellular carcinoma, SPINK1 overexpression drives tumor dedifferentiation and chemoresistance via EGFR-ERK-CDK4/6-E2F2 signaling, with SPINK1 depletion dampening cancer growth 6. SPINK1 acts as a growth factor and apoptosis inhibitor, with elevated serum SPINK1 predicting aggressive disease and serving as a prognostic biomarker 2. Diffuse SPINK1 expression distinguishes oxyntic gland neoplasms from normal tissue 7, and SPINK1 variants may increase pancreatic ductal adenocarcinoma risk 1.

Sources cited
1
In pancreatic tissue, SPINK1 functions as pancreatic secretory trypsin inhibitor, protecting the pancreas by inhibiting prematurely activated trypsin .
PMID: 40140953
2
SPINK1 is synthesized primarily in pancreatic acinar cells and acts as an acute-phase reactant .
PMID: 26656134
3
SPINK1 mutations represent likely etiological factors in tropical calcific pancreatitis, prevalent in southern India .
PMID: 15753608
4
SPINK1 is a molecular subtype classifier in prostate cancer .
PMID: 26074382
5
In hepatocellular carcinoma, SPINK1 overexpression drives tumor dedifferentiation and chemoresistance via EGFR-ERK-CDK4/6-E2F2 signaling, with SPINK1 depletion dampening cancer growth .
PMID: 38030644
6
Diffuse SPINK1 expression distinguishes oxyntic gland neoplasms from normal tissue , and SPINK1 variants may increase pancreatic ductal adenocarcinoma risk .
PMID: 39863113
Disease Associationsβ“˜22
chronic pancreatitisOpen Targets
0.76Strong
hereditary chronic pancreatitisOpen Targets
0.75Strong
acute pancreatitisOpen Targets
0.52Moderate
pancreas diseaseOpen Targets
0.48Moderate
pancreatitisOpen Targets
0.48Moderate
alcoholic pancreatitisOpen Targets
0.45Moderate
diabetes mellitusOpen Targets
0.34Weak
non-alcoholic pancreatitisOpen Targets
0.30Weak
hepatocellular carcinomaOpen Targets
0.12Weak
neoplasmOpen Targets
0.12Weak
cancerOpen Targets
0.10Weak
posterior cortical atrophyOpen Targets
0.10Weak
colorectal carcinomaOpen Targets
0.10Weak
non-small cell lung carcinomaOpen Targets
0.10Suggestive
oral squamous cell carcinomaOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
ovarian cancerOpen Targets
0.08Suggestive
SepsisOpen Targets
0.07Suggestive
esophageal adenocarcinomaOpen Targets
0.06Suggestive
infectionOpen Targets
0.06Suggestive
Pancreatitis, hereditaryUniProt
Tropical calcific pancreatitisUniProt
Pathogenic Variants15
NM_001379610.1(SPINK1):c.194+2T>CPathogenic
Hereditary pancreatitis|Hereditary pancreatitis;Tropical pancreatitis|Chronic pancreatitis|Diabetes mellitus|not provided|SPINK1-related disorder|Hepatocellular carcinoma|Tropical pancreatitis|Colon adenocarcinoma|Familial cancer of breast
β˜…β˜…β˜†β˜†2026
NM_001379610.1(SPINK1):c.27del (p.Ser10fs)Pathogenic
Hereditary pancreatitis|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 10
NM_001379610.1(SPINK1):c.103G>T (p.Glu35Ter)Pathogenic
Hereditary pancreatitis
β˜…β˜…β˜†β˜†2025β†’ Residue 35
NM_001379610.1(SPINK1):c.123G>C (p.Lys41Asn)Likely pathogenic
Hereditary pancreatitis
β˜…β˜†β˜†β˜†2025β†’ Residue 41
NM_001379610.1(SPINK1):c.162del (p.Asn56fs)Likely pathogenic
Hereditary pancreatitis
β˜…β˜†β˜†β˜†2021β†’ Residue 56
NC_000005.10:g.(?_147824641)_(147831792_?)delPathogenic
Hereditary pancreatitis
β˜…β˜†β˜†β˜†2018
NM_001379610.1(SPINK1):c.55+1G>TLikely pathogenic
Hereditary pancreatitis
β˜…β˜†β˜†β˜†2018
NC_000005.10:g.(?_147824655)_(147831583_?)delPathogenic
Hereditary pancreatitis
β˜…β˜†β˜†β˜†2017
NM_001379610.1(SPINK1):c.87+1G>APathogenic
Hereditary pancreatitis
β˜…β˜†β˜†β˜†2016
NM_001379610.1(SPINK1):c.174C>A (p.Cys58Ter)Pathogenic
Hereditary pancreatitis
β˜…β˜†β˜†β˜†2016β†’ Residue 58
NM_001379610.1(SPINK1):c.55+1G>ALikely pathogenic
Hereditary pancreatitis
β˜…β˜†β˜†β˜†2016
NM_001379610.1(SPINK1):c.41T>C (p.Leu14Pro)Pathogenic
Hereditary pancreatitis
β˜†β˜†β˜†β˜†2007β†’ Residue 14
NM_003122.5(SPINK1):c.-191-129_56-932delPathogenic
Hereditary pancreatitis
β˜†β˜†β˜†β˜†2006
NM_003122.5(SPINK1):c.-191-24G>TPathogenic
Tropical pancreatitis
β˜†β˜†β˜†β˜†2002
NM_001379610.1(SPINK1):c.2T>C (p.Met1Thr)Pathogenic
Hereditary pancreatitis
β˜†β˜†β˜†β˜†2000β†’ Residue 1
View on ClinVar β†—
Related Genes
PRSS58Protein interaction95%CTRB2Protein interaction94%PRSS3Protein interaction92%SPINK2Protein interaction90%CFTRProtein interaction89%PRSS1Protein interaction89%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
4%
Lung
2%
Heart
2%
Ovary
2%
Brain
0%
Gene Interaction Network
Click a node to explore
SPINK1PRSS58CTRB2PRSS3SPINK2CFTRPRSS1
PROTEIN STRUCTURE
Preparing viewer…
PDB7QE9 Β· 2.10 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.03LoF Tolerant
pLIβ“˜
0.22Tolerant
Observed/Expected LoF0.45 [0.22–1.03]
RankingsWhere SPINK1 stands among ~20K protein-coding genes
  • #1,452of 20,598
    Most Researched261 Β· top 10%
  • #2,434of 5,498
    Most Pathogenic Variants15
  • #10,186of 17,882
    Most Constrained (LOEUF)1.03
Genes detectedSPINK1
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
SPINK1-induced tumor plasticity provides a therapeutic window for chemotherapy in hepatocellular carcinoma.
PMID: 38030644
Nat Commun Β· 2023
1.00
2
Prostate cancer.
PMID: 26074382
Lancet Β· 2016
0.90
3
Tropical pancreatitis.
PMID: 15753608
Dig Dis Β· 2004
0.80
4
Structural and Biophysical Insights into SPINK1 Bound to Human Cationic Trypsin.
PMID: 35408828
Int J Mol Sci Β· 2022
0.72
5
Functional Roles of SPINK1 in Cancers.
PMID: 33916984
Int J Mol Sci Β· 2021
0.70