SPINK1

Summary

SPINK1 (serine peptidase inhibitor Kazal type 1, HGNC:11244) is a protein-coding gene on chromosome 5q32, encoding Serine protease inhibitor Kazal-type 1 (P00995). Serine protease inhibitor which exhibits anti-trypsin activity. It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a trypsin inhibitor, which is secreted from pancreatic acinar cells into pancreatic juice. It is thought to function in the prevention of trypsin-catalyzed premature activation of zymogens within the pancreas and the pancreatic duct. Mutations in this gene are associated with hereditary pancreatitis and tropical calcific pancreatitis.

Source: NCBI Gene 6690 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary chronic pancreatitis (Strong, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 249 total — 11 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 25
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001379610

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11244
Approved symbol	SPINK1
Name	serine peptidase inhibitor Kazal type 1
Location	5q32
Locus type	gene with protein product
Status	Approved
Aliases	Spink3, PCTT, PSTI, TATI
Ensembl gene	ENSG00000164266
Ensembl biotype	protein_coding
OMIM	167790
Entrez	6690

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000296695, ENST00000505722, ENST00000510027

RefSeq mRNA: 3 — MANE Select: NM_001379610 NM_001354966, NM_001379610, NM_003122

CCDS: CCDS4286

Canonical transcript exons

ENST00000296695 — 4 exons

Exon	Start	End
ENSE00001082880	147829599	147829630
ENSE00001082882	147828022	147828128
ENSE00001082883	147831523	147831671
ENSE00002081650	147824582	147824706

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 99.98.

FANTOM5 (CAGE): breadth broad, TPM avg 48.0574 / max 51580.8830, expressed in 184 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64078	22.4678	122
64077	13.4995	132
64080	11.6716	97
64079	0.2922	29
64081	0.1263	26

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.98	gold quality
islet of Langerhans	UBERON:0000006	99.92	gold quality
epithelial cell of pancreas	CL:0000083	99.90	gold quality
type B pancreatic cell	CL:0000169	99.90	gold quality
pancreatic ductal cell	CL:0002079	99.90	gold quality
pancreas	UBERON:0001264	99.80	gold quality
duodenum	UBERON:0002114	99.38	gold quality
jejunal mucosa	UBERON:0000399	99.37	gold quality
rectum	UBERON:0001052	99.26	gold quality
mucosa of transverse colon	UBERON:0004991	99.22	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.22	gold quality
pylorus	UBERON:0001166	99.07	gold quality
colonic mucosa	UBERON:0000317	98.83	gold quality
ileal mucosa	UBERON:0000331	98.52	gold quality
cardia of stomach	UBERON:0001162	97.27	gold quality
mucosa of urinary bladder	UBERON:0001259	97.03	gold quality
amniotic fluid	UBERON:0000173	96.47	gold quality
gall bladder	UBERON:0002110	95.72	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.72	gold quality
urinary bladder	UBERON:0001255	95.34	gold quality
small intestine	UBERON:0002108	94.47	gold quality
stomach	UBERON:0000945	94.45	gold quality
body of stomach	UBERON:0001161	94.25	gold quality
mucosa of stomach	UBERON:0001199	94.04	gold quality
transverse colon	UBERON:0001157	93.79	gold quality
adult mammalian kidney	UBERON:0000082	92.58	gold quality
fundus of stomach	UBERON:0001160	92.42	gold quality
vermiform appendix	UBERON:0001154	90.18	gold quality
caecum	UBERON:0001153	90.12	gold quality
metanephros cortex	UBERON:0010533	90.06	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-HCAD-31	yes	24830.77
E-GEOD-81547	yes	11334.77
E-MTAB-8495	yes	7563.36
E-ENAD-27	yes	7042.35
E-MTAB-6653	yes	5056.20
E-MTAB-7407	yes	4363.55
E-CURD-98	yes	4340.38
E-MTAB-8410	yes	2313.33
E-MTAB-10485	yes	772.62
E-GEOD-125970	yes	24.81
E-MTAB-5061	yes	22.11
E-HCAD-10	yes	20.69
E-MTAB-6058	no	4.23
E-GEOD-83139	no	2.95
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF1A, PARP1

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Mutations in the PRSS1 gene explain most occurrences of hereditary pancreatitis (HP) but many HP families have no PRSS1 mutation. (PMID:11950815)
• Identification of SPINK1 mutations patients with adult alcoholic and idiopathic chronic pancreatitis suggests an important role for SPINK1 as a predisposing factor in adult chronic pancreatitis. (PMID:11950817)
• Mutations in the pancreatic secretory trypsin inhibitor gene are significantly associated with tropical calcific pancreatitis (PMID:12011155)
• Point mutation in patients with idiopathic chronic pancreatitis. frequency of the N34S SPINKI gene mutation. N34S mutation in the SPINKI gene is strongly associated with ICP, especially with the early-onset type. (PMID:12014716)
• mutations have a possible role in idiopathic chronic pancreatitis, familial pancreatitis, hereditary pancreatitis and tropical pancreatitis (PMID:12120224)
• the N34S variant of SPINK1 is a susceptibility gene for FCPD in the Indian subcontinent, although, by itself, it is not sufficient to cause disease. (PMID:12187509)
• Tropical calcific pancreatitis: strong association with SPINK1 trypsin inhibitor mutations. (PMID:12360463)
• SPINK1/PSTI mutations are associated with tropical pancreatitis and type II diabetes mellitus in Bangladesh. (PMID:12360464)
• No difference was observed in the frequency of PRSS1 or PSTI polymorphisms in neonates carrying or not carrying CF mutations. (PMID:12529713)
• The N34S mutation of SPINK1 appears not to be a distinct genetic risk factor in patients with sporadic pancreatic cancer. (PMID:12649567)
• Association of SPINK1 with cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis patients is statistically significant. (PMID:12825076)
• Results identify two genes, the 67-kd laminin receptor (67LR) and tumor-associated trypsin inhibitor (TATI), that may be involved in the early phases of urothelial tumor development rather than with disease progression. (PMID:12875970)
• in colorectal neoplasms, high levels of trypsin and TATI may be important for malignant tumour formation and/or metastatic process (PMID:12973686)
• The 253C allele for the SPINK1 gene was significantly more frequent in Brazilian pancreatitis patients than controls. (PMID:14526128)
• Mutation not associated with type1 or type 2 diabetes in India and Germany. (PMID:14595541)
• In gastrointestinal cancer, TATI can be used as a complementary tumour marker in addition to CEA. Regulation of TATI synthesis resembles that of acute-phase reactant proteins (PMID:14675563)
• Polymorphisms in SPINK1 are associated with an increased risk of developing pancreatitis but are not a risk for developing pancreatic neoplasms. (PMID:14688470)
• A novel heterozygous splicing mutation and a novel heterozygous microdeletion in the SPINK1 gene in hereditary pancreatitis patients. (PMID:14722925)
• An A to G transition resulting in a substitution of asparagine by serine at codon 34 in exon3 (N34S) of PSTI was associated with acute pancreatitis in a pregnant patient & her father. Her sister showed an intronic sequence variant PSTI, 272 C>T in 3’UTR. (PMID:15367892)
• in most patients with SPINKI-associated chronic pancreatitis, this genetic variant acts as disease modifier or within a polygenic model with other yet unidentified genes or environmental co-factors (PMID:15749232)
• pivotal roles of CFTR and PSTI during pancreatic exocrine secretion (PMID:15749233)
• The SPINK1-N34S mutation is not associated with chronic parotitis. (PMID:15753612)
• The SPINK1 N34S mutation was significantly associated with an increased risk of chronic pancreatits. (PMID:15764155)
• SPINK1 N34S mutation enhances the susceptibility of acute pancreatitis (PMID:15782101)
• High TATI expression in tumour tissue was detected more frequently in patients with early-stage gastric cancer and seems to correlate with a favourable outcome. (PMID:15810949)
• study suggests a balanced expression of TATI and trypsinogen is required in normal tissue and that this balance is disrupted during tumor progression (PMID:16327984)
• only the patient with the combination of both CASR and N34S SPINK1 gene mutation developed pancreatitis, whereas in the healthy parents and children only an isolated CASR or N34S SPINK1 gene mutation could be detected. (PMID:16497624)
• Mutations in the gene encoding cationic trypsinogen have recently been identified to be associated with hereditary pancreatitis. (PMID:16764792)
• protease serine 1 protease(PRSS1) defects seem to be causative for pancreatitis, whereas defects in protease serine 1 protease(SPINK1) are suggested to be associated with the disease (PMID:16954950)
• in Japan the [-215G > A; IVS3 + 2T > C] mutation in the SPINK1 gene may form a unique genetic background for pancreatitis (PMID:16958672)
• SPINK1 gene mutation is associated with another base substitution in chronic pancreatitis patients (PMID:16981266)
• Mutations and variations in pancreatitis patients. (PMID:17003641)
• SPINK1 mutations were associated with idiopathic and familial chronic pancreatitis, whereas the contribution was less evident in alcoholic chronic pancreatitis (PMID:17238043)
• splicing mutation might represent a mechanism for SPINK1-associated chronic pancreatitis, but the N34S mutation is not associated with alternative splicing (PMID:17446841)
• mutations/variants of SPINK1 gene with or without cystic fibrosis transmembrane conductance regulator gene may confer a high risk for recurrent pancreatitis (PMID:17489851)
• The results identify intracellular folding defects as a novel mechanism of SPINK1 deficiency associated with chronic pancreatitis. (PMID:17525091)
• analysis of seven missense mutations which probably cause intracellular retention of the respective mutant proteins (PMID:17568390)
• in the investigated Finnish pedigree with hereditary pancreatitis, the PRSS1 mutation R122H is linked with chronic disease; although the SPINK1 mutation (N34S) was also observed in two individuals, it was not linked with the disease (PMID:17613931)
• Co-inheritance of a novel deletion of the entire SPINK1 gene with a CFTR missense mutation (L997F) is associated with chronic pancreatitis (PMID:17681820)
• Polymorphisms in reg1alpha gene, including the regulatory variants singly or in combination with the known mutations in SPINK1 and/or CTSB genes, are not associated with tropical calcific pancreatitis. (PMID:17990360)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spink1	ENSMUSG00000024503
rattus_norvegicus	Spink1	ENSRNOG00000068869
rattus_norvegicus	Spink1l	ENSRNOG00000090734

Protein

Protein identifiers

Serine protease inhibitor Kazal-type 1 — P00995 (reviewed: P00995)

Alternative names: Pancreatic secretory trypsin inhibitor, Tumor-associated trypsin inhibitor

All UniProt accessions (2): P00995, D6RIU5

UniProt curated annotations — full annotation on UniProt →

Function. Serine protease inhibitor which exhibits anti-trypsin activity. In the pancreas, protects against trypsin-catalyzed premature activation of zymogens. In the male reproductive tract, binds to sperm heads where it modulates sperm capacitance by inhibiting calcium uptake and nitrogen oxide (NO) production.

Subcellular location. Secreted.

Disease relevance. Pancreatitis, hereditary (PCTT) [MIM:167800] A disease characterized by pancreas inflammation, permanent destruction of the pancreatic parenchyma, maldigestion, and severe abdominal pain attacks. Disease susceptibility is associated with variants affecting the gene represented in this entry. Tropical calcific pancreatitis (TCP) [MIM:608189] Idiopathic, juvenile, nonalcoholic form of chronic pancreatitis widely prevalent in several tropical countries. It can be associated with fibrocalculous pancreatic diabetes (FCPD) depending on both environmental and genetic factors. TCP differs from alcoholic pancreatitis by a much younger age of onset, pancreatic calcification, a high incidence of insulin dependent but ketosis resistant diabetes mellitus, and an exceptionally high incidence of pancreatic cancer. Disease susceptibility is associated with variants affecting the gene represented in this entry.

RefSeq proteins (3): NP_001341895, NP_001366539, NP_003113 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001239	Prot_inh_Kazal-m	Family
IPR002350	Kazal_dom	Domain
IPR036058	Kazal_dom_sf	Homologous_superfamily

Pfam: PF00050

UniProt features (22 total): sequence variant 5, strand 5, sequence conflict 3, disulfide bond 3, site 2, signal peptide 1, chain 1, domain 1, helix 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7QE9	X-RAY DIFFRACTION	2.1
1CGI	X-RAY DIFFRACTION	2.3
1CGJ	X-RAY DIFFRACTION	2.3
1HPT	X-RAY DIFFRACTION	2.3
7QE8	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00995-F1	88.70	0.61

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 41–42 (reactive bond for trypsin); 43–44 (necessary for sperm binding)

Disulfide bonds (3): 32–61, 39–58, 47–79

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9925561	Developmental Lineage of Pancreatic Acinar Cells
R-HSA-1266738	Developmental Biology
R-HSA-9734767	Developmental Cell Lineages

MSigDB gene sets: 229 (showing top): GOBP_SINGLE_FERTILIZATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, HNF1_Q6, GOBP_MALE_GAMETE_GENERATION, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_SPERM_CAPACITATION, YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_DN, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_CALCIUM_ION_IMPORT, GOBP_NEGATIVE_REGULATION_OF_CALCIUM_ION_IMPORT, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM3, GOBP_CELL_MATURATION, GOBP_REGULATION_OF_CALCIUM_ION_IMPORT

GO Biological Process (6): obsolete nitric oxide mediated signal transduction (GO:0007263), obsolete negative regulation of nitric oxide mediated signal transduction (GO:0010751), sperm capacitation (GO:0048240), regulation of acrosome reaction (GO:0060046), negative regulation of calcium ion import (GO:0090281), regulation of store-operated calcium entry (GO:2001256)

GO Molecular Function (4): endopeptidase inhibitor activity (GO:0004866), serine-type endopeptidase inhibitor activity (GO:0004867), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (3): extracellular exosome (GO:0070062), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Developmental Cell Lineages of the Exocrine Pancreas	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	1
spermatid development	1
cellular process involved in reproduction in multicellular organism	1
cell maturation	1
acrosome reaction	1
regulation of reproductive process	1
negative regulation of calcium ion transport	1
calcium ion import	1
regulation of calcium ion import	1
store-operated calcium entry	1
regulation of calcium ion transport	1
endopeptidase activity	1
peptidase inhibitor activity	1
endopeptidase regulator activity	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
binding	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

874 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPINK1	PRSS1	P07477	989
SPINK1	PRSS2	P07478	949
SPINK1	PRSS58	Q8IYP2	944
SPINK1	CTRC	Q99895	931
SPINK1	PRSS3	P15951	909
SPINK1	D6RI10	D6RI10	899
SPINK1	CFTR	P13569	880
SPINK1	CTRB2	Q6GPI1	867
SPINK1	CTRB1	P17538	866
SPINK1	TMPRSS15	P98073	810
SPINK1	CTSB	P07858	742
SPINK1	EGFR	P00533	702
SPINK1	CPA1	P15085	697
SPINK1	ANOS1	P23352	670
SPINK1	PROC	P04070	653

IntAct

8 interactions, top by confidence:

A	B	Type	Score
SPINK1	ASPH	psi-mi:“MI:0915”(physical association)	0.560
	SPINK1	psi-mi:“MI:0407”(direct interaction)	0.440
SPINK1	CD59	psi-mi:“MI:0915”(physical association)	0.400
DCAF4	IGLL5	psi-mi:“MI:0914”(association)	0.350
SPINK1	PDIA5	psi-mi:“MI:0914”(association)	0.350
ASPH	SPINK1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): SPINK1 (Reconstituted Complex), SPINK1 (Affinity Capture-MS), ASPH (Two-hybrid), CD59 (Affinity Capture-MS), ST14 (Affinity Capture-MS), PDIA5 (Affinity Capture-MS)

ESM2 similar proteins: A0A2P1BSU3, A0A6B9KZ59, A0A6B9KZ79, A0A6B9KZ83, A0A6B9KZ89, A0A6B9L3M7, A0A7M6UNN1, A2CKF7, A7VN17, A9QLM3, B0JFB8, B3A0N9, B7PCV3, C0HJQ8, F5GTK6, H2ER23, H9KQJ7, L0GCJ1, O08540, O46162, O46163, P00995, P00996, P01001, P09036, P09655, P09656, P0C908, P0CJ12, P0DKM7, P0DKT2, P0DKT3, P0DKT5, P0DM55, P0DQC9, P0DQD0, P0DQG7, P0DQG9, P0DUS7, P0DXW3

Diamond homologs: D0MVC9, D0NJ41, O00468, P00995, P05560, P0DKM7, P0DKM8, P0DKM9, P0DKT1, P0DKT2, P0DKT3, P0DKT4, P0DKT5, P11706, P16895, P82968, P85000, Q6PFE7, Q6PQG3, Q6PQH2, Q8IYR6, Q91590, Q9NQ38, Q9QYM9, Q9QYV1, A2ASQ1, A5YT95, D3ZVP0, O35679, O60575, O62650, O95633, P00996, P00997, P00998, P01003, P01005, P04542, P09036, P09655

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

249 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	4
Uncertain significance	107
Likely benign	82
Benign	4

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
13761	NM_001379610.1(SPINK1):c.2T>C (p.Met1Thr)	Pathogenic
13763	NM_003122.5(SPINK1):c.-191-24G>T	Pathogenic
13764	NM_001379610.1(SPINK1):c.41T>C (p.Leu14Pro)	Pathogenic
13766	NM_003122.5(SPINK1):c.-191-129_56-932del	Pathogenic
1773780	NM_001379610.1(SPINK1):c.103G>T (p.Glu35Ter)	Pathogenic
1779356	NM_001379610.1(SPINK1):c.174C>A (p.Cys58Ter)	Pathogenic
36780	NM_001379610.1(SPINK1):c.27del (p.Ser10fs)	Pathogenic
528778	NC_000005.10:g.(?147824655)(147831583_?)del	Pathogenic
547787	NM_001379610.1(SPINK1):c.87+1G>A	Pathogenic
583901	NC_000005.10:g.(?147824641)(147831792_?)del	Pathogenic
830855	NC_000005.10:g.(?147824661)(147831792_?)del	Pathogenic
1747977	NM_001379610.1(SPINK1):c.55+1G>A	Likely pathogenic
1776795	NM_001379610.1(SPINK1):c.162del (p.Asn56fs)	Likely pathogenic
4688635	NM_001379610.1(SPINK1):c.123G>C (p.Lys41Asn)	Likely pathogenic
633006	NM_001379610.1(SPINK1):c.55+1G>T	Likely pathogenic

SpliceAI

413 predictions. Top by Δscore:

Variant	Effect	Δscore
5:147828016:ACTC:A	donor_loss	1.0000
5:147828018:TCAC:T	donor_loss	1.0000
5:147828019:CACC:C	donor_loss	1.0000
5:147828020:A:AC	donor_gain	1.0000
5:147828020:A:C	donor_loss	1.0000
5:147828020:AC:A	donor_gain	1.0000
5:147828021:C:A	donor_loss	1.0000
5:147828021:C:CG	donor_gain	1.0000
5:147828021:CC:C	donor_gain	1.0000
5:147828021:CCG:C	donor_gain	1.0000
5:147828021:CCGA:C	donor_gain	1.0000
5:147828021:CCGAT:C	donor_gain	1.0000
5:147828124:TTGGC:T	acceptor_gain	1.0000
5:147828125:TGGC:T	acceptor_gain	1.0000
5:147828126:GGC:G	acceptor_gain	1.0000
5:147828126:GGCCT:G	acceptor_loss	1.0000
5:147828129:C:CA	acceptor_loss	1.0000
5:147828129:C:CC	acceptor_gain	1.0000
5:147828130:T:G	acceptor_loss	1.0000
5:147828014:GTACT:G	donor_loss	0.9900
5:147828127:GC:G	acceptor_gain	0.9900
5:147828128:CC:C	acceptor_gain	0.9900
5:147828135:A:AC	acceptor_gain	0.9900
5:147828135:A:C	acceptor_gain	0.9900
5:147829005:T:C	donor_gain	0.9900
5:147824703:TTTCC:T	acceptor_loss	0.9700
5:147824704:TTCCT:T	acceptor_loss	0.9700
5:147824705:TCCT:T	acceptor_loss	0.9700
5:147824706:CCTGC:C	acceptor_loss	0.9700
5:147824707:C:CA	acceptor_loss	0.9700

AlphaMissense

506 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:147828076:C:G	C47S	0.988
5:147828077:A:T	C47S	0.988
5:147828100:C:G	C39S	0.988
5:147828101:A:T	C39S	0.988
5:147828043:C:G	C58S	0.984
5:147828044:A:T	C58S	0.984
5:147824665:C:G	C79S	0.983
5:147824666:A:T	C79S	0.983
5:147828074:C:A	G48W	0.983
5:147828073:C:T	G48E	0.981
5:147824664:G:C	C79W	0.980
5:147828055:T:C	Y54C	0.979
5:147828101:A:G	C39R	0.979
5:147828044:A:G	C58R	0.978
5:147828048:A:C	N56K	0.978
5:147828048:A:T	N56K	0.978
5:147828034:C:G	C61S	0.976
5:147828035:A:T	C61S	0.976
5:147828077:A:G	C47R	0.976
5:147828033:A:C	C61W	0.975
5:147824666:A:G	C79R	0.974
5:147828079:A:T	V46D	0.974
5:147828035:A:G	C61R	0.972
5:147828037:A:G	L60S	0.972
5:147828056:A:C	Y54D	0.969
5:147828073:C:A	G48V	0.966
5:147828068:C:G	D50H	0.965
5:147828076:C:T	C47Y	0.965
5:147824665:C:T	C79Y	0.963
5:147828077:A:C	C47G	0.961

dbSNP variants (sampled 300 via entrez): RS1000064590 (5:147831972 G>A), RS1000084116 (5:147825606 T>C), RS1000135998 (5:147838206 G>A), RS1000137873 (5:147825343 T>C), RS1000519718 (5:147836707 A>G), RS1000536138 (5:147838653 C>T), RS1000582731 (5:147830375 G>A), RS1000647586 (5:147831882 G>A), RS1001186355 (5:147827274 A>G), RS1001285799 (5:147830542 TTGA>T), RS1001322259 (5:147826435 T>C), RS1001478056 (5:147833426 TCAC>T), RS1001542686 (5:147826219 C>G), RS1001679395 (5:147838743 T>C), RS1001794047 (5:147839002 C>T)

Disease associations

OMIM: gene MIM:167790 | disease phenotypes: MIM:167800, MIM:608189, MIM:256300

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary chronic pancreatitis	Strong	Autosomal dominant

Mondo (6): hereditary chronic pancreatitis (MONDO:0008185), chronic pancreatitis (MONDO:0005003), diabetes mellitus (MONDO:0005015), tropical pancreatitis (MONDO:0011986), pancreatitis (MONDO:0004982), congenital nephrotic syndrome, Finnish type (MONDO:0009732)

Orphanet (3): Autosomal dominant hereditary chronic pancreatitis (Orphanet:676), Tropical pancreatitis (Orphanet:103918), Congenital nephrotic syndrome, Finnish type (Orphanet:839)

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000819	Diabetes mellitus
HP:0000952	Jaundice
HP:0001733	Pancreatitis
HP:0001738	Exocrine pancreatic insufficiency
HP:0001824	Weight loss
HP:0001945	Fever
HP:0001977	Abnormal thrombosis
HP:0002013	Vomiting
HP:0002018	Nausea
HP:0002027	Abdominal pain
HP:0002202	Pleural effusion
HP:0002570	Steatorrhea
HP:0002894	Neoplasm of the pancreas
HP:0004395	Malnutrition
HP:0005206	Pancreatic pseudocyst
HP:0005213	Pancreatic calcification
HP:0005236	Chronic calcifying pancreatitis
HP:0006280	Chronic pancreatitis
HP:0006725	Pancreatic adenocarcinoma
HP:0008205	Insulin-dependent but ketosis-resistant diabetes
HP:0009800	Maternal diabetes
HP:0030992	Abnormal pancreatic duct morphology
HP:0410019	Epigastric pain

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001762_454	Obesity-related traits	6.000000e-06
GCST004860_95	Alcoholic chronic pancreatitis	3.000000e-15
GCST006585_325	Blood protein levels	2.000000e-17
GCST009391_1431	Metabolite levels	2.000000e-06
GCST009391_1454	Metabolite levels	6.000000e-06
GCST009391_1728	Metabolite levels	4.000000e-07
GCST009391_2088	Metabolite levels	2.000000e-06
GCST009391_845	Metabolite levels	6.000000e-06
GCST009391_941	Metabolite levels	3.000000e-06
GCST012189_7	Systolic blood pressure and diastolic blood pressure (bivariate analysis)	5.000000e-07

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004736	aspartate aminotransferase measurement
EFO:0010408	triacylglycerol 50:1 measurement
EFO:0010405	triacylglycerol 48:2 measurement
EFO:0010375	phosphatidylcholine 34:1 measurement
EFO:0010373	phosphatidylcholine 32:1 measurement
EFO:0010400	triacylglycerol 46:0 measurement
EFO:0010402	triacylglycerol 46:2 measurement
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D003920	Diabetes Mellitus	C18.452.394.750; C19.246
D010195	Pancreatitis	C06.689.750
D050500	Pancreatitis, Chronic	C06.689.750.830; C23.550.291.500.750
C537262	Hereditary pancreatitis (supp.)
C564276	Tropical Calcific Pancreatitis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs148954387	SPINK1		0.00	0

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	6
Cadmium Chloride	decreases expression, increases expression, affects cotreatment	5
sodium arsenite	increases expression, increases reaction, affects cotreatment, decreases expression	4
Benzo(a)pyrene	increases expression, increases methylation	4
Cyclosporine	increases expression	4
Aflatoxin B1	decreases methylation, increases expression, affects expression	4
sodium arsenate	increases expression, increases abundance	2
Panobinostat	affects cotreatment, increases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
Tetrachlorodibenzodioxin	affects expression, increases expression	2
dicrotophos	decreases expression	1
lead acetate	affects cotreatment, decreases expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
zinc chloride	decreases expression	1
chromous chloride	affects cotreatment, decreases expression	1
butyraldehyde	increases expression	1
chromic oxide	affects cotreatment, decreases expression	1
hydroquinone	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
archazolid B	increases expression	1
NSC 689534	affects binding, increases expression	1
Rosiglitazone	increases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	decreases expression	1
Azathioprine	increases expression	1
Cadmium	increases expression	1
Copper	affects binding, increases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1HR	Abcam A-549 SPINK1 KO 1	Cancer cell line	Male
CVCL_B1HS	Abcam A-549 SPINK1 KO 3	Cancer cell line	Male
CVCL_B2QA	Abcam A-549 SPINK1 KO 2	Cancer cell line	Male
CVCL_C3NE	AsPC-1 SPINK1 #10	Cancer cell line	Female

Clinical trials (associated diseases)

299 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00583479	PHASE4	COMPLETED	Prospective Study of Celiac Block Injection: 1 vs. 2
NCT00744250	PHASE4	TERMINATED	Intraduodenal Aspiration Study to Assess the Bioavailability of Oral Pancrecarb® Compared to Placebo Control
NCT00956839	PHASE4	COMPLETED	Prospective Study of Efficacy of Intra-muscular Vitamin D3 in Tropical Calcific Pancreatitis
NCT00957151	PHASE4	COMPLETED	Evaluation of the Digestive and Metabolic Utilisation of Dietary Protein in Patients With Chronic Pancreatitis
NCT01430234	PHASE4	COMPLETED	Enzyme Suppletion in Exocrine Pancreatic Dysfunction
NCT01642875	PHASE4	UNKNOWN	Early Oral Versus Enteral Nutrition After Pancreatoduodenectomy
NCT05069597	PHASE4	COMPLETED	Study to Evaluate Symptoms of Exocrine Pancreatic Insufficiency in Adult Participants With Cystic Fibrosis or Chronic Pancreatitis Treated With Creon
NCT06937294	PHASE4	RECRUITING	Metformin in Post Chronic Pancreatitis Diabetes Mellitus
NCT07285863	PHASE4	RECRUITING	A Study Of Effect Of Secretin For In Injection (Chirostim) On Pancreatic Fluid Composition In Healthy Subjects
NCT07418593	PHASE4	RECRUITING	Malabsorption Blood Test (MBT) to Determine Exocrine Pancreatic Function and Related Quality of Life in Chronic Pancreatitis
NCT00044746	PHASE4	COMPLETED	Study Evaluating the Safety and Efficacy of Piperacillin/Tazobactam and Ampicillin/Sulbactam in Patients With Diabetic Foot Infections
NCT00069602	PHASE4	COMPLETED	Assessing Continuous Glucose Monitors in Healthy Children
NCT00079638	PHASE4	COMPLETED	Comparative Efficacy Evaluation of Lipids When Treated With Niaspan & Statin or Other Lipid-Modifying Therapies-COMPELL
NCT00095446	PHASE4	COMPLETED	NovoLog Observation Trial in Subjects With Type 1 and Type 2 Diabetes
NCT00101751	PHASE4	COMPLETED	INITIATE Plus (INITiation of Insulin to Reach A1c TargEt) Study
NCT00108615	PHASE4	COMPLETED	Effects of Insulin Sensitizers in Subjects With Impaired Glucose Tolerance
NCT00117780	PHASE4	COMPLETED	Comparison of Insulin Detemir Given Once or Twice Daily in Type 1 Diabetes
NCT00120341	PHASE4	COMPLETED	Anodyne Therapy in Diabetic Sensory Neuropathy
NCT00121355	PHASE4	COMPLETED	Novofine Autocover Safety Needle Versus BD Safety Glide
NCT00135226	PHASE4	ACTIVE_NOT_RECRUITING	ASCEND: A Study of Cardiovascular Events iN Diabetes
NCT00144937	PHASE4	UNKNOWN	Multifactorial Intervention on Cardiovascular Risk Factors in Subjects With Peripheral Arterial Disease
NCT00147251	PHASE4	COMPLETED	Stop Atherosclerosis in Native Diabetics Study
NCT00157638	PHASE4	COMPLETED	Integrating Family Medicine and Pharmacy to Advance Primary Care Therapeutics
NCT00162344	PHASE4	COMPLETED	A Study of Stress Heart Imaging in Patients With Diabetes at Risk for Coronary Disease.
NCT00177138	PHASE4	TERMINATED	Use of Campath for Induction and Maintenance Therapy in Pancreas After Kidney Transplantation
NCT00182494	PHASE4	UNKNOWN	Diabetes Prevention Program in Schizophrenia [DPPS]
NCT00184561	PHASE4	COMPLETED	Effectiveness and Safety of Biphasic Insulin Aspart 70/30 in Subjects With Type 2 Diabetes
NCT00184626	PHASE4	COMPLETED	Comparison of Insulin Glargine Versus Biphasic Insulin Aspart 30/70 or Biphasic Insulin Aspart 30/70 in Combination With Metformin in Subjects With Type 2 Diabetes.
NCT00202618	PHASE4	UNKNOWN	Rationale and Design for Shiga Microalbuminuria Reduction Trial
NCT00209170	PHASE4	COMPLETED	Depression-Diabetes Mechanisms: Urban African Americans
NCT00209417	PHASE4	TERMINATED	Renal Effects of Two Iodinated Contrast Media in Patients at Risk Undergoing Computed Tomography
NCT00212004	PHASE4	TERMINATED	Pioglitazone Protects Diabetes Mellitus (DM) Patients Against Re-Infarction (PPAR Study)
NCT00219440	PHASE4	COMPLETED	A Portion-controlled Diet Will Prevent Weight Gain in Diabetics Treated With ACTOS
NCT00225849	PHASE4	UNKNOWN	Japanese Primary Prevention Project With Aspirin
NCT00231894	PHASE4	COMPLETED	Pioglitazone as a Treatment for Lipid and Glucose Abnormalities In Patients With Schizophrenia
NCT00234871	PHASE4	COMPLETED	Tarka® vs. Lotrel® in Hypertensive, Diabetic Subjects With Renal Disease (TANDEM)
NCT00235014	PHASE4	COMPLETED	A Study for Prevention of Kidney Disease in Diabetic Patients (BENEDICT)
NCT00236379	PHASE4	COMPLETED	A Study of the Effects of Risperidone and Olanzapine on Blood Glucose (Sugar) in Patients With Schizophrenia or Schizoaffective Disorder
NCT00241904	PHASE4	COMPLETED	Reducing Total Cardiovascular Risk in an Urban Community
NCT00263393	PHASE4	COMPLETED	Rural Andhra Pradesh Cardiovascular Prevention Study (RAPCAPS)