Tropical pancreatitis

Summary

Tropical pancreatitis (MONDO:0011986) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 17
• Phenotypes (HPO): 12

Clinical features

Signs & symptoms

Clinical features (HPO)

12 HPO clinical features (Orphanet curated; top 12 by frequency):

HPO ID	Term	Frequency
HP:0005213	Pancreatic calcification	Very frequent (80-99%)
HP:0005236	Chronic calcifying pancreatitis	Very frequent (80-99%)
HP:0410019	Epigastric pain	Very frequent (80-99%)
HP:0002018	Nausea	Frequent (30-79%)
HP:0008205	Insulin-dependent but ketosis-resistant diabetes	Frequent (30-79%)
HP:0030992	Abnormal pancreatic duct morphology	Frequent (30-79%)
HP:0000952	Jaundice	Occasional (5-29%)
HP:0001824	Weight loss	Occasional (5-29%)
HP:0002013	Vomiting	Occasional (5-29%)
HP:0004395	Malnutrition	Occasional (5-29%)
HP:0006725	Pancreatic adenocarcinoma	Occasional (5-29%)
HP:0009800	Maternal diabetes	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	tropical pancreatitis
Mondo ID	MONDO:0011986
MeSH	C564276
OMIM	608189
Orphanet	103918
ICD-11	1645607956
SNOMED CT	724540009
UMLS	C1842402
MedGen	334069
GARD	0016946
Is cancer (heuristic)	no

Also known as: TCP · tropical calcific chronic pancreatitis

Data availability: 17 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary chronic pancreatitis › tropical pancreatitis

Related subtypes (1): autosomal recessive hereditary chronic pancreatitis

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

17 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 3 conflicting classifications of pathogenicity, 2 benign/likely benign, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity; association; risk factor, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
132142	NM_001379610.1(SPINK1):c.194+2T>C	SPINK1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13763	NM_003122.5(SPINK1):c.-191-24G>T	SPINK1	Pathogenic	no assertion criteria provided
13760	NM_001379610.1(SPINK1):c.101A>G (p.Asn34Ser)	SPINK1	Conflicting classifications of pathogenicity; association; risk factor	criteria provided, conflicting classifications
13762	NM_003122.5(SPINK1):c.-191-24G>A	SPINK1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
239503	NM_003122.5(SPINK1):c.-147A>G	SPINK1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
818762	NM_001379610.1(SPINK1):c.126A>G (p.Ile42Met)	SPINK1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
132145	NM_001379610.1(SPINK1):c.199C>T (p.Arg67Cys)	SPINK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1697266	NM_001379610.1(SPINK1):c.80G>A (p.Gly27Glu)	SPINK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
239502	NM_003122.5(SPINK1):c.-142T>C	SPINK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3591866	NM_001379610.1(SPINK1):c.185T>C (p.Phe62Ser)	SPINK1	Uncertain significance	criteria provided, single submitter
3591867	NM_001379610.1(SPINK1):c.88-11T>A	SPINK1	Uncertain significance	criteria provided, single submitter
36779	NM_001379610.1(SPINK1):c.194G>A (p.Arg65Gln)	SPINK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
410699	NM_001379610.1(SPINK1):c.198A>C (p.Lys66Asn)	SPINK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
440301	NM_001379610.1(SPINK1):c.56G>T (p.Gly19Val)	SPINK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
565669	NM_001379610.1(SPINK1):c.-53C>T	SPINK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
239508	NM_001379610.1(SPINK1):c.88-23A>T	SPINK1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
36778	NM_001379610.1(SPINK1):c.163C>T (p.Pro55Ser)	SPINK1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SPINK1	Orphanet:103918	Tropical pancreatitis
SPINK1	Orphanet:700124	Autosomal recessive hereditary chronic pancreatitis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SPINK1	HGNC:11244	ENSG00000164266	P00995	Serine protease inhibitor Kazal-type 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SPINK1	Serine protease inhibitor Kazal-type 1	Serine protease inhibitor which exhibits anti-trypsin activity.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SPINK1	Other/Unknown	no		Prot_inh_Kazal-m, Kazal_dom, Kazal_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	1
epithelial cell of pancreas	1
islet of Langerhans	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SPINK1	192	broad	marker	body of pancreas, islet of Langerhans, epithelial cell of pancreas

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SPINK1	888

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SPINK1	P00995	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Developmental Lineage of Pancreatic Acinar Cells	1	300.5×	0.007	SPINK1
Developmental Cell Lineages	1	223.9×	0.007	SPINK1
Developmental Biology	1	14.5×	0.069	SPINK1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete negative regulation of nitric oxide mediated signal transduction	1	8426.0×	7e-04	SPINK1
regulation of acrosome reaction	1	3370.4×	8e-04	SPINK1
negative regulation of calcium ion import	1	2407.4×	8e-04	SPINK1
obsolete nitric oxide mediated signal transduction	1	1296.3×	0.001	SPINK1
regulation of store-operated calcium entry	1	1053.2×	0.001	SPINK1
sperm capacitation	1	674.1×	0.001	SPINK1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SPINK1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SPINK1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SPINK1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.