Pancreatitis

Summary

Pancreatitis (MONDO:0004982) is a disease (an umbrella term covering 5 Mondo subtypes) with 13 cohort genes (16 GWAS associations across 13 studies) and 176 clinical trials. Top therapeutic interventions include indomethacin, ketorolac, and doripenem.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 13
• GWAS associations: 16
• ClinVar variants: 5
• Clinical trials: 176

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pancreatitis
Mondo ID	MONDO:0004982
EFO	EFO:0000278
MeSH	D010195
DOID	DOID:4989
NCIT	C3306
SNOMED CT	75694006
UMLS	C0030305
MedGen	14586
Is cancer (heuristic)	no

Also known as: inflammation of pancreas · pancreas inflammation

Data availability: 5 ClinVar variants · 16 GWAS associations (13 studies) · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › pancreas disorder › pancreatitis

Related subtypes (13): pancreatic steatorrhea, pancreatic mucinous ductal ectasia, exocrine pancreatic insufficiency, endocrine pancreas disorder, annular pancreas, pancreatic triacylglycerol lipase deficiency, follicular cholangitis and pancreatitis, congenital pancreatic cyst, recurrent acute pancreatitis, accessory pancreas, pancreatic neoplasm, acinar cystic transformation of the pancreas, lymphoepithelial cyst of the pancreas

Subtypes (5): alcoholic pancreatitis, chronic pancreatitis, thiopurine immunosuppressant-induced pancreatitis, acute pancreatitis, autoimmune pancreatitis

Genetics & variants

GWAS landscape

16 GWAS associations across 13 studies. Top hits map to 5 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs12688220	2e-22	MORC4 - EEF1A1P40	T	1.39
rs76866386	2e-16	ABCG8	C	0.38
rs10273639	2e-14	TRBV29-1 - PRSS1	C	1.36
rs148911734	2e-14	SPINK1 - SCGB3A2	T	1.27
rs77768175	3e-09	HECTD4	G	0.54
rs74550709	1e-08	MYBPC1	G	1.65
rs12551781	4e-08	STXBP1	C	0.67
rs4437130	2e-07	RPL21P17 - RN7SKP144	?	6.8
rs62561366	5e-07	PTCH1 - ERCC6L2-AS1	?	7
rs379742	6e-07	PWWP3B - CSGALNACT2P2	T	1.2
rs2995271	8e-07	JCAD - RNU6-598P	T	1.27
rs11988997	6e-06	SAMD12-AS1	T	1.36

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90473884	UK Biobank Whole-Genome Sequencing Consortium	2025	4,688	453,752	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90018789	Sakaue S	2021	3,798	476,104	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90018821	Sakaue S	2021	1,424	476,104	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90077706	Backman JD	2021	980	330,774	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081692	Backman JD	2021	980	330,774	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90077707	Backman JD	2021	868	328,184	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081693	Backman JD	2021	868	328,184	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90018569	Sakaue S	2021	827	177,471	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST001741	Whitcomb DC	2012	676	4,507	Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis.
GCST90018601	Sakaue S	2021	457	177,471	A cross-population atlas of genetic associations for 220 human phenotypes.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	11

MAF distribution

Bucket	Variants
common (>=0.05)	10
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intron_variant	6
intergenic_variant	5
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs12688220	X	107001537	C>G,T	0.261	intron_variant	MORC4 - EEF1A1P40	2e-22	Tier 4: intronic/intergenic
rs76866386	2	43848344	T>C	0.05	intron_variant	ABCG8	2e-16	Tier 4: intronic/intergenic
rs10273639	7	142749077	T>A,C	0.424	intergenic_variant	TRBV29-1 - PRSS1	2e-14	Tier 4: intronic/intergenic
rs148911734	5	147838808	C>A,T		intergenic_variant	SPINK1 - SCGB3A2	2e-14	Tier 4: intronic/intergenic
rs77768175	12	112298314	A>G	0.243	intron_variant	HECTD4	3e-09	Tier 4: intronic/intergenic
rs74550709	12	101595202	A>G		intron_variant	MYBPC1	1e-08	Tier 4: intronic/intergenic
rs12551781	9	127584239	T>A,C	0.05	regulatory_region_variant	STXBP1	4e-08	Tier 3: regulatory
rs4437130	3	2035283	G>A	0.05	intergenic_variant	RPL21P17 - RN7SKP144	2e-07	Tier 4: intronic/intergenic
rs62561366	9	95555669	A>T	0.05	intron_variant	PTCH1 - ERCC6L2-AS1	5e-07	Tier 4: intronic/intergenic
rs379742	X	106250703	G>A,C	0.2	intergenic_variant	PWWP3B - CSGALNACT2P2	6e-07	Tier 4: intronic/intergenic
rs2995271	10	30230903	C>T	0.238	intergenic_variant	JCAD - RNU6-598P	8e-07	Tier 4: intronic/intergenic
rs11988997	8	118753955	C>T	0.071	intron_variant	SAMD12-AS1	6e-06	Tier 4: intronic/intergenic

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

3 conflicting classifications of pathogenicity, 1 conflicting classifications of pathogenicity; association; risk factor, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1383	NM_153704.6(TMEM67):c.1843T>C (p.Cys615Arg)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
43576	NM_000492.4(CFTR):c.1584G>A (p.Glu528=)	CFTR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
7229	NM_000492.4(CFTR):c.2991G>C (p.Leu997Phe)	CFTR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
13760	NM_001379610.1(SPINK1):c.101A>G (p.Asn34Ser)	SPINK1	Conflicting classifications of pathogenicity; association; risk factor	criteria provided, conflicting classifications
217725	NM_153704.6(TMEM67):c.1321C>T (p.Arg441Cys)	TMEM67	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 30 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 2

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
PRSS1	PRSS1	GWAS, Orphanet
PRSS2	PRSS2	GWAS, Orphanet

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TRPV6	Strong	Autosomal dominant	hereditary chronic pancreatitis	7
ABCB4	Limited	Autosomal dominant	pancreatitis	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRPV6	Orphanet:417	Neonatal severe primary hyperparathyroidism
TRPV6	Orphanet:676	Autosomal dominant hereditary chronic pancreatitis
ABCB4	Orphanet:69663	Low phospholipid-associated cholelithiasis
ABCB4	Orphanet:69665	Intrahepatic cholestasis of pregnancy
ABCB4	Orphanet:79305	Progressive familial intrahepatic cholestasis type 3
SPINK1	Orphanet:103918	Tropical pancreatitis
SPINK1	Orphanet:700124	Autosomal recessive hereditary chronic pancreatitis
CFTR	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
CFTR	Orphanet:48	Congenital bilateral absence of vas deferens
CFTR	Orphanet:498359	Aquagenic palmoplantar keratoderma
CFTR	Orphanet:586	Cystic fibrosis
CFTR	Orphanet:60033	Idiopathic bronchiectasis
CFTR	Orphanet:700124	Autosomal recessive hereditary chronic pancreatitis
TBC1D8B	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
TMEM67	Orphanet:140976	RHYNS syndrome
TMEM67	Orphanet:1454	Joubert syndrome with hepatic defect
TMEM67	Orphanet:475	Isolated Joubert syndrome
TMEM67	Orphanet:564	Meckel syndrome
TMEM67	Orphanet:84081	Senior-Boichis syndrome
PRSS1	Orphanet:676	Autosomal dominant hereditary chronic pancreatitis
PRSS2	Orphanet:676	Autosomal dominant hereditary chronic pancreatitis
PTCH1	Orphanet:220386	Semilobar holoprosencephaly
PTCH1	Orphanet:2353	Schilbach-Rott syndrome
PTCH1	Orphanet:280195	Septopreoptic holoprosencephaly
PTCH1	Orphanet:280200	Microform holoprosencephaly
PTCH1	Orphanet:377	Gorlin syndrome
PTCH1	Orphanet:77301	Monosomy 9q22.3 syndrome
PTCH1	Orphanet:93924	Lobar holoprosencephaly
PTCH1	Orphanet:93925	Alobar holoprosencephaly
PTCH1	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly

Cohort genes → proteins

13 cohort genes, 13 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	8
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TRPV6	HGNC:14006	ENSG00000165125	Q9H1D0	Transient receptor potential cation channel subfamily V member 6	gencc
ABCB4	HGNC:45	ENSG00000005471	P21439	Phosphatidylcholine translocator ABCB4	gencc
SPINK1	HGNC:11244	ENSG00000164266	P00995	Serine protease inhibitor Kazal-type 1	clinvar
CFTR	HGNC:1884	ENSG00000001626	P13569	Cystic fibrosis transmembrane conductance regulator	clinvar
CLDN2	HGNC:2041	ENSG00000165376	P57739	Claudin-2	gwas
CNTN4	HGNC:2174	ENSG00000144619	Q8IWV2	Contactin-4	gwas
MORC4	HGNC:23485	ENSG00000133131	Q8TE76	MORC family CW-type zinc finger protein 4	gwas
TBC1D8B	HGNC:24715	ENSG00000133138	Q0IIM8	TBC1 domain family member 8B	gwas
RIPPLY1	HGNC:25117	ENSG00000147223	Q0D2K3	Protein ripply1	gwas
TMEM67	HGNC:28396	ENSG00000164953	Q5HYA8	Meckelin	clinvar
PRSS1	HGNC:9475	ENSG00000204983	P07477	Serine protease 1	gwas
PRSS2	HGNC:9483	ENSG00000275896	P07478	Trypsin-2	gwas
PTCH1	HGNC:9585	ENSG00000185920	Q13635	Protein patched homolog 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRPV6	Transient receptor potential cation channel subfamily V member 6	Calcium selective cation channel that mediates Ca(2+) uptake in various tissues, including the intestine.
ABCB4	Phosphatidylcholine translocator ABCB4	Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion.
SPINK1	Serine protease inhibitor Kazal-type 1	Serine protease inhibitor which exhibits anti-trypsin activity.
CFTR	Cystic fibrosis transmembrane conductance regulator	Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis.
CLDN2	Claudin-2	Forms paracellular channels: polymerizes in tight junction strands with cation- and water-selective channels through the strands, conveying epithelial permeability in a process known as paracellular tight junction permeability.
CNTN4	Contactin-4	Contactins mediate cell surface interactions during nervous system development.
MORC4	MORC family CW-type zinc finger protein 4	Histone methylation reader which binds to non-methylated (H3K4me0), monomethylated (H3K4me1), dimethylated (H3K4me2) and trimethylated (H3K4me3) ‘Lys-4’ on histone H3.
TBC1D8B	TBC1 domain family member 8B	Involved in vesicular recycling, probably as a RAB11B GTPase-activating protein.
RIPPLY1	Protein ripply1	Plays a role in somitogenesis.
TMEM67	Meckelin	Required for ciliary structure and function.
PRSS1	Serine protease 1	Has activity against the synthetic substrates Boc-Phe-Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val-Pro-Arg-Mec.
PRSS2	Trypsin-2	In the ileum, may be involved in defensin processing, including DEFA5.
PTCH1	Protein patched homolog 1	Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH).

Protein-family classification

Druggable: 6 · Difficult: 1 · Unknown: 6 · Druggable fraction: 0.46

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
Transporter	2	12.0×	0.070
Protease	2	5.6×	0.143
Ion channel	1	8.6×	0.221
Antibody/Immunoglobulin	1	2.2×	0.547
Other/Unknown	6	0.8×	0.837
Transcription factor	1	0.6×	0.837

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRPV6	Ion channel	yes		Ankyrin_rpt, Ion_trans_dom, TRPV5/TRPV6
ABCB4	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom
SPINK1	Other/Unknown	no		Prot_inh_Kazal-m, Kazal_dom, Kazal_dom_sf
CFTR	Transporter	yes	2.7.4.3	ABC_transporter-like_ATP-bd, AAA+_ATPase, CFTR/ABCC7
CLDN2	Other/Unknown	no		PMP22/EMP/MP20/Claudin, Claudin2, Claudin
CNTN4	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
MORC4	Transcription factor	no		Znf_CW, HATPase_C_sf, Morc_S5
TBC1D8B	Other/Unknown	no		Rab-GAP-TBC_dom, EF_hand_dom, GRAM
RIPPLY1	Other/Unknown	no		Ripply_fam
TMEM67	Other/Unknown	no		Growth_fac_rcpt_cys_sf, Meckelin
PRSS1	Protease	yes		Trypsin_dom, Peptidase_S1A, Peptidase_S1_PA
PRSS2	Protease	yes		Trypsin_dom, Peptidase_S1A, Peptidase_S1_PA
PTCH1	Other/Unknown	no		SSD, TM_rcpt_patched, HMGCR/SNAP/NPC1-like_SSD

Expression context

Cohort genes with no expression data: 0.

12 cohort genes 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)	13
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	5
pancreas	4
islet of Langerhans	3
right lobe of liver	2
gall bladder	2
buccal mucosa cell	2
duodenum	1
oocyte	1
secondary oocyte	1
epithelial cell of pancreas	1
kidney epithelium	1
pancreatic ductal cell	1
lateral nuclear group of thalamus	1
sperm	1
colonic epithelium	1
placenta	1
tendon of biceps brachii	1
left adrenal gland cortex	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRPV6	125	tissue_specific	marker	body of pancreas, pancreas, duodenum
ABCB4	188	broad	marker	right lobe of liver, secondary oocyte, oocyte
SPINK1	192	broad	marker	body of pancreas, islet of Langerhans, epithelial cell of pancreas
CFTR	193	broad	marker	body of pancreas, gall bladder, pancreas
CLDN2	125	tissue_specific	marker	kidney epithelium, pancreatic ductal cell, gall bladder
CNTN4	214	broad	marker	sperm, buccal mucosa cell, lateral nuclear group of thalamus
MORC4	248	ubiquitous	marker	colonic epithelium, placenta, tendon of biceps brachii
TBC1D8B	237	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland cortex
RIPPLY1	85	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, right lobe of liver
TMEM67	203	ubiquitous	marker	buccal mucosa cell, right uterine tube, calcaneal tendon
PRSS1	127	tissue_specific	marker	body of pancreas, pancreas, islet of Langerhans
PRSS2	125	tissue_specific	marker	body of pancreas, pancreas, islet of Langerhans
PTCH1	275	ubiquitous	marker	tibia, dorsal root ganglion, trigeminal ganglion

Protein interactions among cohort

Intra-cohort edges: 12.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFTR	7,664
PTCH1	3,368
ABCB4	2,333
CNTN4	1,983
PRSS1	1,363
CLDN2	1,279
TRPV6	1,197
TMEM67	1,194
PRSS2	1,004
SPINK1	888

Intra-cohort edges

A	B	Sources
CFTR	PRSS1	intact, string_interaction
CFTR	PRSS2	string_interaction
CFTR	SPINK1	string_interaction
CLDN2	MORC4	string_interaction
MORC4	PRSS1	string_interaction
MORC4	PRSS2	string_interaction
MORC4	RIPPLY1	string_interaction
MORC4	SPINK1	string_interaction
PRSS1	PRSS2	biogrid_interaction, intact
PRSS1	SPINK1	string_interaction
PRSS2	SPINK1	string_interaction
RIPPLY1	TBC1D8B	string_interaction

Structural data

PDB: 10 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CFTR	P13569	58
TRPV6	Q9H1D0	24
PTCH1	Q13635	16
PRSS1	P07477	12
SPINK1	P00995	5
ABCB4	P21439	4
CLDN2	P57739	1
MORC4	Q8TE76	1
TMEM67	Q5HYA8	1
PRSS2	P07478	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CNTN4	Q8IWV2	86.72
TBC1D8B	Q0IIM8	79.33
RIPPLY1	Q0D2K3	61.12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 45. Enrichment computed across 13 evidence-associated genes (11 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 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Activation of Matrix Metalloproteinases	2	56.1×	0.013	PRSS1, PRSS2
Developmental Lineage of Pancreatic Acinar Cells	2	54.6×	0.013	SPINK1, PRSS1
Defective ABCB4 causes PFIC3, ICP3 and GBD1	1	1038.2×	0.014	ABCB4
RHO GTPases regulate CFTR trafficking	1	346.1×	0.032	CFTR
ABC-family protein mediated transport	2	22.1×	0.032	CFTR, ABCB4
GLI proteins bind promoters of Hh responsive genes to promote transcription	1	148.3×	0.049	PTCH1
Ligand-receptor interactions	1	129.8×	0.049	PTCH1
Uptake of dietary cobalamins into enterocytes	1	103.8×	0.053	PRSS1
Alpha-defensins	1	94.4×	0.053	PRSS2
Activation of SMO	1	57.7×	0.077	PTCH1
Chaperone Mediated Autophagy	1	45.1×	0.090	CFTR
ABC transporter disorders	1	39.9×	0.092	ABCB4
TRP channels	1	37.1×	0.092	TRPV6
Tight junction interactions	1	33.5×	0.095	CLDN2
Late endosomal microautophagy	1	29.7×	0.100	CFTR
trans-Golgi Network Vesicle Budding	1	23.1×	0.105	TBC1D8B
Aggrephagy	1	22.6×	0.105	CFTR
Developmental Lineage of Pancreatic Ductal Cells	1	20.8×	0.105	CFTR
Antimicrobial peptides	1	20.4×	0.105	PRSS2
Developmental Cell Lineages	1	20.4×	0.105	SPINK1
Defective CFTR causes cystic fibrosis	1	20.0×	0.105	CFTR
Golgi Associated Vesicle Biogenesis	1	18.2×	0.105	TBC1D8B
Class B/2 (Secretin family receptors)	1	17.3×	0.105	PTCH1
RHOQ GTPase cycle	1	16.5×	0.105	CFTR
Hedgehog ‘off’ state	1	16.2×	0.105	PTCH1
Collagen degradation	1	16.0×	0.105	PRSS2
Post-translational modification: synthesis of GPI-anchored proteins	1	15.3×	0.106	CNTN4
Hedgehog ‘on’ state	1	14.4×	0.108	PTCH1
Regulation of lipid metabolism by PPARalpha	1	12.8×	0.114	ABCB4
Disorders of transmembrane transporters	1	12.7×	0.114	ABCB4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 12 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
sperm capacitation	2	112.3×	0.010	SPINK1, CFTR
digestion	2	104.0×	0.010	PRSS1, PRSS2
response to chlorate	1	702.2×	0.018	PTCH1
obsolete negative regulation of nitric oxide mediated signal transduction	1	702.2×	0.018	SPINK1
neural plate axis specification	1	702.2×	0.018	PTCH1
parathyroid hormone secretion	1	702.2×	0.018	TRPV6
cell proliferation involved in metanephros development	1	702.2×	0.018	PTCH1
response to fenofibrate	1	702.2×	0.018	ABCB4
regulation of intestinal D-glucose absorption	1	702.2×	0.018	CLDN2
extracellular matrix disassembly	2	61.1×	0.018	PRSS1, PRSS2
intracellular pH elevation	1	468.1×	0.019	CFTR
cell differentiation involved in kidney development	1	468.1×	0.019	PTCH1
regulation of bile acid secretion	1	468.1×	0.019	CLDN2
regulation of intestinal lipid absorption	1	468.1×	0.019	CLDN2
transmembrane transport	2	28.1×	0.019	CFTR, ABCB4
positive regulation of phospholipid translocation	1	351.1×	0.019	ABCB4
cellular response to bile acid	1	351.1×	0.019	ABCB4
somite specification	1	280.9×	0.019	RIPPLY1
epidermal cell fate specification	1	280.9×	0.019	PTCH1
negative regulation of centrosome duplication	1	280.9×	0.019	TMEM67
bile acid secretion	1	280.9×	0.019	ABCB4
transepithelial water transport	1	280.9×	0.019	CFTR
regulation of acrosome reaction	1	280.9×	0.019	SPINK1
positive regulation of enamel mineralization	1	280.9×	0.019	CFTR
neural tube patterning	1	234.1×	0.020	PTCH1
hindlimb morphogenesis	1	234.1×	0.020	PTCH1
positive regulation of cholesterol transport	1	200.6×	0.020	ABCB4
negative regulation of cell division	1	200.6×	0.020	PTCH1
mammary gland duct morphogenesis	1	200.6×	0.020	PTCH1
negative regulation of calcium ion import	1	200.6×	0.020	SPINK1

Therapeutics

Drugs indicated for this disease

1 approved, 3 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Icosapent Ethyl	Approved (phase 4)
Doripenem	Phase 3 (in late-stage trials)
Indomethacin	Phase 3 (in late-stage trials)
Magnesium Sulfate Anhydrous	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Hydrocortisone, Naldemedine, Pancrelipase, Pirfenidone, Secretin, Valdecoxib.

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 5 · Undrugged: 8

Druggability breadth: 6 of 13 evidence-associated genes (46%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
TRPV6	ECONAZOLE
CFTR	IVACAFTOR
PRSS1	ARGATROBAN
PRSS2	ARGATROBAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRSS1	17	4
CFTR	14	4
PRSS2	12	4
TRPV6	3	4
ABCB4	1	2
SPINK1	0	0
CLDN2	0	0
CNTN4	0	0
MORC4	0	0
TBC1D8B	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ECONAZOLE	4	TRPV6
IVACAFTOR	4	CFTR
LUMACAFTOR	4	CFTR
TEZACAFTOR	4	CFTR
ELEXACAFTOR	4	CFTR
GLYBURIDE	4	CFTR
ARGATROBAN	4	PRSS1, PRSS2
MELAGATRAN	4	PRSS1, PRSS2
SULFAGUANIDINE	4	PRSS1, PRSS2
BEROTRALSTAT	4	PRSS1, PRSS2
RUTIN	3	CFTR, PRSS1, PRSS2
BAMOCAFTOR	3	CFTR
QUERCETIN	3	CFTR, PRSS1, PRSS2
NAFAMOSTAT	3	PRSS1
OTAMIXABAN	3	PRSS1
CAMOSTAT	3	PRSS1, PRSS2
CAMOSTAT MESILATE	3	PRSS1
MILVEXIAN	3	PRSS1, PRSS2
DABIGATRAN	3	PRSS1, PRSS2
SILIBININ	3	PRSS1, PRSS2
TETRAHYDROCANNABIVARIN	2	TRPV6
BMS-986020	2	ABCB4
GALICAFTOR	2	CFTR
GENISTEIN	2	CFTR
ICENTICAFTOR	2	CFTR
NAVOCAFTOR	2	CFTR
RISELCAFTOR	2	CFTR
GLPG-2737	2	CFTR
EFEGATRAN	2	PRSS1
SEPIMOSTAT	2	PRSS1, PRSS2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PRSS1	674	Binding:616, ADMET:51, Functional:7
CFTR	520	Binding:497, Functional:17, ADMET:5, Toxicity:1
PRSS2	386	Binding:335, ADMET:51
TRPV6	32	Binding:32
ABCB4	4	ADMET:3, Binding:1
PTCH1	4	Binding:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CFTR	2.7.4.3, 5.6.1.6	adenylate kinase, channel-conductance-controlling ATPase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CFTR	520
PRSS1	674
PRSS2	386

Pharmacogenomics

Cohort genes with a PharmGKB record: 13; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
CFTR	1

Chemical tractability of cohort targets

30 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.

Compound	Max phase	Cohort target (bioactivity)
ECONAZOLE	4	TRPV6
IVACAFTOR	4	CFTR
LUMACAFTOR	4	CFTR
TEZACAFTOR	4	CFTR
ELEXACAFTOR	4	CFTR
GLYBURIDE	4	CFTR
ARGATROBAN	4	PRSS1, PRSS2
MELAGATRAN	4	PRSS1, PRSS2
SULFAGUANIDINE	4	PRSS1, PRSS2
BEROTRALSTAT	4	PRSS1, PRSS2
RUTIN	3	CFTR, PRSS1, PRSS2
BAMOCAFTOR	3	CFTR
QUERCETIN	3	CFTR, PRSS1, PRSS2
NAFAMOSTAT	3	PRSS1
OTAMIXABAN	3	PRSS1
CAMOSTAT	3	PRSS1, PRSS2
CAMOSTAT MESILATE	3	PRSS1
MILVEXIAN	3	PRSS1, PRSS2
DABIGATRAN	3	PRSS1, PRSS2
SILIBININ	3	PRSS1, PRSS2
TETRAHYDROCANNABIVARIN	2	TRPV6
BMS-986020	2	ABCB4
GALICAFTOR	2	CFTR
GENISTEIN	2	CFTR
ICENTICAFTOR	2	CFTR
NAVOCAFTOR	2	CFTR
RISELCAFTOR	2	CFTR
GLPG-2737	2	CFTR
EFEGATRAN	2	PRSS1
SEPIMOSTAT	2	PRSS1, PRSS2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	TRPV6, CFTR, PRSS1, PRSS2
B	Phased (≥1) drug, not yet approved	1	ABCB4
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	CNTN4
E	Difficult family or no structure, no drug	7	SPINK1, CLDN2, MORC4, TBC1D8B, RIPPLY1, TMEM67, PTCH1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SPINK1	0	PRSS1, PRSS2
MORC4	0	PRSS2, PRSS1
CLDN2	0	—
CNTN4	0	—
TBC1D8B	0	—
RIPPLY1	0	—
TMEM67	0	—
PTCH1	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 176.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	127
PHASE4	17
PHASE3	10
PHASE2	10
PHASE1	5
PHASE2/PHASE3	4
PHASE1/PHASE2	2
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05659147	PHASE4	ENROLLING_BY_INVITATION	Imaging Biomarkers of Pancreatic Function and Disease
NCT07024199	PHASE4	RECRUITING	Comparison of the Effectiveness of Paracetamol With Ibuprofen or Paracetamol With Metamizole in Treating Pain in Acute Pancreatitis in Children
NCT07083063	PHASE4	RECRUITING	Precise Endoscopic Application of Nitroglycerin in Preventing Post-ERCP Pancreatitis
NCT07262957	PHASE4	RECRUITING	Preventing Postoperative Complications in Patients Undergoing High-risk Pancreatoduodenectomy With a Bundle Approach Including Hydrocortisone, Octreotide, and the Teres Ligament Patch (PANENCA)
NCT00318994	PHASE4	COMPLETED	Evaluation of Pancreatic Tissue Penetration of Meronem® in the Prophylaxis of Septic Complications in Severe Pancreatitis
NCT00428025	PHASE4	TERMINATED	Diclofenac for the Prevention of Post-ERCP Pancreatitis in Higher Risk Patients
NCT00786929	PHASE4	COMPLETED	Acute Pancreatitis and Acute Fluid Collections
NCT00999232	PHASE4	COMPLETED	Assess the Effect of Erythromycin on the Rate of Success in Placement of a Self-propelled Feeding Tube
NCT01070680	PHASE4	COMPLETED	Dexmedetomidine Versus Placebo in Endoscopic Retrograde Cholangiopancreatography (ERCP) Sedation
NCT01132521	PHASE4	SUSPENDED	Ulinastatin in Severe Acute Pancreatitis
NCT01186562	PHASE4	COMPLETED	Sitagliptin Therapy to Improve Outcomes After Islet Autotransplant
NCT01744847	PHASE4	COMPLETED	DGT Versus TPS in Patients With Initial PD Cannulation by Chance; Prospective Multi-center Study
NCT01784445	PHASE4	COMPLETED	Post ERCP Pancreatitis Prevention in Average Risk Patients
NCT02027311	PHASE4	COMPLETED	Etomidate vs. Midazolam for Sedation During ERCP
NCT02281799	PHASE4	WITHDRAWN	Thiopurine Induced Pancreatitis in IBD Patients
NCT02465138	PHASE4	WITHDRAWN	A Randomized Controlled Trial of IV Ketorolac to Prevent Post-ERCP Pancreatitis
NCT02797067	PHASE4	COMPLETED	Rectal Indomethacin to Prevent Post ESWL-pancreatitis
NCT06691893	PHASE3	RECRUITING	Evaluating the Efficacy of RELiZORB in Managing Exocrine Pancreatic Insufficiency in Tube-fed Pancreatitis Patients
NCT00121901	PHASE3	COMPLETED	Does Glyceryl Nitrate Prevent Post-Endoscopic Retrograde Cholangiopancreaticography (ERCP) Pancreatitis?
NCT00142233	PHASE3	COMPLETED	EUROPAC-2 - Pain Treatment of Hereditary and Idiopathic Pancreatitis
NCT00210938	PHASE3	COMPLETED	Doripenem in the Treatment of Complicated Intra-Abdominal Infections
NCT00229060	PHASE3	COMPLETED	Doripenem in the Treatment of Complicated Intra-Abdominal Infections
NCT00419549	PHASE2/PHASE3	TERMINATED	Efficacy Study of Glyceryl-Trinitrate Patch and Parecoxib (Valdecoxib) for the Prevention of Pancreatitis After Endoscopic Retrograde Cholangiopancreatography (ERCP)
NCT00660335	PHASE3	COMPLETED	Safety and Efficacy of Synthetic Human Secretin-Enhanced MRCP in Subjects With Abnormalities of the Pancreas
NCT02050048	PHASE2/PHASE3	TERMINATED	High Volume Lactated Ringer’s Solution and Pancreatitis
NCT02573389	PHASE3	SUSPENDED	Pancreatic Duct Stenting to Prevent Postoperative Pancreatic Fistula (POPF) After Distal Pancreatectomy
NCT02709044	PHASE2/PHASE3	UNKNOWN	Fluid Resuscitation in Acute Pancreatitis
NCT02821546	PHASE3	COMPLETED	Aggressive Fluid Hydration for the Prevention of Post-ERCP Pancreatitis
NCT04021498	PHASE3	TERMINATED	Simvastatin in the Prevention of Recurrent Pancreatitis
NCT07381478	PHASE2/PHASE3	COMPLETED	3°C Saline Injection at the Duodenal Papilla to Prevent Post-ERCP Pancreatitis
NCT07599605	PHASE3	COMPLETED	Prophylaxis Against Post-Endoscopic Retrograde Cholangio-Pancreatography Pancreatitis.
NCT05160506	PHASE2	RECRUITING	Corticosteroids to Treat Pancreatitis
NCT07012772	PHASE2	RECRUITING	COMBO Endoscopy Oropharyngeal Airway in Sedated Endoscopic Retrograde Cholangiopancreatography for Patients
NCT07051980	PHASE2	RECRUITING	Feasibility and Safety of Supraglottic Oxygen Delivery Via an Endotracheal Tube for Non-intubated ERCP Anesthesia: A Two-Stage Phase II Clinical Study
NCT00040131	PHASE2	TERMINATED	Safety and Efficacy Study of IL-10 (Tenovil TM) in the Prevention of Post-ERCP Acute Pancreatitis (Study P02580)(TERMINATED)
NCT00133835	PHASE1/PHASE2	COMPLETED	Comparison of ESWL Alone and ESWL + Endoscopy for Painful Chronic Pancreatitis
NCT00156403	PHASE1/PHASE2	COMPLETED	A Pilot Study of Use of Calcium Channel Blocker to Decrease Inflammation and Pain in Hereditary Pancreatitis
NCT01460615	PHASE2	COMPLETED	Cortisone Treatment for the Prevention of Postoperative Pancreatitis and Pancreatitis-induced Complications After Pancreaticoduodenectomy and Distal Pancreatic Resection
NCT01794858	PHASE2	WITHDRAWN	Therapeutic Hypothermia for Severe Acute Pancreatitis
NCT02025049	PHASE2	TERMINATED	DP-b99 in the Treatment of Acute High-risk Pancreatitis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
INDOMETHACIN	4	3
KETOROLAC	4	3
DORIPENEM	4	2
LACTIC ACID	4	2
APROTININ	4	1
AZATHIOPRINE	4	1
CEFTAZIDIME	4	1
DEXMEDETOMIDINE HYDROCHLORIDE	4	1
DICLOFENAC	4	1
ERYTHROMYCIN	4	1
ETOMIDATE	4	1
FIBRINOGEN I 125	4	1
GLYCERIN	4	1
ISOSORBIDE DINITRATE	4	1
LIDOCAINE HYDROCHLORIDE	4	1
MEPERIDINE	4	1
MEROPENEM	4	1
MIDAZOLAM	4	1
NITROGLYCERIN	4	1
PANCRELIPASE	4	1
PANTOPRAZOLE	4	1
SECRETIN	4	1
SITAGLIPTIN	4	1
VALDECOXIB	4	1
D-LACTIC ACID	3	2
MAGNESIUM	3	1
NITRIC ACID	3	1
PANCREATIN	3	1
ULINASTATIN	3	1
INTERLEUKIN-10	2	1