Exocrine pancreatic insufficiency

Summary

Exocrine pancreatic insufficiency (MONDO:0001684) is a disease with 2 cohort genes and 60 clinical trials. Top therapeutic interventions include pancrelipase, esomeprazole, and omeprazole.

At a glance

• Cohort genes: 2
• ClinVar variants: 2
• Clinical trials: 60

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	exocrine pancreatic insufficiency
Mondo ID	MONDO:0001684
MeSH	D010188
DOID	DOID:13316
ICD-10-CM	K86.81
NCIT	C84316
SNOMED CT	47367009
UMLS	C0267963
MedGen	75647
Anatomy (UBERON)	UBERON:0000017
Is cancer (heuristic)	no

Also known as: exocrine pancreatic insufficiency

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › pancreas disorder › exocrine pancreatic insufficiency

Related subtypes (13): pancreatic steatorrhea, pancreatic mucinous ductal ectasia, endocrine pancreas disorder, pancreatitis, 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 (1): pancreatic insufficiency-anemia-hyperostosis syndrome

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

2 retrieved; paginated sample, class counts are floors:

1 likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1683711	NM_001378183.1(PIEZO2):c.64+1G>A	PIEZO2	Likely pathogenic	criteria provided, single submitter
1707508	NM_014633.5(CTR9):c.85G>A (p.Glu29Lys)	CTR9	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CTR9	Orphanet:528084	Non-specific syndromic intellectual disability
CTR9	Orphanet:654	Nephroblastoma
PIEZO2	Orphanet:1154	Arthrogryposis-oculomotor limitation-electroretinal anomalies syndrome
PIEZO2	Orphanet:2461	Marden-Walker syndrome
PIEZO2	Orphanet:376	Gordon syndrome
PIEZO2	Orphanet:707937	Distal arthrogryposis-progressive scoliosis-thumb deformity-impaired proprioception syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CTR9	HGNC:16850	ENSG00000198730	Q6PD62	RNA polymerase-associated protein CTR9 homolog	clinvar
PIEZO2	HGNC:26270	ENSG00000154864	Q9H5I5	Piezo-type mechanosensitive ion channel component 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CTR9	RNA polymerase-associated protein CTR9 homolog	Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency.
PIEZO2	Piezo-type mechanosensitive ion channel component 2	Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CTR9	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, Ctr9
PIEZO2	Other/Unknown	no		Piezo, Piezo_cap_dom, Piezo_TM25-28

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus epididymis	1
epithelium of nasopharynx	1
palpebral conjunctiva	1
corpus callosum	1
dorsal root ganglion	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CTR9	292	ubiquitous	marker	corpus epididymis, epithelium of nasopharynx, palpebral conjunctiva
PIEZO2	237	broad	marker	sural nerve, corpus callosum, dorsal root ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTR9	4,367
PIEZO2	1,787

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTR9	Q6PD62	21
PIEZO2	Q9H5I5	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 2 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
Dengue virus activates/modulates innate and adaptive immune responses	1	335.9×	0.008	CTR9
Formation of RNA Pol II elongation complex	1	193.6×	0.008	CTR9
RNA Polymerase II Transcription Elongation	1	193.6×	0.008	CTR9
E3 ubiquitin ligases ubiquitinate target proteins	1	193.6×	0.008	CTR9
RNA Polymerase II Pre-transcription Events	1	137.6×	0.009	CTR9
CHD1 and CHD2 subfamily	1	108.8×	0.009	CTR9

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
endodermal cell fate commitment	1	1404.3×	0.004	CTR9
inner cell mass cell differentiation	1	1404.3×	0.004	CTR9
blastocyst growth	1	1404.3×	0.004	CTR9
detection of mechanical stimulus involved in sensory perception	1	1404.3×	0.004	PIEZO2
detection of mechanical stimulus	1	601.9×	0.006	PIEZO2
interleukin-6-mediated signaling pathway	1	561.7×	0.006	CTR9
trophectodermal cell differentiation	1	495.6×	0.006	CTR9
negative regulation of myeloid cell differentiation	1	468.1×	0.006	CTR9
monoatomic cation transport	1	383.0×	0.006	PIEZO2
blastocyst hatching	1	271.8×	0.008	CTR9
transcription elongation by RNA polymerase II	1	221.7×	0.008	CTR9
stem cell population maintenance	1	210.7×	0.008	CTR9
negative regulation of gene expression, epigenetic	1	200.6×	0.008	CTR9
response to mechanical stimulus	1	150.5×	0.010	PIEZO2
cell surface receptor signaling pathway via JAK-STAT	1	145.3×	0.010	CTR9
regulation of membrane potential	1	115.4×	0.011	PIEZO2
cellular response to mechanical stimulus	1	108.0×	0.011	PIEZO2
Wnt signaling pathway	1	49.9×	0.022	CTR9
cellular response to lipopolysaccharide	1	49.0×	0.022	CTR9
negative regulation of transcription by RNA polymerase II	1	8.9×	0.115	CTR9
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	CTR9

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
Pancreas Powder, Porcine	Approved (phase 4)
Liprotamase	Phase 3 (in late-stage trials)
Omeprazole	Phase 3 (in late-stage trials)
Pancrelipase	Phase 3 (in late-stage trials)

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CTR9	1	2
PIEZO2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	CTR9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CTR9	8	Binding:8

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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)
MOLIBRESIB	2	CTR9

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	1	CTR9
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PIEZO2

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)
PIEZO2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 60.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	25
PHASE3	13
PHASE4	11
PHASE2	8
PHASE1	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06477159	PHASE4	RECRUITING	Pancreatic Enzyme Replacement Therapy for Acute Pancreatitis-Associated Exocrine Pancreatic Insufficiency
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
NCT00744250	PHASE4	TERMINATED	Intraduodenal Aspiration Study to Assess the Bioavailability of Oral Pancrecarb® Compared to Placebo Control
NCT01100606	PHASE4	COMPLETED	A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age
NCT01131507	PHASE4	COMPLETED	PR-018: An Open-Label, Safety Extension of Study PR-011
NCT01327703	PHASE4	COMPLETED	Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
NCT01430234	PHASE4	COMPLETED	Enzyme Suppletion in Exocrine Pancreatic Dysfunction
NCT02823964	PHASE4	COMPLETED	EASY: Extended Access to Sollpura Over Years
NCT03859869	PHASE4	TERMINATED	A Study of Creon (Pancrelipase) in Resected and Non-resected Pancreatic Cancer Participants With Exocrine Pancreatic Insufficiency (EPI)
NCT04315311	PHASE4	WITHDRAWN	Study Of Effects Of Oral CREON Capsules In Adult Participants With Exocrine Pancreatic Insufficiency Not Due To Cystic Fibrosis, Chronic Pancreatitis, Pancreatectomy, Or Pancreatic Cancer
NCT06691893	PHASE3	RECRUITING	Evaluating the Efficacy of RELiZORB in Managing Exocrine Pancreatic Insufficiency in Tube-fed Pancreatitis Patients
NCT00297167	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of EUR-1008 (APT-1008) Pancreatic Enzyme Product in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
NCT00408317	PHASE3	COMPLETED	Safety and Efficacy Study of ULTRASE® MT20 in Participants With Cystic Fibrosis (CF) and Exocrine Pancreatic Insufficiency (PI)
NCT00449878	PHASE3	COMPLETED	Liprotamase Efficacy Trial in Patients With Cystic Fibrosis-Related Exocrine Pancreatic Insufficiency
NCT00449904	PHASE3	COMPLETED	Open-Label Phase III Long-Term Safety Trial of Liprotamase
NCT00500084	PHASE3	TERMINATED	Phase III ALTU-135 CP Safety Trial
NCT00559364	PHASE3	COMPLETED	Safety and Efficacy Study of Viokase® 16 for the Correction of Steatorrhea
NCT00662675	PHASE3	COMPLETED	A Study of the Efficacy and Tolerability of Pancrelipase Microtablet (MT) Capsules for the Treatment of Cystic Fibrosis-dependent Exocrine Pancreatic Insufficiency
NCT00788593	PHASE3	COMPLETED	A Randomized, Double-Blind, Dose Response-Control, Crossover Study to Evaluate the Safety and Efficacy of Two Doses of EUR-1008 (APT-1008) in Chronic Pancreatitis (CP) Participants With Exocrine Pancreatic Insufficiency (EPI)
NCT00981214	PHASE3	COMPLETED	Study of Pancreatic Enzyme Product in Pediatric Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
NCT02279498	PHASE3	COMPLETED	SOLUTION: Study of Oral Liprotamase Unit-Matched Therapy Of Non-Porcine Origin in Patients With Cystic Fibrosis
NCT02734810	PHASE3	COMPLETED	SIMPLICITY: Studying Impacts on Malabsorption With Liprotamase in Cystic Fibrosis
NCT03051490	PHASE3	UNKNOWN	RESULT: Reliable, Emergent Solution Using Liprotamase Treatment
NCT07450547	PHASE2	RECRUITING	Phase 2 Study to Assess the Safety and Efficacy of ANG003
NCT07559175	PHASE2	NOT_YET_RECRUITING	A Study to Evaluate Safety and Explore Efficacy of New Lipase NHS7108 in Adult Participants With Exocrine Pancreatic Insufficiency.
NCT00559052	PHASE2	COMPLETED	An Open-Label Study to Evaluate the Intraduodenal Delivery of Enzymes From Administration of VIOKASE16 in Exocrine Pancreatic Insufficiency (EPI)
NCT00743483	PHASE2	COMPLETED	Efficacy of Bucelipase Alfa (BSSL) in Patients With Cystic Fibrosis and Pancreatic Insufficiency
NCT02370537	PHASE2	COMPLETED	A Study to Investigate How Common Pancreatic Exocrine Insufficiency (PEI) is in Patients With Type 2 Diabetes and Also to Investigate the Uptake of a Single Dose of EPANOVA® or OMACOR® in Patients With Different Degrees of PEI
NCT03746483	PHASE2	COMPLETED	OPTION: A Trial to Assess the Safety & Efficacy of MS1819 in Patients With Exocrine Pancreatic Insufficiency Due to Cystic Fibrosis
NCT04375878	PHASE2	COMPLETED	OPTION 2: A Trial to Assess the Safety and Efficacy of MS1819 in Enteric Capsules in Patients With Cystic Fibrosis
NCT05719311	PHASE2	COMPLETED	Study to Assess an Enteric Microgranule Formulation of Adrulipase in Patients With Cystic Fibrosis
NCT00676702	PHASE1	COMPLETED	A Study of the Enzyme Activity and Safety of Pancrelipase in Patients With Severe Exocrine Pancreatic Insufficiency (EPI)
NCT05082051	PHASE1	COMPLETED	Oral CDX-7108 in Healthy Adults and EPI Subjects
NCT06052293	PHASE1	COMPLETED	Phase 1 Study to Assess Safety and Efficacy of ANG003
NCT02175459	Not specified	RECRUITING	Investigating Predictive Factors of Diabetes Occurence After Duodenalpancreatectomy
NCT05112328	Not specified	RECRUITING	The Effects of Pancreatic Enzyme Supplementation in Critically Ill Patients on Enteral Feeding
NCT05710315	Not specified	RECRUITING	Evaluating the Utility of RELiZORB™ for Treating Feeding Intolerance in Critically Ill Adults With Multi-Organ Failure
NCT06756503	Not specified	NOT_YET_RECRUITING	Exocrine Pancreatic Insufficiency and Functional Dyspepsia
NCT06757348	Not specified	NOT_YET_RECRUITING	Fatty Liver and Pancreatic Steatosis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PANCRELIPASE	4	5
ESOMEPRAZOLE	4	1
OMEPRAZOLE	4	1
LIPROTAMASE	3	6
PANCREATIN	3	2
MS-1819	2	2
ELASTASE	-1	2