Chronic diarrheal disease

Summary

Chronic diarrheal disease (MONDO:0044751) is a disease with 4 cohort genes and 27 clinical trials. Top therapeutic interventions include colesevelam, albendazole, and metronidazole.

At a glance

• Cohort genes: 4
• ClinVar variants: 6
• Clinical trials: 27

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	chronic diarrheal disease
Mondo ID	MONDO:0044751
SNOMED CT	236071009
UMLS	C0401151
MedGen	96036
Is cancer (heuristic)	no

Also known as: chronic diarrhea · chronic diarrhoea · diarrheal disease, chronic

Data availability: 6 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 › diarrheal disease › chronic diarrheal disease

Related subtypes (6): secretory diarrhea, diarrheal disease secondary to altered bowel motility, inflammatory diarrhea, acute diarrhea, congenital diarrhea, non-infectious diarrheal disease

Subtypes (1): chronic diarrhea due to glucoamylase deficiency

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

6 retrieved; paginated sample, class counts are floors:

2 likely pathogenic, 2 pathogenic, 1 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
268039	46;XY;t(3;18)(q13.31;q22.1)dn		Pathogenic	criteria provided, single submitter
374107	NM_001370259.2(MEN1):c.654+1del	MEN1	Pathogenic	criteria provided, single submitter
1172627	NM_152641.4(ARID2):c.5061+2T>C	ARID2	Likely pathogenic	criteria provided, single submitter
545432	NM_024494.3(WNT2B):c.205C>T (p.Arg69Ter)	WNT2B	Likely pathogenic	criteria provided, single submitter
410674	NM_198253.3(TERT):c.1931C>T (p.Thr644Met)	TERT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
267932	46;XX;t(1;13)(q11.2;p11.2)dn		Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 18 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TERT	Orphanet:146	Differentiated thyroid carcinoma
TERT	Orphanet:1501	Adrenocortical carcinoma
TERT	Orphanet:1775	Dyskeratosis congenita
TERT	Orphanet:2032	Idiopathic pulmonary fibrosis
TERT	Orphanet:2495	Meningioma
TERT	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
TERT	Orphanet:457246	Clear cell sarcoma of kidney
TERT	Orphanet:618	Familial melanoma
TERT	Orphanet:88	Idiopathic aplastic anemia
WNT2B	Orphanet:714487	Congenital diarrhea-chronic gastrointestinal inflammation-ocular dysgenesis syndrome
ARID2	Orphanet:1465	Coffin-Siris syndrome
MEN1	Orphanet:2965	Prolactinoma
MEN1	Orphanet:314786	Silent pituitary adenoma
MEN1	Orphanet:314790	Null pituitary adenoma
MEN1	Orphanet:652	Multiple endocrine neoplasia type 1
MEN1	Orphanet:97279	Insulinoma
MEN1	Orphanet:99725	Pituitary gigantism
MEN1	Orphanet:99879	Familial isolated hyperparathyroidism

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	clinvar
WNT2B	HGNC:12781	ENSG00000134245	Q93097	Protein Wnt-2b	clinvar
ARID2	HGNC:18037	ENSG00000189079	Q68CP9	AT-rich interactive domain-containing protein 2	clinvar
MEN1	HGNC:7010	ENSG00000133895	O00255	Menin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
WNT2B	Protein Wnt-2b	Ligand for members of the frizzled family of seven transmembrane receptors.
ARID2	AT-rich interactive domain-containing protein 2	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
MEN1	Menin	Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates ‘Lys-4’ of histone H3 (H3K4).

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 3 · 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
Transcription factor	1	2.1×	0.404
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
WNT2B	Other/Unknown	no		Wnt, Wnt2, Wnt_CS
ARID2	Transcription factor	no		ARID_dom, DNA-bd_RFX, Znf_C2H2_type
MEN1	Other/Unknown	no		Menin

Expression context

Cohort genes with no expression data: 0.

3 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
olfactory bulb	1
stromal cell of endometrium	1
type B pancreatic cell	1
buccal mucosa cell	1
germinal epithelium of ovary	1
parietal pleura	1
pancreatic ductal cell	1
secondary oocyte	1
sperm	1
granulocyte	1
lower esophagus mucosa	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
WNT2B	231	broad	marker	germinal epithelium of ovary, buccal mucosa cell, parietal pleura
ARID2	253	ubiquitous	marker	sperm, pancreatic ductal cell, secondary oocyte
MEN1	271	ubiquitous	marker	granulocyte, lower esophagus mucosa, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TERT	5,717
MEN1	5,226
ARID2	2,190
WNT2B	1,512

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MEN1	O00255	69
TERT	O14746	23
ARID2	Q68CP9	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
WNT2B	Q93097	86.85

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 41. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the beta-catenin:TCF transactivating complex	2	60.1×	0.006	TERT, MEN1
TCF dependent signaling in response to WNT	2	58.9×	0.006	TERT, MEN1
Signaling by WNT	2	56.0×	0.006	TERT, MEN1
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	407.9×	0.025	TERT
Formation of the polybromo-BAF (pBAF) complex	1	158.6×	0.039	ARID2
Extension of Telomeres	1	150.3×	0.039	TERT
Telomere Extension By Telomerase	1	114.2×	0.039	TERT
WNT ligand biogenesis and trafficking	1	105.7×	0.039	WNT2B
Telomere Maintenance	1	92.1×	0.039	TERT
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1	92.1×	0.039	MEN1
RHO GTPases activate IQGAPs	1	86.5×	0.039	MEN1
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	1	77.2×	0.039	MEN1
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	75.1×	0.039	ARID2
RNA Polymerase II Transcription	2	11.3×	0.039	ARID2, MEN1
Formation of WDR5-containing histone-modifying complexes	1	66.4×	0.041	MEN1
Deactivation of the beta-catenin transactivating complex	1	58.3×	0.042	MEN1
Gene expression (Transcription)	2	8.9×	0.042	ARID2, MEN1
Chromosome Maintenance	1	52.9×	0.043	TERT
Signaling by TGF-beta Receptor Complex	1	50.1×	0.043	MEN1
Class B/2 (Secretin family receptors)	1	47.6×	0.043	WNT2B
MITF-M-dependent gene expression	1	45.3×	0.043	TERT
Epigenetic regulation by WDR5-containing histone modifying complexes	1	38.6×	0.043	MEN1
RMTs methylate histone arginines	1	36.6×	0.043	ARID2
Transcriptional regulation by RUNX1	1	36.6×	0.043	ARID2
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	36.6×	0.043	MEN1
Generic Transcription Pathway	2	7.5×	0.043	ARID2, MEN1
Signaling by TGFB family members	1	28.8×	0.051	MEN1
MITF-M-regulated melanocyte development	1	28.6×	0.051	TERT
Post-translational protein phosphorylation	1	25.0×	0.056	MEN1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	21.6×	0.062	MEN1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
RNA-templated transcription	1	4213.0×	0.005	TERT
DNA strand elongation	1	4213.0×	0.005	TERT
siRNA transcription	1	4213.0×	0.005	TERT
positive regulation of transdifferentiation	1	4213.0×	0.005	TERT
RNA-templated DNA biosynthetic process	1	2106.5×	0.007	TERT
positive regulation of hair cycle	1	2106.5×	0.007	TERT
lung induction	1	1404.3×	0.007	WNT2B
mesenchymal-epithelial cell signaling	1	1404.3×	0.007	WNT2B
forebrain regionalization	1	842.6×	0.011	WNT2B
positive regulation of protein localization to nucleolus	1	702.2×	0.011	TERT
negative regulation of cyclin-dependent protein serine/threonine kinase activity	1	526.6×	0.011	MEN1
establishment of protein localization to telomere	1	526.6×	0.011	TERT
siRNA processing	1	468.1×	0.011	TERT
T-helper 2 cell differentiation	1	468.1×	0.011	MEN1
coronary artery morphogenesis	1	468.1×	0.011	ARID2
iris morphogenesis	1	468.1×	0.011	WNT2B
homeostatic process	1	421.3×	0.012	ARID2
telomere maintenance via recombination	1	383.0×	0.012	TERT
cornea development in camera-type eye	1	324.1×	0.013	WNT2B
negative regulation of cell population proliferation	2	21.1×	0.014	ARID2, MEN1
osteoblast development	1	247.8×	0.015	MEN1
replicative senescence	1	247.8×	0.015	TERT
positive regulation of vascular associated smooth muscle cell migration	1	247.8×	0.015	TERT
nucleosome disassembly	1	200.6×	0.016	ARID2
DNA biosynthetic process	1	200.6×	0.016	TERT
positive regulation of branching involved in ureteric bud morphogenesis	1	200.6×	0.016	WNT2B
telomere maintenance via telomerase	1	183.2×	0.016	TERT
obsolete negative regulation of DNA-binding transcription factor activity	1	183.2×	0.016	MEN1
response to cadmium ion	1	183.2×	0.016	TERT
regulation of G0 to G1 transition	1	168.5×	0.016	ARID2

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 2

Druggability breadth: 3 of 4 evidence-associated genes (75%) 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
TERT	BERBERINE
MEN1	LOPERAMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MEN1	475	4
TERT	10	4
WNT2B	0	0
ARID2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BERBERINE	4	MEN1, TERT
DOXORUBICIN	4	TERT
LOPERAMIDE	4	MEN1
CANDESARTAN CILEXETIL	4	MEN1
EVANS BLUE FREE ACID	4	MEN1
DIENESTROL	4	MEN1
BEXAROTENE	4	MEN1
IFOSFAMIDE	4	MEN1
PROGESTERONE	4	MEN1
CLOTRIMAZOLE	4	MEN1
AMINOCAPROIC ACID	4	MEN1
LATANOPROST	4	MEN1
FLUORESCEIN	4	MEN1
OXCARBAZEPINE	4	MEN1
SALMETEROL XINAFOATE	4	MEN1
AMIODARONE HYDROCHLORIDE	4	MEN1
TRICLABENDAZOLE	4	MEN1
TRYPAN BLUE FREE ACID	4	MEN1
MIGALASTAT	4	MEN1
DROPERIDOL	4	MEN1
ARIPIPRAZOLE	4	MEN1
AMOXAPINE	4	MEN1
RALOXIFENE HYDROCHLORIDE	4	MEN1
IDARUBICIN	4	MEN1
ACETAMINOPHEN	4	MEN1
OXYBUTYNIN CHLORIDE	4	MEN1
DECAMETHONIUM BROMIDE	4	MEN1
DESLORATADINE	4	MEN1
DITHIAZANINE	4	MEN1
TRIMETREXATE	4	MEN1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TERT	391	Binding:389, Functional:2
MEN1	93	Binding:86, Functional:7
ARID2	7	Binding:7

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TERT	391

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

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)
BERBERINE	4	MEN1, TERT
DOXORUBICIN	4	TERT
LOPERAMIDE	4	MEN1
CANDESARTAN CILEXETIL	4	MEN1
EVANS BLUE FREE ACID	4	MEN1
DIENESTROL	4	MEN1
BEXAROTENE	4	MEN1
IFOSFAMIDE	4	MEN1
PROGESTERONE	4	MEN1
CLOTRIMAZOLE	4	MEN1
AMINOCAPROIC ACID	4	MEN1
LATANOPROST	4	MEN1
FLUORESCEIN	4	MEN1
OXCARBAZEPINE	4	MEN1
SALMETEROL XINAFOATE	4	MEN1
AMIODARONE HYDROCHLORIDE	4	MEN1
TRICLABENDAZOLE	4	MEN1
TRYPAN BLUE FREE ACID	4	MEN1
MIGALASTAT	4	MEN1
DROPERIDOL	4	MEN1
ARIPIPRAZOLE	4	MEN1
AMOXAPINE	4	MEN1
RALOXIFENE HYDROCHLORIDE	4	MEN1
IDARUBICIN	4	MEN1
ACETAMINOPHEN	4	MEN1
OXYBUTYNIN CHLORIDE	4	MEN1
DECAMETHONIUM BROMIDE	4	MEN1
DESLORATADINE	4	MEN1
DITHIAZANINE	4	MEN1
TRIMETREXATE	4	MEN1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	TERT, MEN1
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	2	WNT2B, ARID2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
WNT2B	0	—
ARID2	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 27.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	19
PHASE2	4
PHASE4	2
PHASE2/PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03876717	PHASE4	COMPLETED	Effect of the Sequestrant Colesevelam in Bile Acid Diarrhoea
NCT07436104	PHASE4	COMPLETED	Mortality Control Program for Economically Productive Age Group in Tribal Area of Melghat.
NCT02642250	PHASE2/PHASE3	COMPLETED	Comparative Evaluation of Herbal and Allopathic Drugs for the Treatment of Chronic Diarrhea
NCT01585025	PHASE2	COMPLETED	Obeticholic Acid in Bile Acid Diarrhoea
NCT03270085	PHASE2	COMPLETED	Trial to Understand Efficacy of Colesevelam in Diarrhea Predominant IBS Patients With Bile Acid Malabsorption
NCT05130047	PHASE2	COMPLETED	Aldafermin (NGM282) for Chronic Diarrhea Due to Bile Acid Malabsorption (BAM)
NCT05690321	PHASE2	COMPLETED	Opium Tincture Against Chronic Diarrhea - Patients
NCT06960369	PHASE1	RECRUITING	Efficacy of Repeated Transcranial Magnetic Stimulation Combined With a Live Probiotic Tablet (Combined Bifidobacterium, Lactobacillus, Enterococcus and Bacillus Cereus Tablets, Live) in Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D)
NCT06152289	Not specified	RECRUITING	Development of New Diagnostic Tools in Capsule Endoscopy
NCT06530836	Not specified	ACTIVE_NOT_RECRUITING	Chronic Diarrhea Owing to Underlying Microscopic Colitis
NCT07239934	Not specified	NOT_YET_RECRUITING	Pediatric GI Endoscopy at Assiut University
NCT07581756	Not specified	RECRUITING	Repeated Transcranial Magnetic Stimulation for the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome: A Randomized Clinical Trial
NCT01070277	Not specified	UNKNOWN	Antiparasitic Treatment for Returning Travelers With Chronic Diarrhea
NCT01504048	Not specified	UNKNOWN	Usefulness of Chromoendoscopy in Diagnosing Microscopic Colitis
NCT01545063	Not specified	COMPLETED	CAre of Patients With PArenteral Nutrition At Home
NCT01840891	Not specified	COMPLETED	Secondary Lactose Intolerance Due to Chronic Norovirus Infection
NCT01866774	Not specified	TERMINATED	Evaluation of Fecal Calprotectin Screening and a Gastroenterology Questionnaire for Triaging Children With Chronic Abdominal Pain and/or Diarrhea Referred to a Pediatric Gastroenterology Service
NCT03143517	Not specified	COMPLETED	Fecal Calprotectin Collection Protocol
NCT03261297	Not specified	UNKNOWN	Epidemiology of Chronic Diarrhea Among Children Admitted to Gastroenterology Unit at Assuit University Children Hospital
NCT03269305	Not specified	COMPLETED	An Audit on Management of Chronic Diarrhea
NCT03598010	Not specified	UNKNOWN	Safety, Tolerability and Preliminary Efficacy of Lenodiar Pediatric in Diarrhea
NCT04269174	Not specified	UNKNOWN	The Utility of Biofire Filmarray in Evaluation of Entero Pathogens Triggers in Patients With Chronic Diarrhea
NCT04306939	Not specified	SUSPENDED	Genomic Resources for Enhancing Available Therapies (GREAT1.0) Study
NCT05225493	Not specified	UNKNOWN	HIV Indicator Diseases in Hospital and Primary Care
NCT05702190	Not specified	COMPLETED	Opium Tincture Against Chronic Diarrhea - Healthy
NCT05724381	Not specified	UNKNOWN	Auramine Phenol Staining Technique for Revealing Different Coccidian Parasites
NCT05811091	Not specified	UNKNOWN	Pathological Patterns in Chronic Diarrhea With Normal Colonoscopy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
COLESEVELAM	4	3
ALBENDAZOLE	4	1
METRONIDAZOLE	4	1
OBETICHOLIC ACID	4	1
TINIDAZOLE	4	1
OPIUM	3	2
LACTOSE, ANHYDROUS	3	1
ALDAFERMIN	2	1
CHEMBL4303680	0	1
CHEMBL5197244	0	1
CHEMBL5412701	0	1
CHEMBL1201677	0	1
OPIUM, POWDERED	-1	2