Constipation disorder

Summary

Constipation disorder (MONDO:0002203) is a disease with 9 cohort genes and 620 clinical trials. Top therapeutic interventions include prucalopride, tegaserod, and methylnaltrexone.

At a glance

• Cohort genes: 9
• ClinVar variants: 13
• Clinical trials: 620

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	constipation disorder
Mondo ID	MONDO:0002203
MeSH	D003248
DOID	DOID:2089
ICD-10-CM	K59.0
ICD-11	502284069
NCIT	C37930
SNOMED CT	14760008
UMLS	C0009806
MedGen	1101
Is cancer (heuristic)	no

Also known as: colonic inertia · constipation · Dyschezia

Data availability: 13 ClinVar variants · 1 HPO phenotype.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › intestinal disorder › bowel dysfunction › constipation disorder

Subtypes (2): outlet dysfunction constipation, opioid-induced constipation

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

13 retrieved; paginated sample, class counts are floors:

7 pathogenic, 3 pathogenic/likely pathogenic, 2 likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
267841	46;XX;t(7;13)(p13;q34)dn		Pathogenic	criteria provided, single submitter
267847	46;XY;t(9;11)(q34;p11.2)dn		Pathogenic	criteria provided, single submitter
268035	46;XX;t(19;21)(q13.3;q22.3)dn		Pathogenic	criteria provided, single submitter
132802	NM_001615.4(ACTG2):c.119G>A (p.Arg40His)	ACTG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
210291	NM_001374828.1(ARID1B):c.4479G>A (p.Pro1493=)	ARID1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
375502	NM_001375380.1(EBF3):c.280_283del (p.Glu94fs)	EBF3	Pathogenic	no assertion criteria provided
523355	NM_001122764.3(PPOX):c.1353T>G (p.Tyr451Ter)	PPOX	Pathogenic	criteria provided, single submitter
13919	NM_020975.6(RET):c.2753T>C (p.Met918Thr)	RET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812923	NC_000005.10:g.139189727_139201554del	SIL1	Pathogenic	no assertion criteria provided
659092	NM_012479.4(YWHAG):c.169C>T (p.Arg57Cys)	YWHAG	Pathogenic	criteria provided, multiple submitters, no conflicts
267834	46;X;t(Y;16)(q11.23;p11.2);t(6;21)(p21.3;p13)dn		Likely pathogenic	criteria provided, single submitter
39575	NC_012920.1(MT-TT):m.15923A>G	MT-TT	Likely pathogenic	reviewed by expert panel
623485	NM_014462.3(LSM1):c.231+4A>C	LSM1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 21 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
YWHAG	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
ACTG2	Orphanet:104077	Myopathic intestinal pseudoobstruction
ACTG2	Orphanet:2241	Megacystis-microcolon-intestinal hypoperistalsis syndrome
ACTG2	Orphanet:2604	Familial visceral myopathy
ARID1B	Orphanet:1465	Coffin-Siris syndrome
ARID1B	Orphanet:251056	6q25.2q25.3 microdeletion syndrome
EBF3	Orphanet:658843	Developmental delay-ataxia-hypotonia-facial dysmorphism syndrome
EBF3	Orphanet:96148	Distal deletion 10q syndrome
SIL1	Orphanet:559	Marinesco-Sjögren syndrome
MT-TT	Orphanet:254857	Lethal infantile mitochondrial myopathy
PPOX	Orphanet:79473	Variegate porphyria
RET	Orphanet:146	Differentiated thyroid carcinoma
RET	Orphanet:1848	Renal agenesis, bilateral
RET	Orphanet:247698	Multiple endocrine neoplasia type 2A
RET	Orphanet:247709	Multiple endocrine neoplasia type 2B
RET	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
RET	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
RET	Orphanet:388	Hirschsprung disease
RET	Orphanet:93100	Renal agenesis, unilateral
RET	Orphanet:99361	Isolated familial medullary thyroid carcinoma
RET	Orphanet:99803	Haddad syndrome

Cohort genes → proteins

9 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	9

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
YWHAG	HGNC:12852	ENSG00000170027	P61981	14-3-3 protein gamma	clinvar
ACTG2	HGNC:145	ENSG00000163017	P63267	Actin, gamma-enteric smooth muscle	clinvar
ARID1B	HGNC:18040	ENSG00000049618	Q8NFD5	AT-rich interactive domain-containing protein 1B	clinvar
EBF3	HGNC:19087	ENSG00000108001	Q9H4W6	Transcription factor COE3	clinvar
LSM1	HGNC:20472	ENSG00000175324	O15116	U6 snRNA-associated Sm-like protein LSm1	clinvar
SIL1	HGNC:24624	ENSG00000120725	Q9H173	Nucleotide exchange factor SIL1	clinvar
MT-TT	HGNC:7499	ENSG00000210195		mitochondrially encoded tRNA-Thr (ACN)	clinvar
PPOX	HGNC:9280	ENSG00000143224	P50336	Protoporphyrinogen oxidase	clinvar
RET	HGNC:9967	ENSG00000165731	P07949	Proto-oncogene tyrosine-protein kinase receptor Ret	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
YWHAG	14-3-3 protein gamma	Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways.
ACTG2	Actin, gamma-enteric smooth muscle	Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
ARID1B	AT-rich interactive domain-containing protein 1B	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
EBF3	Transcription factor COE3	Transcriptional activator.
LSM1	U6 snRNA-associated Sm-like protein LSm1	Plays a role in the degradation of histone mRNAs, the only eukaryotic mRNAs that are not polyadenylated.
SIL1	Nucleotide exchange factor SIL1	Required for protein translocation and folding in the endoplasmic reticulum (ER).
PPOX	Protoporphyrinogen oxidase	Catalyzes the 6-electron oxidation of protoporphyrinogen-IX to form protoporphyrin-IX.
RET	Proto-oncogene tyrosine-protein kinase receptor Ret	Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN,…

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 6 · Druggable fraction: 0.22

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
Kinase	1	3.1×	0.687
Enzyme (other)	1	1.3×	0.687
Other/Unknown	6	1.2×	0.687
Transcription factor	1	0.9×	0.687

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
YWHAG	Other/Unknown	no		14-3-3, 14-3-3_CS, 14-3-3_domain
ACTG2	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
ARID1B	Other/Unknown	no		ARID_dom, BAF250/Osa, BAF250_C
EBF3	Transcription factor	no		IPT_dom, Transcription_factor_COE, Ig-like_fold
LSM1	Other/Unknown	no		Sm_dom_euk/arc, LSM_dom_sf, Lsm1
SIL1	Other/Unknown	no		ARM-like, Nucleotide_exch_fac_Fes1, ARM-type_fold
MT-TT	Other/Unknown	no
PPOX	Enzyme (other)	yes	1.3.3.4	Amino_oxidase, Protoporphyrinogen_oxidase, FAD/NAD-bd_sf
RET	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Cadherin-like_dom

Expression context

Cohort genes with no expression data: 0.

8 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)	9
unknown	0

Top tissues across cohort

Tissue	Cohort genes
substantia nigra pars compacta	2
sural nerve	2
lateral nuclear group of thalamus	1
pons	1
cauda epididymis	1
saphenous vein	1
seminal vesicle	1
bone marrow cell	1
colonic epithelium	1
subcutaneous adipose tissue	1
tendon of biceps brachii	1
tibialis anterior	1
gingival epithelium	1
hair follicle	1
parotid gland	1
body of pancreas	1
islet of Langerhans	1
left testis	1
skeletal muscle tissue	1
substantia nigra	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
YWHAG	266	ubiquitous	marker	lateral nuclear group of thalamus, pons, substantia nigra pars compacta
ACTG2	241	broad	marker	seminal vesicle, cauda epididymis, saphenous vein
ARID1B	256	ubiquitous	marker	bone marrow cell, colonic epithelium, sural nerve
EBF3	193	broad	marker	tibialis anterior, subcutaneous adipose tissue, tendon of biceps brachii
LSM1	296	ubiquitous	marker	parotid gland, gingival epithelium, hair follicle
SIL1	251	ubiquitous	marker	islet of Langerhans, body of pancreas, left testis
MT-TT	118	broad	yes	skeletal muscle tissue, sural nerve, substantia nigra
PPOX	264	ubiquitous	marker	right uterine tube, olfactory segment of nasal mucosa, epithelium of bronchus
RET	193	broad	marker	substantia nigra pars reticulata, dorsal root ganglion, substantia nigra pars compacta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RET	4,203
SIL1	4,196
YWHAG	3,643
ARID1B	2,131
LSM1	2,060
PPOX	1,525
EBF3	655
ACTG2	133
MT-TT	0

Structural data

PDB: 7 · AlphaFold-only: 1 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RET	P07949	34
YWHAG	P61981	22
ACTG2	P63267	4
SIL1	Q9H173	4
PPOX	P50336	3
ARID1B	Q8NFD5	2
EBF3	Q9H4W6	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LSM1	O15116	89.59

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 82. Enrichment computed across 9 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Regulation of localization of FOXO transcription factors	1	158.6×	0.064	YWHAG
Regulation of CDH1 Function	1	158.6×	0.064	ACTG2
Deadenylation-dependent mRNA decay	1	146.4×	0.064	LSM1
SARS-CoV-2 targets host intracellular signalling and regulatory pathways	1	146.4×	0.064	YWHAG
Activation of BAD and translocation to mitochondria	1	126.9×	0.064	YWHAG
Heme biosynthesis	1	126.9×	0.064	PPOX
mRNA decay by 5’ to 3’ exoribonuclease	1	126.9×	0.064	LSM1
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	1	112.0×	0.064	YWHAG
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	1	112.0×	0.064	YWHAG
Formation of the nephric duct	1	105.7×	0.064	RET
Formation of the canonical BAF (cBAF) complex	1	105.7×	0.064	ARID1B
MITF-M-regulated melanocyte development	2	38.1×	0.064	YWHAG, ARID1B
Activation of BH3-only proteins	1	82.8×	0.066	YWHAG
NPAS4 regulates expression of target genes	1	82.8×	0.066	RET
Formation of the ureteric bud	1	82.8×	0.066	RET
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	76.1×	0.067	ARID1B
Regulation of endogenous retroelements	1	61.4×	0.074	ARID1B
FOXO-mediated transcription	1	56.0×	0.074	YWHAG
RHO GTPases activate PKNs	1	52.9×	0.074	YWHAG
Formation of the dystrophin-glycoprotein complex (DGC)	1	51.4×	0.074	ACTG2
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	50.1×	0.074	ARID1B
Intrinsic Pathway for Apoptosis	1	48.8×	0.074	YWHAG
Smooth Muscle Contraction	1	44.3×	0.074	ACTG2
Regulation of MITF-M-dependent genes involved in pigmentation	1	44.3×	0.074	ARID1B
RET signaling	1	43.3×	0.074	RET
Centrosome maturation	1	42.3×	0.074	YWHAG
SPOP-mediated proteasomal degradation of PD-L1(CD274)	1	38.1×	0.077	YWHAG
RNA Polymerase II Transcription	2	7.5×	0.077	YWHAG, ARID1B
MITF-M-dependent gene expression	1	30.2×	0.078	ARID1B
Transcriptional and post-translational regulation of MITF-M expression and activity	1	29.7×	0.078	YWHAG

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
embryonic epithelial tube formation	1	1053.2×	0.018	RET
posterior midgut development	1	1053.2×	0.018	RET
positive regulation of metanephric glomerulus development	1	702.2×	0.018	RET
porphyrin-containing compound biosynthetic process	1	526.6×	0.018	PPOX
ureter maturation	1	526.6×	0.018	RET
Peyer’s patch morphogenesis	1	526.6×	0.018	RET
GDF15-GFRAL signaling pathway	1	526.6×	0.018	RET
mesenchyme migration	1	421.3×	0.018	ACTG2
cellular response to acetaldehyde	1	421.3×	0.018	ACTG2
positive regulation of DNA-templated transcription	3	10.5×	0.018	ARID1B, EBF3, RET
positive regulation of T cell mediated immune response to tumor cell	1	300.9×	0.021	YWHAG
lymphocyte migration into lymphoid organs	1	234.1×	0.021	RET
deadenylation-dependent decapping of nuclear-transcribed mRNA	1	210.7×	0.021	LSM1
cotranslational protein targeting to membrane	1	210.7×	0.021	SIL1
obsolete protoporphyrinogen IX biosynthetic process	1	210.7×	0.021	PPOX
heme B biosynthetic process	1	210.7×	0.021	PPOX
histone mRNA catabolic process	1	210.7×	0.021	LSM1
heme A biosynthetic process	1	191.5×	0.021	PPOX
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	191.5×	0.021	RET
positive regulation of cell size	1	162.0×	0.024	RET
glial cell-derived neurotrophic factor receptor signaling pathway	1	150.5×	0.024	RET
membrane protein proteolysis	1	131.7×	0.024	RET
positive regulation of cell adhesion mediated by integrin	1	131.7×	0.024	RET
neuron cell-cell adhesion	1	123.9×	0.024	RET
enteric nervous system development	1	123.9×	0.024	RET
cellular response to interleukin-6	1	123.9×	0.024	ACTG2
response to pain	1	110.9×	0.025	RET
regulation of axonogenesis	1	110.9×	0.025	RET
negative regulation of protein kinase activity	1	105.3×	0.025	YWHAG
neuron maturation	1	100.3×	0.026	RET

Therapeutics

Drugs indicated for this disease

32 approved, 13 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Alvimopan	Approved (phase 4)
Bisacodyl	Approved (phase 4)
Cascara Sagrada	Approved (phase 4)
Castor Oil	Approved (phase 4)
Danthron	Approved (phase 4)
Glycerin	Approved (phase 4)
Lactitol	Approved (phase 4)
Lactulose	Approved (phase 4)
Linaclotide	Approved (phase 4)
Lubiprostone	Approved (phase 4)
Magnesium Carbonate	Approved (phase 4)
Magnesium Citrate	Approved (phase 4)
Magnesium Hydroxide	Approved (phase 4)
Magnesium Oxide	Approved (phase 4)
Mannitol	Approved (phase 4)
Methylcellulose	Approved (phase 4)
Mineral Oil	Approved (phase 4)
Naldemedine	Approved (phase 4)
Naloxegol	Approved (phase 4)
Naloxone	Approved (phase 4)
Oxyphenisatine	Approved (phase 4)
POLYETHYLENE GLYCOL 3350	Approved (phase 4)
Phenolphthalein	Approved (phase 4)
Plecanatide	Approved (phase 4)
Polyethylene Glycol	Approved (phase 4)
Prucalopride	Approved (phase 4)
Senna	Approved (phase 4)
Sodium Phosphate, Dibasic, Anhydrous	Approved (phase 4)
Sodium Phosphate, Monobasic	Approved (phase 4)
Sorbitol	Approved (phase 4)
Tegaserod	Approved (phase 4)
Tenapanor	Approved (phase 4)
Bevenopran	Phase 3 (in late-stage trials)
Elobixibat	Phase 3 (in late-stage trials)
Konjac Mannan	Phase 3 (in late-stage trials)
Maltodextrin	Phase 3 (in late-stage trials)
Methylnaltrexone	Phase 3 (in late-stage trials)
Mosapride	Phase 3 (in late-stage trials)
POLYETHYLENE GLYCOL 4000	Phase 3 (in late-stage trials)
Pectin	Phase 3 (in late-stage trials)
Potassium Chloride	Phase 3 (in late-stage trials)
Simeticone	Phase 3 (in late-stage trials)
Sodium Bicarbonate	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Wheat Bran	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Alcohol, Alfuzosin, Docusate, Hydromorphone, Itopride, Lactobacillus Acidophilus, Pradigastat, Propylene Glycol, Psyllium Husk, Vancomycin.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 7

Druggability breadth: 3 of 9 evidence-associated genes (33%) 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
RET	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RET	135	4
YWHAG	1	2
ACTG2	0	0
ARID1B	0	0
EBF3	0	0
LSM1	0	0
SIL1	0	0
MT-TT	0	0
PPOX	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	RET
AFATINIB	4	RET
VEMURAFENIB	4	RET
FEDRATINIB	4	RET
TIVOZANIB	4	RET
LENVATINIB	4	RET
AXITINIB	4	RET
SORAFENIB	4	RET
DASATINIB ANHYDROUS	4	RET
ALECTINIB	4	RET
RUXOLITINIB	4	RET
INFIGRATINIB PHOSPHATE	4	RET
INFIGRATINIB	4	RET
IBRUTINIB	4	RET
PALBOCICLIB	4	RET
REGORAFENIB	4	RET
ENTRECTINIB	4	RET
TOFACITINIB CITRATE	4	RET
FOSTAMATINIB	4	RET
CABOZANTINIB	4	RET
BARICITINIB	4	RET
TOFACITINIB	4	RET
CAPIVASERTIB	4	RET
CERITINIB	4	RET
VANDETANIB	4	RET
NILOTINIB	4	RET
BOSUTINIB	4	RET
GILTERITINIB	4	RET
BRIGATINIB	4	RET
UPADACITINIB	4	RET

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
RET	1,586	Binding:1573, Functional:10, ADMET:3
YWHAG	12	Binding:11, Functional:1
PPOX	5	Binding:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PPOX	1.3.3.4	protoporphyrinogen oxidase
RET	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
RET	1,586

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; 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)
PONATINIB	4	RET
AFATINIB	4	RET
VEMURAFENIB	4	RET
FEDRATINIB	4	RET
TIVOZANIB	4	RET
LENVATINIB	4	RET
AXITINIB	4	RET
SORAFENIB	4	RET
DASATINIB ANHYDROUS	4	RET
ALECTINIB	4	RET
RUXOLITINIB	4	RET
INFIGRATINIB PHOSPHATE	4	RET
INFIGRATINIB	4	RET
IBRUTINIB	4	RET
PALBOCICLIB	4	RET
REGORAFENIB	4	RET
ENTRECTINIB	4	RET
TOFACITINIB CITRATE	4	RET
FOSTAMATINIB	4	RET
CABOZANTINIB	4	RET
BARICITINIB	4	RET
TOFACITINIB	4	RET
CAPIVASERTIB	4	RET
CERITINIB	4	RET
VANDETANIB	4	RET
NILOTINIB	4	RET
BOSUTINIB	4	RET
GILTERITINIB	4	RET
BRIGATINIB	4	RET
UPADACITINIB	4	RET

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RET
B	Phased (≥1) drug, not yet approved	1	YWHAG
C	Druggable family + PDB, no drug	1	PPOX
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	6	ACTG2, ARID1B, EBF3, LSM1, SIL1, MT-TT

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ACTG2	0	—
ARID1B	0	—
EBF3	0	—
LSM1	0	—
SIL1	0	—
MT-TT	0	—
PPOX	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 620.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	361
PHASE4	77
PHASE3	68
PHASE2	67
PHASE1	17
PHASE1/PHASE2	12
PHASE2/PHASE3	11
EARLY_PHASE1	7

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03119584	PHASE4	ACTIVE_NOT_RECRUITING	Efficacy of Linaclotide in Type II Diabetics With Chronic Constipation
NCT05805436	PHASE4	RECRUITING	Preop Laxatives in Robotic Urologic Surgery
NCT05821309	PHASE4	RECRUITING	Evaluation of Fecal Microbiome Changes After Antegrade Continence Enema Placement and Initiation of Bowel Flush Regimen
NCT06777758	PHASE4	RECRUITING	Comparison of Remimazolam and Propofol in Endoscopic Examinations and Treatments
NCT06825260	PHASE4	RECRUITING	PEG3350 vs Senna After Urogyn Surgery
NCT06959758	PHASE4	RECRUITING	Effects of Probiotics (BioKid LR - Contains Nine Different Species of Probiotics Bacteria Including L. Reuteri) in Children With Functional Constipation
NCT07431957	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of Linaclotide in Chronic Constipation
NCT00149877	PHASE4	COMPLETED	Efficacy, Safety and Tolerability of Tegaserod in Patients With Chronic Constipation
NCT00153114	PHASE4	COMPLETED	PolyethyleneGlycol3350 Laxative vs Placebo in Constipated Children
NCT00153127	PHASE4	COMPLETED	Comparison of PolyethyleneGlycol and Placebo for Relief of Constipation From Constipating Medications
NCT00153140	PHASE4	COMPLETED	Polyethyleneglycol3350 vs Tegaserod in Treatment of Patients With Chronic Constipation
NCT00153153	PHASE4	COMPLETED	Extended Use of Polyethyleneglycol3350 Laxative in Constipated Patients
NCT00157638	PHASE4	COMPLETED	Integrating Family Medicine and Pharmacy to Advance Primary Care Therapeutics
NCT00164125	PHASE4	COMPLETED	An Open Label Study of Chronic Polyethyleneglycol3350 Use in Constipated Patients
NCT00171522	PHASE4	COMPLETED	Preference of Tegaserod vs. PEG 3350 in Patients With Constipation
NCT00256984	PHASE4	COMPLETED	Study of Stapled Transanal Rectal Resection (STARR) Surgery in Refractory Constipation Associated With Obstructive Defecation Syndrome (ODS)
NCT00276354	PHASE4	COMPLETED	Study of Long-term Use of Forlax® in Elderly Patients With Chronic Constipation
NCT00286520	PHASE4	COMPLETED	Treatment of Fecal Incontinence and Constipation in Patients With Spinal Cord Injury
NCT00319670	PHASE4	COMPLETED	A Pilot Study of a New MiraLax® Dose Formulation For Use in Constipated Children
NCT00348634	PHASE4	TERMINATED	Effect of Tegaserod on Orocecal Transit in Elderly Chronic Constipation Patients
NCT00452335	PHASE4	COMPLETED	Safety and Efficacy of Lubiprostone in Pediatric Patients With Constipation
NCT00521872	PHASE4	COMPLETED	Stapled Trans Anal Rectal Resection (STARR) for Outlet Obstruction: Functional and Morphological Outcome
NCT00583609	PHASE4	COMPLETED	A Pilot Study of a New PEG3350 Dose Formulation For Use in Constipated Children
NCT00603681	PHASE4	COMPLETED	Comparison of PEG Solutions With and Without Electrolytes in the Treatment of Constipation
NCT00712543	PHASE4	COMPLETED	A Preference Study Comparing Kristalose® and Liquid Lactulose
NCT00763399	PHASE4	COMPLETED	Effect of Probiotics on Intestinal Bacterial Population and Immune Modulation
NCT00770432	PHASE4	COMPLETED	Study Comparing PEG 3350 Laxative to Placebo in the Treatment of Occasional Constipation (Study CL2007-12)(P08216)
NCT00799201	PHASE4	TERMINATED	Enteral Naloxone Versus a Traditional Bowel Regimen for the Prevention of Opioid Induced Constipation in Trauma Patients
NCT00844831	PHASE4	COMPLETED	Effects of Lubiprostone on Small Bowel and Colonic Bacteria: A Correlation Study With Segmental and Whole Gut Transit
NCT00949377	PHASE4	WITHDRAWN	Can Methylnaltrexone Safely Treat Opioid Related Constipation in the Emergency Department?
NCT01003249	PHASE4	TERMINATED	Dysfunctional Voiding and Lower Urinary Tract Symptoms With Baclofen
NCT01096290	PHASE4	TERMINATED	Comparison of Lubiprostone and Placebo for the Relief of Constipation From Constipating Medications
NCT01114997	PHASE4	TERMINATED	Effect of Lidocaine and Esmolol to Improve the Quality of Recovery
NCT01170039	PHASE4	COMPLETED	The Effectiveness of Lubiprostone in Constipated Diabetics
NCT01180725	PHASE4	COMPLETED	Investigation of Dried Plums in the Treatment of Adults With Constipation
NCT01189409	PHASE4	TERMINATED	Polyethylene Glycol (PEG) Versus Sennosides Study in Opioid-Induced Constipation in Cancer Patients
NCT01230840	PHASE4	COMPLETED	Effect of Wheat Dextrin on Calcium and Magnesium Absorption
NCT01236534	PHASE4	COMPLETED	Lubiprostone in Patients With Multiple Sclerosis Associated Constipation
NCT01267370	PHASE4	COMPLETED	Soy Polysaccharide Fiber for the Treatment of Chronic Constipation in Children: a Randomized, Double-blind Trial
NCT01333787	PHASE4	COMPLETED	Dietary Fiber Mixture in Constipated Pediatric Patients

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PRUCALOPRIDE	4	58
TEGASEROD	4	24
METHYLNALTREXONE	4	17
LUBIPROSTONE	4	14
LINACLOTIDE	4	12
POLYETHYLENE GLYCOL 3350	4	12
BISACODYL	4	10
LACTULOSE	4	10
DOCUSATE	4	8
GLYCOPYRRONIUM	4	7
ALVIMOPAN	4	6
NALOXEGOL	4	5
NALOXONE	4	4
INULIN	4	3
KETOROLAC	4	3
ORPHENADRINE	4	3
OXYCODONE	4	3
PYRIDOSTIGMINE	4	3
GABAPENTIN	4	2
HYDROMORPHONE HYDROCHLORIDE	4	2
SORBITOL	4	2
ALFUZOSIN	4	1
ALFUZOSIN HYDROCHLORIDE	4	1
BACLOFEN	4	1
BUPIVACAINE HYDROCHLORIDE	4	1
CELECOXIB	4	1
CHOLECALCIFEROL	4	1
DESIPRAMINE	4	1
DEXAMETHASONE	4	1
DIAZEPAM	4	1