Digestive system disorder

Summary

Digestive system disorder (MONDO:0004335) is a disease (an umbrella term covering 31 Mondo subtypes) caused by MYO5B (GenCC Strong), with 8 cohort genes (100 GWAS associations across 93 studies) and 145 clinical trials. Top therapeutic interventions include domperidone, ursodiol, and alectinib.

At a glance

• Causal gene: MYO5B (GenCC Strong)
• Umbrella term: 31 Mondo subtypes
• Cohort genes: 8
• GWAS associations: 100
• ClinVar variants: 2
• Clinical trials: 145

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	digestive system disorder
Mondo ID	MONDO:0004335
MeSH	D005767
DOID	DOID:77
ICD-10-CM	K00-K95
ICD-11	1256772020
NCIT	C2990
SNOMED CT	53619000
UMLS	C4023588
MedGen	892790
Anatomy (UBERON)	UBERON:0005409
Is cancer (heuristic)	no

Also known as: digestive disease · digestive system disease · digestive system disease or disorder · digestive system disorder · disease of digestive system · disease or disorder of digestive system · disorder of digestive system · gastroenterological system disease · gastroenterological system disorder · gastrointestinal disorder · gastrointestinal system disease · gastrointestinal system disorder · stomach or intestinal disorder

Data availability: 2 ClinVar variants · 100 GWAS associations (93 studies) · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 31 Mondo subtypes.

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

Related subtypes (18): disorder of orbital region, integumentary system disorder, musculoskeletal system disorder, urinary system disorder, syndromic disease, auditory system disorder, breast disorder, connective tissue disorder, cardiovascular disorder, reproductive system disorder, immune system disorder, nervous system disorder, respiratory system disorder, endocrine system disorder, hematologic disorder, mouth disorder, disorder of visual system, otorhinolaryngologic disease

Subtypes (31): benign digestive system neoplasm, autoimmune disorder of gastrointestinal tract, gastrointestinal mucositis, diarrheal disease, pancreas disorder, hepatobiliary disorder, digestive system cancer, peptic ulcer disease, stomach disorder, intestinal disorder, Meckel diverticulum, Cronkhite-Canada syndrome, diverticulosis, small-intestinal, diverticulosis of bowel, hernia, and retinal detachment, congenital enteropathy due to enteropeptidase deficiency, hereditary mixed polyposis syndrome, caudal duplication, Moyamoya disease with early-onset achalasia, hyperplastic polyposis syndrome, thoraco-abdominal enteric duplication, digestive duplication, juvenile polyposis syndrome, umbilical cord ulceration-intestinal atresia syndrome, growth retardation-mild developmental delay-chronic hepatitis syndrome, common mesentery, neoplasm of oropharynx, gastrointestinal polyp, digestive system neuroendocrine neoplasm, digestive system infectious disorder, upper digestive tract disorder, congenital peritoneal encapsulation

Genetics & variants

GWAS landscape

100 GWAS associations across 93 studies. Top hits map to 33 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
chr6:32655446	5e-142		C	0.27
rs6717024	1e-34	ARHGAP15	C	1.13
rs3747207	5e-20	PNPLA3	G	0.17
chr15:32718211	4e-19		A	0.08
rs535816044	6e-15	CMAHP, CARMIL1	A	3.25
rs4333882	2e-14	SLC35F3	G	1.08
rs7609897	1e-13	COLQ	T	0.93
rs182777539	2e-13	MARCHF1	T	2.69
rs540878969	4e-13	IFITM8P - RN7SKP135	G	3.48
rs561844774	5e-13	PSME2P1 - KRT8P32	G	3.21
rs185375271	5e-13	RN7SL250P - SOX17	T	2.4
rs760364725	6e-13	SPINT2	CA	1.06
rs576089196	6e-13	CRTAC1 - R3HCC1L	C	3.31
rs61823192	1e-12	LYPLAL1-DT	T	0.83
rs535733797	2e-12	TAFA2	C	3.24
chr20:62357358	2e-12		C	0.06
rs75446182	4e-12	ZNF708	C	4.22
rs182656335	1e-11	MTAP	C	3.38
rs564110465	1e-11	RPL17P38 - PRDM4	G	4.18
rs193051903	1e-11	RAB10	G	3.73
rs570640158	2e-11	RNU1-61P	C	1.07
rs11428277	2e-11	ENTPD7	G	1.07
rs1802575	2e-11	EFEMP1	C	1.08
rs17883623	2e-11	NF1	A	2.51
rs551625977	2e-11	GBF1	G	2.72
rs577965638	2e-11	LINC02335	T	1.93
rs146353134	2e-11	ATP13A4	C	2.4
rs9270430	3e-11	HLA-DRB1 - HLA-DQA1	C	0.07
rs559853058	3e-11	NRP1	G	2.81
rs536003228	3e-11	RNU7-51P - RNU6ATAC28P	G	2.3

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90476069	Verma A	2024	60,074	337,851	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473852	UK Biobank Whole-Genome Sequencing Consortium	2025	45,567	412,873	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90103953	Tangden T	2022	34,948	302,536	A genome-wide association study in a large community-based cohort identifies multiple loci associated with susceptibility to bacterial and viral infections.
GCST90473888	UK Biobank Whole-Genome Sequencing Consortium	2025	32,598	425,842	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90080813	Backman JD	2021	26,789	340,046	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084799	Backman JD	2021	26,789	340,046	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90473893	UK Biobank Whole-Genome Sequencing Consortium	2025	24,855	433,585	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90436356	Zhou W	2018	22,138	334,783	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90081368	Backman JD	2021	20,497	366,069	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90085354	Backman JD	2021	20,497	366,069	Exome sequencing and analysis of 454,787 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	1
Tier 3: regulatory	0
Tier 4: intronic/intergenic	49

MAF distribution

Bucket	Variants
common (>=0.05)	19
low_freq (0.01-0.05)	1
rare (<0.01)	20
unknown	10

Functional consequences

Consequence	Count
intron_variant	30
unknown	10
intergenic_variant	7
non_coding_transcript_exon_variant	2
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
chr6:32655446							5e-142	Tier 4: intronic/intergenic
rs6717024	2	143551211	C>A,G	0.18	intron_variant	ARHGAP15	1e-34	Tier 4: intronic/intergenic
rs3747207	22	43928975	G>A,C,T	0.219	intron_variant	PNPLA3	5e-20	Tier 4: intronic/intergenic
chr15:32718211							4e-19	Tier 4: intronic/intergenic
rs535816044	6	25428289	A>G	0.001	intron_variant	CMAHP, CARMIL1	6e-15	Tier 4: intronic/intergenic
rs4333882	1	234217153	A>G,T	0.19	intron_variant	SLC35F3	2e-14	Tier 4: intronic/intergenic
rs7609897	3	15461174	G>C,T	0.21	intron_variant	COLQ	1e-13	Tier 4: intronic/intergenic
rs182777539	4	163763008	T>C	0.001	intron_variant	MARCHF1	2e-13	Tier 4: intronic/intergenic
rs540878969	8	63532786	G>A,C,T	0	intron_variant	IFITM8P - RN7SKP135	4e-13	Tier 4: intronic/intergenic
rs561844774	5	98273009	G>A	0	intergenic_variant	PSME2P1 - KRT8P32	5e-13	Tier 4: intronic/intergenic
rs185375271	8	54442007	T>A,C	0	intron_variant	RN7SL250P - SOX17	5e-13	Tier 4: intronic/intergenic
rs760364725	19	38266675	TC>T	0.48	intron_variant	SPINT2	6e-13	Tier 4: intronic/intergenic
rs576089196	10	98058846	C>T	0	intergenic_variant	CRTAC1 - R3HCC1L	6e-13	Tier 4: intronic/intergenic
rs61823192	1	219121228	C>T	0.03	intron_variant	LYPLAL1-DT	1e-12	Tier 4: intronic/intergenic
rs535733797	12	62072533	C>A	0	intron_variant	TAFA2	2e-12	Tier 4: intronic/intergenic
chr20:62357358							2e-12	Tier 4: intronic/intergenic
rs75446182	19	21318085	C>A	0.001	intron_variant	ZNF708	4e-12	Tier 4: intronic/intergenic
rs182656335	9	21898840	C>G	0.002	intron_variant	MTAP	1e-11	Tier 4: intronic/intergenic
rs564110465	12	107729176	G>A,T	0.001	intergenic_variant	RPL17P38 - PRDM4	1e-11	Tier 4: intronic/intergenic
rs193051903	2	26035015	G>A	0	intron_variant	RAB10	1e-11	Tier 4: intronic/intergenic
rs570640158	6	32550016	T>C,G	0.26	non_coding_transcript_exon_variant	RNU1-61P	2e-11	Tier 4: intronic/intergenic
rs11428277	10	99665257	GAAA>G,GA,GAA,GAAAA,GAAAAA,GAAAAAA,GAAAAAAA,GAAAAAAAAAAAA	0.18	intron_variant	ENTPD7	2e-11	Tier 4: intronic/intergenic
rs1802575	2	55866069	G>C	0.13	3_prime_UTR_variant	EFEMP1	2e-11	Tier 2: splice/UTR
rs17883623	17	31341927	A>G	0.001	intron_variant	NF1	2e-11	Tier 4: intronic/intergenic
rs551625977	10	102313277	G>A	0.001	intron_variant	GBF1	2e-11	Tier 4: intronic/intergenic
rs577965638	13	55144752	T>G	0.001	intron_variant	LINC02335	2e-11	Tier 4: intronic/intergenic
rs146353134	3	193572076	C>T	0	intergenic_variant	ATP13A4	2e-11	Tier 4: intronic/intergenic
rs9270430	6	32590884	C>G,T	0.121	intergenic_variant	HLA-DRB1 - HLA-DQA1	3e-11	Tier 4: intronic/intergenic
rs559853058	10	33257400	G>A	0.002	intron_variant	NRP1	3e-11	Tier 4: intronic/intergenic
rs536003228	14	83221543	G>A,C	0.001	intergenic_variant	RNU7-51P - RNU6ATAC28P	3e-11	Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
267828	46;XY;t(7;19)(q32;q13.1)dn		Pathogenic	criteria provided, single submitter
267859	46;XX;t(17;18)(p13;p11.2)dn		Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
MYO5B	Strong	Autosomal recessive	digestive system disorder	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYO5B	Orphanet:2290	Microvillus inclusion disease
MYO5B	Orphanet:480491	MYO5B-related progressive familial intrahepatic cholestasis
MYO5B	Orphanet:79306	Progressive familial intrahepatic cholestasis type 1
FOXF1	Orphanet:210122	Congenital alveolar capillary dysplasia
FOXP1	Orphanet:391372	FOXP1 Syndrome
FOXP1	Orphanet:52417	MALT lymphoma
FOXP1	Orphanet:585877	B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality

Cohort genes → proteins

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	7
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MYO5B	HGNC:7603	ENSG00000167306	Q9ULV0	Unconventional myosin-Vb	gencc
ZNF326	HGNC:14104	ENSG00000162664	Q5BKZ1	DBIRD complex subunit ZNF326	gwas
CRTC1	HGNC:16062	ENSG00000105662	Q6UUV9	CREB-regulated transcription coactivator 1	gwas
LRRC8D	HGNC:16992	ENSG00000171492	Q7L1W4	Volume-regulated anion channel subunit LRRC8D	gwas
LRRC8C	HGNC:25075	ENSG00000171488	Q8TDW0	Volume-regulated anion channel subunit LRRC8C	gwas
FOXF1	HGNC:3809	ENSG00000103241	Q12946	Forkhead box protein F1	gwas
FOXP1	HGNC:3823	ENSG00000114861	Q9H334	Forkhead box protein P1	gwas
BARX1	HGNC:955	ENSG00000131668	Q9HBU1	Homeobox protein BarH-like 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYO5B	Unconventional myosin-Vb	May be involved in vesicular trafficking via its association with the CART complex.
ZNF326	DBIRD complex subunit ZNF326	Core component of the DBIRD complex, a multiprotein complex that acts at the interface between core mRNP particles and RNA polymerase II (RNAPII) and integrates transcript elongation with the regulation of alternative splicing: the DBIRD c…
CRTC1	CREB-regulated transcription coactivator 1	Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites.
LRRC8D	Volume-regulated anion channel subunit LRRC8D	Non-essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes.
LRRC8C	Volume-regulated anion channel subunit LRRC8C	Non-essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes.
FOXF1	Forkhead box protein F1	Probable transcription activator for a number of lung-specific genes.
FOXP1	Forkhead box protein P1	Transcriptional repressor.
BARX1	Homeobox protein BarH-like 1	Transcription factor, which is involved in craniofacial development, in odontogenesis and in stomach organogenesis.

Protein-family classification

Druggable: 0 · Difficult: 4 · Unknown: 4 · 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	3	3.1×	0.187
Scaffold/PPI	1	2.2×	0.569
Other/Unknown	4	0.9×	0.755

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYO5B	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Dilute_dom
ZNF326	Other/Unknown	no		AKAP95, ZF_C2H2_AKAP95
CRTC1	Other/Unknown	no		TORC_N, TORC_M, TORC_C
LRRC8D	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, LRRC8_Pannexin-like
LRRC8C	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, LRRC8_Pannexin-like
FOXF1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2
FOXP1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_2, FOXP-CC
BARX1	Transcription factor	no		HTH_motif, HD, Homeodomain-like_sf

Expression context

Cohort genes with no expression data: 0.

7 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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
mucosa of stomach	2
ileal mucosa	1
jejunal mucosa	1
lower esophagus mucosa	1
C1 segment of cervical spinal cord	1
spinal cord	1
sural nerve	1
olfactory bulb	1
paraflocculus	1
type B pancreatic cell	1
inferior vagus X ganglion	1
subthalamic nucleus	1
trigeminal ganglion	1
cartilage tissue	1
secondary oocyte	1
sperm	1
muscle layer of sigmoid colon	1
right lung	1
cardia of stomach	1
oviduct epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYO5B	228	broad	marker	ileal mucosa, lower esophagus mucosa, jejunal mucosa
ZNF326	254	ubiquitous	marker	sural nerve, C1 segment of cervical spinal cord, spinal cord
CRTC1	218	ubiquitous	marker	olfactory bulb, type B pancreatic cell, paraflocculus
LRRC8D	285	ubiquitous	marker	inferior vagus X ganglion, subthalamic nucleus, trigeminal ganglion
LRRC8C	246	ubiquitous	marker	sperm, secondary oocyte, cartilage tissue
FOXF1	202	broad	marker	muscle layer of sigmoid colon, mucosa of stomach, right lung
FOXP1	256	ubiquitous	marker	pancreatic ductal cell, oviduct epithelium, cardia of stomach
BARX1	100	tissue_specific	yes	mucosa of stomach, body of stomach, stomach

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYO5B	3,604
FOXP1	2,939
FOXF1	1,694
ZNF326	1,666
LRRC8D	1,139
BARX1	1,068
LRRC8C	1,053
CRTC1	683

Intra-cohort edges

A	B	Sources
BARX1	FOXF1	string_interaction
FOXF1	FOXP1	biogrid_interaction

Structural data

PDB: 6 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LRRC8C	Q8TDW0	8
MYO5B	Q9ULV0	4
CRTC1	Q6UUV9	3
LRRC8D	Q7L1W4	1
FOXP1	Q9H334	1
BARX1	Q9HBU1	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FOXF1	Q12946	59.41
ZNF326	Q5BKZ1	54.04

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 8 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
Miscellaneous transport and binding events	2	146.4×	8e-04	LRRC8D, LRRC8C
Transport of small molecules	3	12.6×	0.006	LRRC8D, LRRC8C, MYO5B
Formation of lateral plate mesoderm	1	380.7×	0.010	FOXF1
Regulation of CDH11 gene transcription	1	173.0×	0.016	FOXF1
Transcriptional regulation of pluripotent stem cells	1	90.6×	0.023	FOXP1
Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes	1	79.3×	0.023	CRTC1
Aquaporin-mediated transport	1	61.4×	0.025	MYO5B
Expression of BMAL (ARNTL), CLOCK, and NPAS2	1	48.8×	0.027	CRTC1
Vasopressin regulates renal water homeostasis via Aquaporins	1	44.3×	0.027	MYO5B
Heme signaling	1	35.9×	0.029	CRTC1
Transcriptional activation of mitochondrial biogenesis	1	34.0×	0.029	CRTC1

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
taurine transmembrane transport	2	702.2×	2e-04	LRRC8D, LRRC8C
monoatomic anion transmembrane transport	2	702.2×	2e-04	LRRC8D, LRRC8C
aspartate transmembrane transport	2	351.1×	4e-04	LRRC8D, LRRC8C
protein hexamerization	2	351.1×	4e-04	LRRC8D, LRRC8C
cellular response to osmotic stress	2	300.9×	4e-04	LRRC8D, LRRC8C
detection of wounding	1	2106.5×	0.006	FOXF1
embryonic ectodermal digestive tract morphogenesis	1	2106.5×	0.006	FOXF1
right lung morphogenesis	1	2106.5×	0.006	FOXF1
regulation of macrophage colony-stimulating factor production	1	2106.5×	0.006	FOXP1
regulation of monocyte differentiation	1	1053.2×	0.008	FOXP1
lateral mesodermal cell differentiation	1	1053.2×	0.008	FOXF1
regulation of defense response to bacterium	1	1053.2×	0.008	FOXP1
negative regulation of membrane hyperpolarization	1	1053.2×	0.008	CRTC1
positive regulation of interleukin-21 production	1	702.2×	0.010	FOXP1
trachea development	1	702.2×	0.010	FOXF1
regulation of chemokine (C-X-C motif) ligand 2 production	1	702.2×	0.010	FOXP1
regulation of interleukin-12 production	1	526.6×	0.010	FOXP1
epithelial cell differentiation involved in mammary gland alveolus development	1	526.6×	0.010	FOXF1
positive regulation of hydrogen peroxide-mediated programmed cell death	1	526.6×	0.010	FOXP1
respiratory tube development	1	421.3×	0.010	FOXF1
digestive system development	1	421.3×	0.010	BARX1
venous blood vessel development	1	421.3×	0.010	FOXF1
mesenchyme migration	1	421.3×	0.010	FOXF1
ductus arteriosus closure	1	421.3×	0.010	FOXF1
regulation of endothelial tube morphogenesis	1	421.3×	0.010	FOXP1
regulation of DNA-templated transcription elongation	1	351.1×	0.011	ZNF326
negative regulation of mast cell degranulation	1	351.1×	0.011	FOXF1
ureter development	1	351.1×	0.011	FOXF1
positive regulation of B cell receptor signaling pathway	1	300.9×	0.012	FOXP1
morphogenesis of a branching structure	1	263.3×	0.012	FOXF1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 8

Druggability breadth: 0 of 8 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
MYO5B	0	0
ZNF326	0	0
CRTC1	0	0
LRRC8D	0	0
LRRC8C	0	0
FOXF1	0	0
FOXP1	0	0
BARX1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; 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	8	MYO5B, ZNF326, CRTC1, LRRC8D, LRRC8C, FOXF1, FOXP1, BARX1

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)
MYO5B	0	—
ZNF326	0	—
CRTC1	0	—
LRRC8D	0	—
LRRC8C	0	—
FOXF1	0	—
FOXP1	0	—
BARX1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 145.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	86
PHASE2	19
PHASE3	12
PHASE1	11
PHASE1/PHASE2	8
PHASE4	6
PHASE2/PHASE3	2
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06271538	PHASE4	RECRUITING	Evaluation of Efficacy of Skål Pro Powder on Symptoms of Irritable Bowel Syndrome
NCT01318928	PHASE4	UNKNOWN	The Treatment of Periodontal Diseases
NCT02267681	PHASE4	COMPLETED	Opioid Effects on Cognitive Function Following Colonoscopy
NCT02764671	PHASE4	UNKNOWN	Safety and Immunogenicity of Recombinant Hepatitis B Vaccines in the Neonates
NCT03646292	PHASE4	COMPLETED	Antidiabetic Drugs for Steatotic Liver Disease
NCT03723447	PHASE4	COMPLETED	Intraoperative TAP Block With Bupivacaine/Dexamethasone Against Liposomal Bupivacaine (Exparel®)
NCT01696734	PHASE3	RECRUITING	Domperidone in Treating Patients With Gastrointestinal Disorders
NCT06817161	PHASE3	RECRUITING	Benefit of Transcutaneous Auricular Vagus Nerve Stimulation in Improving Quality of Life in First Line Treatment of Ovarian Cancer:
NCT07076641	PHASE3	NOT_YET_RECRUITING	Efficacy and Safety of Intravenous Lidocaine Versus Placebo in Patients Receiving Morphine-rachi Analgesia
NCT07114406	PHASE3	NOT_YET_RECRUITING	A Study to Evaluate Safety and Efficacy of PBK_M2502
NCT07222800	PHASE3	RECRUITING	Symbiotic-GI-03: A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Chemotherapy in Adult Participants With Metastatic Colorectal Cancer
NCT01009593	PHASE3	TERMINATED	Efficacy and Tolerability of ABT-869 Versus Sorafenib in Advanced Hepatocellular Carcinoma (HCC)
NCT01304394	PHASE3	COMPLETED	Safety During Use of Paediatric Triple Chamber Bag Formulas
NCT01485328	PHASE3	COMPLETED	Protocol: Phytomedicine-AMARGOL®, Clinical Trial for Efficacy Proof on Therapeutics
NCT01964430	PHASE3	COMPLETED	Nab-paclitaxel and Gemcitabine vs Gemcitabine Alone as Adjuvant Therapy for Patients With Resected Pancreatic Cancer (the Apact Study)
NCT02044952	PHASE2/PHASE3	UNKNOWN	Efficacy and Safety Study of Tripterygium Glycoside in the Treatment of Crohn’s Disease for Induction Remission
NCT03008460	PHASE3	COMPLETED	Efficacy, Safety and Tolerability of Eziclen®/Izinova® Versus Klean-prep® on Bowel Cleansing in Adolescents Undergoing Colonoscopy
NCT03509220	PHASE3	COMPLETED	Safety and Efficacy of PBK-1701TC for Bowel Cleansing Before Colonoscopy
NCT05253287	PHASE2/PHASE3	COMPLETED	Growth Hormone in Decompensated Liver Cirrhosis
NCT05923918	PHASE3	UNKNOWN	A Study to Evaluate Safety and Efficacy of PBK_M2101
NCT03408886	PHASE2	ACTIVE_NOT_RECRUITING	Microbiota Transfer Therapy for Adults With Autism Spectrum Disorder (ASD) Who Have Gastrointestinal Disorders
NCT05252078	PHASE2	RECRUITING	Anlotinib Hydrochloride Capsules Combined With TQB2450 Injection in Esophageal Squamous Cell Carcinoma Patients
NCT05494060	PHASE2	RECRUITING	XELOX Combined With Anlotinib and Penpulimab vs XELOX as Adjuvant Therapy in ctDNA Positive Gastric and Esophagogastric Junction Adenocarcinoma
NCT05602935	PHASE2	ACTIVE_NOT_RECRUITING	Efficacy and Safety of SOX Regimen Combined With Camrelizumab as Neoadjuvant Treatment in Locally Advanced Gastric Cancer: a Phase II, Single-arm Study
NCT00072943	PHASE2	COMPLETED	A Humanized Anti-Interferon-γ Monoclonal Antibody (HuZAF) for Moderate to Severe Crohn’s Disease
NCT01037049	PHASE2	UNKNOWN	Optimum Timing for Surgery After Pre-operative Radiotherapy 6 vs 12 Weeks
NCT01176227	PHASE1/PHASE2	COMPLETED	Efficacy of a Multi-strain Probiotic in the Treatment of Irritable Bowel Syndrome (IBS)
NCT01483248	PHASE1/PHASE2	UNKNOWN	Human Menstrual Blood-derived Mesenchymal Stem Cells for Patients With Liver Cirrhosis
NCT01695850	PHASE2	COMPLETED	A Double-blinded,Double-dummy Clinical Trial of Chinese Herbal Medicine (MaZiRenWan) for Functional Constipation
NCT01710644	PHASE1/PHASE2	COMPLETED	Efficacy and Tolerability of NM-BL in Patients With Exocrine Pancreatic Insufficiency Due to Cystic Fibrosis
NCT01887834	PHASE1/PHASE2	COMPLETED	Efficacy of a Multi-strain Probiotic in the Treatment of Irritable Bowel Syndrome
NCT01890837	PHASE1/PHASE2	COMPLETED	Effect of TU-100 in Patients With Irritable Bowel Syndrome (IBS)
NCT02189707	PHASE2	COMPLETED	Effects of Probiotic Supplementation on Colonic Transit Time and Gastrointestinal Symptoms in Adults With Constipation.
NCT02613403	PHASE2	TERMINATED	Efficacy and Safety of Grazoprevir (+) Uprifosbuvir (+) Ruzasvir (MK-3682B) (MK-5172 + MK-3682 + MK-8408) Fixed Dose Combination in Chronic HCV Participants Failing Prior Antiviral Treatment (MK-3682-021)
NCT02647866	PHASE2	COMPLETED	Study of a Monoclonal Antibody KHK4083 in Moderate Ulcerative Colitis
NCT03011255	PHASE2	UNKNOWN	Combination of Radiation Therapy and Peptide Specific CTL Therapy in Treating Patients With Esophageal Cancer
NCT03037385	PHASE1/PHASE2	COMPLETED	Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors
NCT03535727	PHASE1/PHASE2	COMPLETED	A Study of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan in Metastatic Pancreatic Cancer
NCT03549494	PHASE2	COMPLETED	Evaluation of Ocoxin®-Viusid® in Advanced Stomach Cancer and Gastric Esophagogastric Junction
NCT03559543	PHASE2	COMPLETED	Evaluation of Ocoxin®-Viusid® in Metastatic Colorectal Adenocarcinoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DOMPERIDONE	4	2
URSODIOL	4	2
ALECTINIB	4	1
ALFENTANIL	4	1
DROPERIDOL	4	1
EMPAGLIFLOZIN	4	1
EPINEPHRINE	4	1
FENTANYL	4	1
GLECAPREVIR	4	1
MESALAMINE	4	1
METRONIDAZOLE	4	1
OZANIMOD	4	1
PANCRELIPASE	4	1
PIBRENTASVIR	4	1
PIOGLITAZONE	4	1
PRALSETINIB	4	1
RIFAXIMIN	4	1
SORAFENIB	4	1
CATEQUENTINIB	3	4
ULIMORELIN	3	2
BENMELSTOBART	3	1
LINIFANIB	3	1
PENPULIMAB	3	1
ROCATINLIMAB	3	1
SENNA	3	1
BERBERINE URSODEOXYCHOLATE	2	2
ZAMAGLUTENASE	2	2
EMRICASAN	2	1
RACEPINEPHRINE	2	1
IDRX-42	1	1