WNT2B

Summary

WNT2B (Wnt family member 2B, HGNC:12781) is a protein-coding gene on chromosome 1p13.2, encoding Protein Wnt-2b (Q93097). Ligand for members of the frizzled family of seven transmembrane receptors.

This gene encodes a member of the wingless-type MMTV integration site (WNT) family of highly conserved, secreted signaling factors. WNT family members function in a variety of developmental processes including regulation of cell growth and differentiation and are characterized by a WNT-core domain. This gene may play a role in human development as well as carcinogenesis. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 7482 — RefSeq curated summary.

At a glance

• Gene–disease (curated): diarrhea 9 (Strong, GenCC)
• GWAS associations: 52
• Clinical variants (ClinVar): 125 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 4
• MANE Select transcript: NM_024494

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12781
Approved symbol	WNT2B
Name	Wnt family member 2B
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	XWNT2
Ensembl gene	ENSG00000134245
Ensembl biotype	protein_coding
OMIM	601968
Entrez	7482

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000256640, ENST00000369684, ENST00000369686, ENST00000478360, ENST00000870348, ENST00000941629, ENST00000941630, ENST00000941631

RefSeq mRNA: 3 — MANE Select: NM_024494 NM_001291880, NM_004185, NM_024494

CCDS: CCDS76188, CCDS846, CCDS847

Canonical transcript exons

ENST00000369684 — 5 exons

Exon	Start	End
ENSE00000913289	112517121	112517385
ENSE00001450631	112508965	112509444
ENSE00003553152	112514874	112515094
ENSE00003658629	112516140	112516417
ENSE00003705385	112520280	112530165

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 96.97.

FANTOM5 (CAGE): breadth broad, TPM avg 5.9059 / max 429.2535, expressed in 654 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4677	3.1813	476
4678	1.9947	372
4675	0.5238	225
4676	0.2061	110

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	96.97	gold quality
buccal mucosa cell	CL:0002336	95.86	gold quality
parietal pleura	UBERON:0002400	89.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.35	gold quality
skin of hip	UBERON:0001554	86.71	gold quality
pleura	UBERON:0000977	83.54	gold quality
cranial nerve II	UBERON:0000941	83.41	gold quality
upper leg skin	UBERON:0004262	82.07	gold quality
colonic epithelium	UBERON:0000397	82.02	gold quality
ovary	UBERON:0000992	80.99	gold quality
right ovary	UBERON:0002118	79.43	gold quality
left ovary	UBERON:0002119	79.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.64	gold quality
lower esophagus mucosa	UBERON:0035834	77.99	gold quality
right lung	UBERON:0002167	77.83	gold quality
vagina	UBERON:0000996	77.67	gold quality
skin of abdomen	UBERON:0001416	77.65	gold quality
visceral pleura	UBERON:0002401	76.93	gold quality
pigmented layer of retina	UBERON:0001782	76.88	gold quality
retina	UBERON:0000966	76.87	gold quality
skin of leg	UBERON:0001511	76.74	gold quality
zone of skin	UBERON:0000014	76.55	gold quality
nipple	UBERON:0002030	76.45	gold quality
gingival epithelium	UBERON:0001949	76.03	gold quality
tendon of biceps brachii	UBERON:0008188	75.50	silver quality
rectum	UBERON:0001052	75.48	gold quality
mucosa of paranasal sinus	UBERON:0005030	75.31	gold quality
left uterine tube	UBERON:0001303	75.12	gold quality
seminal vesicle	UBERON:0000998	74.93	gold quality
ectocervix	UBERON:0012249	74.83	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-11	yes	7.95
E-ANND-3	yes	5.84

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI2

miRNA regulators (miRDB)

68 targeting WNT2B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-609	99.82	64.26	505
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548G-5P	99.78	71.12	3085

Literature-anchored findings (GeneRIF, showing 36)

• This is the first report on differential regulation of WNT2 and WNT2B mRNAs in human cancer cell lines. (PMID:11712082)
• Wnt-2b mRNA is expressed in human ovarian cancer cells (PMID:12072409)
• REVIEW: Anti-WNT2B monoclonal antibodies, WNT2B RNAi compounds, or small molecule WNT2B inhibitors could be developed as novel therapeutic agents for gastric cancer and esophageal cancer in the field of clinical oncology. (PMID:16273293)
• in addition to alternative promoters and RNA splicing, an alternative translation start in Wnt13B and Wnt13C mRNAs increases the complexity of both human wnt13 expression and functions (PMID:16407296)
• Heplipin induced KG-1 cell apoptosis is related with Wntl3 and ATPase3. (PMID:17649721)
• Hedgehog signals and bHLH transcription factors are involved in WNT2B upregulation, which is counteracted by BMP, WNT and Notch signals. (PMID:19360354)
• High Wnt2B overexpression is associated with ovarian cancer metastasis and drug resistance. (PMID:22635028)
• secretion of WNT2B and WNT9B and stabilization of beta-catenin (CTNNB1) upon virus infection negatively regulate expression of representative inducible genes IFNB1, IFIT1 and TNF in a CTNNB1-dependent effector mechanism (PMID:23785285)
• these results indicate that the high-expression levels of Gli1 and Wnt2B might play a pivotal role during tumorigenesis of pancreatic cancer (PMID:25120849)
• Results showed that miR-185-3p contributs to radioresistance of nasopharyngeal carcinoma via modulation of WNT2B expression. (PMID:25297925)
• ACSL5 mediates antiproliferative activities via Wnt2B palmitoylation with diminished Wnt activity. The molecular pathway is probably relevant for intestinal homeostasis, overwhelmed by other pathways in carcinogenesis. (PMID:25356045)
• the present study detected abnormal upregulation in the levels of Wnt2b and Wnt7b, and hypothesized that the alterations may be due to the ectopic opening of chromatin structure. (PMID:26548512)
• A549-Luc-positive cells showed cytotoxicity following exposure to the Ad-shWnt2B vector. The percentage of viable cells was significantly lower in A549-Luc cells treated with Ad-shWnt2B than with Ad-scramble (p<0.01 versus control or Ad-scramble, respectively). (PMID:27793913)
• we identified two independent SNPs (i.e., WNT2B rs1175649 G>T and BTRC rs61873997 G>A) that showed a predictive role in CM-specific survival, with an effect-allele-attributed hazards ratio (adjusted hazards ratio) of 1.99 (95% confidence interval = 1.41-2.81, P = 8.10 x 10(-5)) and 0.61 (0.46-0.80, 3.12x10(-4)), respectively. (PMID:28499756)
• Wnt2B co-operates with Frizzled7 to mediate mesenchymal to epithelial transition in colorectal cancer. (PMID:28560804)
• The findings provided new insights into the pathophysiology of liver fibrosis by characterizing Wnt2b as a novel endogenous suppressor of TLR4 signaling, maintaining tissue homeostasis during the early stage of hepatic fibrosis-associated liver diseases. (PMID:28638086)
• Altered WNT2B expression in bladder wall fibroblasts alters expression of the apoptosis inductor TNFSF10. (PMID:29131138)
• Individuals with homozygous nonsense mutations in WNT2B demonstrate severe intestinal dysregulation. (PMID:29909964)
• downregulation of ACSL5 and Wnt2B could play an important role in the development of bronchial-alveolar structures in congenital pulmonary airway malformations (CPAMs). (PMID:30463708)
• While miR-370-3p upregulation led to decreased osteogenic differentiation, LINC00707 overexpression could reverse this suppression, indicating that LINC00707 acts as a competing endogenous RNA (ceRNA) for miR-370-3p. Moreover, LINC00707 could act as a ceRNA to upregulate WNT2B via miR-370-3p inhibition (PMID:30795799)
• Overexpression of WNTB2 in KGN partially reversed the growth-inhibitory effects of miR-324 overexpression. miR-324 regulates the proliferation of KGN cells in PCOs and be essential in the management of PCOS. (PMID:31215527)
• WNT2b Activates Epithelial-mesenchymal Transition Through FZD4: Relevance in Penetrating Crohn s Disease. (PMID:31359032)
• MiR-338-3p enhances the sensitivity of ovarian cancer cells to cisplatin by downregulating WNT2B. (PMID:31769245)
• MiR-449b-5p inhibits human glioblastoma cell proliferation by inactivating WNT2B/Wnt/beta-catenin signaling pathway. (PMID:32495889)
• Canonical Wnts Mediate CD8(+) T Cell Noncytolytic Anti-HIV-1 Activity and Correlate with HIV-1 Clinical Status. (PMID:32887752)
• miR-188-5p inhibits proliferation, migration, and invasion in gallbladder carcinoma by targeting Wnt2b and Smad2. (PMID:33236530)
• Novel variants in the stem cell niche factor WNT2B define the disease phenotype as a congenital enteropathy with ocular dysgenesis. (PMID:33526876)
• miR-27b-5p inhibits BeWo cells fusion by regulating WNT2B and enzyme involved in progesterone synthesis. (PMID:33639023)
• Contribution of WNT2B Genetic Variants to Ischemic Stroke Occurrence in a Chinese Han Population. (PMID:34009855)
• High Glucose-Induced Human Kidney Cell Apoptosis and Inflammatory Injury Are Alleviated by Circ_0008529 Knockdown via Circ_0008529-Mediated miR-485-5p/WNT2B Signaling. (PMID:35913598)
• Wnt2b and Wnt5a expression is highly associated with M2 TAMs in nonsmall cell lung cancer. (PMID:36102318)
• Upregulation of Wnt2b exerts neuroprotective effect by alleviating mitochondrial dysfunction in Alzheimer’s disease. (PMID:36852442)
• [Fibroblasts overpressing WNT2b cause impairment of intestinal mucosal barrier]. (PMID:36946039)
• [Mechanism of intestinal injury induced by WNT2B high-expressed fibroblasts in Crohn’s disease]. (PMID:37385803)
• WNT2B activates macrophages via NF-kappaB signaling pathway in inflammatory bowel disease. (PMID:38489235)
• WNT2B Deficiency Causes Enhanced Susceptibility to Colitis Due to Increased Inflammatory Cytokine Production. (PMID:38697357)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	wnt2bb	ENSDARG00000032234
mus_musculus	Wnt2b	ENSMUSG00000027840
rattus_norvegicus	Wnt2b	ENSRNOG00000014385
drosophila_melanogaster	Wnt2	FBGN0004360
drosophila_melanogaster	Wnt5	FBGN0010194
drosophila_melanogaster	Wnt10	FBGN0031903
caenorhabditis_elegans		WBGENE00000857
caenorhabditis_elegans		WBGENE00000858
caenorhabditis_elegans	lin-44	WBGENE00003029

Paralogs (18): WNT16 (ENSG00000002745), WNT8A (ENSG00000061492), WNT8B (ENSG00000075290), WNT11 (ENSG00000085741), WNT2 (ENSG00000105989), WNT3 (ENSG00000108379), WNT5B (ENSG00000111186), WNT5A (ENSG00000114251), WNT6 (ENSG00000115596), WNT1 (ENSG00000125084), WNT10A (ENSG00000135925), WNT9A (ENSG00000143816), WNT3A (ENSG00000154342), WNT7A (ENSG00000154764), WNT9B (ENSG00000158955), WNT4 (ENSG00000162552), WNT10B (ENSG00000169884), WNT7B (ENSG00000188064)

Protein

Protein identifiers

Protein Wnt-2b — Q93097 (reviewed: Q93097)

Alternative names: Protein Wnt-13

All UniProt accessions (2): Q93097, Q5TEH8

UniProt curated annotations — full annotation on UniProt →

Function. Ligand for members of the frizzled family of seven transmembrane receptors. Functions in the canonical Wnt/beta-catenin signaling pathway. Plays a redundant role in embryonic lung development.

Subunit / interactions. Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity. The complex with AFM may represent the physiological form in body fluids. Interacts with FZD4 and FZD5.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Isoform 1 is expressed in adult heart, brain, placenta, lung, prostate, testis, ovary, small intestine and colon. In the adult brain, it is mainly found in the caudate nucleus, subthalamic nucleus and thalamus. Also detected in fetal brain, lung and kidney. Isoform 2 is expressed in fetal brain, fetal lung, fetal kidney, caudate nucleus, testis and cancer cell lines.

Post-translational modifications. Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.

Disease relevance. Diarrhea 9 (DIAR9) [MIM:618168] An autosomal recessive form of chronic diarrhea characterized by neonatal-onset of osmotic diarrhea that is not substrate specific, abnormal crypt and villus architecture, and significant fat malabsorption evidenced by high levels of fecal fat. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the Wnt family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q93097-1	2	yes
Q93097-2	1

RefSeq proteins (3): NP_001278809, NP_004176, NP_078613* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005817	Wnt	Family
IPR009140	Wnt2	Family
IPR018161	Wnt_CS	Conserved_site
IPR043158	Wnt_C	Homologous_superfamily

Pfam: PF00110

UniProt features (24 total): disulfide bond 11, sequence conflict 5, sequence variant 2, glycosylation site 2, signal peptide 1, chain 1, splice variant 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q93097-F1	86.85	0.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 243

Disulfide bonds (11): 309–340, 325–335, 339–379, 355–370, 357–367, 362–363, 107–118, 158–166, 168–188, 237–251, 239–246

Glycosylation sites (2): 117, 283

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3238698	WNT ligand biogenesis and trafficking
R-HSA-373080	Class B/2 (Secretin family receptors)

MSigDB gene sets: 245 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_EPITHELIUM_DEVELOPMENT, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_REGULATION_OF_MORPHOGENESIS_OF_A_BRANCHING_STRUCTURE, GOBP_CARTILAGE_DEVELOPMENT, KEGG_HEDGEHOG_SIGNALING_PATHWAY, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_EPITHELIAL_TUBE_BRANCHING_INVOLVED_IN_LUNG_MORPHOGENESIS, GOBP_LUNG_MORPHOGENESIS, GOBP_DEVELOPMENTAL_INDUCTION, AP4_Q6, GOBP_NEUROGENESIS, GOBP_KIDNEY_EPITHELIUM_DEVELOPMENT

GO Biological Process (18): chondrocyte differentiation (GO:0002062), lens development in camera-type eye (GO:0002088), male gonad development (GO:0008584), cellular response to starvation (GO:0009267), forebrain regionalization (GO:0021871), neuron differentiation (GO:0030182), cell fate commitment (GO:0045165), canonical Wnt signaling pathway (GO:0060070), lung induction (GO:0060492), mesenchymal-epithelial cell signaling (GO:0060638), iris morphogenesis (GO:0061072), cornea development in camera-type eye (GO:0061303), hematopoietic stem cell proliferation (GO:0071425), positive regulation of branching involved in ureteric bud morphogenesis (GO:0090190), multicellular organism development (GO:0007275), Wnt signaling pathway (GO:0016055), animal organ development (GO:0048513), system development (GO:0048731)

GO Molecular Function (4): frizzled binding (GO:0005109), cytokine activity (GO:0005125), signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by WNT	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	5
cell differentiation	3
camera-type eye development	2
cartilage development	1
gonad development	1
development of primary male sexual characteristics	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
regionalization	1
forebrain development	1
generation of neurons	1
cellular developmental process	1
Wnt signaling pathway	1
organ induction	1
regulation of embryonic development	1
lung field specification	1
regulation of branching involved in lung morphogenesis	1
cell-cell signaling	1
anatomical structure morphogenesis	1
camera-type eye morphogenesis	1
hemopoiesis	1
stem cell proliferation	1
branching involved in ureteric bud morphogenesis	1
positive regulation of multicellular organismal process	1
regulation of branching involved in ureteric bud morphogenesis	1
positive regulation of morphogenesis of an epithelium	1
multicellular organismal process	1
cell surface receptor signaling pathway	1
multicellular organism development	1
G protein-coupled receptor binding	1
receptor ligand activity	1
protein binding	1
binding	1
cellular anatomical structure	1
external encapsulating structure	1

Protein interactions and networks

STRING

1496 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WNT2B	DKK3	Q9UBP4	858
WNT2B	FZD4	Q9ULV1	851
WNT2B	LRP5	O75197	847
WNT2B	FZD8	Q9H461	841
WNT2B	DKK2	Q9UBU2	840
WNT2B	DKK1	O94907	830
WNT2B	DKK4	Q9UBT3	826
WNT2B	LRP6	O75581	810
WNT2B	FZD3	Q9NPG1	781
WNT2B	FZD9	O00144	777
WNT2B	DKKL1	Q9UK85	762
WNT2B	FZD1	Q9UP38	759
WNT2B	FZD7	O75084	742
WNT2B	CTNNB1	P35222	725
WNT2B	FZD5	Q13467	715

IntAct

11 interactions, top by confidence:

A	B	Type	Score
WNT2B	IKBIP	psi-mi:“MI:0403”(colocalization)	0.660
IKBIP	WNT2B	psi-mi:“MI:0915”(physical association)	0.660
IKBIP	IKBKB	psi-mi:“MI:0914”(association)	0.500
WNT2B	AFM	psi-mi:“MI:0915”(physical association)	0.400
WNT2B	PGRMC2	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): WNT2B (Far Western), WNT2B (Affinity Capture-MS), WNT2B (Co-localization), WNT2B (Affinity Capture-RNA), WNT2B (Two-hybrid)

ESM2 similar proteins: A0M8S1, A0M8T2, A1X153, A4D7S0, O00755, O70283, P09544, P21552, P22726, P28465, P87387, Q07DV4, Q07DW8, Q07DX7, Q07DY7, Q07DZ8, Q07E18, Q07E31, Q07E44, Q09YI4, Q09YJ6, Q09YK7, Q09YN1, Q108U2, Q1KYK4, Q1KYK5, Q1KYK6, Q1KYK7, Q1KYL1, Q2IBB0, Q2IBB5, Q2IBE2, Q2IBF4, Q2IBG1, Q2QL76, Q2QL85, Q2QL96, Q2QLA5, Q2QLB6, Q2QLC7

Diamond homologs: A0M8S1, A0M8T2, A1X153, A4D7S0, B2GUT4, O00755, O13267, O15978, O42122, O70283, P04426, P04628, P09544, P09615, P10108, P17553, P21551, P21552, P22724, P22725, P22726, P22727, P24257, P24383, P27467, P28047, P28465, P31285, P31286, P33945, P34888, P34889, P41221, P43446, P47793, P49337, P49338, P49339, P49340, P49893

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
WNT2B	up-regulates	FZD3	binding
WNT2B	up-regulates	LRP5	binding
SOSTDC1	“down-regulates activity”	WNT2B

Disease & clinical

Clinical variants and AI predictions

ClinVar

125 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	57
Likely benign	59
Benign	2

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2132434	NM_024494.3(WNT2B):c.250C>T (p.Gln84Ter)	Pathogenic
2796114	NM_024494.3(WNT2B):c.799C>T (p.Arg267Ter)	Pathogenic
545432	NM_024494.3(WNT2B):c.205C>T (p.Arg69Ter)	Likely pathogenic

SpliceAI

735 predictions. Top by Δscore:

Variant	Effect	Δscore
1:112515090:CAGAA:C	donor_gain	1.0000
1:112515091:AGAA:A	donor_gain	1.0000
1:112515092:GAA:G	donor_gain	1.0000
1:112515092:GAAG:G	donor_gain	1.0000
1:112515093:AA:A	donor_gain	1.0000
1:112515093:AAGT:A	donor_loss	1.0000
1:112515094:AGT:A	donor_loss	1.0000
1:112515095:G:GG	donor_gain	1.0000
1:112516363:GCT:G	donor_gain	1.0000
1:112517120:GGCT:G	acceptor_gain	1.0000
1:112517382:GCAG:G	donor_gain	1.0000
1:112517383:CAGG:C	donor_loss	1.0000
1:112517384:AGG:A	donor_loss	1.0000
1:112517386:G:GA	donor_loss	1.0000
1:112517386:G:GG	donor_gain	1.0000
1:112517387:T:A	donor_loss	1.0000
1:112517390:G:GG	donor_gain	1.0000
1:112509442:GTG:G	donor_gain	0.9900
1:112514870:GCA:G	acceptor_loss	0.9900
1:112514872:A:AG	acceptor_gain	0.9900
1:112514873:G:GG	acceptor_gain	0.9900
1:112514873:GGTAC:G	acceptor_gain	0.9900
1:112516135:TCTA:T	acceptor_loss	0.9900
1:112516136:CTA:C	acceptor_loss	0.9900
1:112516137:TAGGT:T	acceptor_loss	0.9900
1:112516138:A:AG	acceptor_gain	0.9900
1:112516139:G:GG	acceptor_gain	0.9900
1:112516139:G:T	acceptor_loss	0.9900
1:112516139:GGTA:G	acceptor_gain	0.9900
1:112516370:G:GT	donor_gain	0.9900

AlphaMissense

2514 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:112515039:G:C	W116C	1.000
1:112515039:G:T	W116C	1.000
1:112520408:T:C	F359L	1.000
1:112520409:T:G	F359C	1.000
1:112520410:C:A	F359L	1.000
1:112520410:C:G	F359L	1.000
1:112514947:T:A	C86S	0.999
1:112514948:G:C	C86S	0.999
1:112515037:T:A	W116R	0.999
1:112515037:T:C	W116R	0.999
1:112515045:T:G	C118W	0.999
1:112516166:G:C	A144P	0.999
1:112516283:T:C	F183L	0.999
1:112516285:T:A	F183L	0.999
1:112516285:T:G	F183L	0.999
1:112516291:G:C	W185C	0.999
1:112516291:G:T	W185C	0.999
1:112516341:T:G	F202C	0.999
1:112516399:T:A	N221K	0.999
1:112516399:T:G	N221K	0.999
1:112517154:T:A	C239S	0.999
1:112517155:G:C	C239S	0.999
1:112517160:G:T	G241C	0.999
1:112517175:T:A	C246S	0.999
1:112517176:G:A	C246Y	0.999
1:112517176:G:C	C246S	0.999
1:112517191:G:A	C251Y	0.999
1:112517192:C:G	C251W	0.999
1:112517195:G:C	W252C	0.999
1:112517195:G:T	W252C	0.999

dbSNP variants (sampled 300 via entrez): RS1000148190 (1:112499473 A>G), RS1000193999 (1:112474517 A>G), RS1000216159 (1:112496568 G>A,C), RS1000256537 (1:112487184 A>G), RS1000288712 (1:112503092 C>A,T), RS1000330394 (1:112490682 G>C,T), RS1000396298 (1:112523835 C>T), RS1000426333 (1:112487376 G>A), RS1000440219 (1:112509019 G>A,C,T), RS1000501442 (1:112502127 C>G,T), RS1000544828 (1:112476507 C>G), RS1000596684 (1:112503486 C>T), RS1000638919 (1:112508294 A>G), RS1000726317 (1:112482403 A>G), RS1000769517 (1:112523359 A>C)

Disease associations

OMIM: gene MIM:601968 | disease phenotypes: MIM:618168

GenCC curated gene-disease

Disease	Classification	Inheritance
diarrhea 9	Strong	Autosomal recessive

Mondo (2): diarrhea 9 (MONDO:0032575), chronic diarrheal disease (MONDO:0044751)

Orphanet (0):

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001508	Failure to thrive
HP:0002014	Diarrhea
HP:0011473	Villous atrophy

GWAS associations

52 associations (top):

Study	Trait	p-value
GCST002991_4	Pancreatic cancer	7.000000e-07
GCST004562_118	Waist circumference adjusted for body mass index	3.000000e-06
GCST004562_66	Waist circumference adjusted for body mass index	1.000000e-07
GCST004562_7	Waist circumference adjusted for body mass index	4.000000e-08
GCST004563_143	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	1.000000e-07
GCST004563_73	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	3.000000e-07
GCST005434_26	Pancreatic cancer	6.000000e-06
GCST005978_5	Diastolic blood pressure	3.000000e-09
GCST005979_6	Systolic blood pressure	1.000000e-12
GCST006010_2	Mean arterial pressure	6.000000e-12
GCST006031_2	Potassium levels	2.000000e-08
GCST006190_22	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-18
GCST006190_29	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	4.000000e-26
GCST006192_18	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	4.000000e-15
GCST006192_4	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-23
GCST006193_13	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3.000000e-28
GCST006193_53	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3.000000e-20
GCST006195_24	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	6.000000e-19
GCST006195_45	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-26
GCST006288_256	Heel bone mineral density	2.000000e-07
GCST006288_606	Heel bone mineral density	1.000000e-18
GCST006288_711	Heel bone mineral density	6.000000e-13
GCST006979_999	Heel bone mineral density	4.000000e-53
GCST007267_175	Systolic blood pressure	2.000000e-23
GCST007294_13	Body fat distribution (trunk fat ratio)	9.000000e-19
GCST007294_32	Body fat distribution (trunk fat ratio)	1.000000e-08
GCST007295_163	Body fat distribution (leg fat ratio)	8.000000e-07
GCST007295_7	Body fat distribution (leg fat ratio)	7.000000e-16
GCST007703_86	Systolic blood pressure	5.000000e-14
GCST007704_68	Diastolic blood pressure	4.000000e-18

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference
EFO:0008002	physical activity measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0009283	potassium measurement
EFO:0006527	smoking status measurement
EFO:0009270	heel bone mineral density
EFO:0004341	body fat distribution
EFO:0005763	pulse pressure measurement
EFO:0009929	Beta blocking agent use measurement
EFO:0009928	Diuretic use measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0004771	visual cortical surface area measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

43 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	6
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
sotorasib	affects cotreatment, decreases expression	1
bufotalin	increases expression	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
hydroquinone	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
tetrachlorodian	decreases expression	1
deguelin	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
PKF115-584	affects expression	1
bisphenol S	increases expression	1
apatinib	affects cotreatment, decreases expression	1
trametinib	decreases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1
Microplastics	increases abundance, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8Y7	Ubigene HCT 116 WNT2B KO	Cancer cell line	Male

Clinical trials (associated diseases)

27 trials via MONDO — disease-level, not drug-specific.

Trial	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.
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)
NCT02642250	PHASE2/PHASE3	COMPLETED	Comparative Evaluation of Herbal and Allopathic Drugs for the Treatment of Chronic Diarrhea
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
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