Alternative titles; symbols
HGNC Approved Gene Symbol: WNT2B
Cytogenetic location: 1p13.2 Genomic coordinates (GRCh38): 1:112,466,541-112,530,165 (from NCBI)
Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
---|---|---|---|---|
1p13.2 | Diarrhea 9 | 618168 | Autosomal recessive | 3 |
Katoh et al. (1996) cloned a novel WNT gene from a human gastric cancer cDNA library. Sequence analysis revealed that WNT13 was the human homolog of Xwnt2, a WNT gene cloned from Xenopus by Wolda and Moon (1992). Katoh et al. (1996) reported that the WNT13 gene encodes a 372-amino acid polypeptide including a putative secretory signal peptide. Northern blot analysis revealed that WNT13 was expressed as a 2.5-kb mRNA in fetal brain, lung, and kidney. Unlike most other WNTs, which tend to have restricted expression in adult tissues, its transcript was found in a wide variety of adult tissues.
Katoh et al. (1996) used fluorescence in situ hybridization to map the WNT13 gene to chromosome 1p13.
In a Kuwaiti brother and sister and a Vietnamese boy with neonatal-onset chronic diarrhea (DIAR9; 618168), O'Connell et al. (2018) identified homozygosity for nonsense mutations in the WNT2B gene, R69X (601968.0001) and R105X (601968.0002), respectively. Analysis of patient intestinal enteroid cultures indicated alterations in canonical WNT and microbial pattern-recognition signaling.
Ober et al. (2006) used a screen for mutations affecting endodermal organ morphogenesis to identify a unique phenotype, which they called 'prometheus' (prt). Prometheus mutants exhibit profound, though transient, defects in liver specification. Positional cloning revealed that prt encodes a previously unidentified Wnt2b homolog. Prt/Wnt2bb is expressed in restricted bilateral domains in the lateral plate mesoderm directly adjacent to the liver-forming endoderm. Mosaic analyses showed the requirement for Prt/Wnt2bb in the lateral plate mesoderm, in agreement with the inductive properties of Wnt signaling. Taken together, Ober et al. (2006) concluded that their data revealed an unexpected positive role for Wnt signaling in liver specification, and indicate a possible common theme for the localized formation of endodermal organs along the gut tube.
In a Kuwaiti brother and sister with neonatal-onset chronic diarrhea (DIAR9; 618168), O'Connell et al. (2018) identified homozygosity for a c.205C-T transition (c.205C-T, NM_024494) in the WNT2B gene, resulting in an arg69-to-ter (R69X) substitution. Their unaffected parents and 3 unaffected sibs were heterozygous for the mutation, which was detected in heterozygous state 3 times in the gnomAD database and 1 time in the ExAC database. Immunofluorescence showed diminished staining for OLFM4 (614061), a marker for intestinal stem cells, and enteroid cultures generated from patient intestinal epithelium could not be expanded and did not survive passage. Quantitative RT-PCR of patient enteroids showed a 10-fold increase in LEF1 (153245) mRNA and a 100-fold reduction in TLR4 (603030) expression compared to controls, indicating alterations in canonical WNT and microbial pattern-recognition signaling.
In a 7-year-old Vietnamese boy with neonatal-onset chronic diarrhea (DIAR9; 618168), O'Connell et al. (2018) identified homozygosity for a c.313C-T transition (c.313C-T, NM_024494) in the WNT2B gene, resulting in an arg105-to-ter (R105X) substitution. His unaffected parents were heterozygous for the mutation, which was not found in the ExAC or gnomAD databases.
Katoh, M., Hirai, M., Sugimura, T., Terada, M. Cloning, expression and chromosomal localization of Wnt-13, a novel member of the Wnt gene family. Oncogene 13: 873-876, 1996. [PubMed: 8761309]
O'Connell, A. E., Zhou, F., Shah, M. S., Murphy, Q., Rickner, H., Kelsen, J., Boyle, J., Doyle, J. J., Gangwani, B., Thiagarajah, J. R., Kamin, D. S., Goldsmith, J. D., Richmond, C., Breault, D. T., Agrawal, P. B. Neonatal-onset chronic diarrhea caused by homozygous nonsense WNT2B mutations. Am. J. Hum. Genet. 103: 131-137, 2018. [PubMed: 29909964] [Full Text: https://doi.org/10.1016/j.ajhg.2018.05.007]
Ober, E. A., Verkade, H., Field, H. A., Stainier, D. Y. R. Mesodermal Wnt2b signalling positively regulates liver specification. Nature 442: 688-691, 2006. [PubMed: 16799568] [Full Text: https://doi.org/10.1038/nature04888]
Wolda, S. L., Moon, R. T. Cloning and developmental expression in Xenopus laevis of seven additional members of the Wnt family. Oncogene 7: 1941-1947, 1992. [PubMed: 1408135]