Protein Wnt-9b

WNT9B
Identifiers
Aliases	WNT9B, WNT14B, WNT15, Wnt family member 9B
External IDs	OMIM: 602864; MGI: 1197020; HomoloGene: 2551; GeneCards: WNT9B; OMA:WNT9B - orthologs
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q21.32 Start 46,833,201 bp[1] End 46,886,730 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 E1|11 67.47 cM Start 103,618,190 bp[2] End 103,640,647 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gonad duodenum human kidney prefrontal cortex placenta apex of heart superior frontal gyrus primary visual cortex right frontal lobe right auricle of heart Top expressed in interventricular septum medullary collecting duct cortical collecting duct surface ectoderm labioscrotal swelling semi-lunar valve cloacal membrane lateral geniculate nucleus maxillary prominence mandibular prominence More reference expression data BioGPS n/a
Gene ontology Molecular function frizzled binding signaling receptor binding co-receptor binding receptor ligand activity Cellular component extracellular region extracellular space Biological process kidney morphogenesis cell-cell signaling cellular response to starvation mesonephric duct formation multicellular organism development male genitalia development cornea development in camera-type eye branching morphogenesis of an epithelial tube kidney rudiment formation collecting duct development regulation of asymmetric cell division embryonic cranial skeleton morphogenesis kidney development Wnt signaling pathway, planar cell polarity pathway cellular response to retinoic acid mesenchymal stem cell maintenance involved in nephron morphogenesis establishment of planar polarity involved in nephron morphogenesis nephron tubule morphogenesis roof of mouth development metanephric tubule development in utero embryonic development regulation of tube size mesonephric tubule development uterus morphogenesis response to retinoic acid regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis cell fate commitment branching involved in ureteric bud morphogenesis positive regulation of catalytic activity metanephric tubule formation regulation of protein phosphorylation negative regulation of stem cell population maintenance midbrain dopaminergic neuron differentiation non-canonical Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation Wnt signaling pathway neuron differentiation regulation of signaling receptor activity canonical Wnt signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7484 22412 Ensembl ENSG00000158955 ENSG00000276799 ENSMUSG00000018486 UniProt O14905 O35468 RefSeq (mRNA) NM_003396 NM_001320458 NM_011719 RefSeq (protein) NP_001307387 NP_003387 NP_035849 Location (UCSC) Chr 17: 46.83 – 46.89 Mb Chr 11: 103.62 – 103.64 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Protein Wnt-9b (formerly WNT15^[5]) is a protein that in humans is encoded by the WNT9B gene.^[6]

The WNT family of genes produce glycolipoproteins that are involved with signaling and developmental processes. Like other Wnt genes, WNT9B codes for the WNT9B protein which participates in the canonical Wnt/β-catenin signaling pathway. WNT9B is a gene found on chromosome 17 in region 17q21. It can be traced to function in the establishment of the kidneys, because WNT9 is critical for morphogenesis of the nephron.^[7]

This gene can impact kidney function in more than one way. Improper expression of the gene can cause cyst development on the kidney tubules, and in mice, mutant WNT9 genes that cause lower protein concentrations resulted in failure of the kidneys to thrive shortly after birth.^[8]

WNT9B is a gene that often expressed in the epithelial cells of the Wolffian duct in early male and female embryos. In the embryos, Wnt11 is expressed at the branching points of the kidney tubules while WNT9B is expressed in a higher concentration at the stalk of the tubules.^[9] WNT9B has also been tied to the involvement of neural differentiation by induction of retinoic acid, according to the NCBI.^[10]

WNT9B is expressed in the developing urogenital sinus epithelium (anlage of the prostate) and in the Wollfian duct.^[11][12][13] Autosomal dominant WNT9B pathogenic variants cause embryonic developmental sequence defects: Mayer-Rokitansky-Küster-Hauser syndrome in females, and Zinner syndrome in males.^[14] Syndrome presentation in males includes prostatic and seminal vesicle cysts, enlarged prostate, kidney agenesis, and ejaculatory duct obstruction. WNT9B mutant mice have absent Wolffian ducts, epididymis and vas deferens, without urogenital sinus-derived mesonephric duct and mesenchymal-derived tubular epithelia.^[15] HNF1B transcriptionally regulates WNT9B;^[16] HNF1B too has been cited as a cause of Mayer-Rokitansky-Küster-Hauser syndrome.^[17] Inheritance of a rare pathogenic mutation of WNT9B has been shown to carry significant risk of the subsequent development of prostate cancer.^[18] Estimated risk ranged from 2- to 12-fold across numerous independent study populations. Common genetic variation of HNF1B too has been established to impact prostate cancer risk.^[19][20] In mouse models, activation of the WNT pathway causes prostate intraepithelial neoplasia.^[21]

References

1. ENSG00000276799 GRCh38: Ensembl release 89: ENSG00000158955, ENSG00000276799 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000018486 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Garriock RJ, Warkman AS, Meadows SM, D'Agostino S, Krieg PA (2007). "Census of vertebrate Wnt genes: isolation and developmental expression of Xenopus Wnt2, Wnt3, Wnt9a, Wnt9b, Wnt10a, and Wnt16". Developmental Dynamics. 236 (5): 1249–58. doi:10.1002/dvdy.21156. PMID 17436276. S2CID 21016668.
6. "Entrez Gene: Wnt9b wingless-type MMTV integration site family, member 9B".
7. Karner C, Chirumamilla R, Aoki S, et al. (2009). "Wnt9b signaling regulates planar cell polarity and kidney tubule morphogenesis". Nat Genet. 41 (7): 793–799. doi:10.1038/ng.400. PMC 2761080. PMID 19543268.
8. Karner C, Chirumamilla R, Aoki S, et al. (2009). "Wnt9b signaling regulates planar cell polarity and kidney tubule morphogenesis". Nat Genet. 41 (7): 793–799. doi:10.1038/ng.400. PMC 2761080. PMID 19543268.
9. Carroll T, Park J, Hayashi S, Majumdar A, McMahon A, et al. (2005). "Wnt9b Plays a Central Role in the Regulation of Mesenchymal to Epithelial Transitions Underlying Organogenesis of the Mammalian Urogenital System". Developmental Cell. 9 (2): 283–292. doi:10.1016/j.devcel.2005.05.016. PMID 16054034.
10. "WNT9B Wnt family member 9B [Homo sapiens (human)]". NCBI Genes & Expression. 2021-04-06. Retrieved 2021-04-14.
11. Blum R, Gupta R, Burger P, Ontiveros C, Salm S, Xiong X, Kamb A, Wesche H, Marshall L, Cutler G, Wand X, Zavadil J, Moscatelli D, Wilson EL (2009). "Molecular signatures of prostate stem cells reveal novel signaling pathways and provide insights into prostate cancer". PLOS ONE. 4 (5) e5722. Bibcode:2009PLoSO...4.5722B. doi:10.1371/journal.pone.0005722. PMC 2684642. PMID 19478945.
12. Lee D, Olson A, Wang J, Kim W, Mi J, Zeng H, Le V, Aldahl J, Hiroto A, Wu X, Sun Z (Jan 2021). "Androgen action in cell fate and communication during prostate development at single-cell resolution". Development. 148 (1) dev.196048. doi:10.1242/dev.196048. PMC 7823163. PMID 33318148.
13. Mehta V, Abler L, Keil K, Schmitz C, Joshi P, Vezina C (Nov 2011). "Atlas of Wnt and R-spondin gene expression in the developing male mouse lower urogenital tract". Dev Dyn. 240 (11): 2548–60. doi:10.1002/dvdy.22741. PMC 3177998. PMID 21936019.
14. Waschk D, Tewes A, Romer T, Hucke J, Kapczuk K, Schippert C, Hillemanns P, Wieacker P, Ledig S (May 2016). "Mutations in WNT9B are associated with Mayer-Rokitansky-Kuster-Hauser syndrome". Clin Genet. 89 (5): 590–6. doi:10.1111/cge.12701. PMID 26610373.
15. Carroll T, Park J, Hayashi S, Majumdar A, McMahon A (Aug 2005). "Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system". Dev Cell. 9 (2): 283–92. doi:10.1016/j.devcel.2005.05.016. PMID 16054034.
16. Lokmane L, Heliot C, Garcia-Villalba P, Fabre M, Cereghini S (Jan 2010). "vHNF1 functions in distinct regulatory circuits to control ureteric bud branching and early nephrogenesis". Development. 137 (2): 347–57. doi:10.1242/dev.042226. PMID 20040500.
17. Thompson E, Tran M, Robevska G, Ayers K, van der Bergen J, Bhaskaran P, Haan E, Cereghini S, Vash-Margita A, Margetts M, Hensley A, Nguyen Q, Sinclair A, Koopman P, Pelosi E (Mar 2023). "Functional genomics analysis identifies loss of HNF1B function as a cause of Mayer-Rokitansky-Küster-Hauser syndrome". Hum Mol Genet. 32 (6): 1032–47. doi:10.1093/hmg/ddac262. PMC 9990990. PMID 36282544.
18. Dupont W, Jones A, MVP, Smith J (Jan 2025). "Coding Variants of the Genitourinary Development Gene WNT9B Carry High Risk for Prostate Cancer". JCO Precis Oncol. 9 (9) e2400569. doi:10.1200/PO-24-00569. PMC 11980042. PMID 39874495.
19. Grisanzio C, Werner L, Takeda D, Awoyemi B, Pomerantz M, Yamada H, Sooriakumaran P, Robinson B, Leung R, Schinzel A, Mills I, Ross-Adams H, Neal D, Kido M, Yamamoto T, Petrozziello G, Stack E, Lis R, Kantoff P, Loda M, Sartor O, Egawa S, Tewari A, Hahn W, Freedman M (Jul 2012). "Genetic and functional analyses implicate the NUDT11, HNF1B, and SLC22A3 genes in prostate cancer pathogenesis". Proc Natl Acad Sci U S A. 109 (28): 11252–7. Bibcode:2012PNAS..10911252G. doi:10.1073/pnas.1200853109. PMC 3396469. PMID 22730461.
20. Gudmundsson J, Sulem P, Steinthorsdottir V, Bergthorsson J, Thorleifsson G, Manolescu A (Aug 2007). "Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes". Nat Genet. 39 (8): 977–83. doi:10.1038/ng2062. PMID 17603485.
21. Yu X, Wang Y, Jian M, Bierie B, Roy-Burman P, Shen M, Taketo M, Wills M, Matusik R (Feb 2009). "Activation of beta-Catenin in mouse prostate causes HGPIN and continuous prostate growth after castration". Prostate. 69 (3): 249–62. doi:10.1002/pros.20877. PMC 4437562. PMID 18991257.