WNT7A

WNT7A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4UZQ
Identifiers
Aliases	WNT7A , Wnt family member 7A, Wnt-7a
External IDs	OMIM: 601570; MGI: 98961; HomoloGene: 20969; GeneCards: WNT7A; OMA:WNT7A - orthologs
Gene location (Human) Chr. Chromosome 3 (human) [1] Band 3p25.1 Start 13,816,258 bp [1] End 13,880,071 bp [1]
Gene location (Mouse) Chr. Chromosome 6 (mouse) [2] Band 6 D1|6 40.45 cM Start 91,340,963 bp [2] End 91,388,345 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone ganglionic eminence prefrontal cortex gonad right frontal lobe cingulate gyrus anterior cingulate cortex Amygdala right lung Brodmann area 9 Top expressed in surface ectoderm set of lens fibers corneal epithelium epithelium of lens paramesonephric duct corneal endothelium epithelium of vagina medial ganglionic eminence ventricular zone Rostral migratory stream More reference expression data BioGPS More reference expression data
Gene ontology Molecular function receptor ligand activity cytokine activity frizzled binding protein binding signaling receptor binding Cellular component endocytic vesicle membrane endoplasmic reticulum lumen plasma membrane extracellular fluid extracellular region cell surface Golgi lumen extracellular exosome presynapse synapse Biological process positive regulation of synapse assembly cellular response to transforming growth factor beta stimulus excitatory synapse assembly roof of mouth development non-canonical Wnt signaling pathway cell fate commitment response to estradiol positive regulation of epithelial cell proliferation involved in wound healing chondrocyte differentiation axonogenesis somatic stem cell population maintenance uterus morphogenesis stem cell development positive regulation of canonical Wnt signaling pathway negative regulation of neurogenesis synapse organization somatic stem cell division embryonic digit morphogenesis positive regulation of protein localization to synapse embryonic axis specification sex differentiation negative regulation of apoptotic process positive regulation of JNK cascade wound healing Wnt signaling pathway involved in wound healing, spreading of epidermal cells response to estrogen limb development positive regulation of endothelial cell migration positive regulation of transcription, DNA-templated multicellular organism development regulation of axonogenesis dendritic spine morphogenesis synaptic vesicle recycling uterus development regulation of axon diameter skeletal muscle satellite cell activation positive regulation of gene expression cartilage development regulation of cell population proliferation embryonic limb morphogenesis skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration angiogenesis oviduct development establishment of cell polarity central nervous system vasculogenesis positive regulation of excitatory postsynaptic potential positive regulation of cell population proliferation canonical Wnt signaling pathway synapse assembly positive regulation of excitatory synapse assembly dorsal/ventral pattern formation cell proliferation in forebrain embryonic forelimb morphogenesis neurotransmitter secretion cartilage condensation lens fiber cell development cerebellar granule cell differentiation positive regulation of transcription by RNA polymerase II embryonic hindlimb morphogenesis Wnt signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7476 22421 Ensembl ENSG00000154764 ENSMUSG00000030093 UniProt O00755 P24383 RefSeq (mRNA) NM_004625 NM_009527 NM_001363757 RefSeq (protein) NP_004616 NP_033553 NP_001350686 Location (UCSC) Chr 3: 13.82 – 13.88 Mb Chr 6: 91.34 – 91.39 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Protein Wnt-7a is a protein that in humans is encoded by the WNT7A gene. ^{[5] [6] [7]}

Function

The WNT gene family consists of structurally related genes that encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It encodes a protein showing 99% amino acid identity to the mouse Wnt7A protein. This gene not only guides the development of the anterior-posterior axis in the female reproductive tract but also plays a critical role in uterine smooth muscle pattering and maintenance of adult uterine function. It is also responsive to changes in the levels of sex steroid hormone in the female reproductive tract. Decreased expression of this gene in human uterine leiomyoma is found to be inversely associated with the expression of estrogen receptor alpha. ^[7]

Santos syndrome

Santos syndrome is characterized by short stature, fibular agenesis or hypoplasia, clubfeet with oligodactyly, acromial dimples, limited forearm/hand range of motion, and severe nail hypoplasia or anonychia. It is caused by a homozygous mutation in the WNT7A gene, leading to a phenotype similar to Fuhrmann syndrome but with preaxial polydactyly and less severe limb defects. The inheritance pattern is autosomal dominant with incomplete penetrance. ^[8] This mutation has a recent origin (73 years) and is located inside a Native-american homozygous haplotype. ^[9] It was discovered by Silvana Santos, a Brazilian researcher who won the 100 Woman BBC prize in 2024.

References

1. GRCh38: Ensembl release 89: ENSG00000154764 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000030093 – 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. Ikegawa S, Kumano Y, Okui K, Fujiwara T, Takahashi E, Nakamura Y (Dec 1996). "Isolation, characterization and chromosomal assignment of the human WNT7A gene". Cytogenet Cell Genet. 74 (1–2): 149–52. doi:10.1159/000134404. PMID   8893824.
6. Bui TD, Lako M, Lejeune S, Curtis AR, Strachan T, Lindsay S, Harris AL (Jun 1997). "Isolation of a full-length human WNT7A gene implicated in limb development and cell transformation, and mapping to chromosome 3p25". Gene. 189 (1): 25–9. doi:10.1016/S0378-1119(96)00808-6. PMID   9161407.
7. "Entrez Gene: WNT7A wingless-type MMTV integration site family, member 7A".
8. Alves, Leandro U; Santos, Silvana; Musso, Camila M; Ezquina, Suzana AM; Opitz, John M; Kok, Fernando; Otto, Paulo A; Mingroni-Netto, Regina C (December 2017). "Santos syndrome is caused by mutation in the WNT7A gene". Journal of Human Genetics. 62 (12): 1073–1078. doi:10.1038/jhg.2017.86.
9. de Farias, Allysson Allan; Nunes, Kelly; Lemes, Renan Barbosa; Moura, Ronald; Fernandes, Gustavo Ribeiro; Melo, Uirá Souto; Zatz, Mayana; Kok, Fernando; Santos, Silvana (8 November 2018). "Origin and age of the causative mutations in KLC2, IMPA1, MED25 and WNT7A unravelled through Brazilian admixed populations". Scientific Reports. 8 (1). doi:10.1038/s41598-018-35022-1. PMC   6224410 .

Further reading

• Smolich BD, McMahon JA, McMahon AP, Papkoff J (1994). "Wnt family proteins are secreted and associated with the cell surface". Mol. Biol. Cell. 4 (12): 1267–75. doi:10.1091/mbc.4.12.1267. PMC   275763 . PMID   8167409.
• Huguet EL, McMahon JA, McMahon AP, et al. (1994). "Differential expression of human Wnt genes 2, 3, 4, and 7B in human breast cell lines and normal and disease states of human breast tissue". Cancer Res. 54 (10): 2615–21. PMID   8168088.
• Parr BA, McMahon AP (1998). "Sexually dimorphic development of the mammalian reproductive tract requires Wnt-7a". Nature. 395 (6703): 707–10. Bibcode:1998Natur.395..707P. doi:10.1038/27221. PMID   9790192. S2CID   4423065.
• Calvo R, West J, Franklin W, et al. (2001). "Altered HOX and WNT7A expression in human lung cancer". Proc. Natl. Acad. Sci. U.S.A. 97 (23): 12776–81. doi: 10.1073/pnas.97.23.12776 . PMC   18840 . PMID   11070089.
• Li S, Chiang TC, Davis GR, et al. (2001). "Decreased expression of Wnt7a mRNA is inversely associated with the expression of estrogen receptor-alpha in human uterine leiomyoma". J. Clin. Endocrinol. Metab. 86 (1): 454–7. doi: 10.1210/jcem.86.1.7276 . PMID   11232041.
• Couse JF, Dixon D, Yates M, et al. (2002). "Estrogen receptor-alpha knockout mice exhibit resistance to the developmental effects of neonatal diethylstilbestrol exposure on the female reproductive tract". Dev. Biol. 238 (2): 224–38. doi: 10.1006/dbio.2001.0413 . PMID   11784006.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Caricasole A, Ferraro T, Iacovelli L, et al. (2003). "Functional characterization of WNT7A signaling in PC12 cells: interaction with A FZD5 x LRP6 receptor complex and modulation by Dickkopf proteins". J. Biol. Chem. 278 (39): 37024–31. doi: 10.1074/jbc.M300191200 . PMID   12857724.
• Tuli R, Tuli S, Nandi S, et al. (2003). "Transforming growth factor-beta-mediated chondrogenesis of human mesenchymal progenitor cells involves N-cadherin and mitogen-activated protein kinase and Wnt signaling cross-talk". J. Biol. Chem. 278 (42): 41227–36. doi: 10.1074/jbc.M305312200 . PMID   12893825.
• Ohira T, Gemmill RM, Ferguson K, et al. (2003). "WNT7a induces E-cadherin in lung cancer cells". Proc. Natl. Acad. Sci. U.S.A. 100 (18): 10429–34. Bibcode:2003PNAS..10010429O. doi: 10.1073/pnas.1734137100 . PMC   193578 . PMID   12937339.
• Timmreck LS, Pan HA, Reindollar RH, Gray MR (2004). "WNT7A mutations in patients with Müllerian duct abnormalities". Journal of Pediatric and Adolescent Gynecology. 16 (4): 217–21. doi:10.1016/S1083-3188(03)00124-4. PMID   14550385.
• Hwang SG, Ryu JH, Kim IC, et al. (2004). "Wnt-7a causes loss of differentiated phenotype and inhibits apoptosis of articular chondrocytes via different mechanisms". J. Biol. Chem. 279 (25): 26597–604. doi: 10.1074/jbc.M401401200 . PMID   15082716.
• Winn RA, Marek L, Han SY, et al. (2005). "Restoration of Wnt-7a expression reverses non-small cell lung cancer cellular transformation through frizzled-9-mediated growth inhibition and promotion of cell differentiation". J. Biol. Chem. 280 (20): 19625–34. doi: 10.1074/jbc.M409392200 . PMID   15705594.
• Lyu J, Joo CK (2005). "Wnt-7a up-regulates matrix metalloproteinase-12 expression and promotes cell proliferation in corneal epithelial cells during wound healing". J. Biol. Chem. 280 (22): 21653–60. doi: 10.1074/jbc.M500374200 . PMID   15802269.
• Woods CG, Stricker S, Seemann P, et al. (2006). "Mutations in WNT7A Cause a Range of Limb Malformations, Including Fuhrmann Syndrome and Al-Awadi/Raas-Rothschild/Schinzel Phocomelia Syndrome". Am. J. Hum. Genet. 79 (2): 402–8. doi:10.1086/506332. PMC   1559483 . PMID   16826533.
• Winn RA, Van Scoyk M, Hammond M, et al. (2006). "Antitumorigenic effect of Wnt 7a and Fzd 9 in non-small cell lung cancer cells is mediated through ERK-5-dependent activation of peroxisome proliferator-activated receptor gamma". J. Biol. Chem. 281 (37): 26943–50. doi: 10.1074/jbc.M604145200 . PMID   16835228.
• Lindberg D, Akerström G, Westin G (2007). "Mutational analyses of WNT7A and HDAC11 as candidate tumour suppressor genes in sporadic malignant pancreatic endocrine tumours". Clin. Endocrinol. 66 (1): 110–4. doi:10.1111/j.1365-2265.2006.02694.x. PMID   17201809. S2CID   21975021.
• Thrasivoulou C, Millar M, Ahmed A (2013). "Activation of intracellular calcium by multiple Wnt ligands and translocation of β-catenin into the nucleus: a convergent model of Wnt/Ca2+ and Wnt/β-catenin pathways". J. Biol. Chem. 288 (50): 35651–35659. doi: 10.1074/jbc.M112.437913 . PMC   3861617 . PMID   24158438.