WNT7A

WNT7A
Identifiers
AliasesWNT7A, Wnt family member 7A, Wnt-7a
External IDsOMIM: 601570; MGI: 98961; GeneCards: WNT7A
Available structures
PDBOrtholog search: PDBe RCSB
Orthologs
DatabasesNCBI: entry; OMA: entry
SpeciesHumanMouse
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 MbChr 6: 91.34 – 91.39 Mb
PubMed search
Wikidata
View/Edit HumanView/Edit Mouse

Protein Wnt-7a is a protein that in humans is encoded by the WNT7A gene.

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.

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. This mutation has a recent origin (73 years) and is located inside a Native-american homozygous haplotype. It was discovered by Silvana Santos, a Brazilian researcher who won the 100 Woman BBC prize in 2024.

Knockout and functional evidence

The signaling molecule Wnt7-a is expressed within the female embryo, controlling the proper establishment of the uterus and the anterior-posterior axis within the female reproductive tract. Prenatal knockout of the Wnt7-a gene disrupts the early stages of the female reproductive tract, resulting in the lack of a comprehensive analysis of the gene’s role in development. However, a conditional knockout of the gene after birth, provided greater insight into the role of the gene in terms of uterine development. Initial appearance between the control mice and mutant mice appear similar, as both models presented with a vagina, cervix, oviduct, and ovary. In postnatal development, the Wnt7-a-null mice failed to develop endometrial glands and lacked the expression of genes Foxa2, Hoxa10, Hoxa11, Msx1, and Wnt16. The lack of endometrial glands within the mice resulted in infertility, as blastocyst failed to implant in the immature uterus. Loss of Wnt7-a during prenatal development results in absence of normal female anatomy and infertility while loss of Wnt7-a during postnatal development results in the presence of normal female anatomy and infertility.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000154764 – Ensembl, May 2017
  2. 1 2 3 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 (December 1996). "Isolation, characterization and chromosomal assignment of the human WNT7A gene". Cytogenetics and Cell Genetics. 74 (1–2): 149–152. doi:10.1159/000134404. PMID 8893824.
  6. ↑ Bui TD, Lako M, Lejeune S, Curtis AR, Strachan T, Lindsay S, et al. (June 1997). "Isolation of a full-length human WNT7A gene implicated in limb development and cell transformation, and mapping to chromosome 3p25". Gene. 189 (1): 25–29. doi:10.1016/S0378-1119(96)00808-6. PMID 9161407.
  7. 1 2 "Entrez Gene: WNT7A wingless-type MMTV integration site family, member 7A".
  8. ↑ Alves LU, Santos S, Musso CM, Ezquina SA, Opitz JM, Kok F, et al. (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. PMID 28855715.
  9. ↑ de Farias AA, Nunes K, Lemes RB, Moura R, Fernandes GR, Melo US, et al. (November 2018). "Origin and age of the causative mutations in KLC2, IMPA1, MED25 and WNT7A unravelled through Brazilian admixed populations". Scientific Reports. 8 (1) 16552. doi:10.1038/s41598-018-35022-1. PMC 6224410. PMID 30410084.
  10. ↑ Dunlap KA, Filant J, Hayashi K, Rucker EB, Song G, Deng JM, et al. (August 2011). "Postnatal deletion of Wnt7a inhibits uterine gland morphogenesis and compromises adult fertility in mice". Biology of Reproduction. 85 (2): 386–396. doi:10.1095/biolreprod.111.091769. PMC 3142262. PMID 21508348.

Further reading