Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

WNT4

contributors: mct/npt - updated : 08-01-2015

HGNC name	wingless-type MMTV integration site family, member 4
HGNC id	12783

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	MDFH mullerian aplasia and hyperandrogenism SERKAL female sex reversal and dysgenesis of kidneys, adrenals, and lungs
Location	1p36.12      Physical location : 22.443.799 - 22.469.519
Synonym name	WNT-4 protein
Synonym symbol(s)	WNT-4, RP1-224A6.7, SERKAL

DNA

TYPE	functioning gene
STRUCTURE	25.72 kb     5 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_030761 5 - 3905 NP_110388 36.7 351 - 2007 17720811

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth tongue       Endocrine pancreas         Reproductive female system ovary       Homo sapiens WNT4 mRNA   female system breast mammary gland     Respiratory lung         Visual eye

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal, pregnancy

Text	placenta
	WNT4 mRNA and protein were present in ovaries throughout fetal development

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

C-terminal arginine residue and binds to CPZ through the cysteine-rich domain (CRD)

conjugated

GlycoP

HOMOLOGY

interspecies

homolog to murine Wnt4

Homologene

FAMILY

WNT family

CATEGORY

secretory , signaling

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
text	exracellular matrix

basic FUNCTION	playing a role in sex-determination cascade, in the development and maintenance of the female phenotype in women by regulation of mullerian-duct formation and control of ovarian steroidogenesis
	may have a role in oocyte selection and follicle formation and maturation in human ovaries
	required for normal antral follicle development and may act by regulating granulosa cell functions including steroidogenesis
	WNT4-induced decrease of myostatin plays a functional role during hypertrophy, and WNT4 protein may be a key factor that regulates the extent of differentiation in satellite and myoblasts cells
	play a critical role not only in the development of the reproductive system but also in the formation of the kidneys, adrenals, pituitary gland, and mammary tissues
	involved in the regulation of müllerian duct development and ovarian androgen biosynthesis and also contribute to follicle development and/or maintenance
	modulates canonical WNT signaling and acts as regulator of beta-cell proliferation and inflammatory cytokine release
	have crucial roles in adipogenesis as positive regulator
	found to signal via the CTNNB1 pathway in Sertoli cells, suggesting a self-reinforcing positive feedback loop
	new role in mammalian neuromuscular junction formation that could be mediated by MUSK, a key receptor in synaptogenesis
	critical for mammalian kidney development, since nephrogenesis fails in its absence
	having functions in the ovarian-determination pathway, and involved in sexual differentiation by suppressing male sexual differentiation, promoting Müllerian duct differentiation, and maintaining oocyte health
	RSPO1 and WNT4 are two new regulators of cell proliferation in the early gonad regardless of its sex, in addition to the specific role of these genes in ovarian differentiation
	acts downstream of BMP2 and functions via CTNNB1 Signaling pathway to regulate endometrial stromal cell differentiation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

hormonal

a component

INTERACTION

DNA

RNA

small molecule

protein	DAX1 (antagonize SRY)
	thyroid hormone may regulate terminal differentiation of growth plate chondrocytes in part by modulating Wnt signaling pathways through the induction of CPZ and subsequent CPZ-enhanced activation of WNT4
	NOTCH signalling pathway regulates a NT4 function that patterns the proximal pronephric anlagen
	TMPO over-expression increased, while additional WNT4 secretion suppressed PPARG expression
	MUSK is a WNT4 receptor (WNT4 not only interacts with MUSK ectodomain but also mediates MUSK activation)
	SOX11 represents a synergistic factor for WT1 in regulating the WNT4 gene expression that is critical for nephrogenesis during kidney ontogeny
	interactions of WNT4, RSPO1, and other factors such as forkhead transcription factor 2 in ovarian development and function

cell & other

REGULATION

repressed by

by RAS and forced WNT4 expression inhibits RAS-induced cell motility

Other	inhibition of DAX1 in Sertoli and Leydig cells
	its expression in the ovary seems to be regulated by R-spondin 1 (RSPO1), a thrombospondin family member protein

ASSOCIATED DISORDERS

corresponding disease(s)

MDFH , SERKAL

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in breast carcinoma constitutional germinal mutation       in 46,XY disorders of sex determination and 46,XY complete gonadal dysgenesis constitutional       gain of function by deletion of either FGF9 or FGFR2 in an XY gonad resulted in up-regulation of WNT4 and male-to-female sex reversal

Susceptibility

to osteoporosis

Variant & Polymorphism SNP	increasing the risk of osteoporosis

Candidate gene	female sex determining
Marker
Therapy target

ANIMAL & CELL MODELS

	Wnt4 and Foxl2 double knockout mice ovaries produce testis-like tubules and spermatogonia
	Wnt4-deficiency leads disturbed development of the internal genitalia in mouse, and to a dramatic reduction of mouse oocytes