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WNT4 Wnt family member 4 [ Homo sapiens (human) ]

Gene ID: 54361, updated on 21-Apr-2019

Summary

Official Symbol
WNT4provided by HGNC
Official Full Name
Wnt family member 4provided by HGNC
Primary source
HGNC:HGNC:12783
See related
Ensembl:ENSG00000162552 MIM:603490
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
WNT-4; SERKAL
Summary
The WNT gene family consists of structurally related genes which 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, and is the first signaling molecule shown to influence the sex-determination cascade. It encodes a protein which shows 98% amino acid identity to the Wnt4 protein of mouse and rat. This gene and a nuclear receptor known to antagonize the testis-determining factor play a concerted role in both the control of female development and the prevention of testes formation. This gene and another two family members, WNT2 and WNT7B, may be associated with abnormal proliferation in breast tissue. Mutations in this gene can result in Rokitansky-Kuster-Hauser syndrome and in SERKAL syndrome. [provided by RefSeq, Jul 2008]
Expression
Biased expression in skin (RPKM 8.0), ovary (RPKM 4.5) and 13 other tissues See more
Orthologs

Genomic context

See WNT4 in Genome Data Viewer
Location:
1p36.12
Exon count:
8
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 1 NC_000001.11 (22117305..22143981, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (22443798..22470474, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC112268223 Neighboring gene long intergenic non-protein coding RNA 339 Neighboring gene M-phase phosphoprotein 6 pseudogene Neighboring gene cell division cycle 42 Neighboring gene uncharacterized LOC105376845 Neighboring gene uncharacterized LOC105376850 Neighboring gene uncharacterized LOC107985377

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Mullerian aplasia and hyperandrogenism
MedGen: C2675014 OMIM: 158330 GeneReviews: Not available
Compare labs
Serkal syndrome
MedGen: C2678492 OMIM: 611812 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese.
NHGRI GWA Catalog
Genome-wide association meta-analysis identifies new endometriosis risk loci.
NHGRI GWA Catalog
Genome-wide association study link novel loci to endometriosis.
NHGRI GWA Catalog
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
NHGRI GWA Catalog
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
NHGRI GWA Catalog
Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment.
NHGRI GWA Catalog
Wnt signaling and Dupuytren's disease.
NHGRI GWA Catalog

Pathways from BioSystems

  • Axon guidance, organism-specific biosystem (from KEGG)
    Axon guidance, organism-specific biosystemAxon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are...
  • Axon guidance, conserved biosystem (from KEGG)
    Axon guidance, conserved biosystemAxon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are...
  • BMP2-WNT4-FOXO1 Pathway in Human Primary Endometrial Stromal Cell Differentiation, organism-specific biosystem (from WikiPathways)
    BMP2-WNT4-FOXO1 Pathway in Human Primary Endometrial Stromal Cell Differentiation, organism-specific biosystemThis pathway is based on figure 6 from Li et al. BMP2 is activated by cAMP which promotes WNT4 expression in Human Primary Endometrial Stromal Cells (HPESCs) through SMAD1/5/8. WNT4 then induces FOXO...
  • Basal cell carcinoma, organism-specific biosystem (from KEGG)
    Basal cell carcinoma, organism-specific biosystemCancer of the skin is the most common cancer in Caucasians and basal cell carcinomas (BCC) account for 90% of all skin cancers. The vast majority of BCC cases are sporadic, though there is a rare fam...
  • Basal cell carcinoma, conserved biosystem (from KEGG)
    Basal cell carcinoma, conserved biosystemCancer of the skin is the most common cancer in Caucasians and basal cell carcinomas (BCC) account for 90% of all skin cancers. The vast majority of BCC cases are sporadic, though there is a rare fam...
  • Beta-catenin independent WNT signaling, organism-specific biosystem (from REACTOME)
    Beta-catenin independent WNT signaling, organism-specific biosystemHumans and mice have 19 identified WNT proteins that were originally classified as either 'canonical' or 'non-canonical' depending upon whether they were able to transform the mouse mammary epithelia...
  • Breast cancer, organism-specific biosystem (from KEGG)
    Breast cancer, organism-specific biosystemBreast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gla...
  • Breast cancer, conserved biosystem (from KEGG)
    Breast cancer, conserved biosystemBreast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gla...
  • Class B/2 (Secretin family receptors), organism-specific biosystem (from REACTOME)
    Class B/2 (Secretin family receptors), organism-specific biosystemThis family is known as Family B (secretin-receptor family, family 2) G-protein-coupled receptors. Family B GPCRs include secretin, calcitonin, parathyroid hormone/parathyroid hormone-related peptide...
  • DNA Damage Response (only ATM dependent), organism-specific biosystem (from WikiPathways)
    DNA Damage Response (only ATM dependent), organism-specific biosystemThis is the second pathway out of two pathways which deals with DNA damage response. It has two central gene products (ATM and TP53) which are connected with the first DNA damage response pathway. In...
  • GPCR ligand binding, organism-specific biosystem (from REACTOME)
    GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
  • HTLV-I infection, organism-specific biosystem (from KEGG)
    HTLV-I infection, organism-specific biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
  • HTLV-I infection, conserved biosystem (from KEGG)
    HTLV-I infection, conserved biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
  • Hippo signaling pathway, organism-specific biosystem (from KEGG)
    Hippo signaling pathway, organism-specific biosystemHippo signaling is an evolutionarily conserved signaling pathway that controls organ size from flies to humans. In humans and mice, the pathway consists of the MST1 and MST2 kinases, their cofactor S...
  • Hippo signaling pathway, conserved biosystem (from KEGG)
    Hippo signaling pathway, conserved biosystemHippo signaling is an evolutionarily conserved signaling pathway that controls organ size from flies to humans. In humans and mice, the pathway consists of the MST1 and MST2 kinases, their cofactor S...
  • Melanogenesis, organism-specific biosystem (from KEGG)
    Melanogenesis, organism-specific biosystemCutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory cont...
  • Melanogenesis, conserved biosystem (from KEGG)
    Melanogenesis, conserved biosystemCutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory cont...
  • Negative regulation of TCF-dependent signaling by WNT ligand antagonists, organism-specific biosystem (from REACTOME)
    Negative regulation of TCF-dependent signaling by WNT ligand antagonists, organism-specific biosystemSeveral unrelated families of secreted proteins antagonize WNT signaling. Secreted frizzled-related proteins (sFRPs) have a cysteine rich domain (CRD) that is also found in FZD and ROR receptors, wh...
  • PCP/CE pathway, organism-specific biosystem (from REACTOME)
    PCP/CE pathway, organism-specific biosystemThe planar cell polarity (PCP) pathway controls the establishment of polarity within the plane of a sheet of cells. PCP was initially characterized in Drosophila, where it controls the arrangement o...
  • Pathways in cancer, organism-specific biosystem (from KEGG)
    Pathways in cancer, organism-specific biosystem
    Pathways in cancer
  • Proteoglycans in cancer, organism-specific biosystem (from KEGG)
    Proteoglycans in cancer, organism-specific biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
  • Proteoglycans in cancer, conserved biosystem (from KEGG)
    Proteoglycans in cancer, conserved biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by GPCR, organism-specific biosystem (from REACTOME)
    Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
  • Signaling by Wnt, organism-specific biosystem (from REACTOME)
    Signaling by Wnt, organism-specific biosystemWNT signaling pathways control a wide range of developmental and adult process in metozoans including cell proliferation, cell fate decisions, cell polarity and stem cell maintenance (reviewed in Sai...
  • Signaling pathways regulating pluripotency of stem cells, organism-specific biosystem (from KEGG)
    Signaling pathways regulating pluripotency of stem cells, organism-specific biosystemPluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date i...
  • Signaling pathways regulating pluripotency of stem cells, conserved biosystem (from KEGG)
    Signaling pathways regulating pluripotency of stem cells, conserved biosystemPluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date i...
  • TCF dependent signaling in response to WNT, organism-specific biosystem (from REACTOME)
    TCF dependent signaling in response to WNT, organism-specific biosystem19 WNT ligands and 10 FZD receptors have been identified in human cells; interactions amongst these ligands and receptors vary in a developmental and tissue-specific manner and lead to activation of ...
  • Thyroid hormone signaling pathway, organism-specific biosystem (from KEGG)
    Thyroid hormone signaling pathway, organism-specific biosystemThe thyroid hormones (THs) are important regulators of growth, development and metabolism. The action of TH is mainly mediated by T3 (3,5,3'-triiodo-L-thyronine). Thyroid hormones, L-thyroxine (T4) a...
  • WNT ligand biogenesis and trafficking, organism-specific biosystem (from REACTOME)
    WNT ligand biogenesis and trafficking, organism-specific biosystem19 WNT proteins have been identified in human cells. The WNTs are members of a conserved metazoan family of secreted morphogens that activate several signaling pathways in the responding cell: the c...
  • Wnt Signaling Pathway, organism-specific biosystem (from WikiPathways)
    Wnt Signaling Pathway, organism-specific biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...
  • Wnt Signaling Pathway and Pluripotency, organism-specific biosystem (from WikiPathways)
    Wnt Signaling Pathway and Pluripotency, organism-specific biosystemThis pathway was adapted from several resources and is designed to provide a theoretical frame-work for examining Wnt signaling and interacting components in the context of embryonic stem-cell plurip...
  • Wnt signaling, organism-specific biosystem (from KEGG)
    Wnt signaling, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
  • Wnt signaling, conserved biosystem (from KEGG)
    Wnt signaling, conserved biosystemFunctional set; Cellular processes; Cell signaling
  • Wnt signaling pathway, organism-specific biosystem (from KEGG)
    Wnt signaling pathway, organism-specific biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...
  • Wnt signaling pathway, conserved biosystem (from KEGG)
    Wnt signaling pathway, conserved biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...
  • mTOR signaling pathway, organism-specific biosystem (from KEGG)
    mTOR signaling pathway, organism-specific biosystemThe mammalian (mechanistic) target of rapamycin (mTOR) is a highly conserved serine/threonine protein kinase, which exists in two complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2). mTORC1 conta...
  • mTOR signaling pathway, conserved biosystem (from KEGG)
    mTOR signaling pathway, conserved biosystemThe mammalian (mechanistic) target of rapamycin (mTOR) is a highly conserved serine/threonine protein kinase, which exists in two complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2). mTORC1 conta...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
receptor ligand activity IDA
Inferred from Direct Assay
more info
PubMed 
transcription corepressor activity ISS
Inferred from Sequence or Structural Similarity
more info
 
Process Evidence Code Pubs
Wnt signaling pathway TAS
Traceable Author Statement
more info
 
adrenal gland development IEP
Inferred from Expression Pattern
more info
PubMed 
branching involved in ureteric bud morphogenesis IEA
Inferred from Electronic Annotation
more info
 
canonical Wnt signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to starvation IEA
Inferred from Electronic Annotation
more info
 
cellular response to transforming growth factor beta stimulus IEP
Inferred from Expression Pattern
more info
PubMed 
embryonic epithelial tube formation IEA
Inferred from Electronic Annotation
more info
 
epithelial to mesenchymal transition IEP
Inferred from Expression Pattern
more info
PubMed 
female gonad development IEA
Inferred from Electronic Annotation
more info
 
female sex determination IMP
Inferred from Mutant Phenotype
more info
PubMed 
hormone metabolic process IEA
Inferred from Electronic Annotation
more info
 
immature T cell proliferation in thymus IEA
Inferred from Electronic Annotation
more info
 
kidney development IEP
Inferred from Expression Pattern
more info
PubMed 
liver development IEP
Inferred from Expression Pattern
more info
PubMed 
male gonad development IEP
Inferred from Expression Pattern
more info
PubMed 
male gonad development IMP
Inferred from Mutant Phenotype
more info
PubMed 
mammary gland epithelium development IEP
Inferred from Expression Pattern
more info
PubMed 
mesenchymal to epithelial transition IEA
Inferred from Electronic Annotation
more info
 
metanephric mesenchymal cell differentiation NAS
Non-traceable Author Statement
more info
PubMed 
metanephric nephron morphogenesis IEA
Inferred from Electronic Annotation
more info
 
metanephric tubule formation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of androgen biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of apoptotic signaling pathway IEA
Inferred from Electronic Annotation
more info
 
negative regulation of cell differentiation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of cell migration IEA
Inferred from Electronic Annotation
more info
 
negative regulation of fibroblast growth factor receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
 
negative regulation of gene expression IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of male gonad development IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of steroid biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of testicular blood vessel morphogenesis IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of testosterone biosynthetic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of transcription, DNA-templated IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of transcription, DNA-templated ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of wound healing IEA
Inferred from Electronic Annotation
more info
 
non-canonical Wnt signaling pathway via MAPK cascade IDA
Inferred from Direct Assay
more info
PubMed 
oocyte development IEA
Inferred from Electronic Annotation
more info
 
paramesonephric duct development IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of GTPase activity IEA
Inferred from Electronic Annotation
more info
 
positive regulation of aldosterone biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of bone mineralization IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of collagen biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of cortisol biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of dermatome development IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of focal adhesion assembly IEA
Inferred from Electronic Annotation
more info
 
positive regulation of meiotic nuclear division IEA
Inferred from Electronic Annotation
more info
 
positive regulation of osteoblast differentiation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of stress fiber assembly IEA
Inferred from Electronic Annotation
more info
 
positive regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription, DNA-templated ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
regulation of cell-cell adhesion IEA
Inferred from Electronic Annotation
more info
 
regulation of signaling receptor activity IEA
Inferred from Electronic Annotation
more info
 
renal vesicle formation IEA
Inferred from Electronic Annotation
more info
 
renal vesicle induction IEA
Inferred from Electronic Annotation
more info
 
smooth muscle cell differentiation IEA
Inferred from Electronic Annotation
more info
 
somatotropin secreting cell differentiation IEA
Inferred from Electronic Annotation
more info
 
tertiary branching involved in mammary gland duct morphogenesis IEA
Inferred from Electronic Annotation
more info
 
thyroid-stimulating hormone-secreting cell differentiation IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
Golgi lumen TAS
Traceable Author Statement
more info
 
cell surface ISS
Inferred from Sequence or Structural Similarity
more info
 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
endocytic vesicle membrane TAS
Traceable Author Statement
more info
 
endoplasmic reticulum lumen TAS
Traceable Author Statement
more info
 
extracellular exosome TAS
Traceable Author Statement
more info
 
extracellular matrix IEA
Inferred from Electronic Annotation
more info
 
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
protein Wnt-4
Names
wingless-type MMTV integration site family, member 4

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008974.1 RefSeqGene

    Range
    5001..30722
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_030761.5NP_110388.2  protein Wnt-4 precursor

    See identical proteins and their annotated locations for NP_110388.2

    Status: REVIEWED

    Source sequence(s)
    AF316543, AL031281, AL445253, BC057781
    Consensus CDS
    CCDS223.1
    UniProtKB/Swiss-Prot
    P56705
    Related
    ENSP00000290167.5, ENST00000290167.11
    Conserved Domains (1) summary
    pfam00110
    Location:45351
    wnt; wnt family

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p12 Primary Assembly

    Range
    22117305..22143981 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011541598.2XP_011539900.1  protein Wnt-4 isoform X2

    See identical proteins and their annotated locations for XP_011539900.1

    UniProtKB/Swiss-Prot
    P56705
    Conserved Domains (1) summary
    pfam00110
    Location:1296
    wnt; wnt family
  2. XM_011541597.2XP_011539899.1  protein Wnt-4 isoform X1

    Conserved Domains (1) summary
    pfam00110
    Location:71373
    wnt; wnt family
  3. XM_011541599.1XP_011539901.1  protein Wnt-4 isoform X3

    Conserved Domains (1) summary
    cl19568
    Location:67127
    wnt; wnt family
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