WLS (Wnt Ligand Secretion Mediator)

Key regulator of Wnt signaling pathway involved in development and cancer

Gene Information Card

Symbol WLS
Full Name Wnt Ligand Secretion Mediator
Gene Type Protein coding
Chromosomal Location 1p31.3
NCBI Gene ID 79971 ncbi.nlm.nih.gov/gene/79971
Ensembl ID ENSG00000116729
UniProt ID Q5T9L3
OMIM ID 611514
HGNC ID 24938
Aliases GPR177, MGC131981, MGC149531, MGC149532

Description

The WLS gene encodes a transmembrane protein that acts as a cargo receptor essential for the secretion of Wnt ligands. It binds Wnt proteins in the Golgi apparatus and facilitates their transport to the cell surface, thereby regulating Wnt signaling pathways critical for embryonic development, cell proliferation, and differentiation. Mutations in WLS are associated with developmental disorders and various cancers.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Autosomal recessive Robinow syndrome Loss-of-function mutations impair Wnt secretion, disrupting developmental signaling OMIM #616331
Colorectal cancer Overexpression of WLS enhances Wnt ligand secretion, promoting tumor growth COSMIC, PubMed
Breast cancer WLS upregulation correlates with poor prognosis and metastatic potential COSMIC, PubMed

Expression Profile

Tissue Expression
Tissue nTPM level
Brain 12.5 Medium
Heart 8.3 Low
Liver 6.1 Low
Kidney 15.2 Medium
Lung 9.8 Low
Pancreas 4.7 Low
Placenta 20.1 High
Testis 18.6 High
Cell Line Expression
Cell Line nTPM Notes
HEK 293 22.4 High expression
HeLa 15.1 Medium expression
MCF7 12.8 Medium expression
A549 9.3 Low expression
HepG2 7.5 Low expression
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.1000C>T (p.Arg334Ter) Nonsense <0.01% Loss of function; associated with Robinow syndrome
c.742G>A (p.Gly248Arg) Missense <0.01% Impaired Wnt binding; developmental defects
c.1234A>G (p.Thr412Ala) Missense 0.02% Reduced secretion activity; cancer-related
Mutation functional classification

Loss of Function (LOF)

Nonsense and missense mutations that disrupt Wnt ligand binding or transport, leading to reduced Wnt signaling; associated with Robinow syndrome.

Gain of Function (GOF)

Not well characterized; overexpression in cancers suggests potential gain-of-function via increased Wnt secretion.

Dominant Negative (DN)

Not reported for WLS.

Pathways

• Wnt signaling pathway (Reactome: R-HSA-195721)
• Wnt ligand biogenesis and secretion (Reactome: R-HSA-3238698)
• Signaling by WNT (Reactome: R-HSA-195721)

Protein Summary

WLS is a multi-pass transmembrane protein localized to the Golgi apparatus and plasma membrane. It functions as a Wnt ligand chaperone, binding palmitoylated Wnt proteins and escorting them from the Golgi to the cell surface for secretion. The protein contains a conserved domain essential for Wnt interaction and is regulated by post-translational modifications. WLS is critical for paracrine and autocrine Wnt signaling, influencing cell fate decisions during development and tissue homeostasis.

Related Products

Product name Cat.No. Species Gene ID
WLS Knockout HEK293 Cell Line EDJ-KQ3607 Human 79971 Details Get a Quote
WLS Knockout A-549 Cell Line EDJ-KQ25523 Human 79971 Details Get a Quote
WLS Knockout HCT 116 Cell Line EDJ-KQ25524 Human 79971 Details Get a Quote
WLS Knockout HeLa Cell Line EDJ-KQ25525 Human 79971 Details Get a Quote
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