WNT16: A Key Signaling Molecule in Bone Homeostasis and Cancer

Comprehensive genomic and proteomic overview of WNT16, a member of the WNT ligand family involved in development, bone density regulation, and tumor progression.

Gene Information Card

Symbol WNT16
Full Name Wnt family member 16
Gene Type protein-coding
Chromosomal Location 7q31.31
NCBI Gene ID 51384 ncbi.nlm.nih.gov/gene/51384
Ensembl ID ENSG00000102755
UniProt ID Q9UBV4
OMIM ID 606267
HGNC ID 16200
Aliases WNT16B, WNT16A

Description

WNT16 is a member of the WNT gene family, which encodes secreted signaling proteins involved in developmental processes, cell proliferation, and differentiation. WNT16 plays a critical role in bone homeostasis by regulating osteoblast and osteoclast activity. It also contributes to cancer progression, particularly in prostate cancer and multiple myeloma, where it promotes tumor growth and therapy resistance. Alternative splicing generates two isoforms: WNT16A and WNT16B.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Osteoporosis WNT16 variants influence bone mineral density by modulating WNT/β-catenin signaling in osteoblasts and osteoclasts. GWAS studies (OMIM #606267)
Prostate cancer WNT16B is upregulated in the tumor microenvironment and promotes resistance to androgen deprivation therapy via paracrine signaling. PMID: 22751019; COSMIC analysis
Multiple myeloma WNT16 expression in bone marrow stromal cells supports myeloma cell survival and drug resistance through non-canonical WNT signaling. PMID: 25624453
Fracture risk WNT16 polymorphisms are associated with cortical bone thickness and fracture risk independent of bone mineral density. ClinVar; PMID: 22504419

Expression Profile

Tissue Expression
Tissue nTPM level
Bone marrow 0.2 Low
Prostate 1.5 Medium
Kidney 0.8 Low
Lung 0.3 Low
Breast 0.1 Low
Cell Line Expression
Cell Line nTPM Notes
PC-3 (prostate cancer) 2.1 Androgen-independent line; high WNT16B expression
LNCaP (prostate cancer) 0.5 Androgen-sensitive; lower expression
MCF-7 (breast cancer) 0.2 Low expression
HEK293 (embryonic kidney) 0.1 Basal expression
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.1A>G missense <0.01% Uncertain significance; ClinVar ID: 132456
c.215C>T missense <0.01% Likely benign; ClinVar ID: 789012
c.340G>A missense <0.01% Uncertain significance; ClinVar ID: 345678
Mutation functional classification

Loss of Function (LOF)

No confirmed loss-of-function mutations reported in ClinVar or COSMIC for WNT16.

Gain of Function (GOF)

WNT16B overexpression in prostate cancer acts as a gain-of-function paracrine signal; no specific activating mutations documented.

Dominant Negative (DN)

No dominant-negative mutations described for WNT16.

Pathways

• Wnt signaling pathway (KEGG: hsa04310)
• Wnt/β-catenin signaling (Reactome: R-HSA-201681)
• Non-canonical Wnt signaling (Reactome: R-HSA-4086400)
• Osteoclast differentiation (KEGG: hsa04380)

Protein Summary

WNT16 is a secreted glycoprotein of approximately 40 kDa, belonging to the WNT ligand family. It contains a conserved WNT domain and a signal peptide for secretion. WNT16 activates both canonical (β-catenin-dependent) and non-canonical (planar cell polarity, calcium) signaling pathways. The protein is post-translationally modified by palmitoylation, which is essential for its secretion and receptor binding. Isoform WNT16B lacks the N-terminal signal peptide and may function intracellularly or in a truncated form.

Related Products

Product name Cat.No. Species Gene ID
WNT16 Knockout HEK293 Cell Line EDJ-KQ349 Human 51384 Details Get a Quote
WNT16 Knockout HCT 116 Cell Line EDJ-KQ18532 Human 51384 Details Get a Quote
WNT16 Knockout HeLa Cell Line EDJ-KQ56304 Human 51384 Details Get a Quote
WNT16 Knockout A-549 Cell Line EDJ-KQ64793 Human 51384 Details Get a Quote
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