SHISA2
Shisa Family Member 2: A Regulator of Wnt and FGF Signaling in Development and Disease
Gene Information Card
| Symbol | SHISA2 |
|---|---|
| Full Name | shisa family member 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 13q12.13 |
| NCBI Gene ID | 387914 ncbi.nlm.nih.gov/gene/387914 |
| Ensembl ID | ENSG00000180228 |
| UniProt ID | Q6ZSZ6 |
| OMIM ID | 617327 |
| HGNC ID | 34488 |
| Aliases | hShisa2, FLJ22662, MGC138290 |
Description
SHISA2 (shisa family member 2) encodes a transmembrane protein that localizes to the endoplasmic reticulum and Golgi apparatus. It functions as a negative regulator of both Wnt and FGF signaling pathways by retaining Frizzled and FGF receptors in the endoplasmic reticulum, thereby preventing their maturation and cell surface expression. SHISA2 is involved in embryonic development, particularly in head formation and neural crest specification, and its dysregulation has been implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (general) | SHISA2 promoter hypermethylation leads to reduced expression, potentially contributing to tumorigenesis via aberrant Wnt/FGF signaling. | PubMed: 23469143 |
| Gastric cancer | Reduced SHISA2 expression correlates with poor prognosis; acts as a tumor suppressor by inhibiting Wnt signaling. | PubMed: 23469143 |
| Colorectal cancer | SHISA2 downregulation promotes cell proliferation and invasion through activation of Wnt/β-catenin signaling. | PubMed: 23469143 |
| Neurodevelopmental disorders | SHISA2 variants may affect neural crest development, but specific disease associations are not yet established. | OMIM: 617327 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 4.2 | Low |
| Heart | 3.1 | Low |
| Liver | 1.5 | Not detected |
| Kidney | 2.8 | Low |
| Testis | 5.6 | Medium |
| Thyroid | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 2.1 | Low expression |
| HEK293 | 1.8 | Low expression |
| MCF7 | 3.5 | Moderate expression |
| A549 | 2.9 | Low expression |
| K562 | 1.2 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Likely loss of start codon, predicted loss of function |
| c.214C>T (p.Arg72Trp) | Missense | Rare | Unknown significance; not reported in ClinVar |
| c.367G>A (p.Gly123Ser) | Missense | Rare | Unknown significance; not reported in ClinVar |
Mutation functional classification
Loss of Function (LOF)
Promoter hypermethylation and rare missense variants (e.g., p.Met1?) are predicted to reduce SHISA2 expression or function, leading to aberrant Wnt/FGF signaling.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SHISA2.
Dominant Negative (DN)
No dominant-negative mutations have been described for SHISA2.
View complete mutation data：
Gene Ontology (GO)
| • endoplasmic reticulum (GO:0005783) | • Golgi apparatus (GO:0005794) |
| • integral component of membrane (GO:0016021) | • negative regulation of Wnt signaling pathway (GO:0030176) |
| • negative regulation of fibroblast growth factor receptor signaling pathway (GO:0045740) | • limb development (GO:0060173) |
Pathways
• Wnt signaling pathway (negative regulation)
• FGF signaling pathway (negative regulation)
Protein Summary
SHISA2 is a 115-amino acid transmembrane protein with a single transmembrane domain. It resides in the endoplasmic reticulum and Golgi, where it binds to immature forms of Frizzled and FGF receptors, preventing their glycosylation and transport to the plasma membrane. This action dampens Wnt and FGF signaling, critical for embryonic patterning and cell proliferation. SHISA2 is widely expressed in adult tissues, with highest levels in testis and brain. Epigenetic silencing via promoter methylation is observed in several cancers, suggesting a tumor suppressor role.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SHISA2 Knockout HEK293 Cell Line | EDJ-KQ15249 | Human | 387914 | Details Get a Quote |
| SHISA2 Knockout HeLa Cell Line | EDJ-KQ60001 | Human | 387914 | Details Get a Quote |
| SHISA2 Knockout A-549 Cell Line | EDJ-KQ68462 | Human | 387914 | Details Get a Quote |
| SHISA2 Knockout HCT 116 Cell Line | EDJ-KQ76840 | Human | 387914 | Details Get a Quote |
