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Target intelligence / Profile preview
Cornichon family AMPA receptor auxiliary protein 4 (CNIH4)
- Target
- CNIH4
- Molecular classification
- Cargo-sorting receptor (secretory pathway), Auxiliary protein for AMPA receptor complex (based on gene family), Protein trafficking regulator
01
Overview
Cornichon family AMPA receptor auxiliary protein 4 (CNIH4) is a transmembrane cargo-sorting receptor localized primarily in the early secretory pathway, including the endoplasmic reticulum (ER) and ER-Golgi intermediate compartment. CNIH4 interacts with newly synthesized G protein–coupled receptors (GPCRs), recruiting them into COPII-coated vesicles for ER export and promoting their cell surface expression. Overexpression facilitates the maturation of certain mutant GPCRs, while knockdown impairs trafficking and retention. In cancer, CNIH4 is implicated in pro-metastatic regulatory loops—modulating secretion of transforming growth factor alpha (TGFα) and signaling pathways that promote metastasis in colon cancer. Increased CNIH4 expression correlates with poor prognosis and cancer stemness features in head and neck squamous cell carcinoma and shows prognostic significance in hepatocellular and fibrolamellar carcinoma. CNIH4 is a proposed biomarker for prognosis, cancer stemness, and tumor immune microenvironment and may affect immune response by influencing infiltration and checkpoint molecule expression in the tumor microenvironment.
- Other names
- Protein cornichon homolog 4CNIH-4HSPC163Cornichon homolog 4Cornichon family AMPA receptor auxiliary protein 4CNIH4_HUMAN
02
Mechanism of action
No described mechanism for drugs targeting CNIH4. Indirectly, it modulates secretion and GPCR maturation/export, which may influence downstream targets
03
Biological functions
Endoplasmic reticulum to Golgi vesicle-mediated protein exportGPCR trafficking, maturation, and cell surface expressionRegulation of protein secretion, signal transductionCell cycle regulationDNA repairCancer stemness and cell proliferation association
04
Disease associations
Cancer (colon cancer metastasis, hepatocellular carcinoma, fibrolamellar carcinoma, head and neck squamous cell carcinoma)Inflammation (potential immune response modulation)Other (found in disease-related signaling pathways and associated with tumor progression and immune escape in HNSCC)
05
Safety considerations
No direct therapeutic safety concerns reported, but dysregulation of CNIH4 is associated with cancer progression, altered immune infiltration, and pro-metastatic signaling, which could pose challenges for therapy
06
Biomarkers
Prognostic biomarker for overall survival in hepatocellular carcinoma and head and neck squamous cell carcinomaPotential biomarker for cancer stemness and tumor immune microenvironment in HNSCC
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