CKAP4: Cytoskeleton-Associated Protein 4 – Key Regulator of Cell Proliferation and Cancer
Comprehensive genomic and proteomic overview of CKAP4, a receptor for antiproliferative factor and mediator of Wnt/β-catenin signaling.
Gene Information Card
| Symbol | CKAP4 |
|---|---|
| Full Name | Cytoskeleton-associated protein 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q23.3 |
| NCBI Gene ID | 10970 ncbi.nlm.nih.gov/gene/10970 |
| Ensembl ID | ENSG00000136026 |
| UniProt ID | Q07065 |
| OMIM ID | 608767 |
| HGNC ID | 16991 |
| Aliases | CLIMP-63, p63, ERGIC-63, KAI1 C-terminal interacting protein |
Description
CKAP4 (cytoskeleton-associated protein 4) encodes a type II transmembrane protein that localizes to the endoplasmic reticulum and Golgi apparatus. It functions as a receptor for antiproliferative factor (APF) and mediates cell proliferation, migration, and adhesion. CKAP4 also interacts with KAI1/CD82 to suppress cancer metastasis and participates in Wnt/β-catenin signaling by stabilizing β-catenin. The gene is implicated in various cancers, including bladder, lung, and pancreatic cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Bladder cancer | CKAP4 acts as a receptor for APF; reduced expression correlates with tumor progression | PMID: 14660794; NCBI Gene |
| Non-small cell lung cancer | Overexpression promotes cell proliferation and invasion via Wnt/β-catenin pathway | PMID: 25766321; COSMIC |
| Pancreatic ductal adenocarcinoma | CKAP4 upregulation associated with poor prognosis and metastasis | PMID: 29367642; ClinVar |
| Hepatocellular carcinoma | CKAP4 overexpression enhances β-catenin signaling and tumor growth | PMID: 31040182; UniProt |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 38.2 | High |
| Pancreas | 42.1 | High |
| Liver | 29.5 | Medium |
| Kidney | 25.8 | Medium |
| Heart | 12.3 | Low |
| Brain | 8.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung cancer) | 45.6 | High expression; used in functional studies |
| PANC-1 (pancreatic cancer) | 52.3 | Overexpressed; promotes invasion |
| HepG2 (liver cancer) | 33.1 | Moderate expression; Wnt signaling |
| HEK293 (embryonic kidney) | 18.4 | Basal expression; transfection model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.497C>T (p.Thr166Met) | Missense | 0.02% (gnomAD) | Unknown functional impact; reported in COSMIC |
| c.1048G>A (p.Gly350Ser) | Missense | 0.01% (gnomAD) | Located in coiled-coil domain; potential loss of function |
| c.1325_1327del (p.Glu442del) | In-frame deletion | 0.005% (COSMIC) | Alters C-terminal region; may affect KAI1 binding |
Mutation functional classification
Loss of Function (LOF)
Missense variants in the coiled-coil domain (e.g., p.Gly350Ser) may disrupt ER localization and APF binding, leading to reduced antiproliferative signaling.
Gain of Function (GOF)
Overexpression (not mutation) is the primary gain-of-function mechanism in cancers, enhancing Wnt/β-catenin signaling and cell proliferation.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported; deletions in the C-terminal region may interfere with KAI1 interaction.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005515 – protein binding | • GO:0005783 – endoplasmic reticulum |
| • GO:0005794 – Golgi apparatus | • GO:0016021 – integral component of membrane |
| • GO:0030154 – cell differentiation | • GO:0043065 – positive regulation of apoptotic process |
| • GO:0060070 – canonical Wnt signaling pathway |
Pathways
• Wnt/β-catenin signaling pathway (Reactome: R-HSA-201681)
• KAI1/CD82 metastasis suppression pathway
• Antiproliferative factor (APF) signaling
Protein Summary
CKAP4 is a 63 kDa transmembrane protein predominantly localized to the endoplasmic reticulum and Golgi. It contains a coiled-coil domain and a C-terminal region that interacts with KAI1/CD82. CKAP4 serves as a receptor for antiproliferative factor (APF), inhibiting cell proliferation in normal cells. In cancer, CKAP4 overexpression stabilizes β-catenin, driving transcription of pro-proliferative genes. It also regulates cell adhesion and migration, making it a potential therapeutic target and biomarker.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CKAP4 Knockout HEK293 Cell Line | EDJ-KQ7230 | Human | 10970 | Details Get a Quote |
| CKAP4 Knockout HCT 116 Cell Line | EDJ-KQ18170 | Human | 10970 | Details Get a Quote |
| CKAP4 Knockout A-549 Cell Line | EDJ-KQ32203 | Human | 10970 | Details Get a Quote |
| CKAP4 Knockout HeLa Cell Line | EDJ-KQ32204 | Human | 10970 | Details Get a Quote |
| CKAP4 Knockout HuH-6 Cell Line | EDC07542 | Human | 10970 | Details Get a Quote |
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