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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CLIP4
CAP-Gly domain containing linker protein family member 4
Chromosome 2 · 2p23.2
NCBI Gene: 79745Ensembl: ENSG00000115295.21HGNC: HGNC:26108UniProt: A0A8I5KXU9
25PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingmicrotubule plus-end bindingcytoplasmic microtubule organizationnucleuschronic kidney diseasesquamous cell lung carcinomaovarian cancerrhabdomyosarcoma
✦AI Summary

CLIP4 (CAP-Gly domain containing linker protein family member 4) is a microtubule-associated protein with established roles in cell migration and tumor biology. The protein localizes to microtubule plus-ends and the cell cortex, where it regulates cytoplasmic microtubule organization [based on GO annotations]. Beyond its canonical cytoskeletal functions, CLIP4 has emerged as a critical player in cancer pathogenesis across multiple malignancies. In hepatocellular carcinoma, CLIP4 expression is upregulated by endoplasmic reticulum stress and promotes cell proliferation, migration, and epithelial-mesenchymal transition (EMT) through the ERS-RELA-miR-222-5p-CLIP4 regulatory network 1. Conversely, CLIP4 exhibits tumor-suppressive functions in gastric cancer, where miR-135b-5p-mediated downregulation of CLIP4 promotes malignancy by activating JAK2/STAT3 signaling 2. In breast cancer, CLIP4 downregulation correlates with poor prognosis and triple-negative status 3. CLIP4 holds significant clinical utility as a biomarker. Hypermethylated CLIP4 is a component of diagnostic panels for colorectal cancer (sensitivity 95%, specificity 81.7% when combined with CK20) 4 and gastric cancer risk stratification 5. CLIP4 mutations associate with synchronous metastasis in small renal cell carcinomas 6. Additionally, CLIP4 methylation patterns serve as circulating tumor DNA biomarkers for predicting recurrence in gastric cancer 7, establishing CLIP4 as a multi-functional protein with both context-dependent oncogenic and tumor-suppressive roles.

Sources cited
1
CLIP4 is upregulated by endoplasmic reticulum stress and promotes hepatocellular carcinoma cell proliferation, migration, and EMT through the ERS-RELA-miR-222-5p-CLIP4 network
PMID: 39920578
2
miR-135b-5p targets CLIP4 to promote gastric cancer progression, and CLIP4 exerts tumor suppression by inhibiting JAK2/STAT3 signaling
PMID: 39121973
3
CLIP4 is downregulated in breast cancer and shows tumor-suppressive characteristics, with expression negatively correlated with ER, PR, HER2 status and poor prognosis associations
PMID: 33575272
4
Hypermethylated CLIP4 combined with CK20 achieves 95% sensitivity and 81.7% specificity for colorectal cancer diagnosis
PMID: 34965217
5
CLIP4 promoter methylation is associated with gastric cancer progression and progression from gastritis to gastric cancer
PMID: 28418867
6
CLIP4 mutations are found in small clear cell renal cell carcinomas with synchronous metastasis, and CLIP4 promotes cell migration and viability
PMID: 27283491
7
CLIP4 methylation patterns in circulating tumor DNA predict recurrence-free survival and overall survival in gastric and gastroesophageal junction cancer
PMID: 39369091
8
CLIP4 mutations are identified in germline analysis of young non-smoking women with lung adenocarcinoma as a candidate predisposition gene
PMID: 30032850
Disease Associationsⓘ20
chronic kidney diseaseOpen Targets
0.37Weak
squamous cell lung carcinomaOpen Targets
0.36Weak
ovarian cancerOpen Targets
0.27Weak
rhabdomyosarcomaOpen Targets
0.26Weak
neuroblastoma, susceptibility to, 3Open Targets
0.21Weak
hereditary neoplastic syndromeOpen Targets
0.21Weak
Inherited cancer-predisposing syndromeOpen Targets
0.21Weak
pyogenic granulomaOpen Targets
0.17Weak
Pseudo-fracturesOpen Targets
0.11Weak
post term pregnancyOpen Targets
0.09Suggestive
ankylosing spondylitisOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
squamous cell carcinomaOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.07Suggestive
diabetes mellitusOpen Targets
0.07Suggestive
type 2 diabetes mellitusOpen Targets
0.07Suggestive
tooth diseaseOpen Targets
0.07Suggestive
dental cariesOpen Targets
0.07Suggestive
denturesOpen Targets
0.07Suggestive
gangreneOpen Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CLIP2Shared pathway100%ZNF114Protein interaction78%KATNA1Shared pathway50%WDR73Shared pathway50%KATNBL1Shared pathway50%TBCBShared pathway33%
Tissue Expression6 tissues
Ovary
100%
Heart
95%
Lung
79%
Brain
74%
Liver
13%
Bone Marrow
8%
Gene Interaction Network
Click a node to explore
CLIP4CLIP2ZNF114KATNA1WDR73KATNBL1TBCB
PROTEIN STRUCTURE
Preparing viewer…
PDB2Z0W · 2.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.72LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.53 [0.40–0.72]
RankingsWhere CLIP4 stands among ~20K protein-coding genes
  • #12,958of 20,598
    Most Researched25
  • #5,562of 17,882
    Most Constrained (LOEUF)0.72
Genes detectedCLIP4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Endoplasmic reticulum stress-related CLIP4 plays a procarcinogenic role in hepatocellular carcinoma: an integrated analysis.
PMID: 39920578
BMC Cancer · 2025
1.00
2
Coupling of serum CK20 and hyper-methylated
PMID: 34965217
Aging (Albany NY) · 2021
0.90
3
FOXC2 and CLIP4 : a potential biomarker for synchronous metastasis of ≤7-cm clear cell renal cell carcinomas.
PMID: 27283491
Oncotarget · 2016
0.80
4
miR-135b-5p promotes gastric carcinogenesis by targeting CLIP4-mediated JAK2/STAT3 signal pathway.
PMID: 39121973
Cell Signal · 2024
0.70
5
Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies.
PMID: 28418867
Oncotarget · 2017
0.60