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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CLIP1
CAP-Gly domain containing linker protein 1
Chromosome 12 · 12q24.31
NCBI Gene: 6249Ensembl: ENSG00000130779.23HGNC: HGNC:10461UniProt: B3KXA5
128PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
microtubulecytosolcentrosomemicrotubule bindingnon-small cell lung carcinomacancermelanocytic neoplasmspitz nevus
✦AI Summary

CLIP1 (CAP-Gly domain containing linker protein 1) is a microtubule plus-end binding protein that regulates microtubule dynamics and intracellular trafficking. Primary functions include promoting microtubule growth and bundling, linking cytoplasmic vesicles to microtubules for transport, and regulating macropinocytosis and endosome trafficking. CLIP1 possesses RNA-binding activity with specificity for UGGGGAGG motifs 1. Mechanistically, CLIP1 modulates inflammatory signaling by regulating TIRAP ubiquitination and degradation through interaction with TFPI2, thereby suppressing TLR4/NF-κB-mediated responses 2. Clinically, CLIP1 alterations are implicated in multiple cancers. CLIP1-LTK fusion represents a novel oncogenic driver in 0.4% of non-small-cell lung adenocarcinomas, demonstrating constitutively activated kinase activity responsive to ALK inhibitor lorlatinib treatment 3. CLIP1-RAF1 fusion is a recurrent driver event in infantile fibrosarcomas, promoting cell proliferation and migration through constitutive MAPK and PI3K-AKT pathway activation 4. Additionally, CLIP1 mutations are associated with vascular invasion in poorly differentiated thyroid cancer 5, and reduced CLIP1 expression serves as a potential biomarker in prostate cancer 6. Notably, CLIP1 loss-of-function mutations cause autosomal recessive intellectual disability, highlighting its essential role in neuronal development and axonal transport 7.

Sources cited
1
CLIP1-LTK fusion is an oncogenic driver in NSCLC with constitutively activated kinase activity responsive to lorlatinib treatment
PMID: 34819663
2
CLIP1 regulates TIRAP ubiquitination to suppress TLR4/NF-κB-mediated inflammatory response in ischemia-reperfusion injury
PMID: 39617791
3
CLIP1-RAF1 is a novel fusion protein in infantile fibrosarcoma-like tumors that constitutively upregulates MAPK and PI3K-AKT signaling
PMID: 38629245
4
CLIP1 possesses RNA-binding activity with UGGGGAGG binding motif specificity
PMID: 34921931
5
CLIP1 deficiency causes autosomal recessive intellectual disability through impaired microtubule-mediated axonal transport
PMID: 24569606
6
CLIP1 expression is downregulated in prostate cancer as a potential biomarker for early diagnosis
PMID: 39112820
7
CLIP1 mutations are associated with vascular invasion phenotype in poorly differentiated thyroid carcinoma
PMID: 37932340
8
CLIP1-LTK fusion occurs in 0.4% of lung adenocarcinomas as a druggable oncogenic rearrangement
PMID: 35777135
Disease Associationsⓘ20
non-small cell lung carcinomaOpen Targets
0.58Moderate
cancerOpen Targets
0.53Moderate
autosomal recessive non-syndromic intellectual disabilityOpen Targets
0.37Weak
melanocytic neoplasmOpen Targets
0.37Weak
spitz nevusOpen Targets
0.37Weak
Short statureOpen Targets
0.33Weak
liver diseaseOpen Targets
0.27Weak
cervical squamous cell carcinomaOpen Targets
0.22Weak
esophageal diseaseOpen Targets
0.21Weak
papillary thyroid carcinomaOpen Targets
0.19Weak
acute myeloid leukemiaOpen Targets
0.19Weak
Hodgkins lymphomaOpen Targets
0.19Weak
melanomaOpen Targets
0.19Weak
gastric carcinomaOpen Targets
0.19Weak
hepatocellular carcinomaOpen Targets
0.19Weak
head and neck squamous cell carcinomaOpen Targets
0.19Weak
colon adenocarcinomaOpen Targets
0.19Weak
lung carcinomaOpen Targets
0.19Weak
lung adenocarcinomaOpen Targets
0.19Weak
gastric adenocarcinomaOpen Targets
0.19Weak
Pathogenic Variants1
NM_001247997.2(CLIP1):c.430C>T (p.Arg144Ter)Pathogenic
Short stature
☆☆☆☆2001→ Residue 144
View on ClinVar ↗
Related Genes
MTORProtein interaction99%RAC1Protein interaction99%CLASRPProtein interaction97%TUBA1AProtein interaction97%CLASP2Protein interaction96%CLASP1Protein interaction96%
Tissue Expression6 tissues
Heart
100%
Lung
91%
Brain
73%
Liver
47%
Ovary
33%
Bone Marrow
28%
Gene Interaction Network
Click a node to explore
CLIP1MTORRAC1CLASRPTUBA1ACLASP2CLASP1
PROTEIN STRUCTURE
Preparing viewer…
PDB2E3H · 1.45 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.46Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.35 [0.28–0.46]
RankingsWhere CLIP1 stands among ~20K protein-coding genes
  • #3,646of 20,598
    Most Researched128 · top quartile
  • #4,813of 5,498
    Most Pathogenic Variants1
  • #2,551of 17,882
    Most Constrained (LOEUF)0.46 · top quartile
Genes detectedCLIP1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The CLIP1-LTK fusion is an oncogenic driver in non-small-cell lung cancer.
PMID: 34819663
Nature · 2021
1.00
2
Hypothermic oxygenated perfusion inhibits CLIP1-mediated TIRAP ubiquitination via TFPI2 to reduce ischemia‒reperfusion injury of the fatty liver.
PMID: 39617791
Exp Mol Med · 2024
0.90
3
RAF1 gene fusions are recurrent driver events in infantile fibrosarcoma-like mesenchymal tumors.
PMID: 38629245
J Pathol · 2024
0.80
4
Biological and clinical perspectives of the actionable gene fusions and amplifications involving tyrosine kinase receptors in lung cancer.
PMID: 35777135
Cancer Treat Rev · 2022
0.70
5
Two novel RNA-binding proteins identification through computational prediction and experimental validation.
PMID: 34921931
Genomics · 2022
0.60