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26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NCK1
NCK adaptor protein 1
Chromosome 3 · 3q22.3
NCBI Gene: 4690Ensembl: ENSG00000158092.8HGNC: HGNC:7664UniProt: A0A0S2Z4Y3
268PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of cap-dependent translational initiationpositive regulation of cap-independent translational initiationnegative regulation of PERK-mediated unfolded protein responseprotein phosphatase type 1 complexAbnormality of the skeletal systemessential hypertensionaortic valve diseasehypertension
✦AI Summary

NCK1 (NCK adaptor protein 1) is a cytoplasmic adaptor protein that plays critical roles in cellular signaling, immune regulation, and disease pathogenesis. The protein contains one SH2 domain and three SH3 domains that mediate protein-protein interactions, linking tyrosine-phosphorylated receptors to downstream effectors 1. NCK1 is essential for T cell receptor signaling and regulatory T cell (Treg) development, functioning through the AKT pathway to regulate FoxP3 expression and FoxO1 nuclear localization 2. In the nervous system, NCK1 is predominantly expressed in neurons and plays vital roles in neurite outgrowth and spinal cord injury responses, with its downregulation after injury correlating with reduced cell viability and impaired neurite development 3. Clinically, NCK1 expression is significantly upregulated in high-grade astrocytomas and serves as an independent prognostic marker associated with poor survival in glioblastoma patients 4. Recent research has identified NCK1's involvement in inflammatory skin diseases through its interaction with Rac1, where disruption of the Rac1-NCK1 complex reduces STAT3 and NF-κB signaling in keratinocytes 5. While NCK1 and NCK2 were previously considered functionally redundant, emerging evidence demonstrates paralog-specific roles, highlighting the importance of distinguishing their unique functions 1.

Sources cited
1
NCK1 contains SH2 and SH3 domains for protein interactions and has paralog-specific functions distinct from NCK2
PMID: 39392452
2
NCK1 regulates regulatory T cell development through AKT pathway and FoxP3 expression
PMID: 39963999
3
NCK1 is expressed in neurons and is downregulated after spinal cord injury, affecting cell viability and neurite development
PMID: 34928232
4
NCK1 is upregulated in high-grade astrocytomas and serves as a prognostic marker for poor survival
PMID: 30146921
5
NCK1 interacts with Rac1 in inflammatory skin diseases and regulates STAT3/NF-κB signaling in keratinocytes
PMID: 39661704
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.30Weak
essential hypertensionOpen Targets
0.28Weak
aortic valve diseaseOpen Targets
0.28Weak
hypertensionOpen Targets
0.27Weak
Delayed pubertyOpen Targets
0.25Weak
chronic laryngitisOpen Targets
0.22Weak
myocardial infarctionOpen Targets
0.20Weak
obesityOpen Targets
0.20Weak
angina pectorisOpen Targets
0.18Weak
chronic lymphocytic leukemiaOpen Targets
0.15Weak
multiple myelomaOpen Targets
0.15Weak
Hodgkins lymphomaOpen Targets
0.15Weak
coronary atherosclerosisOpen Targets
0.14Weak
Sensorineural hearing impairmentOpen Targets
0.12Weak
hearing lossOpen Targets
0.11Weak
prostate carcinomaOpen Targets
0.11Weak
Chest painOpen Targets
0.11Weak
melanomaOpen Targets
0.09Suggestive
triple-negative breast cancerOpen Targets
0.09Suggestive
overnutritionOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CBLProtein interaction100%CFL1Protein interaction100%CFL2Protein interaction100%DOCK1Protein interaction100%CTTNProtein interaction100%FYB1Protein interaction100%
Tissue Expression6 tissues
Lung
100%
Heart
94%
Liver
92%
Bone Marrow
91%
Ovary
74%
Brain
65%
Gene Interaction Network
Click a node to explore
NCK1CBLCFL1CFL2DOCK1CTTNFYB1
PROTEIN STRUCTURE
Preparing viewer…
PDB5QU8 · 0.93 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.72LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.49 [0.34–0.72]
RankingsWhere NCK1 stands among ~20K protein-coding genes
  • #1,387of 20,598
    Most Researched268 · top 10%
  • #5,553of 17,882
    Most Constrained (LOEUF)0.72
Genes detectedNCK1
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
LncRNA NCK1-AS1-mediated regulatory functions in human diseases.
PMID: 36131072
Clin Transl Oncol · 2023
1.00
2
Expression and clinicopathological significance of Nck1 in human astrocytoma progression.
PMID: 30146921
Int J Neurosci · 2019
0.90
3
Mechanism of Bile Acid in Regulating Platelet Function and Thrombotic Diseases.
PMID: 38922767
Adv Sci (Weinh) · 2024
0.80
4
Adapting to change: resolving the dynamic and dual roles of NCK1 and NCK2.
PMID: 39392452
Biochem J · 2024
0.80
5
lncRNA Biomarkers of Glioblastoma Multiforme.
PMID: 38790894
Biomedicines · 2024
0.70