NLK (Nemo Like Kinase) Gene
A serine/threonine kinase involved in Wnt and TGF-β signaling pathways
Gene Information Card
| Symbol | NLK |
|---|---|
| Full Name | Nemo Like Kinase |
| Gene Type | Protein coding |
| Chromosomal Location | 17q11.2 |
| NCBI Gene ID | 51701 ncbi.nlm.nih.gov/gene/51701 |
| Ensembl ID | ENSG00000108771 |
| UniProt ID | Q9UBE8 |
| OMIM ID | 603278 |
| HGNC ID | 17858 |
| Aliases | NLK1, Nemo-like kinase, serine/threonine-protein kinase NLK |
Description
NLK (Nemo Like Kinase) encodes a serine/threonine protein kinase that belongs to the CMGC group of kinases. It is involved in multiple signaling pathways, including Wnt and TGF-β, where it phosphorylates transcription factors such as TCF/LEF and SMADs to modulate gene expression. NLK plays roles in cell proliferation, differentiation, and apoptosis, and its dysregulation is implicated in various cancers and neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | NLK inhibits Wnt/β-catenin signaling by phosphorylating TCF/LEF, reducing transcriptional activity; loss of NLK expression may promote tumorigenesis | PMID: 15601826 |
| Hepatocellular carcinoma | NLK suppresses TGF-β-induced epithelial-mesenchymal transition (EMT) via SMAD phosphorylation; reduced NLK correlates with metastasis | PMID: 19351800 |
| Neurodevelopmental disorders | NLK mutations identified in patients with intellectual disability and autism spectrum disorder; altered kinase activity affects neuronal signaling | ClinVar: RCV000626014 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.7 | Low |
| Testis | 15.2 | Medium |
| Lung | 7.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.1 | Cervical cancer cell line |
| HEK293 | 8.5 | Embryonic kidney cell line |
| HepG2 | 6.8 | Hepatocellular carcinoma cell line |
| SH-SY5Y | 14.3 | Neuroblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | <0.01% | Reduced kinase activity; associated with neurodevelopmental delay (ClinVar) |
| c.1246G>A (p.Gly416Arg) | Missense | <0.01% | Impaired substrate phosphorylation; reported in autism spectrum disorder (ClinVar) |
| c.1489_1491del (p.Lys497del) | In-frame deletion | <0.01% | Altered protein stability; observed in colorectal cancer (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg339Trp) reduce kinase activity, impairing Wnt/TGF-β signaling regulation.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in curated databases.
Dominant Negative (DN)
Some deletions (e.g., p.Lys497del) may act in a dominant-negative manner by disrupting protein interactions.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004674 - protein serine/threonine kinase activity | • GO:0005524 - ATP binding |
| • GO:0006468 - protein phosphorylation | • GO:0016055 - Wnt signaling pathway |
| • GO:0007179 - transforming growth factor beta receptor signaling pathway | • GO:0045944 - positive regulation of transcription by RNA polymerase II |
Pathways
• Wnt signaling pathway (KEGG: hsa04310)
• TGF-beta signaling pathway (KEGG: hsa04350)
• MAPK signaling pathway (KEGG: hsa04010)
Protein Summary
NLK is a 515-amino acid serine/threonine kinase with a conserved kinase domain. It phosphorylates TCF/LEF transcription factors to inhibit Wnt/β-catenin signaling and SMAD proteins to modulate TGF-β responses. NLK also interacts with other signaling molecules, influencing cell cycle, apoptosis, and differentiation. Its expression is ubiquitous but enriched in brain and testis. Structural studies reveal an N-terminal kinase domain and a C-terminal regulatory region.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NLK Knockout HEK293 Cell Line | EDJ-KQ716 | Human | 51701 | Details Get a Quote |
| NLK Knockout A-549 Cell Line | EDJ-KQ19332 | Human | 51701 | Details Get a Quote |
| NLK Knockout HCT 116 Cell Line | EDJ-KQ19333 | Human | 51701 | Details Get a Quote |
| NLK Knockout HeLa Cell Line | EDJ-KQ19334 | Human | 51701 | Details Get a Quote |
| NLK Knockout HAP1 Cell Line | EDC08215 | Human | 51701 | Details Get a Quote |
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