STK4 (Serine/Threonine Kinase 4)
A key regulator of Hippo signaling, apoptosis, and T-cell function; implicated in cancer and immunodeficiency.
Gene Information Card
| Symbol | STK4 |
|---|---|
| Full Name | Serine/Threonine Kinase 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 20q13.12 |
| NCBI Gene ID | 6789 ncbi.nlm.nih.gov/gene/6789 |
| Ensembl ID | ENSG00000101109 |
| UniProt ID | Q13043 |
| OMIM ID | 604965 |
| HGNC ID | 11408 |
| Aliases | MST1, KRS2, TIIAC, YS, STK4 |
Description
STK4 (serine/threonine kinase 4), also known as MST1, is a core component of the Hippo signaling pathway. It regulates apoptosis, cell proliferation, and organ size control. STK4 phosphorylates and activates LATS1/2 kinases, leading to YAP/TAZ inactivation. It also plays a critical role in T-cell homeostasis and immune regulation. Loss-of-function mutations cause primary immunodeficiency and are implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primary immunodeficiency with T-cell deficiency | Loss-of-function mutations impair T-cell survival and proliferation | OMIM #614868; ClinVar |
| Hepatocellular carcinoma | Reduced STK4 expression promotes YAP activation and tumor growth | PMID: 25873174; COSMIC |
| Colorectal cancer | STK4 downregulation correlates with poor prognosis and metastasis | PMID: 26678085; COSMIC |
| Prostate cancer | STK4 inactivation via promoter methylation or mutation | PMID: 23542167; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Spleen | 18.3 | High |
| Lung | 8.1 | Medium |
| Brain | 5.2 | Low |
| Heart | 6.7 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.2 | Hepatocellular carcinoma cell line |
| Jurkat | 22.5 | T-cell leukemia line |
| A549 | 9.8 | Lung adenocarcinoma |
| MCF7 | 7.3 | Breast cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.349C>T (p.Arg117*) | Nonsense | Rare | Loss of function; truncation |
| c.791G>A (p.Arg264Gln) | Missense | Rare | Impaired kinase activity |
| c.1061_1062del (p.Glu354Valfs*12) | Frameshift | Rare | Loss of function |
| c.1400T>C (p.Ile467Thr) | Missense | Rare | Reduced protein stability |
Mutation functional classification
Loss of Function (LOF)
Most reported STK4 mutations are loss-of-function, leading to impaired Hippo signaling, defective apoptosis, and T-cell deficiency.
Gain of Function (GOF)
Not well documented; no recurrent gain-of-function mutations reported in major databases.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg264Gln) may act in a dominant-negative manner by disrupting dimerization or kinase activity.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hippo signaling pathway (KEGG: hsa04390)
• Apoptosis (KEGG: hsa04210)
• T-cell receptor signaling pathway (KEGG: hsa04660)
Protein Summary
STK4 (MST1) is a 487-amino-acid serine/threonine kinase containing an N-terminal kinase domain, a regulatory SARAH domain, and a C-terminal dimerization region. It is activated by autophosphorylation and caspase cleavage. STK4 phosphorylates LATS1/2 and MOB1 to suppress YAP/TAZ transcriptional coactivators. It also promotes apoptosis via FOXO3 phosphorylation. In the immune system, STK4 is essential for T-cell survival and migration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| STK4 Knockout HEK293 Cell Line | EDJ-KQ1235 | Human | 6789 | Details Get a Quote |
| STK40 Knockout HEK293 Cell Line | EDJ-KQ2690 | Human | 83931 | Details Get a Quote |
| STK4 Knockout HCT 116 Cell Line | EDJ-KQ19225 | Human | 6789 | Details Get a Quote |
| STK4 Knockout A-549 Cell Line | EDJ-KQ20584 | Human | 6789 | Details Get a Quote |
| STK4 Knockout HeLa Cell Line | EDJ-KQ20585 | Human | 6789 | Details Get a Quote |
| STK40 Knockout A-549 Cell Line | EDJ-KQ23511 | Human | 83931 | Details Get a Quote |
| STK40 Knockout HCT 116 Cell Line | EDJ-KQ23512 | Human | 83931 | Details Get a Quote |
| STK40 Knockout HeLa Cell Line | EDJ-KQ23513 | Human | 83931 | Details Get a Quote |
