HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
STK40
serine/threonine kinase 40
Chromosome 1 · 1p34.3
NCBI Gene: 83931Ensembl: ENSG00000196182.12HGNC: HGNC:21373UniProt: Q8N2I9
37PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingnucleoplasmcytosolregulation of MAPK cascadeneurodegenerative diseaseneuroinflammatory disordernephrotic syndromeCongenital pulmonary alveolar proteinosis
✦AI Summary

STK40 is a pseudokinase that functions as a substrate adaptor for the CRL4COP1/DET1 E3 ubiquitin ligase complex, facilitating targeted protein degradation through K48-linked polyubiquitination 12. The protein lacks kinase activity due to substitutions of conserved residues that prevent ATP binding, but retains a functional C-terminal sequence that enables binding to COP1 1. STK40 regulates multiple cellular processes by promoting proteasomal degradation of key transcription factors including FOXO1/4, c-Jun, and P57Kip2 234. In T cell biology, STK40 promotes pathological TH1/TH17 differentiation and limits T cell exhaustion during chr1 viral infection by controlling AP-1 signaling 23. The protein also regulates trophoblast fusion in placental development and has been implicated in various disease contexts including autoimmune diseases, preeclampsia, psoriasis, and cancer 456. STK40 can modulate NF-κB and JNK/MAPK signaling pathways and may serve as a negative regulator of YAP/TAZ in the Hippo pathway 56. These diverse functions position STK40 as an important regulatory hub controlling cell fate decisions through post-translational mechanisms.

Sources cited
1
STK40 is a pseudokinase that binds COP1 and lacks ATP-binding activity
PMID: 28089446
2
STK40 promotes TH1/TH17 differentiation by facilitating FOXO1/4 degradation through COP1
PMID: 39565845
3
STK40 limits T cell exhaustion by promoting COP1-dependent degradation of c-Jun
PMID: 41272167
4
STK40 inhibits trophoblast fusion by mediating COP1 ubiquitination to degrade P57
PMID: 39304928
5
STK40 is involved in NF-κB and JNK/MAPK pathway regulation in keratinocytes
PMID: 28085489
6
STK40 identified as a novel activator of YAP/TAZ in the Hippo pathway
PMID: 40869130
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.46Moderate
neuroinflammatory disorderOpen Targets
0.46Moderate
nephrotic syndromeOpen Targets
0.27Weak
Congenital pulmonary alveolar proteinosisOpen Targets
0.07Suggestive
Neonatal acute respiratory distress with surfactant metabolism deficiencyOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.06Suggestive
gastric cancerOpen Targets
0.05Suggestive
major depressive disorderOpen Targets
0.05Suggestive
idiopathic pulmonary fibrosisOpen Targets
0.05Suggestive
congenital lobar emphysemaOpen Targets
0.05Suggestive
colorectal carcinomaOpen Targets
0.05Suggestive
surfactant metabolism dysfunction, pulmonary, 1Open Targets
0.05Suggestive
autoimmune pulmonary alveolar proteinosisOpen Targets
0.05Suggestive
familial primary pulmonary hypoplasiaOpen Targets
0.05Suggestive
anorexia nervosaOpen Targets
0.05Suggestive
attention deficit hyperactivity disorderOpen Targets
0.05Suggestive
Pulmonary capillary hemangiomatosisOpen Targets
0.04Suggestive
pulmonary blastomaOpen Targets
0.04Suggestive
obsessive-compulsive disorderOpen Targets
0.04Suggestive
surfactant metabolism dysfunction, pulmonary, 2Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SLAShared pathway100%FOSProtein interaction100%ETV1Protein interaction90%TRIB3Protein interaction90%ETV5Protein interaction83%FOSL2Protein interaction81%
Tissue Expression6 tissues
Lung
100%
Ovary
79%
Liver
74%
Heart
71%
Brain
25%
Bone Marrow
19%
Gene Interaction Network
Click a node to explore
STK40SLAFOSETV1TRIB3ETV5FOSL2
PROTEIN STRUCTURE
Preparing viewer…
PDB5L2Q · 2.53 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.42Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.26 [0.17–0.42]
RankingsWhere STK40 stands among ~20K protein-coding genes
  • #10,703of 20,598
    Most Researched37
  • #2,181of 17,882
    Most Constrained (LOEUF)0.42 · top quartile
Genes detectedSTK40
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Pseudokinase STK40 promotes T
PMID: 39565845
Sci Adv · 2024
1.00
2
Pseudokinase STK40 limits T cell exhaustion through COP1-dependent degradation of AP1-family transcription factors.
PMID: 41272167
Nat Immunol · 2025
0.90
3
STK40 inhibits trophoblast fusion by mediating COP1 ubiquitination to degrade P57
PMID: 39304928
J Transl Med · 2024
0.80
4
microRNA-130a Promotes Human Keratinocyte Viability and Migration and Inhibits Apoptosis Through Direct Regulation of STK40-Mediated NF-κB Pathway and Indirect Regulation of SOX9-Meditated JNK/MAPK Pathway: A Potential Role in Psoriasis.
PMID: 28085489
DNA Cell Biol · 2017
0.70
5
Integrative High-Throughput RNAi Screening Identifies BRSK1, STK32C and STK40 as Novel Activators of YAP/TAZ.
PMID: 40869130
Int J Mol Sci · 2025
0.60