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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
STK4
serine/threonine kinase 4
Chromosome 20 Β· 20q13.12
NCBI Gene: 6789Ensembl: ENSG00000101109.14HGNC: HGNC:11408UniProt: A0A087WVN8
243PubMed Papers
21Diseases
0Drugs
19Pathogenic Variants
FUNCTIONAL ROLE
ApoptosisKinase
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cell morphogenesispositive regulation of protein phosphorylationprotein phosphorylationpositive regulation of peptidyl-serine phosphorylationcombined immunodeficiency due to STK4 deficiencycombined immunodeficiency due to DOCK8 deficiencycombined immunodeficiencyimmunodeficiency disease
✦AI Summary

STK4 (serine/threonine kinase 4), also known as MST1, is a critical regulator of multiple cellular processes including apoptosis, tissue homeostasis, and immune function. As a core component of the Hippo signaling pathway, STK4 forms complexes with regulatory proteins to phosphorylate and activate downstream effectors like LATS1/2, ultimately leading to YAP1 inactivation and growth suppression 1. The kinase promotes apoptosis through caspase-mediated cleavage, nuclear translocation, and phosphorylation of targets including histone H2B and FOXO transcription factors 2. STK4 regulates metabolic processes by controlling mitochondrial function in adipose tissue, where its inhibition increases mitochondrial mass and energy expenditure while conferring resistance to diet-induced obesity 3. The protein also modulates autophagy and cellular senescence through phosphorylation of RNA-binding proteins like AUF1, affecting glucose metabolism 2. Clinically, STK4 deficiency causes a severe primary immunodeficiency (Immunodeficiency 110) characterized by lymphoproliferation, autoimmunity, and increased susceptibility to EBV-associated malignancies 45. Additionally, STK4 contributes to endometrial receptivity through phosphorylation of Nur77, affecting embryo implantation success 6. Pharmacological inhibition of STK4 shows therapeutic potential for enhancing tissue repair and regeneration 1.

Sources cited
1
STK4 is a core component of the Hippo pathway that regulates organ size and can be pharmacologically targeted for tissue regeneration
PMID: 27535619
2
STK4 suppresses mitochondrial function in adipose tissues and its inhibition improves metabolic profiles in obesity
PMID: 33758424
3
STK4 phosphorylates AUF1 to regulate cellular senescence and glucose metabolism
PMID: 40711448
4
STK4 deficiency causes primary immunodeficiency with EBV-associated lymphoproliferative disorders
PMID: 34604912
5
STK4 defects are associated with combined immunodeficiencies and ALPS-like phenotypes
PMID: 34447369
6
STK4 phosphorylates Nur77 to regulate endometrial receptivity and embryo implantation
PMID: 36623453
Disease Associationsβ“˜21
combined immunodeficiency due to STK4 deficiencyOpen Targets
0.76Strong
combined immunodeficiency due to DOCK8 deficiencyOpen Targets
0.47Moderate
combined immunodeficiencyOpen Targets
0.46Moderate
immunodeficiency diseaseOpen Targets
0.34Weak
severe combined immunodeficiencyOpen Targets
0.33Weak
neurodegenerative diseaseOpen Targets
0.30Weak
neuroinflammatory disorderOpen Targets
0.20Weak
genetic disorderOpen Targets
0.19Weak
bipolar I disorderOpen Targets
0.15Weak
bipolar disorderOpen Targets
0.15Weak
frozen shoulderOpen Targets
0.12Weak
mathematical abilityOpen Targets
0.09Suggestive
combined immunodeficiency with skin granulomasOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
severe combined immunodeficiency due to CARD11 deficiencyOpen Targets
0.09Suggestive
immunodeficiency 18Open Targets
0.08Suggestive
combined immunodeficiency due to CTPS1 deficiencyOpen Targets
0.08Suggestive
reticular dysgenesisOpen Targets
0.08Suggestive
X-Linked Combined Immunodeficiency DiseasesOpen Targets
0.08Suggestive
common variable immunodeficiencyOpen Targets
0.08Suggestive
Immunodeficiency 110 with lymphoproliferationUniProt
Pathogenic Variants19
NM_006282.5(STK4):c.343C>T (p.Arg115Ter)Pathogenic
Combined immunodeficiency due to STK4 deficiency
β˜…β˜…β˜†β˜†2026β†’ Residue 115
NM_006282.5(STK4):c.442C>T (p.Arg148Ter)Pathogenic
Combined immunodeficiency due to STK4 deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 148
NM_006282.5(STK4):c.733C>T (p.Arg245Ter)Pathogenic
Combined immunodeficiency due to STK4 deficiency
β˜…β˜…β˜†β˜†2023β†’ Residue 245
NM_006282.5(STK4):c.349C>T (p.Arg117Ter)Pathogenic
Combined immunodeficiency due to STK4 deficiency|Inherited Immunodeficiency Diseases|STK4-related disorder
β˜…β˜…β˜†β˜†2023β†’ Residue 117
NM_006282.5(STK4):c.871C>T (p.Arg291Ter)Pathogenic
Combined immunodeficiency due to STK4 deficiency
β˜…β˜†β˜†β˜†2025β†’ Residue 291
NM_006282.5(STK4):c.1135_1138del (p.Gly379fs)Pathogenic
Combined immunodeficiency due to STK4 deficiency
β˜…β˜†β˜†β˜†2025β†’ Residue 379
NM_006282.5(STK4):c.297G>A (p.Trp99Ter)Pathogenic
Combined immunodeficiency due to STK4 deficiency
β˜…β˜†β˜†β˜†2025β†’ Residue 99
NM_006282.5(STK4):c.92dup (p.Asp31fs)Pathogenic
Combined immunodeficiency due to STK4 deficiency
β˜…β˜†β˜†β˜†2024β†’ Residue 31
NM_006282.5(STK4):c.775A>T (p.Lys259Ter)Likely pathogenic
Combined immunodeficiency due to STK4 deficiency
β˜…β˜†β˜†β˜†2024β†’ Residue 259
NM_006282.5(STK4):c.964G>T (p.Glu322Ter)Pathogenic
Combined immunodeficiency due to STK4 deficiency
β˜…β˜†β˜†β˜†2024β†’ Residue 322
NM_006282.5(STK4):c.994C>T (p.Arg332Ter)Pathogenic
Combined immunodeficiency due to STK4 deficiency
β˜…β˜†β˜†β˜†2024β†’ Residue 332
NM_006282.5(STK4):c.749G>A (p.Trp250Ter)Pathogenic
Combined immunodeficiency due to STK4 deficiency
β˜…β˜†β˜†β˜†2023β†’ Residue 250
NM_006282.5(STK4):c.36-1G>ALikely pathogenic
Combined immunodeficiency due to STK4 deficiency
β˜…β˜†β˜†β˜†2023
NM_006282.5(STK4):c.1103del (p.Met368fs)Pathogenic
Combined immunodeficiency due to STK4 deficiency
β˜…β˜†β˜†β˜†2023β†’ Residue 368
NM_006282.5(STK4):c.395C>A (p.Ser132Ter)Likely pathogenic
Severe combined immunodeficiency disease
β˜…β˜†β˜†β˜†2023β†’ Residue 132
NM_006282.5(STK4):c.831+2T>CLikely pathogenic
Severe combined immunodeficiency disease
β˜…β˜†β˜†β˜†2022
NM_006282.5(STK4):c.961-2A>GLikely pathogenic
Combined immunodeficiency due to STK4 deficiency
β˜…β˜†β˜†β˜†2021
NM_006282.5(STK4):c.373G>T (p.Glu125Ter)Pathogenic
Combined immunodeficiency due to STK4 deficiency
β˜…β˜†β˜†β˜†2020β†’ Residue 125
NM_006282.5(STK4):c.922C>T (p.Gln308Ter)Pathogenic
Combined immunodeficiency due to STK4 deficiency
β˜…β˜†β˜†β˜†2020β†’ Residue 308
View on ClinVar β†—
Related Genes
RASSF1Protein interaction97%MOB1AProtein interaction97%FOXO1Protein interaction97%FOXO3Protein interaction97%FOXO4Protein interaction97%CASP3Protein interaction95%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
57%
Brain
40%
Ovary
20%
Liver
19%
Heart
15%
Gene Interaction Network
Click a node to explore
STK4RASSF1MOB1AFOXO1FOXO3FOXO4CASP3
PROTEIN STRUCTURE
Preparing viewer…
PDB8PAV Β· 1.90 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.60LoF Tolerant
pLIβ“˜
0.07Tolerant
Observed/Expected LoF0.43 [0.32–0.60]
RankingsWhere STK4 stands among ~20K protein-coding genes
  • #1,608of 20,598
    Most Researched243 Β· top 10%
  • #2,213of 5,498
    Most Pathogenic Variants19
  • #4,105of 17,882
    Most Constrained (LOEUF)0.60 Β· top quartile
Genes detectedSTK4
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Rapid identification of primary atopic disorders (PAD) by a clinical landmark-guided, upfront use of genomic sequencing.
PMID: 39381601
Allergol Select Β· 2024
1.00
2
STK3/STK4 signalling in adipocytes regulates mitophagy and energy expenditure.
PMID: 33758424
Nat Metab Β· 2021
0.90
3
Primary Immune Regulatory Disorders With an Autoimmune Lymphoproliferative Syndrome-Like Phenotype: Immunologic Evaluation, Early Diagnosis and Management.
PMID: 34447369
Front Immunol Β· 2021
0.80
4
SNORD88B-mediated WRN nucleolar trafficking drives self-renewal in liver cancer initiating cells and hepatocarcinogenesis.
PMID: 39112443
Nat Commun Β· 2024
0.72
5
Mst1-mediated phosphorylation of Nur77 improves the endometrial receptivity in human and mice.
PMID: 36623453
EBioMedicine Β· 2023
0.70