STK4

Chr 20q13.12

serine/threonine kinase 4

Aliases:: MST1, KRS2, YSK3
MANE:: ENST00000372806.8

OMIM: 604965 ↗NCBI: 6789 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

AlphaFold predicted structure

STK4 · Q13043

v62025-08-01

Predicted Aligned Error matrix for STK4 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

75.9/ 100

Confident

487 residues

Confidence breakdown

Very high(≥ 90)49%
Confident(70–90)19%
Low(50–70)8%
Very low(< 50)24%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

COVID-19 research
BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease
BIALLELIC, autosomal or pseudoautosomal
Cytopenia - NOT Fanconi anaemia
Unknown
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Paediatric disorders - additional genes
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

combined immunodeficiency due to STK4 deficiency
0.76
severe combined immunodeficiency
0.55
combined immunodeficiency
0.46
combined immunodeficiency due to DOCK8 deficiency
0.46
immunodeficiency disease
0.34
neurodegenerative disease
0.30
autoimmune disorder of central nervous system
0.20
hereditary disease
0.19
bipolar disorder
0.12
bipolar I disorder
0.11

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Serine/threonine-protein kinase 4

Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes