STK3
serine/threonine kinase 3
Basic information
Region (hg38): 8:98371228-98942827
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the STK3 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 17 | 17 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 17 | 0 | 0 |
Variants in STK3
This is a list of pathogenic ClinVar variants found in the STK3 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 8-98427986-G-C | not specified | Likely benign (Apr 01, 2024) | ||
| 8-98427998-T-C | not specified | Uncertain significance (Jan 10, 2023) | ||
| 8-98428008-C-G | not specified | Uncertain significance (Sep 03, 2024) | ||
| 8-98428010-G-C | not specified | Uncertain significance (Dec 03, 2024) | ||
| 8-98428037-C-T | not specified | Uncertain significance (Jun 30, 2022) | ||
| 8-98428101-C-T | not specified | Uncertain significance (Dec 01, 2022) | ||
| 8-98428271-G-A | not specified | Uncertain significance (Oct 08, 2024) | ||
| 8-98428362-T-C | not specified | Uncertain significance (Oct 31, 2024) | ||
| 8-98428466-G-A | not specified | Uncertain significance (Mar 06, 2023) | ||
| 8-98428520-G-A | not specified | Uncertain significance (Apr 13, 2022) | ||
| 8-98428590-T-C | not specified | Uncertain significance (Jul 28, 2021) | ||
| 8-98428598-A-C | not specified | Uncertain significance (Dec 05, 2024) | ||
| 8-98428640-C-T | not specified | Uncertain significance (Dec 19, 2022) | ||
| 8-98428650-A-G | not specified | Uncertain significance (Jan 08, 2024) | ||
| 8-98428736-C-G | not specified | Uncertain significance (Jan 26, 2023) | ||
| 8-98428784-G-A | Benign (Jul 13, 2018) | |||
| 8-98428796-A-G | not specified | Uncertain significance (Mar 16, 2024) | ||
| 8-98428832-C-A | not specified | Uncertain significance (Feb 13, 2024) | ||
| 8-98428880-C-A | Benign (Jul 13, 2018) | |||
| 8-98428925-C-T | not specified | Uncertain significance (Nov 06, 2023) | ||
| 8-98428975-C-T | Likely benign (Oct 01, 2024) | |||
| 8-98429067-C-T | not specified | Uncertain significance (Dec 17, 2023) | ||
| 8-98429133-C-G | not specified | Uncertain significance (Dec 19, 2023) | ||
| 8-98429216-T-C | not specified | Uncertain significance (May 31, 2023) | ||
| 8-98429232-G-A | not specified | Uncertain significance (Oct 27, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| STK3 | protein_coding | protein_coding | ENST00000523601 | 11 | 541425 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 6.20e-7 | 0.972 | 124897 | 1 | 56 | 124954 | 0.000228 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.58 | 194 | 266 | 0.728 | 0.0000133 | 3478 |
| Missense in Polyphen | 37 | 83.419 | 0.44354 | 1072 | ||
| Synonymous | 0.583 | 81 | 88.0 | 0.921 | 0.00000478 | 881 |
| Loss of Function | 2.06 | 14 | 25.1 | 0.557 | 0.00000126 | 335 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000783 | 0.000776 |
| Ashkenazi Jewish | 0.0000995 | 0.0000993 |
| East Asian | 0.0000591 | 0.0000551 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000282 | 0.000274 |
| Middle Eastern | 0.0000591 | 0.0000551 |
| South Asian | 0.000110 | 0.0000980 |
| Other | 0.000336 | 0.000330 |
dbNSFP
Source:
- Function
- FUNCTION: 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. Phosphorylates NKX2-1 (By similarity). Phosphorylates NEK2 and plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosome, and its ability to phosphorylate CROCC and CEP250. In conjunction with SAV1, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation. Positively regulates RAF1 activation via suppression of the inhibitory phosphorylation of RAF1 on 'Ser-259'. Phosphorylates MOBKL1A and RASSF2. Phosphorylates MOBKL1B on 'Thr-74'. Acts cooperatively with MOBKL1B to activate STK38. {ECO:0000250|UniProtKB:Q9JI10, ECO:0000269|PubMed:15688006, ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:18328708, ECO:0000269|PubMed:18362890, ECO:0000269|PubMed:19525978, ECO:0000269|PubMed:20212043, ECO:0000269|PubMed:21076410, ECO:0000269|PubMed:21104395, ECO:0000269|PubMed:28087714, ECO:0000269|PubMed:8566796, ECO:0000269|PubMed:8816758}.;
- Pathway
- Hippo signaling pathway - Homo sapiens (human);Hippo signaling pathway - multiple species - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);MAPK Signaling Pathway;Signal Transduction;Signaling by Hippo
(Consensus)
Recessive Scores
- pRec
- 0.113
Intolerance Scores
- loftool
- rvis_EVS
- -0.36
- rvis_percentile_EVS
- 28.93
Haploinsufficiency Scores
- pHI
- 0.140
- hipred
- Y
- hipred_score
- 0.665
- ghis
- 0.579
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.958
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Stk3
- Phenotype
- immune system phenotype; skeleton phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype;
Zebrafish Information Network
- Gene name
- stk3
- Affected structure
- whole organism
- Phenotype tag
- abnormal
- Phenotype quality
- decreased length
Gene ontology
- Biological process
- neural tube formation;endocardium development;protein phosphorylation;apoptotic process;signal transduction;central nervous system development;negative regulation of cell population proliferation;signal transduction by protein phosphorylation;stress-activated protein kinase signaling cascade;positive regulation of protein binding;activation of protein kinase activity;hippo signaling;intracellular signal transduction;positive regulation of apoptotic process;positive regulation of fat cell differentiation;positive regulation of JNK cascade;negative regulation of organ growth;protein stabilization;positive regulation of DNA-binding transcription factor activity;positive regulation of protein kinase B signaling;primitive hemopoiesis;cell differentiation involved in embryonic placenta development;regulation of cell differentiation involved in embryonic placenta development;positive regulation of protein serine/threonine kinase activity;negative regulation of canonical Wnt signaling pathway;hepatocyte apoptotic process;positive regulation of extrinsic apoptotic signaling pathway via death domain receptors
- Cellular component
- nucleus;cytoplasm;cytosol;protein-containing complex
- Molecular function
- magnesium ion binding;protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;identical protein binding;protein serine/threonine kinase activator activity;protein dimerization activity