STK10
protein-codingserine/threonine kinase 10
Gene summary
This gene encodes a member of the Ste20 family of serine/threonine protein kinases, and is similar to several known polo-like kinase kinases. The protein can associate with and phosphorylate polo-like kinase 1, and overexpression of a kinase-dead version of the protein interferes with normal cell cycle progression. The kinase can also negatively regulate interleukin 2 expression in T-cells via the mitogen activated protein kinase kinase 1 pathway. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~146.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to STK10 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005990.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 2 | 2 | 8 | ||
| missense | 140 | 3 | 2 | 145 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 149 | 5 | 4 | 158 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005981.3 | 19 | MANE Select | |
| Ensembl | ENSP00000176763.5 | 19 | MANE Select | |
| Ensembl | ENSP00000428806.1 | 7 | Standard | |
| Ensembl | ENSP00000547845.1 | 19 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Progesterone-mediated oocyte maturation - Homo sapiens (human)
- Neutrophil degranulation
- Innate Immune System
- Immune System
Biological Process
- protein phosphorylation
- cell cycle
- signal transduction by protein phosphorylation
- stress-activated protein kinase signaling cascade
- activation of protein kinase activity
Molecular Function
- protein serine/threonine kinase activity
- protein binding
- ATP binding
- identical protein binding
- protein homodimerization activity
Cellular Component
- cytoplasm
- plasma membrane
- specific granule membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000176763
- Coding exons
- 19
- Length
- 146314
- Individuals with no LoFs
- 125567
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 180
- Defined
- 125748
- p
- 0.000720
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.47 | 495 | 596 | 0.831 | 0.0000373 | 6405 |
| Missense (PolyPhen) | 172 | 236.84 | 0.72624 | 2491 | ||
| Synonymous | -0.108 | 241 | 239 | 1.01 | 0.0000152 | 1788 |
| Loss of Function | 2.77 | 31 | 52.7 | 0.588 | 0.00000303 | 564 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00081 | 0.00080 | rare |
| Latino/Admixed American | 0.00038 | 0.00038 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00045 | 0.00044 | rare |
| Finnish | 0.0039 | 0.0039 | notable |
| European (Non-Finnish) | 0.00035 | 0.00034 | rare |
| South Asian | 0.00074 | 0.00069 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo. {ECO:0000269|PubMed:11903060, ECO:0000269|PubMed:12639966, ECO:0000269|PubMed:19255442}.;
- Disease
- DISEASE: Testicular germ cell tumor (TGCT) [MIM:273300]: A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. {ECO:0000269|PubMed:16175573}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.139
Intolerance Scores
- LoFtool
- 0.868
- RVIS EVS
- -0.92
- RVIS percentile EVS
- 9.78
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.785
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |