STK3

serine/threonine kinase 3

Basic information

Region (hg38): 8:98371227-98942827

Links

ENSG00000104375 ∙ NCBI:6788 ∙ OMIM:605030 ∙ HGNC:11406 ∙ Uniprot:Q13188 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STK3 gene.

• Inborn genetic diseases (12 variants)

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			12			12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	12	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
8-98427998-T-C		not specified	Uncertain significance (Jan 10, 2023)
8-98428037-C-T		not specified	Uncertain significance (Jun 30, 2022)
8-98428101-C-T		not specified	Uncertain significance (Dec 01, 2022)
8-98428362-T-C		not specified	Uncertain significance (Feb 24, 2022)
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)
8-98428640-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)
8-98428832-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)
8-98429067-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)
8-98429261-C-T		not specified	Uncertain significance (Feb 11, 2022)
8-98429282-G-A		not specified	Uncertain significance (Nov 09, 2021)
8-98429317-C-G		not specified	Uncertain significance (Aug 01, 2022)
8-98455849-T-C		not specified	Uncertain significance (Sep 23, 2023)
8-98526777-T-A		not specified	Uncertain significance (Oct 17, 2023)
8-98526778-A-T		not specified	Uncertain significance (Jun 30, 2022)
8-98526806-A-C		not specified	Uncertain significance (Oct 06, 2021)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

• 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