RPS6KB1
ribosomal protein S6 kinase B1, the group of AGC family kinases
Basic information
Region (hg38): 17:59893045-59950574
Previous symbols: [ "STK14A" ]
Links
Phenotypes
GenCC
Source:
- hypertrophic cardiomyopathy (Limited), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (9 variants)
- not provided (3 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RPS6KB1 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 | 1 | |||||
| missense | 9 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 1 | 1 | 2 | |||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 9 | 0 | 1 |
Variants in RPS6KB1
This is a list of pathogenic ClinVar variants found in the RPS6KB1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 17-59893199-G-T | not specified | Uncertain significance (Jun 23, 2023) | ||
| 17-59893236-G-A | not specified | Uncertain significance (Dec 19, 2022) | ||
| 17-59893245-G-A | not specified | Uncertain significance (Sep 23, 2023) | ||
| 17-59893260-G-A | not specified | Uncertain significance (Nov 16, 2022) | ||
| 17-59893299-G-T | not specified | Uncertain significance (Jan 02, 2024) | ||
| 17-59893307-G-C | not specified | Uncertain significance (Sep 22, 2022) | ||
| 17-59893319-G-A | Benign (Apr 09, 2018) | |||
| 17-59893333-C-G | Likely benign (Dec 09, 2017) | |||
| 17-59910562-G-T | not specified | Uncertain significance (Feb 28, 2024) | ||
| 17-59914627-T-A | Benign (Jun 26, 2018) | |||
| 17-59926487-A-G | not specified | Uncertain significance (Oct 06, 2021) | ||
| 17-59945506-G-A | not specified | Uncertain significance (Apr 25, 2022) | ||
| 17-59945514-G-C | not specified | Uncertain significance (Jan 11, 2023) | ||
| 17-59946594-T-C | not specified | Uncertain significance (Aug 08, 2023) | ||
| 17-59946640-A-C | not specified | Uncertain significance (Jan 06, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RPS6KB1 | protein_coding | protein_coding | ENST00000225577 | 15 | 57479 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.973 | 0.0271 | 125735 | 0 | 13 | 125748 | 0.0000517 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.90 | 105 | 293 | 0.359 | 0.0000147 | 3458 |
| Missense in Polyphen | 25 | 114.89 | 0.2176 | 1426 | ||
| Synonymous | 1.17 | 81 | 95.5 | 0.848 | 0.00000469 | 977 |
| Loss of Function | 4.53 | 5 | 33.2 | 0.151 | 0.00000193 | 366 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000213 | 0.000213 |
| Ashkenazi Jewish | 0.000101 | 0.0000992 |
| East Asian | 0.0000594 | 0.0000544 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.0000550 | 0.0000527 |
| Middle Eastern | 0.0000594 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function. Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex. The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative feedback mechanism for the RPS6KB1 anti- apoptotic function. Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1- 2 complex, constitutively phosphorylates and inhibits GSK3B. May be involved in cytoskeletal rearrangement through binding to neurabin. Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR (PubMed:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:23429703). Following activation by mTORC1, phosphorylates EPRS and thereby plays a key role in fatty acid uptake by adipocytes and also most probably in interferon-gamma-induced translation inhibition (PubMed:28178239). {ECO:0000269|PubMed:11500364, ECO:0000269|PubMed:12801526, ECO:0000269|PubMed:14673156, ECO:0000269|PubMed:15071500, ECO:0000269|PubMed:15341740, ECO:0000269|PubMed:16286006, ECO:0000269|PubMed:17052453, ECO:0000269|PubMed:17053147, ECO:0000269|PubMed:17936702, ECO:0000269|PubMed:18952604, ECO:0000269|PubMed:19085255, ECO:0000269|PubMed:19720745, ECO:0000269|PubMed:19935711, ECO:0000269|PubMed:19995915, ECO:0000269|PubMed:23429703, ECO:0000269|PubMed:28178239}.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Gastric cancer - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Fc gamma R-mediated phagocytosis - Homo sapiens (human);TGF-beta signaling pathway - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Insulin resistance - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Longevity regulating pathway - multiple species - Homo sapiens (human);Acute myeloid leukemia - Homo sapiens (human);Breast cancer - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Leucine Stimulation on Insulin Signaling;IGF-Core;IL-5 Signaling Pathway;AMP-activated Protein Kinase (AMPK) Signaling;Target Of Rapamycin (TOR) Signaling;Leptin signaling pathway;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Follicle Stimulating Hormone (FSH) signaling pathway;Prolactin Signaling Pathway;Interleukin-11 Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;JAK-STAT;Apoptosis-related network due to altered Notch3 in ovarian cancer;Kit receptor signaling pathway;IL-6 signaling pathway;BDNF-TrkB Signaling;Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling;IL-4 Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;EGF-EGFR Signaling Pathway;Cytoplasmic Ribosomal Proteins;Insulin Signaling;IL-2 Signaling Pathway;G13 Signaling Pathway;Interferon type I signaling pathways;ErbB Signaling Pathway;Signal Transduction;mtor signaling pathway;regulation of eif-4e and p70s6 kinase;il-2 receptor beta chain in t cell activation;il 4 signaling pathway;nfat and hypertrophy of the heart ;phosphoinositides and their downstream targets;skeletal muscle hypertrophy is regulated via akt-mtor pathway;rac1 cell motility signaling pathway;ctcf: first multivalent nuclear factor;mTORC1-mediated signalling;mTOR signalling;TCR;KitReceptor;Fibroblast growth factor-1;insulin Mam;BCR;IL-7 signaling;EGFR1;JAK STAT pathway and regulation;IL2;EPO signaling;a6b1 and a6b4 Integrin signaling;RXR and RAR heterodimerization with other nuclear receptor;Angiopoietin receptor Tie2-mediated signaling;IL4;Leptin;IL6;TNFalpha;VEGF;mTOR signaling pathway;Insulin Pathway;CDC42 signaling events;Regulation of Telomerase;IL2 signaling events mediated by PI3K;IGF1 pathway;Signaling events mediated by Stem cell factor receptor (c-Kit);IL4-mediated signaling events;TGF-beta receptor signaling;Integrins in angiogenesis;insulin
(Consensus)
Recessive Scores
- pRec
- 0.623
Intolerance Scores
- loftool
- rvis_EVS
- -0.49
- rvis_percentile_EVS
- 22.09
Haploinsufficiency Scores
- pHI
- 0.622
- hipred
- Y
- hipred_score
- 0.831
- ghis
- 0.640
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Rps6kb1
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); immune system phenotype; 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); reproductive system 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;
Gene ontology
- Biological process
- G1/S transition of mitotic cell cycle;behavioral fear response;skeletal muscle contraction;protein phosphorylation;apoptotic process;signal transduction;germ cell development;aging;response to nutrient;long-term memory;response to heat;response to wounding;response to mechanical stimulus;response to glucose;skeletal muscle atrophy;response to electrical stimulus involved in regulation of muscle adaptation;positive regulation of smooth muscle cell migration;cell migration;peptidyl-serine phosphorylation;TOR signaling;response to lipopolysaccharide;cellular response to insulin stimulus;response to testosterone;response to glucagon;response to tumor necrosis factor;intracellular signal transduction;negative regulation of apoptotic process;response to leucine;protein kinase B signaling;long-chain fatty acid import;response to ethanol;positive regulation of translation;positive regulation of mitotic cell cycle;positive regulation of translational initiation;regulation of glucose import;negative regulation of insulin receptor signaling pathway;phosphatidylinositol-mediated signaling;positive regulation of skeletal muscle tissue growth;positive regulation of smooth muscle cell proliferation;cellular response to interferon-gamma;cellular response to growth factor stimulus;cellular response to dexamethasone stimulus;negative regulation of extrinsic apoptotic signaling pathway
- Cellular component
- nucleus;nucleoplasm;cytoplasm;mitochondrion;mitochondrial outer membrane;cytosol;cell surface;cell junction;neuron projection;synapse;perinuclear region of cytoplasm
- Molecular function
- protein kinase activity;protein serine/threonine kinase activity;ribosomal protein S6 kinase activity;protein serine/threonine/tyrosine kinase activity;protein binding;ATP binding;kinase activity;PDZ domain binding;peptide binding;identical protein binding;protein phosphatase 2A binding