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GeneBe

RPS6KA1

ribosomal protein S6 kinase A1, the group of MicroRNA protein coding host genes|AGC family kinases|MAPK activated protein kinases

Basic information

Region (hg38): 1:26529760-26575030

Links

ENSG00000117676NCBI:6195OMIM:601684HGNC:10430Uniprot:Q15418AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RPS6KA1 gene.

  • Inborn genetic diseases (21 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RPS6KA1 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
21
clinvar
21
nonsense
0
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
?
0
non coding
?
0
Total 0 0 21 0 0

Variants in RPS6KA1

This is a list of pathogenic ClinVar variants found in the RPS6KA1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
1-26551408-G-A Inborn genetic diseases Uncertain significance (Dec 27, 2022)2339734
1-26551689-G-A Inborn genetic diseases Uncertain significance (May 03, 2023)2543048
1-26551709-C-T Inborn genetic diseases Uncertain significance (Mar 01, 2023)2459059
1-26553391-G-A Inborn genetic diseases Uncertain significance (Feb 01, 2023)2454522
1-26554632-A-G Inborn genetic diseases Uncertain significance (Dec 06, 2022)2333245
1-26554682-G-A Inborn genetic diseases Uncertain significance (Nov 09, 2021)2301171
1-26555153-T-G Inborn genetic diseases Uncertain significance (Aug 04, 2023)2615911
1-26558866-G-A Inborn genetic diseases Uncertain significance (May 04, 2023)2519687
1-26558893-G-A Inborn genetic diseases Uncertain significance (Feb 09, 2023)2482574
1-26558909-C-T Inborn genetic diseases Uncertain significance (Sep 01, 2021)2362321
1-26560759-G-A Inborn genetic diseases Uncertain significance (Mar 07, 2023)2463742
1-26560786-G-T Inborn genetic diseases Uncertain significance (Oct 12, 2022)2318302
1-26561532-C-A Inborn genetic diseases Uncertain significance (Jul 05, 2023)2593799
1-26561580-C-T Inborn genetic diseases Uncertain significance (Aug 13, 2021)2244711
1-26561602-G-A Inborn genetic diseases Uncertain significance (Dec 21, 2022)2389502
1-26571913-C-T Inborn genetic diseases Uncertain significance (Nov 30, 2021)2262762
1-26572205-A-G Inborn genetic diseases Uncertain significance (May 03, 2023)2542904
1-26573248-G-A Inborn genetic diseases Uncertain significance (Jun 30, 2023)2609213
1-26574085-A-G Inborn genetic diseases Uncertain significance (Jun 06, 2023)2557735
1-26574104-C-T Inborn genetic diseases Uncertain significance (Jul 14, 2023)2611895
1-26574160-G-T Inborn genetic diseases Uncertain significance (Jul 26, 2022)2303756

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RPS6KA1protein_codingprotein_codingENST00000531382 2145270
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.001910.9981257200281257480.000111
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.992794600.6070.00002864829
Missense in Polyphen69160.340.430331743
Synonymous0.4791791870.9550.00001141498
Loss of Function3.881237.70.3180.00000160462

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0002960.000296
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.0003300.000277
European (Non-Finnish)0.0001020.0000967
Middle Eastern0.000.00
South Asian0.00006530.0000653
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin- derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the pre-initiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro- apoptotic function. Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (By similarity). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression. Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). {ECO:0000250|UniProtKB:P18653, ECO:0000250|UniProtKB:Q63531, ECO:0000269|PubMed:10679322, ECO:0000269|PubMed:11684016, ECO:0000269|PubMed:12213813, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:15342917, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:16763566, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:9430688}.;
Pathway
mTOR signaling pathway - Homo sapiens (human);Long-term potentiation - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);Thermogenesis - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);Intracellular Signalling Through Adenosine Receptor A2b and Adenosine;Intracellular Signalling Through Adenosine Receptor A2a and Adenosine;EGF-Core;WNT-Core;IL-5 Signaling Pathway;Leptin signaling pathway;Human Thyroid Stimulating Hormone (TSH) signaling pathway;B Cell Receptor Signaling Pathway;Interleukin-11 Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;JAK-STAT;Kit receptor signaling pathway;BDNF-TrkB Signaling;Angiopoietin Like Protein 8 Regulatory Pathway;TYROBP Causal Network;EGF-EGFR Signaling Pathway;Cytoplasmic Ribosomal Proteins;Insulin Signaling;Developmental Biology;Signaling by GPCR;RAGE;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Signal Transduction;Recycling pathway of L1;Signaling by Interleukins;role of erk5 in neuronal survival pathway;role of egf receptor transactivation by gpcrs in cardiac hypertrophy;trefoil factors initiate mucosal healing;transcription factor creb and its extracellular signals;melanocyte development and pigmentation pathway;erk1/erk2 mapk signaling pathway;mapkinase signaling pathway;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;Toll-Like Receptors Cascades;Senescence-Associated Secretory Phenotype (SASP);Cellular Senescence;Cellular responses to stress;Innate Immune System;Immune System;KitReceptor;Fibroblast growth factor-1;Nuclear Events (kinase and transcription factor activation);Neuronal System;BCR;cell cycle: g2/m checkpoint;Cellular responses to external stimuli;IL-7 signaling;Signaling by NTRK1 (TRKA);CREB phosphorylation;Signaling by NTRKs;ERK/MAPK targets;EGFR1;MAPK targets/ Nuclear events mediated by MAP kinases;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;growth hormone signaling pathway;MyD88 dependent cascade initiated on endosome;JAK STAT pathway and regulation;VEGFR3 signaling in lymphatic endothelium;IL11;EPO signaling;L1CAM interactions;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Axon guidance;IL5;RSK activation;CREB phosphorylation through the activation of Ras;Post NMDA receptor activation events;Activation of NMDA receptor and postsynaptic events;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;Signaling by Receptor Tyrosine Kinases;VEGF;Gastrin-CREB signalling pathway via PKC and MAPK;G alpha (q) signalling events;GPCR downstream signalling;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;mTOR signaling pathway;Trk receptor signaling mediated by the MAPK pathway;FGF signaling pathway (Consensus)

Recessive Scores

pRec
0.220

Intolerance Scores

loftool
rvis_EVS
-1.07
rvis_percentile_EVS
7.43

Haploinsufficiency Scores

pHI
0.808
hipred
Y
hipred_score
0.639
ghis
0.612

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.999

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Rps6ka1
Phenotype

Gene ontology

Biological process
protein phosphorylation;apoptotic process;cell cycle;signal transduction;positive regulation of cell growth;intracellular signal transduction;negative regulation of apoptotic process;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;regulation of translation in response to stress;regulation of DNA-templated transcription in response to stress;positive regulation of cell differentiation;positive regulation of transcription by RNA polymerase II;hepatocyte proliferation;positive regulation of hepatic stellate cell activation
Cellular component
nucleus;nucleoplasm;cytosol
Molecular function
magnesium ion binding;protein serine/threonine kinase activity;ribosomal protein S6 kinase activity;protein serine/threonine/tyrosine kinase activity;protein binding;ATP binding;kinase activity;cysteine-type endopeptidase inhibitor activity involved in apoptotic process