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GeneBe

RPS6KA5

ribosomal protein S6 kinase A5, the group of AGC family kinases|MAPK activated protein kinases

Basic information

Region (hg38): 14:90847860-91060641

Links

ENSG00000100784NCBI:9252OMIM:603607HGNC:10434Uniprot:O75582AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RPS6KA5 gene.

  • Inborn genetic diseases (24 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RPS6KA5 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
24
clinvar
24
nonsense
0
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
0
non coding
0
Total 0 0 24 0 0

Variants in RPS6KA5

This is a list of pathogenic ClinVar variants found in the RPS6KA5 region.

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

Position Type Phenotype Significance ClinVar
14-90872111-G-A not specified Uncertain significance (Oct 26, 2022)2319628
14-90872121-T-C not specified Likely benign (Oct 05, 2023)3156231
14-90872123-T-A not specified Uncertain significance (May 18, 2023)2528181
14-90872217-G-A not specified Uncertain significance (Sep 20, 2023)3156230
14-90873703-G-C not specified Uncertain significance (Oct 14, 2023)3156229
14-90873790-G-T not specified Uncertain significance (Jul 25, 2023)2613672
14-90875258-A-T not specified Uncertain significance (Aug 13, 2021)2352244
14-90875262-A-C not specified Uncertain significance (Feb 15, 2023)2470653
14-90875302-G-C not specified Uncertain significance (Nov 08, 2022)2374234
14-90875306-A-G not specified Uncertain significance (Dec 27, 2023)3156228
14-90875359-T-C not specified Uncertain significance (Sep 01, 2021)2370743
14-90890570-T-G not specified Uncertain significance (Jul 19, 2023)2612667
14-90894517-T-G not specified Uncertain significance (Dec 28, 2022)2339774
14-90894531-C-T not specified Uncertain significance (Nov 08, 2022)2324429
14-90900165-C-T not specified Uncertain significance (Feb 14, 2023)2455846
14-90900652-G-A not specified Uncertain significance (Oct 25, 2023)3156227
14-90902839-G-A not specified Uncertain significance (Feb 28, 2023)2490259
14-90902859-A-T not specified Uncertain significance (Mar 04, 2024)3156226
14-90902945-C-T not specified Uncertain significance (Nov 28, 2023)3156235
14-90902969-T-C not specified Uncertain significance (Jan 16, 2024)3156234
14-90906267-T-C not specified Uncertain significance (Jun 03, 2022)2293540
14-90920240-C-G not specified Uncertain significance (Sep 20, 2023)3156233
14-90920275-T-C not specified Uncertain significance (Dec 03, 2021)2263926
14-90947443-G-C not specified Uncertain significance (Jan 04, 2024)3156232
14-90947487-T-G not specified Uncertain significance (Jan 27, 2022)2274413

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RPS6KA5protein_codingprotein_codingENST00000261991 17190182
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9990.000913125736071257430.0000278
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.173074340.7070.00002265307
Missense in Polyphen93179.910.516932249
Synonymous0.09391591610.9910.000009181494
Loss of Function5.10437.90.1060.00000200484

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001230.000123
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00004440.0000440
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes (PubMed:11909979, PubMed:12569367, PubMed:12763138, PubMed:9687510, PubMed:18511904, PubMed:9873047). Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin (PubMed:11909979, PubMed:9873047). Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression (PubMed:12628924, PubMed:18511904). In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress (PubMed:12628924). In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential (PubMed:12763138). Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation (PubMed:12569367). Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A (PubMed:15010469). Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto- oncogenes c-fos/FOS and c-jun/JUN (PubMed:12773393). May also phosphorylate 'Ser-28' of histone H3 (PubMed:12773393). Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14) (PubMed:12773393). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro- inflammatory cytokines (By similarity). Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors (By similarity). Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury (By similarity). Phosphorylates TRIM7 at 'Ser- 107' in response to growth factor signaling via the MEK/ERK pathway, thereby stimulating its ubiquitin ligase activity (PubMed:25851810). {ECO:0000250|UniProtKB:Q8C050, ECO:0000269|PubMed:11909979, ECO:0000269|PubMed:12569367, ECO:0000269|PubMed:12628924, ECO:0000269|PubMed:12763138, ECO:0000269|PubMed:12773393, ECO:0000269|PubMed:15010469, ECO:0000269|PubMed:18511904, ECO:0000269|PubMed:25851810, ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9873047}.;
Pathway
Neurotrophin signaling pathway - Homo sapiens (human);Bladder cancer - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);EGF-Core;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Structural Pathway of Interleukin 1 (IL-1);Bladder Cancer;MAPK Signaling Pathway;ERK Pathway in Huntington,s Disease;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;p38 MAPK Signaling Pathway;EGF-EGFR Signaling Pathway;Insulin Signaling;Interferon type I signaling pathways;Serotonin HTR1 Group and FOS Pathway;Serotonin Receptor 4-6-7 and NR3C Signaling;Developmental Biology;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Signal Transduction;Recycling pathway of L1;Signaling by Interleukins;transcription factor creb and its extracellular signals;p38 mapk signaling pathway;erk1/erk2 mapk 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;CD209 (DC-SIGN) signaling;C-type lectin receptors (CLRs);Innate Immune System;Immune System;Nuclear Events (kinase and transcription factor activation);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;ErbB1 downstream signaling;MyD88 dependent cascade initiated on endosome;NCAM signaling for neurite out-growth;L1CAM interactions;Axon guidance;TNFalpha;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;Signaling by Receptor Tyrosine Kinases;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;LPA4-mediated signaling events;Signaling mediated by p38-alpha and p38-beta;Trk receptor signaling mediated by the MAPK pathway (Consensus)

Recessive Scores

pRec
0.310

Intolerance Scores

loftool
rvis_EVS
-0.18
rvis_percentile_EVS
40.45

Haploinsufficiency Scores

pHI
0.663
hipred
Y
hipred_score
0.806
ghis
0.508

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
1.00

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Rps6ka5
Phenotype
homeostasis/metabolism phenotype; cellular 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); 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); immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic 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);

Gene ontology

Biological process
negative regulation of cytokine production;stimulatory C-type lectin receptor signaling pathway;regulation of transcription, DNA-templated;protein phosphorylation;inflammatory response;epidermal growth factor receptor signaling pathway;axon guidance;histone phosphorylation;positive regulation of CREB transcription factor activity;positive regulation of histone phosphorylation;positive regulation of histone acetylation;intracellular signal transduction;histone H3-S10 phosphorylation;histone H3-S28 phosphorylation;histone H2A-S1 phosphorylation;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of NF-kappaB transcription factor activity;interleukin-1-mediated signaling pathway
Cellular component
nucleus;nucleoplasm;cytoplasm
Molecular function
magnesium ion binding;protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding