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GeneBe

RPS6KA4

ribosomal protein S6 kinase A4, the group of AGC family kinases|MAPK activated protein kinases|MicroRNA protein coding host genes

Basic information

Region (hg38): 11:64359147-64372215

Links

ENSG00000162302NCBI:8986OMIM:603606HGNC:10433Uniprot:O75676AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RPS6KA4 gene.

  • Inborn genetic diseases (28 variants)
  • not provided (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RPS6KA4 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
3
clinvar
2
clinvar
5
missense
28
clinvar
1
clinvar
29
nonsense
0
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
0
non coding
0
Total 0 0 28 3 3

Variants in RPS6KA4

This is a list of pathogenic ClinVar variants found in the RPS6KA4 region.

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

Position Type Phenotype Significance ClinVar
11-64360237-C-A Inborn genetic diseases Uncertain significance (Sep 16, 2021)2249966
11-64360272-A-G Benign (May 10, 2021)1227675
11-64360289-A-C Inborn genetic diseases Uncertain significance (Jul 13, 2021)2405627
11-64360294-T-G Inborn genetic diseases Uncertain significance (Nov 15, 2021)2226750
11-64360525-A-G Inborn genetic diseases Uncertain significance (Mar 29, 2023)2531242
11-64361727-C-T Inborn genetic diseases Uncertain significance (Apr 19, 2023)2569618
11-64361737-G-C Inborn genetic diseases Uncertain significance (Feb 03, 2022)2275726
11-64361871-C-T Inborn genetic diseases Uncertain significance (Aug 02, 2021)2240126
11-64361883-C-A Inborn genetic diseases Uncertain significance (Jun 27, 2022)2357186
11-64361883-C-T Inborn genetic diseases Uncertain significance (Sep 14, 2021)2249352
11-64361902-C-T Inborn genetic diseases Uncertain significance (Nov 03, 2022)2208846
11-64361919-C-T Inborn genetic diseases Uncertain significance (Jan 26, 2023)2455048
11-64361956-C-T Benign (Jun 21, 2018)787911
11-64365341-C-T Inborn genetic diseases Uncertain significance (Jun 06, 2023)2557969
11-64365370-C-G Inborn genetic diseases Uncertain significance (May 01, 2022)2362162
11-64368484-A-G Inborn genetic diseases Uncertain significance (Apr 22, 2022)2285088
11-64368504-C-T Inborn genetic diseases Uncertain significance (Oct 25, 2022)2310657
11-64368572-G-A Likely benign (Jul 01, 2022)2641923
11-64369458-C-G Inborn genetic diseases Uncertain significance (Nov 15, 2021)2261284
11-64369476-C-T Inborn genetic diseases Uncertain significance (Aug 02, 2021)2240260
11-64369522-G-A Inborn genetic diseases Uncertain significance (Apr 25, 2022)2285408
11-64369577-G-A Inborn genetic diseases Uncertain significance (Jan 06, 2023)2474238
11-64369717-G-A Inborn genetic diseases Uncertain significance (May 09, 2022)2288237
11-64369793-T-C Inborn genetic diseases Uncertain significance (Oct 26, 2022)2320107
11-64369866-C-T Benign (Jun 21, 2018)776621

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RPS6KA4protein_codingprotein_codingENST00000334205 1713068
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9970.002851256880121257000.0000477
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense3.702905290.5480.00003924891
Missense in Polyphen68195.730.347421830
Synonymous1.972042430.8400.00001961622
Loss of Function5.07539.30.1270.00000209406

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0002480.000243
Ashkenazi Jewish0.0002060.000199
East Asian0.00006150.0000544
Finnish0.000.00
European (Non-Finnish)0.00002830.0000264
Middle Eastern0.00006150.0000544
South Asian0.00003270.0000327
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 factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. 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. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide- stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. 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. {ECO:0000269|PubMed:11035004, ECO:0000269|PubMed:12773393, ECO:0000269|PubMed:9792677}.;
Pathway
TNF signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);MAPK Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Insulin Signaling;Interferon type I signaling pathways;Developmental Biology;Recycling pathway of L1;ErbB1 downstream signaling;L1CAM interactions;Axon guidance;Signaling mediated by p38-alpha and p38-beta (Consensus)

Recessive Scores

pRec
0.206

Intolerance Scores

loftool
rvis_EVS
-0.31
rvis_percentile_EVS
32.06

Haploinsufficiency Scores

pHI
0.478
hipred
Y
hipred_score
0.785
ghis
0.530

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
S
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.984

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Rps6ka4
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); hematopoietic system phenotype; immune system 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); homeostasis/metabolism phenotype;

Gene ontology

Biological process
negative regulation of cytokine production;regulation of transcription, DNA-templated;protein phosphorylation;inflammatory response;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;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;cytosol
Molecular function
magnesium ion binding;protein serine/threonine kinase activity;ribosomal protein S6 kinase activity;protein binding;ATP binding