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

ENSG00000162302 ∙ NCBI:8986 ∙ OMIM:603606 ∙ HGNC:10433 ∙ Uniprot:O75676 ∙ 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 RPS6KA4 gene.

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	2	5
missense			40		1	41
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	40	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
11-64359256-T-G		not specified	Uncertain significance (Dec 20, 2023)
11-64360237-C-A		not specified	Uncertain significance (Sep 16, 2021)
11-64360272-A-G			Benign (May 10, 2021)
11-64360289-A-C		not specified	Uncertain significance (Jul 13, 2021)
11-64360294-T-G		not specified	Uncertain significance (Nov 15, 2021)
11-64360525-A-G		not specified	Uncertain significance (Mar 29, 2023)
11-64360590-A-G		not specified	Uncertain significance (Jan 08, 2024)
11-64361727-C-T		not specified	Uncertain significance (Apr 19, 2023)
11-64361737-G-C		not specified	Uncertain significance (Feb 03, 2022)
11-64361852-A-G		not specified	Likely benign (Sep 22, 2023)
11-64361871-C-T		not specified	Uncertain significance (Aug 02, 2021)
11-64361883-C-A		not specified	Uncertain significance (Jun 27, 2022)
11-64361883-C-G		not specified	Uncertain significance (Dec 13, 2023)
11-64361883-C-T		not specified	Uncertain significance (Sep 14, 2021)
11-64361902-C-T		not specified	Uncertain significance (Nov 03, 2022)
11-64361919-C-T		not specified	Uncertain significance (Jan 26, 2023)
11-64361956-C-T			Benign (Jun 21, 2018)
11-64361983-G-A		not specified	Uncertain significance (Mar 07, 2024)
11-64365341-C-T		not specified	Uncertain significance (Jun 06, 2023)
11-64365370-C-G		not specified	Uncertain significance (May 01, 2022)
11-64368187-C-T		not specified	Uncertain significance (Nov 13, 2023)
11-64368484-A-G		not specified	Uncertain significance (Apr 22, 2022)
11-64368504-C-T		not specified	Uncertain significance (Oct 25, 2022)
11-64368550-G-T		not specified	Uncertain significance (Jan 23, 2024)
11-64368572-G-A			Likely benign (Jul 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RPS6KA4	protein_coding	protein_coding	ENST00000334205	17	13068

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00285	125688	0	12	125700	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.70	290	529	0.548	0.0000392	4891
Missense in Polyphen		68	195.73	0.34742		1830
Synonymous	1.97	204	243	0.840	0.0000196	1622
Loss of Function	5.07	5	39.3	0.127	0.00000209	406

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000248	0.000243
Ashkenazi Jewish	0.000206	0.000199
East Asian	0.0000615	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000283	0.0000264
Middle Eastern	0.0000615	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

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

• 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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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