RPS6KA2

ribosomal protein S6 kinase A2, the group of AGC family kinases|MAPK activated protein kinases|MicroRNA protein coding host genes

Basic information

Region (hg38): 6:166409363-166906451

Links

ENSG00000071242 ∙ NCBI:6196 ∙ OMIM:601685 ∙ HGNC:10431 ∙ Uniprot:Q15349 ∙ 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 RPS6KA2 gene.

• Inborn genetic diseases (17 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RPS6KA2 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				2	1	3
missense			16	1		17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region						0
non coding				1		1
Total	0	1	16	4	1

Variants in RPS6KA2

This is a list of pathogenic ClinVar variants found in the RPS6KA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-166412777-C-G			Benign (Jul 13, 2018)
6-166412782-G-T		not specified	Uncertain significance (Jul 12, 2022)
6-166413793-C-G			Likely pathogenic (Feb 06, 2024)
6-166413816-C-T		not specified	Uncertain significance (May 23, 2023)
6-166413885-G-A		not specified	Uncertain significance (Feb 16, 2023)
6-166413894-T-C		not specified	Uncertain significance (Feb 10, 2022)
6-166418248-C-T		not specified	Uncertain significance (Oct 03, 2022)
6-166418284-C-T		not specified	Uncertain significance (Jun 24, 2022)
6-166419933-G-A		not specified	Uncertain significance (Dec 19, 2022)
6-166423303-C-T		Autism spectrum disorder	association (-)
6-166423304-G-A			Benign/Likely benign (Mar 01, 2023)
6-166430535-C-T		not specified	Likely benign (Aug 17, 2021)
6-166430536-G-A		not specified	Uncertain significance (Jun 02, 2023)
6-166430565-C-T		not specified	Uncertain significance (Sep 17, 2021)
6-166430593-A-C		not specified	Uncertain significance (Jan 10, 2023)
6-166448785-C-A		not specified	Uncertain significance (Oct 17, 2023)
6-166451148-G-A			Likely benign (Mar 01, 2023)
6-166451216-G-A		not specified	Uncertain significance (Dec 06, 2021)
6-166459460-C-T		not specified	Uncertain significance (Nov 07, 2022)
6-166459541-C-T		not specified	Uncertain significance (May 24, 2023)
6-166459545-A-G		not specified	Uncertain significance (Oct 26, 2021)
6-166504534-T-C		not specified	Uncertain significance (Jul 15, 2021)
6-166531281-G-A			Likely benign (Oct 01, 2022)
6-166531288-C-T		not specified	Uncertain significance (Jul 11, 2023)
6-166538733-A-G		not specified	Uncertain significance (Jun 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RPS6KA2	protein_coding	protein_coding	ENST00000503859	22	497088

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00941	0.991	125717	0	31	125748	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.58	310	467	0.664	0.0000298	4836
Missense in Polyphen		85	163.06	0.52128		1670
Synonymous	0.171	195	198	0.985	0.0000140	1430
Loss of Function	4.55	13	46.4	0.280	0.00000265	496

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000335	0.000333
Ashkenazi Jewish	0.00	0.00
East Asian	0.000113	0.000109
Finnish	0.0000953	0.0000924
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.000113	0.000109
South Asian	0.0000673	0.0000653
Other	0.000163	0.000163

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 transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation. May function as tumor suppressor in epithelial ovarian cancer cells. {ECO:0000269|PubMed:16878154, ECO:0000269|PubMed:7623830}.
• 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);Prolactin Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;EGF-EGFR Signaling Pathway;Cytoplasmic Ribosomal Proteins;Insulin Signaling;Developmental Biology;Signaling by GPCR;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Signal Transduction;Recycling pathway of L1;Signaling by Interleukins;Prolactin;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;Nuclear Events (kinase and transcription factor activation);Neuronal System;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;MyD88 dependent cascade initiated on endosome;JAK STAT pathway and regulation;EPO signaling;L1CAM interactions;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Axon guidance;Leptin;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 (Consensus)

Recessive Scores

• pRec: 0.120

Intolerance Scores

• rvis_EVS: -1.02
• rvis_percentile_EVS: 8.14

Haploinsufficiency Scores

• pHI: 0.623
• hipred: Y
• hipred_score: 0.706
• ghis: 0.519

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.960

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rps6ka2
• Phenotype: muscle phenotype; homeostasis/metabolism 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)

Gene ontology

• Biological process: protein phosphorylation;signal transduction;negative regulation of cell population proliferation;intracellular signal transduction;positive regulation of apoptotic process;negative regulation of cell cycle
• Cellular component: nucleus;nucleoplasm;cytoplasm;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