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

ENSG00000117676 ∙ NCBI:6195 ∙ OMIM:601684 ∙ HGNC:10430 ∙ Uniprot:Q15418 ∙ 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 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			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
1-26536962-C-T		not specified	Likely benign (Dec 18, 2023)
1-26536963-G-A		not specified	Likely benign (Jan 19, 2024)
1-26545931-C-T		not specified	Uncertain significance (Nov 21, 2022)
1-26546028-G-A		not specified	Likely benign (Mar 05, 2024)
1-26551408-G-A		not specified	Uncertain significance (Dec 27, 2022)
1-26551689-G-A		not specified	Uncertain significance (May 03, 2023)
1-26551709-C-T		not specified	Uncertain significance (Mar 01, 2023)
1-26553391-G-A		not specified	Uncertain significance (Feb 01, 2023)
1-26554632-A-G		not specified	Uncertain significance (Dec 06, 2022)
1-26554682-G-A		not specified	Uncertain significance (Nov 09, 2021)
1-26554695-G-A		not specified	Uncertain significance (Jan 24, 2024)
1-26554706-A-T		not specified	Uncertain significance (Jan 02, 2024)
1-26555153-T-G		not specified	Uncertain significance (Aug 04, 2023)
1-26558866-G-A		not specified	Uncertain significance (May 04, 2023)
1-26558893-G-A		not specified	Uncertain significance (Feb 09, 2023)
1-26558909-C-T		not specified	Uncertain significance (Sep 01, 2021)
1-26560759-G-A		not specified	Uncertain significance (Mar 07, 2023)
1-26560786-G-T		not specified	Uncertain significance (Oct 12, 2022)
1-26561532-C-A		not specified	Uncertain significance (Jul 05, 2023)
1-26561580-C-T		not specified	Uncertain significance (Aug 13, 2021)
1-26561602-G-A		not specified	Uncertain significance (Dec 21, 2022)
1-26571504-A-T		not specified	Uncertain significance (Dec 27, 2023)
1-26571913-C-T		not specified	Uncertain significance (Nov 30, 2021)
1-26572205-A-G		not specified	Uncertain significance (May 03, 2023)
1-26573248-G-A		not specified	Uncertain significance (Jun 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RPS6KA1	protein_coding	protein_coding	ENST00000531382	21	45270

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00191	0.998	125720	0	28	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.99	279	460	0.607	0.0000286	4829
Missense in Polyphen		69	160.34	0.43033		1743
Synonymous	0.479	179	187	0.955	0.0000114	1498
Loss of Function	3.88	12	37.7	0.318	0.00000160	462

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000296	0.000296
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000330	0.000277
European (Non-Finnish)	0.000102	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

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

• 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

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

Mouse Genome Informatics

• Gene name: Rps6ka1

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