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
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (22 variants)
- not provided (3 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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 21 | 1 | 22 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice variant | 1 | 1 | ||||
| non coding | 0 | |||||
| Total | 0 | 0 | 22 | 0 | 3 |
Variants in RPS6KA4
This is a list of pathogenic ClinVar variants found in the RPS6KA4 region.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 11-64360237-C-A | Inborn genetic diseases | Uncertain significance (Sep 16, 2021) | ||
| 11-64360272-A-G | Benign (May 10, 2021) | |||
| 11-64360289-A-C | Inborn genetic diseases | Uncertain significance (Jul 13, 2021) | ||
| 11-64360294-T-G | Inborn genetic diseases | Uncertain significance (Nov 15, 2021) | ||
| 11-64360525-A-G | Inborn genetic diseases | Uncertain significance (Mar 29, 2023) | ||
| 11-64361727-C-T | Inborn genetic diseases | Uncertain significance (Apr 19, 2023) | ||
| 11-64361737-G-C | Inborn genetic diseases | Uncertain significance (Feb 03, 2022) | ||
| 11-64361871-C-T | Inborn genetic diseases | Uncertain significance (Aug 02, 2021) | ||
| 11-64361883-C-A | Inborn genetic diseases | Uncertain significance (Jun 27, 2022) | ||
| 11-64361883-C-T | Inborn genetic diseases | Uncertain significance (Sep 14, 2021) | ||
| 11-64361902-C-T | Inborn genetic diseases | Uncertain significance (Nov 03, 2022) | ||
| 11-64361919-C-T | Inborn genetic diseases | Uncertain significance (Jan 26, 2023) | ||
| 11-64361956-C-T | Benign (Jun 21, 2018) | |||
| 11-64365341-C-T | Inborn genetic diseases | Uncertain significance (Jun 06, 2023) | ||
| 11-64365370-C-G | Inborn genetic diseases | Uncertain significance (May 01, 2022) | ||
| 11-64368484-A-G | Inborn genetic diseases | Uncertain significance (Apr 22, 2022) | ||
| 11-64368504-C-T | Inborn genetic diseases | Uncertain significance (Oct 25, 2022) | ||
| 11-64369458-C-G | Inborn genetic diseases | Uncertain significance (Nov 15, 2021) | ||
| 11-64369476-C-T | Inborn genetic diseases | Uncertain significance (Aug 02, 2021) | ||
| 11-64369522-G-A | Inborn genetic diseases | Uncertain significance (Apr 25, 2022) | ||
| 11-64369577-G-A | Inborn genetic diseases | Uncertain significance (Jan 06, 2023) | ||
| 11-64369717-G-A | Inborn genetic diseases | Uncertain significance (May 09, 2022) | ||
| 11-64369793-T-C | Inborn genetic diseases | Uncertain significance (Oct 26, 2022) | ||
| 11-64369866-C-T | Benign (Jun 21, 2018) | |||
| 11-64370333-G-T | Inborn genetic diseases | Uncertain significance (Dec 06, 2022) |
GnomAD
Source:
| 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:
- 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
| 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