MAPKAPK5
MAPK activated protein kinase 5, the group of MAPK activated protein kinases
Basic information
Region (hg38): 12:111842013-111902222
Links
Phenotypes
GenCC
Source:
- neurocardiofaciodigital syndrome (Limited), mode of inheritance: AR
- neurocardiofaciodigital syndrome (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Neurocardiofaciodigital syndrome | AR | Audiologic/Otolaryngologic; Cardiovascular | Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; The condition can involve congenital cardiac anomalies, and awareness may allow early management | Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic | 33442026; 35575217; 36581449 |
ClinVar
This is a list of variants' phenotypes submitted to
- Neurocardiofaciodigital syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAPKAPK5 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 | 17 | 18 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 1 | 0 | 17 | 1 | 0 |
Variants in MAPKAPK5
This is a list of pathogenic ClinVar variants found in the MAPKAPK5 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 12-111842743-G-A | not specified | Uncertain significance (Oct 17, 2023) | ||
| 12-111842750-A-G | not specified | Uncertain significance (Jun 09, 2022) | ||
| 12-111842764-A-G | not specified | Uncertain significance (Dec 27, 2022) | ||
| 12-111866184-C-T | not specified | Uncertain significance (Nov 16, 2021) | ||
| 12-111866217-A-C | not specified | Uncertain significance (Nov 17, 2022) | ||
| 12-111867587-A-ATG | Neurocardiofaciodigital syndrome | Pathogenic (May 04, 2022) | ||
| 12-111868788-G-T | Neurocardiofaciodigital syndrome | Pathogenic (Aug 16, 2023) | ||
| 12-111870287-G-A | not specified | Likely benign (Oct 25, 2022) | ||
| 12-111870322-C-T | not specified | Uncertain significance (Dec 13, 2021) | ||
| 12-111871102-G-C | not specified | Uncertain significance (Apr 12, 2023) | ||
| 12-111880457-C-T | Syndromic disease | Uncertain significance (Jun 24, 2022) | ||
| 12-111880484-C-A | not specified | Uncertain significance (Nov 15, 2023) | ||
| 12-111880505-C-T | not specified | Uncertain significance (Oct 12, 2021) | ||
| 12-111880508-C-T | not specified | Uncertain significance (Nov 28, 2023) | ||
| 12-111883589-CT-C | Neurocardiofaciodigital syndrome | Pathogenic (Aug 16, 2023) | ||
| 12-111886011-C-T | not specified | Uncertain significance (May 12, 2024) | ||
| 12-111886029-T-C | not specified | Uncertain significance (Oct 27, 2023) | ||
| 12-111888523-A-C | not specified | Uncertain significance (Jun 16, 2023) | ||
| 12-111888535-C-G | not specified | Uncertain significance (Dec 13, 2023) | ||
| 12-111888593-A-AT | Neurocardiofaciodigital syndrome | Pathogenic (Sep 22, 2022) | ||
| 12-111888934-G-A | not specified | Uncertain significance (Jul 28, 2021) | ||
| 12-111888964-C-T | Neurocardiofaciodigital syndrome | Pathogenic (May 19, 2023) | ||
| 12-111890126-C-T | Neurocardiofaciodigital syndrome | Pathogenic (Aug 16, 2023) | ||
| 12-111892969-C-T | not specified | Uncertain significance (Sep 29, 2022) | ||
| 12-111893050-G-A | Uncertain significance (Aug 26, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MAPKAPK5 | protein_coding | protein_coding | ENST00000551404 | 14 | 54562 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.354 | 0.646 | 124643 | 0 | 12 | 124655 | 0.0000481 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.42 | 144 | 252 | 0.571 | 0.0000132 | 3108 |
| Missense in Polyphen | 29 | 77.894 | 0.3723 | 995 | ||
| Synonymous | 0.825 | 85 | 95.2 | 0.893 | 0.00000538 | 852 |
| Loss of Function | 3.68 | 6 | 26.4 | 0.227 | 0.00000124 | 332 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000960 | 0.0000936 |
| Ashkenazi Jewish | 0.000105 | 0.0000993 |
| East Asian | 0.0000579 | 0.0000556 |
| Finnish | 0.0000464 | 0.0000464 |
| European (Non-Finnish) | 0.0000376 | 0.0000354 |
| Middle Eastern | 0.0000579 | 0.0000556 |
| South Asian | 0.0000654 | 0.0000654 |
| Other | 0.000165 | 0.000165 |
dbNSFP
Source:
- Function
- FUNCTION: Tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras- induced senescence and phosphorylating p53/TP53. Involved in post- transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement. {ECO:0000269|PubMed:17254968, ECO:0000269|PubMed:17728103, ECO:0000269|PubMed:19166925, ECO:0000269|PubMed:21329882, ECO:0000269|PubMed:9628874}.;
- Pathway
- MAPK signaling pathway - Homo sapiens (human);EGF-Core;MAPK6-MAPK4 signaling;MAPK Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;p38 MAPK Signaling Pathway;Signal Transduction;Gene expression (Transcription);p38 mapk signaling pathway;Generic Transcription Pathway;Oxidative Stress Induced Senescence;MAPK6/MAPK4 signaling;Cellular Senescence;Cellular responses to stress;RNA Polymerase II Transcription;Cellular responses to external stimuli;IL-7 signaling;MAPK family signaling cascades;JAK STAT pathway and regulation;EPO signaling;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;VEGF;Signaling mediated by p38-alpha and p38-beta
(Consensus)
Recessive Scores
- pRec
- 0.138
Intolerance Scores
- loftool
- 0.702
- rvis_EVS
- -0.63
- rvis_percentile_EVS
- 17.03
Haploinsufficiency Scores
- pHI
- 0.521
- hipred
- Y
- hipred_score
- 0.740
- ghis
- 0.678
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.891
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Mapkapk5
- 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); normal phenotype; neoplasm; cellular 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);
Gene ontology
- Biological process
- MAPK cascade;activation of MAPK activity;regulation of translation;signal transduction;Ras protein signal transduction;peptidyl-serine phosphorylation;negative regulation of TOR signaling;positive regulation of telomere maintenance via telomerase;intracellular signal transduction;protein autophosphorylation;positive regulation of telomerase activity;stress-induced premature senescence;regulation of signal transduction by p53 class mediator;positive regulation of telomere capping
- Cellular component
- nucleus;nucleoplasm;cytoplasm;cytosol
- Molecular function
- p53 binding;protein serine/threonine kinase activity;calmodulin-dependent protein kinase activity;MAP kinase kinase activity;protein binding;calmodulin binding;ATP binding;calcium-dependent protein serine/threonine kinase activity;mitogen-activated protein kinase binding