MAPK15

mitogen-activated protein kinase 15, the group of Mitogen-activated protein kinases

Basic information

Region (hg38): 8:143716340-143722458

Links

ENSG00000181085 ∙ NCBI:225689 ∙ OMIM:618616 ∙ HGNC:24667 ∙ Uniprot:Q8TD08 ∙ 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 MAPK15 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAPK15 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			50	3	1	54
nonsense				1		1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	50	4	1

Variants in MAPK15

This is a list of pathogenic ClinVar variants found in the MAPK15 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-143716441-G-A		not specified	Uncertain significance (Mar 24, 2023)
8-143717733-G-A			Likely benign (Nov 01, 2022)
8-143717742-G-A		not specified	Uncertain significance (Jul 06, 2021)
8-143717746-C-T		not specified	Uncertain significance (Mar 04, 2024)
8-143717754-A-G		not specified	Uncertain significance (May 01, 2024)
8-143718047-A-C		not specified	Likely benign (May 26, 2024)
8-143718068-C-A		not specified	Uncertain significance (May 01, 2024)
8-143718251-G-C		not specified	Uncertain significance (Aug 16, 2022)
8-143718267-A-C		not specified	Uncertain significance (Oct 05, 2021)
8-143718784-T-C		not specified	Uncertain significance (Dec 02, 2022)
8-143718793-T-C		not specified	Uncertain significance (Sep 17, 2021)
8-143718799-G-A		not specified	Uncertain significance (Jun 22, 2021)
8-143718807-G-A		not specified	Uncertain significance (Apr 20, 2023)
8-143718828-G-A		not specified	Uncertain significance (Sep 16, 2021)
8-143718832-G-C		not specified	Uncertain significance (Aug 05, 2023)
8-143718846-C-A		not specified	Uncertain significance (Jul 26, 2022)
8-143718856-G-A		not specified	Likely benign (Feb 27, 2024)
8-143718894-C-G		not specified	Uncertain significance (Feb 03, 2022)
8-143718895-G-C		not specified	Uncertain significance (Apr 04, 2023)
8-143719026-G-C		not specified	Uncertain significance (Jan 22, 2024)
8-143719060-T-A		not specified	Uncertain significance (Feb 13, 2024)
8-143719071-C-G		not specified	Uncertain significance (May 14, 2024)
8-143719110-G-A		not specified	Uncertain significance (Apr 15, 2024)
8-143719150-C-A			Likely benign (Dec 31, 2019)
8-143719362-A-G		not specified	Uncertain significance (Mar 15, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAPK15	protein_coding	protein_coding	ENST00000338033	14	6200

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.87e-21	0.000420	125518	0	224	125742	0.000891

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.35	415	345	1.20	0.0000226	3415
Missense in Polyphen		149	131.66	1.1317		1398
Synonymous	-0.170	156	153	1.02	0.0000104	1194
Loss of Function	-0.534	30	27.0	1.11	0.00000157	271

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00411	0.00398
Ashkenazi Jewish	0.00	0.00
East Asian	0.00169	0.00163
Finnish	0.0000970	0.0000924
European (Non-Finnish)	0.000750	0.000721
Middle Eastern	0.00169	0.00163
South Asian	0.000758	0.000752
Other	0.00162	0.00147

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Atypical MAPK protein that regulates several process such as autophagy, ciliogenesis, protein trafficking/secretion and genome integrity, in a kinase activity-dependent manner (PubMed:22948227, PubMed:24618899, PubMed:29021280, PubMed:21847093, PubMed:20733054). Controls both, basal and starvation-induced autophagy throught its interaction with GABARAP, MAP1LC3B and GABARAPL1 leading to autophagosome formation, SQSTM1 degradation and reduced MAP1LC3B inhibitory phosphorylation (PubMed:22948227). Regulates primary cilium formation and the localization of ciliary proteins involved in cilium structure, transport, and signaling (PubMed:29021280). Prevents the relocation of the sugar-adding enzymes from the Golgi to the endoplasmic reticulum, thereby restricting the production of sugar-coated proteins (PubMed:24618899). Upon amino-acid starvation, mediates transitional endoplasmic reticulum site disassembly and inhibition of secretion (PubMed:21847093). Binds to chromatin leading to MAPK15 activation and interaction with PCNA, that which protects genomic integrity by inhibiting MDM2- mediated degradation of PCNA (PubMed:20733054). Regulates DA transporter (DAT) activity and protein expression via activation of RhoA (PubMed:28842414). In response to H(2)O(2) treatment phosphorylates ELAVL1, thus preventing it from binding to the PDCD4 3'UTR and rendering the PDCD4 mRNA accessible to miR-21 and leading to its degradation and loss of protein expression (PubMed:26595526). Also functions in a kinase activity-independent manner as a negative regulator of growth (By similarity). Phosphorylates in vitro FOS and MBP (PubMed:11875070, PubMed:16484222, PubMed:20638370, PubMed:19166846). During oocyte maturation, plays a key role in the microtubule organization and meiotic cell cycle progression in oocytes, fertilized eggs, and early embryos (By similarity). Interacts with ESRRA promoting its re-localization from the nucleus to the cytoplasm and then prevents its transcriptional activity (PubMed:21190936). {ECO:0000250|UniProtKB:Q80Y86, ECO:0000250|UniProtKB:Q9Z2A6, ECO:0000269|PubMed:11875070, ECO:0000269|PubMed:16484222, ECO:0000269|PubMed:19166846, ECO:0000269|PubMed:20638370, ECO:0000269|PubMed:20733054, ECO:0000269|PubMed:21190936, ECO:0000269|PubMed:21847093, ECO:0000269|PubMed:22948227, ECO:0000269|PubMed:24618899, ECO:0000269|PubMed:26595526, ECO:0000269|PubMed:28842414, ECO:0000269|PubMed:29021280}.
• Pathway: IL-17 signaling pathway - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.178

Intolerance Scores

• loftool: 0.938
• rvis_EVS: 0.57
• rvis_percentile_EVS: 81.73

Haploinsufficiency Scores

• pHI: 0.157
• hipred: N
• hipred_score: 0.439
• ghis: 0.453

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.940

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mapk15

Gene ontology

• Biological process: MAPK cascade;regulation of COPII vesicle coating;cellular response to DNA damage stimulus;endoplasmic reticulum organization;positive regulation of cell population proliferation;regulation of gene expression;regulation of autophagy;negative regulation of cell migration;positive regulation of telomere maintenance via telomerase;intracellular signal transduction;protein autophosphorylation;positive regulation of telomerase activity;dopamine uptake;regulation of cilium assembly;positive regulation of telomere capping;protein localization to ciliary transition zone;positive regulation of metaphase/anaphase transition of meiosis I;positive regulation of spindle assembly
• Cellular component: extracellular region;nucleus;cytoplasm;autophagosome;Golgi apparatus;centriole;cell-cell junction;bicellular tight junction;axoneme;cytoplasmic vesicle;ciliary basal body;meiotic spindle
• Molecular function: chromatin binding;protein kinase activity;MAP kinase activity;protein binding;ATP binding;kinase activity;SH3 domain binding