MKNK2

MAPK interacting serine/threonine kinase 2, the group of MAPK activated protein kinases

Basic information

Region (hg38): 19:2037465-2051244

Previous symbols: [ "GPRK7" ]

Links

ENSG00000099875 ∙ NCBI:2872 ∙ OMIM:605069 ∙ HGNC:7111 ∙ Uniprot:Q9HBH9 ∙ 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 MKNK2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MKNK2 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			31	1		32
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	31	1	0

Variants in MKNK2

This is a list of pathogenic ClinVar variants found in the MKNK2 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-2039618-C-T		not specified	Uncertain significance (Oct 09, 2024)
19-2039623-T-A		not specified	Uncertain significance (Jun 28, 2022)
19-2039672-G-A		not specified	Uncertain significance (Dec 09, 2024)
19-2039677-G-A		not specified	Uncertain significance (Feb 28, 2024)
19-2039738-C-T		not specified	Uncertain significance (Aug 12, 2024)
19-2039755-G-A		not specified	Uncertain significance (Aug 08, 2023)
19-2039755-G-T		not specified	Uncertain significance (Jan 24, 2025)
19-2039853-G-A			Likely benign (Feb 01, 2025)
19-2040143-A-G		not specified	Uncertain significance (Oct 27, 2023)
19-2040156-G-C		not specified	Uncertain significance (May 22, 2023)
19-2040173-G-A		not specified	Uncertain significance (Nov 09, 2024)
19-2040174-C-T		not specified	Uncertain significance (Feb 26, 2025)
19-2041063-G-C		not specified	Uncertain significance (Feb 18, 2025)
19-2041144-G-A		not specified	Uncertain significance (Jan 29, 2025)
19-2042024-G-A		not specified	Uncertain significance (Jan 09, 2024)
19-2042041-G-A			Benign (Jun 14, 2018)
19-2042471-T-G		not specified	Uncertain significance (Nov 17, 2022)
19-2042841-G-A		not specified	Uncertain significance (Nov 29, 2023)
19-2042850-G-C		not specified	Uncertain significance (Mar 03, 2022)
19-2042861-A-G		not specified	Uncertain significance (Jan 10, 2023)
19-2043537-C-T		not specified	Uncertain significance (Aug 08, 2023)
19-2043543-A-G		not specified	Uncertain significance (Apr 13, 2022)
19-2043555-G-A		not specified	Uncertain significance (Oct 29, 2024)
19-2046223-C-T		not specified	Uncertain significance (Mar 15, 2024)
19-2046393-G-A		not specified	Uncertain significance (Oct 06, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MKNK2	protein_coding	protein_coding	ENST00000250896	13	13774

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000140	0.992	125697	0	50	125747	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.885	232	273	0.849	0.0000168	2992
Missense in Polyphen		76	92.399	0.82252		946
Synonymous	-2.29	147	116	1.27	0.00000798	859
Loss of Function	2.35	12	24.6	0.488	0.00000122	279

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000607	0.000604
Ashkenazi Jewish	0.000233	0.000198
East Asian	0.000164	0.000163
Finnish	0.0000993	0.0000924
European (Non-Finnish)	0.000121	0.000114
Middle Eastern	0.000164	0.000163
South Asian	0.000103	0.0000980
Other	0.00136	0.00130

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal. {ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11463832, ECO:0000269|PubMed:12897141, ECO:0000269|PubMed:16111636, ECO:0000269|PubMed:17965020, ECO:0000269|PubMed:18299328, ECO:0000269|PubMed:20823271, ECO:0000269|PubMed:20927323, ECO:0000269|PubMed:21149447}.
• Pathway: HIF-1 signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);EGF-Core;Structural Pathway of Interleukin 1 (IL-1);MAPK Signaling Pathway;4-hydroxytamoxifen, Dexamethasone, and Retinoic Acids Regulation of p27 Expression;erk1/erk2 mapk signaling pathway (Consensus)

Recessive Scores

• pRec: 0.148

Intolerance Scores

• loftool: 0.735
• rvis_EVS: -0.58
• rvis_percentile_EVS: 18.78

Haploinsufficiency Scores

• pHI: 0.181
• hipred: Y
• hipred_score: 0.564
• ghis: 0.568

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mknk2
• Phenotype: normal phenotype

Gene ontology

• Biological process: regulation of translation;protein phosphorylation;cell surface receptor signaling pathway;peptidyl-serine phosphorylation;hemopoiesis;intracellular signal transduction;protein autophosphorylation;cellular response to arsenic-containing substance;extrinsic apoptotic signaling pathway in absence of ligand
• Cellular component: nucleus;nucleoplasm;cytoplasm;nuclear body;PML body
• Molecular function: protein serine/threonine kinase activity;calmodulin-dependent protein kinase activity;protein binding;calmodulin binding;ATP binding;calcium-dependent protein serine/threonine kinase activity;metal ion binding