MAP4K2

mitogen-activated protein kinase kinase kinase kinase 2, the group of Mitogen-activated protein kinase kinase kinase kinases

Basic information

Region (hg38): 11:64784918-64803241

Previous symbols: [ "RAB8IP" ]

Links

ENSG00000168067 ∙ NCBI:5871 ∙ OMIM:603166 ∙ HGNC:6864 ∙ Uniprot:Q12851 ∙ 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 MAP4K2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAP4K2 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					2	2
missense			48		2	50
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	48	0	4

Variants in MAP4K2

This is a list of pathogenic ClinVar variants found in the MAP4K2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-64789547-C-T		not specified	Uncertain significance (Apr 11, 2023)
11-64789559-G-A		not specified	Uncertain significance (Oct 09, 2024)
11-64789579-G-C		not specified	Uncertain significance (May 18, 2023)
11-64789582-C-T			Benign (May 18, 2018)
11-64789736-G-T		not specified	Uncertain significance (Nov 07, 2024)
11-64789948-C-T		not specified	Uncertain significance (Feb 21, 2024)
11-64790230-G-C		not specified	Uncertain significance (May 24, 2023)
11-64790411-A-G		not specified	Uncertain significance (Aug 03, 2022)
11-64791918-T-G		not specified	Uncertain significance (Oct 03, 2023)
11-64791932-G-A		not specified	Uncertain significance (Feb 06, 2024)
11-64791956-A-G		not specified	Uncertain significance (Apr 28, 2023)
11-64791969-C-T		not specified	Uncertain significance (Feb 06, 2024)
11-64791972-G-A		not specified	Uncertain significance (Jun 03, 2022)
11-64791978-C-T		not specified	Uncertain significance (Sep 16, 2021)
11-64792044-G-A		not specified	Uncertain significance (Mar 23, 2022)
11-64792080-A-G		not specified	Uncertain significance (Nov 09, 2023)
11-64792197-G-A		not specified	Uncertain significance (Mar 01, 2023)
11-64792268-G-A			Benign (Mar 05, 2018)
11-64792369-C-T		not specified	Uncertain significance (Nov 09, 2021)
11-64796285-C-T			Benign (May 18, 2018)
11-64796286-G-A		not specified	Uncertain significance (Apr 29, 2024)
11-64796297-C-T		not specified	Uncertain significance (Jul 12, 2022)
11-64796300-T-C		not specified	Uncertain significance (Jan 03, 2024)
11-64796313-A-C		not specified	Uncertain significance (Jun 16, 2024)
11-64796360-A-G		not specified	Uncertain significance (Jul 10, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAP4K2	protein_coding	protein_coding	ENST00000294066	32	14424

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.54e-11	1.00	125652	0	96	125748	0.000382

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.60	370	468	0.791	0.0000271	5223
Missense in Polyphen		58	102.64	0.56507		1241
Synonymous	-1.33	225	201	1.12	0.0000124	1649
Loss of Function	3.41	27	54.0	0.500	0.00000267	590

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000763	0.000763
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000218	0.000217
Finnish	0.000555	0.000554
European (Non-Finnish)	0.000408	0.000396
Middle Eastern	0.000218	0.000217
South Asian	0.000199	0.000196
Other	0.000342	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extent of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Mediates also the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion. {ECO:0000269|PubMed:11784851, ECO:0000269|PubMed:15456887, ECO:0000269|PubMed:17584736, ECO:0000269|PubMed:7477268, ECO:0000269|PubMed:7515885, ECO:0000269|PubMed:9712898}.
• Pathway: MAPK signaling pathway - Homo sapiens (human);EGF-Core;TNF alpha Signaling Pathway;MAPK Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Insulin Signaling;tnf/stress related signaling;IL-7 signaling;role of mal in rho-mediated activation of srf;JAK STAT pathway and regulation;EPO signaling;TNFalpha;VEGF;TNF receptor signaling pathway (Consensus)

Recessive Scores

• pRec: 0.742

Intolerance Scores

• loftool: 0.744
• rvis_EVS: -1.04
• rvis_percentile_EVS: 7.83

Haploinsufficiency Scores

• pHI: 0.177
• hipred: Y
• hipred_score: 0.695
• ghis: 0.543

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Map4k2

Gene ontology

• Biological process: activation of MAPKKK activity;protein phosphorylation;vesicle targeting;immune response;JNK cascade;activation of JUN kinase activity;signal transduction by protein phosphorylation;stress-activated protein kinase signaling cascade;activation of protein kinase activity;intracellular signal transduction;innate immune response;positive regulation of JNK cascade
• Cellular component: Golgi membrane;cytoplasm;basolateral plasma membrane
• Molecular function: protein serine/threonine kinase activity;protein binding;ATP binding;MAP kinase kinase kinase kinase activity;mitogen-activated protein kinase kinase kinase binding