MAP4K1

mitogen-activated protein kinase kinase kinase kinase 1, the group of Mitogen-activated protein kinase kinase kinase kinases

Basic information

Region (hg38): 19:38587641-38618882

Links

ENSG00000104814 ∙ NCBI:11184 ∙ OMIM:601983 ∙ HGNC:6863 ∙ Uniprot:Q92918 ∙ 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 MAP4K1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAP4K1 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				3		3
missense			26	1		27
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	26	5	0

Variants in MAP4K1

This is a list of pathogenic ClinVar variants found in the MAP4K1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-38587707-G-C			Likely benign (Jul 07, 2018)
19-38587810-C-T		not specified	Likely benign (Dec 19, 2023)
19-38593286-G-C		not specified	Uncertain significance (Dec 13, 2023)
19-38593306-G-A		not specified	Uncertain significance (Apr 18, 2023)
19-38593312-G-T		not specified	Uncertain significance (Jan 26, 2022)
19-38595489-T-A		not specified	Uncertain significance (Mar 29, 2023)
19-38595698-G-T			Likely benign (Mar 01, 2024)
19-38595707-C-A			Likely benign (Mar 01, 2024)
19-38596318-T-G		not specified	Uncertain significance (Nov 06, 2023)
19-38596425-G-C		not specified	Uncertain significance (Feb 15, 2023)
19-38596446-G-C		not specified	Uncertain significance (Mar 16, 2022)
19-38597090-T-C		not specified	Uncertain significance (Dec 01, 2022)
19-38597337-G-A		not specified	Uncertain significance (Dec 07, 2021)
19-38597522-G-A		not specified	Uncertain significance (Jan 02, 2024)
19-38600087-G-A		not specified	Uncertain significance (May 05, 2023)
19-38600149-C-A		not specified	Uncertain significance (Apr 07, 2023)
19-38601483-G-A		not specified	Uncertain significance (Jul 17, 2023)
19-38605576-G-A		not specified	Uncertain significance (Sep 01, 2021)
19-38605586-G-A		not specified	Uncertain significance (Apr 09, 2022)
19-38605610-G-A		not specified	Uncertain significance (Apr 20, 2024)
19-38605651-C-T		not specified	Uncertain significance (Feb 16, 2023)
19-38605690-A-T		not specified	Uncertain significance (Nov 29, 2023)
19-38605721-G-A		not specified	Uncertain significance (Dec 06, 2021)
19-38607886-C-T		not specified	Uncertain significance (Dec 27, 2022)
19-38607890-A-T			Likely benign (Mar 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAP4K1	protein_coding	protein_coding	ENST00000591517	32	31242

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.989	0.0108	124783	0	30	124813	0.000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.13	279	470	0.594	0.0000277	5316
Missense in Polyphen		75	180.91	0.41456		2037
Synonymous	0.0775	190	191	0.993	0.0000118	1688
Loss of Function	5.62	9	53.3	0.169	0.00000279	606

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000978	0.000961
Ashkenazi Jewish	0.000100	0.0000993
East Asian	0.00	0.00
Finnish	0.000186	0.000186
European (Non-Finnish)	0.0000707	0.0000618
Middle Eastern	0.00	0.00
South Asian	0.0000332	0.0000327
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine-protein kinase, which may play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. May play a role in hematopoietic lineage decisions and growth regulation. Able to autophosphorylate. {ECO:0000269|PubMed:24362026, ECO:0000269|PubMed:8824585}.
• Pathway: MAPK signaling pathway - Homo sapiens (human);EGF-Core;Androgen Receptor Network in Prostate Cancer;B Cell Receptor Signaling Pathway;Cardiac Hypertrophic Response;Signaling of Hepatocyte Growth Factor Receptor;TGF-beta Signaling Pathway;MAPK Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;EGF-EGFR Signaling Pathway;Insulin Signaling;T-Cell antigen Receptor (TCR) Signaling Pathway;mapkinase signaling pathway;TCR;TGF_beta_Receptor;BCR signaling pathway;Signaling events mediated by Stem cell factor receptor (c-Kit);JNK signaling in the CD4+ TCR pathway;TCR signaling in naïve CD4+ T cells (Consensus)

Intolerance Scores

• loftool: 0.542
• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.73

Haploinsufficiency Scores

• pHI: 0.745
• hipred: Y
• hipred_score: 0.694
• ghis: 0.554

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.854

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Map4k1
• Phenotype: hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: activation of MAPKKK activity;protein phosphorylation;activation of JUN kinase activity;cell population proliferation;peptidyl-serine phosphorylation;signal transduction by protein phosphorylation;stress-activated protein kinase signaling cascade;activation of protein kinase activity;protein autophosphorylation;cellular response to phorbol 13-acetate 12-myristate
• Cellular component: cytoplasm;membrane
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;MAP kinase kinase kinase kinase activity