MAP4K4

mitogen-activated protein kinase kinase kinase kinase 4, the group of Mitogen-activated protein kinase kinase kinase kinases

Basic information

Region (hg38): 2:101696850-101894690

Links

ENSG00000071054 ∙ NCBI:9448 ∙ OMIM:604666 ∙ HGNC:6866 ∙ Uniprot:O95819 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Moderate), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAP4K4 gene.

• Inborn_genetic_diseases (101 variants)
• not_provided (86 variants)
• not_specified (2 variants)
• MAP4K4-related_neurodevelopmental_delay (1 variants)
• Imperforate_anus (1 variants)
• MAP4K4-related_autism_spectrum_disorder (1 variants)
• Renal_dysplasia (1 variants)
• Cerebral_arteriovenous_malformation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAP4K4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001395002.1. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	2	2	6
missense	2	4	134	7		147
nonsense	2		4			6
start loss						0
frameshift	1	2	6			9
splice donor/acceptor (+/-2bp)			5			5
Total	5	6	151	9	2

Highest pathogenic variant AF is 0.00000936938

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAP4K4	protein_coding	protein_coding	ENST00000347699	30	197838

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.10e-7	124644	0	12	124656	0.0000481

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.74	320	664	0.482	0.0000369	8035
Missense in Polyphen		105	235.05	0.44672		2791
Synonymous	0.755	229	244	0.939	0.0000134	2344
Loss of Function	7.29	7	75.3	0.0930	0.00000445	857

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000125	0.000124
Ashkenazi Jewish	0.0000993	0.0000993
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000533	0.0000531
Middle Eastern	0.00	0.00
South Asian	0.0000384	0.0000327
Other	0.000166	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine kinase that may play a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr-322. {ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:9890973}.
• Pathway: MAPK signaling pathway - Homo sapiens (human);EGF-Core;Oxidative Stress Induced Senescence;MAPK Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Insulin Signaling;double stranded rna induced gene expression;cd40l signaling pathway;signal transduction through il1r;tnf/stress related signaling;nf-kb signaling pathway;nfkb activation by nontypeable hemophilus influenzae;keratinocyte differentiation;mapkinase signaling pathway;Oxidative Stress Induced Senescence;Cellular Senescence;Cellular responses to stress;ceramide signaling pathway;Cellular responses to external stimuli;Direct p53 effectors;TNF receptor signaling pathway ;EPHB forward signaling;Ceramide signaling pathway (Consensus)

Recessive Scores

• pRec: 0.226

Intolerance Scores

• loftool: 0.258
• rvis_EVS: -1.44
• rvis_percentile_EVS: 3.95

Haploinsufficiency Scores

• pHI: 0.515
• hipred: Y
• hipred_score: 0.786
• ghis: 0.579

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.961

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Map4k4
• Phenotype: embryo 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); limbs/digits/tail phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: map4k4
• Affected structure: gastrulation
• Phenotype tag: abnormal
• Phenotype quality: disrupted

Gene ontology

• Biological process: MAPK cascade;negative regulation of cell-matrix adhesion;protein phosphorylation;signal transduction by protein phosphorylation;microvillus assembly;positive regulation of cell migration;stress-activated protein kinase signaling cascade;positive regulation of ARF protein signal transduction;activation of protein kinase activity;intracellular signal transduction;negative regulation of apoptotic process;positive regulation of GTPase activity;regulation of JNK cascade;neuron projection morphogenesis;positive regulation of keratinocyte migration;positive regulation of focal adhesion assembly;negative regulation of insulin secretion involved in cellular response to glucose stimulus;negative regulation of neuron projection regeneration;positive regulation of adherens junction organization
• Cellular component: cytoplasm;focal adhesion
• Molecular function: creatine kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;microtubule binding