MAP4K3

protein-coding

mitogen-activated protein kinase kinase kinase kinase 3, the group of Mitogen-activated protein kinase kinase kinase kinases

Gene summary

This gene encodes a member of the mitogen-activated protein kinase kinase kinase kinase family. The encoded protein activates key effectors in cell signalling, among them c-Jun. Alternatively spliced transcripts encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

Previous symbols:

RAB8IPL1

MANE transcript

NM_003618.4

Inheritance

—

ClinVar variants

U:121B:6

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr2:39,249,266-39,437,301

External References & Databases

Ensembl (ENSG00000011566)

Transcript & Mutation Effects

hg38 • Region Span ~188.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MAP4K3 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 101

not providedTotal: 4

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

EpendymomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003618.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	2 clinvar		3
missense			106 clinvar	3 clinvar		109
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			13 clinvar	1 clinvar		14
Total	0	0	121	6	0	127

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 50 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003618.4	RefSeq	NP_003609.2	34	MANE Select
ENST00000263881.8	Ensembl	ENSP00000263881.3	34	MANE Select
NM_001270425.2	RefSeq	NP_001257354.1	33	Standard
NM_001410753.1	RefSeq	NP_001397682.1	31	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

MAPK signaling pathway - Homo sapiens (human)
EGF-Core
MAPK Signaling Pathway
Angiopoietin Like Protein 8 Regulatory Pathway
Insulin Signaling

Biological Process

activation of MAPKKK activity
protein phosphorylation
JNK cascade
response to UV
signal transduction by protein phosphorylation

Molecular Function

protein kinase activity
protein serine/threonine kinase activity
protein binding
ATP binding
MAP kinase kinase kinase kinase activity

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263881
Coding exons: 34
Length: 188047
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 125748
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.45	374	461	0.811	0.0000221	5869
Missense (PolyPhen)		147	240.91	0.61019		3070
Synonymous	-1.11	173	155	1.11	0.00000772	1591
Loss of Function	5.54	15	62.1	0.242	0.00000296	787

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.00015	0.00014	rare
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.000034	0.000033	rare
Other	0.00018	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. {ECO:0000269|PubMed:9275185}.;

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.662
RVIS EVS: -0.51
RVIS percentile EVS: 21.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.923

Gene Damage Prediction

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