MAP4K1
protein-codingmitogen-activated protein kinase kinase kinase kinase 1, the group of Mitogen-activated protein kinase kinase kinase kinases
Gene summary
Enables ATP binding activity and MAP kinase kinase kinase kinase activity. Involved in several processes, including JNK cascade; cellular response to phorbol 13-acetate 12-myristate; and protein phosphorylation. Located in membrane. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~31.2 kbGenCC 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 MAP4K1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001042600.3. 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 | 2 | 4 | 6 | |||
| missense | 74 | 3 | 77 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 81 | 7 | 0 | 88 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001036065.1 | 31 | MANE Select | |
| Ensembl | ENSP00000380066.1 | 31 | MANE Select | |
| RefSeq | NP_009112.1 | 32 | Standard | |
| Ensembl | ENSP00000468396.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- MAPK signaling pathway - Homo sapiens (human)
- EGF-Core
- Androgen Receptor Network in Prostate Cancer
- B Cell Receptor Signaling Pathway
- Cardiac Hypertrophic Response
Biological Process
- activation of MAPKKK activity
- protein phosphorylation
- activation of JUN kinase activity
- cell population proliferation
- peptidyl-serine phosphorylation
Molecular Function
- protein kinase activity
- protein serine/threonine kinase activity
- protein binding
- ATP binding
- MAP kinase kinase kinase kinase activity
Cellular Component
- cytoplasm
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000591517
- Coding exons
- 32
- Length
- 31242
- Individuals with no LoFs
- 124783
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 30
- Defined
- 124813
- p
- 0.000120
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.13 | 279 | 470 | 0.594 | 0.0000277 | 5316 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00092 | 0.00090 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00019 | 0.00019 | rare |
| European (Non-Finnish) | 0.000071 | 0.000062 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- 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}.;
Intolerance Scores
- LoFtool
- 0.542
- RVIS EVS
- -0.56
- RVIS percentile EVS
- 19.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.854
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |