MAP4K4

Chr 2q11.2

mitogen-activated protein kinase kinase kinase kinase 4

Aliases:: HGK, NIK, FLH21957
MANE:: ENST00000324219.9

OMIM: 604666 ↗NCBI: 9448 ↗Ensembl ↗

Annotations refreshed 10 hours ago.

Predicted protein structure

AlphaFold predicted structure

MAP4K4 · O95819

v62025-08-01

Predicted Aligned Error matrix for MAP4K4 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

65.5/ 100

Low

1,239 residues

Confidence breakdown

Very high(≥ 90)24%
Confident(70–90)35%
Low(50–70)5%
Very low(< 50)37%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
RASopathies
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

neurodegenerative disease
0.57
hereditary disease
0.53
multiple congenital anomalies/dysmorphic syndrome-intellectual disability
0.50
RASopathy
0.40
asthma
0.38
lysosomal storage disease
0.36
Parkinson disease
0.35
adrenal gland hyperfunction
0.29
early-onset non-syndromic cataract
0.27
imperforate anus
0.27

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Mitogen-activated protein kinase kinase kinase kinase 4

Serine/threonine kinase that plays a role in the response to environmental stress and cytokines such as TNF. Appears to act upstream of the JUN N-terminal pathway (PubMed:9890973). Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). Phosphorylates SMAD1 on Thr-322 (PubMed:21690388)