KSR2

Chr 12q24.22-q24.23

kinase suppressor of ras 2

Aliases:: FLJ25965
MANE:: ENST00000339824.7

OMIM: 610737 ↗NCBI: 283455 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

KSR2 · Q6VAB6

v62025-08-01

Predicted Aligned Error matrix for KSR2 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

60.8/ 100

Low

950 residues

Confidence breakdown

Very high(≥ 90)20%
Confident(70–90)26%
Low(50–70)5%
Very low(< 50)49%

Open interactive 3D viewer

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

Clinical relevance (Genomics England PanelApp)

Moderate Evidence (Amber)

Severe early-onset obesity
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Disease associations (Open Targets)

cancer
0.59
hypertrophic cardiomyopathy
0.57
Noonan syndrome
0.53
type 2 diabetes mellitus
0.52
Costello syndrome
0.50
diabetes mellitus
0.41
cardiofaciocutaneous syndrome
0.37
insomnia
0.33
autoimmune disorder of central nervous system
0.33
cervical carcinoma
0.31

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

Protein function (UniProt)

Kinase suppressor of Ras 2

Location-regulated scaffold connecting MEK to RAF. Has very low protein kinase activity and can phosphorylate MAP2K1 at several Ser and Thr residues with very low efficiency (in vitro). Acts as MAP2K1/MEK1-dependent allosteric activator of BRAF; upon binding to MAP2K1/MEK1, dimerizes with BRAF and promotes BRAF-mediated phosphorylation of MAP2K1/MEK1 (PubMed:29433126). Interaction with BRAF enhances KSR2-mediated phosphorylation of MAP2K1 (in vitro). Blocks MAP3K8 kinase activity and MAP3K8-mediated signaling. Acts as a negative regulator of MAP3K3-mediated activation of ERK, JNK and NF-kappa-B pathways, inhibiting MAP3K3-mediated interleukin-8 production