KSR2

kinase suppressor of ras 2, the group of RAF family

Basic information

Region (hg38): 12:117453012-117968990

Links

ENSG00000171435NCBI:283455OMIM:610737HGNC:18610Uniprot:Q6VAB6AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KSR2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KSR2 gene is commonly pathogenic or not.

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.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
1
clinvar
51
clinvar
13
clinvar
65
missense
71
clinvar
6
clinvar
2
clinvar
79
nonsense
1
clinvar
1
start loss
0
frameshift
1
clinvar
1
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
1
clinvar
1
splice region
1
9
1
11
non coding
16
clinvar
9
clinvar
25
Total 0 2 74 73 24

Variants in KSR2

This is a list of pathogenic ClinVar variants found in the KSR2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
12-117467158-C-T KSR2-related disorder Likely benign (Sep 16, 2024)3358574
12-117467212-T-C KSR2-related disorder Likely benign (Aug 03, 2020)3352669
12-117467213-G-A KSR2-related disorder Likely benign (Oct 04, 2023)3030694
12-117469644-T-C Benign (Jan 31, 2024)1599375
12-117469652-G-A KSR2-related disorder Likely benign (Jan 09, 2024)2889798
12-117469679-A-G Likely benign (Dec 10, 2021)1548791
12-117469689-T-C KSR2-related disorder Uncertain significance (Jan 17, 2024)3349072
12-117469698-C-T KSR2-related disorder Uncertain significance (Sep 01, 2023)2634120
12-117469701-C-A KSR2-related disorder Uncertain significance (Mar 25, 2024)3357859
12-117469701-C-T KSR2-related disorder Uncertain significance (Feb 23, 2024)3355354
12-117469707-C-T KSR2-related disorder Uncertain significance (May 13, 2024)3354079
12-117469747-A-G not specified Uncertain significance (Aug 07, 2024)3536652
12-117469751-A-G not specified • KSR2-related disorder Benign (Jan 22, 2024)768590
12-117469782-A-G not specified Uncertain significance (Nov 08, 2024)3536659
12-117469798-A-G KSR2-related disorder Likely benign (Jan 13, 2022)3355277
12-117469806-C-T Likely benign (Oct 26, 2022)1988610
12-117471191-C-T KSR2-related disorder Uncertain significance (Feb 09, 2024)3349572
12-117471192-G-A KSR2-related disorder Benign/Likely benign (Jul 01, 2023)1587466
12-117471211-C-T KSR2-related disorder Uncertain significance (Nov 17, 2023)3349269
12-117471227-G-A KSR2-related disorder Likely benign (Jan 18, 2024)3050227
12-117471271-G-A KSR2-related disorder • not specified Uncertain significance (Apr 29, 2024)3040890
12-117471308-A-G KSR2-related disorder Likely benign (May 26, 2021)3057800
12-117476465-C-A KSR2-related disorder Uncertain significance (May 29, 2024)3347683
12-117476469-G-A KSR2-related disorder Likely benign (Dec 16, 2021)3029894
12-117476497-G-C KSR2-related disorder Uncertain significance (Mar 15, 2024)3350206

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
KSR2protein_codingprotein_codingENST00000339824 20515972
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.007.85e-7124647081246550.0000321
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense3.343746050.6180.00003956217
Missense in Polyphen86198.960.432262082
Synonymous1.542262570.8780.00001821871
Loss of Function6.15248.00.04170.00000239535

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00002910.0000291
Ashkenazi Jewish0.000.00
East Asian0.0001120.000111
Finnish0.00004640.0000464
European (Non-Finnish)0.00003580.0000354
Middle Eastern0.0001120.000111
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: 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). 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. {ECO:0000269|PubMed:12975377, ECO:0000269|PubMed:16039990, ECO:0000269|PubMed:21441910}.;
Pathway
Ras signaling pathway - Homo sapiens (human);EGF-Ncore;TNF alpha Signaling Pathway;Ras Signaling;MAP2K and MAPK activation;Disease;Signal Transduction;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Signaling by RAS mutants;Signaling by high-kinase activity BRAF mutants;Signaling by moderate kinase activity BRAF mutants;Paradoxical activation of RAF signaling by kinase inactive BRAF;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction (Consensus)

Recessive Scores

pRec
0.120

Haploinsufficiency Scores

pHI
0.408
hipred
Y
hipred_score
0.768
ghis
0.549

Essentials

essential_gene_CRISPR
essential_gene_CRISPR2
N
essential_gene_gene_trap
gene_indispensability_pred
E
gene_indispensability_score
0.996

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Ksr2
Phenotype
growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan);

Gene ontology

Biological process
protein phosphorylation;Ras protein signal transduction;calcium-mediated signaling;positive regulation of cold-induced thermogenesis
Cellular component
cytosol;plasma membrane
Molecular function
protein serine/threonine kinase activity;protein binding;ATP binding;metal ion binding