KSR2

kinase suppressor of ras 2, the group of RAF family

Basic information

Region (hg38): 12:117453012-117968990

Links

ENSG00000171435 ∙ NCBI:283455 ∙ OMIM:610737 ∙ HGNC:18610 ∙ Uniprot:Q6VAB6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• KSR2-related_disorder (260 variants)
• not_provided (104 variants)
• not_specified (77 variants)
• Autism (1 variants)
• Obesity (1 variants)
• Hypertensive_disorder (1 variants)
• Diabetes_mellitus (1 variants)
• Hyperlipidemia (1 variants)
• Type_2_diabetes_mellitus (1 variants)
• Class_III_obesity (1 variants)

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. These statistics are base on transcript: NM_000173598.6. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	96	15	112
missense			182	5	2	189
nonsense		1	3	1		5
start loss						0
frameshift		1	1			2
splice donor/acceptor (+/-2bp)		1	1			2
Total	0	3	188	102	17

Highest pathogenic variant AF is 0.00000273682

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KSR2	protein_coding	protein_coding	ENST00000339824	20	515972

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	7.85e-7	124647	0	8	124655	0.0000321

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.34	374	605	0.618	0.0000395	6217
Missense in Polyphen		86	198.96	0.43226		2082
Synonymous	1.54	226	257	0.878	0.0000182	1871
Loss of Function	6.15	2	48.0	0.0417	0.00000239	535

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000291	0.0000291
Ashkenazi Jewish	0.00	0.00
East Asian	0.000112	0.000111
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.0000358	0.0000354
Middle Eastern	0.000112	0.000111
South Asian	0.00	0.00
Other	0.00	0.00

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_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

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

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