KSR2

protein-coding

kinase suppressor of ras 2, the group of RAF family

Gene summary

Enables protein serine/threonine kinase activity. Predicted to be involved in Ras protein signal transduction; calcium-mediated signaling; and positive regulation of cold-induced thermogenesis. Predicted to act upstream of or within positive regulation of MAPK cascade. Predicted to be located in membrane. Predicted to be active in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_173598.6

Inheritance

—

ClinVar variants

P:4U:328B:154

Top phenotype

KSR2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr12:117,453,012-117,968,990

External References & Databases

Ensembl (ENSG00000171435)

Transcript & Mutation Effects

hg38 • Region Span ~516.0 kb

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GenCC 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 KSR2 variants in ClinVar

10 Conditions Cataloged

KSR2-related disorderTotal: 434

not providedTotal: 150

not specifiedTotal: 115

AutismTotal: 1

ObesityTotal: 1

Diabetes mellitusTotal: 1

Hypertensive disorderTotal: 1

HyperlipidemiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173598.6. 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			7 clinvar	135 clinvar	11 clinvar	153
missense			305 clinvar	5 clinvar	2 clinvar	312
nonsense		1 clinvar	7 clinvar	1 clinvar		9
start loss						0
frameshift		2 clinvar	6 clinvar			8
splice donor/acceptor (+/-2bp)		1 clinvar	3 clinvar			4
Total	0	4	328	141	13	486

Highest pathogenic variant AF is 0.0000027368167

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173598.6	RefSeq	NP_775869.4	20	MANE Select
ENST00000339824.7	Ensembl	ENSP00000339952.4	20	MANE Select
ENST00001134991.1	Ensembl	ENSP00000807830.1	20	Standard
XM_011538224.4	RefSeq	XP_011536526.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ras signaling pathway - Homo sapiens (human)
EGF-Ncore
TNF alpha Signaling Pathway
Ras Signaling
MAP2K and MAPK activation

Biological Process

protein phosphorylation
Ras protein signal transduction
calcium-mediated signaling
positive regulation of cold-induced thermogenesis

Molecular Function

protein serine/threonine kinase activity
protein binding
ATP binding
metal ion binding

Cellular Component

cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000339824
Coding exons: 20
Length: 515972
Individuals with no LoFs: 124647
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 124655
p: 0.0000321

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.34	374	605	0.618	0.0000395	6217
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.120

Essentials

Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.996

Gene Damage Prediction

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