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Non-Syndromic Monogenic Obesity via the KSR2 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
KSR2 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15173KSR281479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Marissa Cloutier, PhD

Clinical Features and Genetics

Clinical Features

Non-syndromic monogenic obesity is a group of single-gene disorders with obesity as an isolated or predominant feature. Obesity is defined as an increase in fat mass that is sufficient to adversely affect health and reduce longevity (Fontaine et al. 2003. PubMed ID: 12517229). Clinically, body-mass index (BMI) is the accepted measure of adipose mass. For adults, a BMI greater than 30 is typically used to diagnose a person as obese. BMI is a multifactorial trait that is frequently influenced by multiple genes as well as environmental and lifestyle factors (Gusev et al. 2014. PubMed ID: 25439723). However, to date, eleven genes have been specifically implicated in non-syndromic monogenic obesity: LEP, LEPR, SH2B1, POMC, PCSK1, MC4R, NTRK2, BDNF, SIM1, KSR2, and TUB (Pigeyre et al. 2016. PubMed ID: 27154742).

KSR2-related obesity is characterized by severe early-onset obesity (<10 years of age), hyperphagia in childhood, low heart rate, reduced basal metabolic rate, and severe insulin resistance (Pearce et al. 2013. PubMed ID: 24209692). Importantly, the Pearce et al. study provided anecdotal evidence that carriers of suspected pathogenic KSR2 variants respond well to the common anti-diabetes medication Metformin. Therefore, this molecular diagnosis may provide information that would guide treatment decisions for patients.


Pathogenic variants in KSR2 cause autosomal dominant non-syndromic obesity. The KSR2 gene encodes the kinase suppressor of Ras2 (KSR2) protein which regulates energy consumption, metabolic expenditure, and substrate utilization via the Ras/Raf/MEK/ERK signaling pathway. KSR2 is an intracellular scaffolding protein. In response to growth factor signaling, it translocates to the plasma membrane where it catalyzes MEK phosphorylation by scaffolding Ras, Raf, and MEK in a complex (Michaud et al. 1997. PubMed ID: 9371754; Roy et al. 2002. PubMed ID: 11850406). Through this process KSR2 activates gene expression by coordinating the ERK signaling cascade in both time and space.

Functional studies in cell culture have determined that pathogenic variants in the KSR2 gene disrupt Raf-MEK-ERK signaling causing decreases in fatty acid oxidation and glucose oxidation. These defects are attenuated by the application of the diabetes drug metformin (Pearce et al. 2013. PubMed ID: 24209692).

The predominant inheritance of KSR2-related obesity is autosomal dominant; however, one severely obese individual has been described with compound heterozygous rare variants, and recessive inheritance has not been ruled out (Pearce et al. 2013. PubMed ID: 24209692). Incomplete penetrance and variable expressivity was also noted in this study, so some carriers may be unaffected or mildly affected. The causative variants include missense, nonsense, and frameshift alterations, the majority of which cluster to the C-terminal kinase domain. To date, no founder variants, large gene rearrangements, or de novo variants have been described.

Clinical Sensitivity - Sequencing with CNV PG-Select

In a study of 2,101 severely obese individuals of mixed European ancestry, 2.1% were found to have rare variants in the KSR2 gene in contrast with 1.0% of matched controls (Pearce et al. 2013. PubMed ID: 24209692). These data provide a rough estimate of clinical sensitivity at approximately 1%. Analytical sensitivity is expected to be high because all reported causative variants are detectable by sequencing.

Testing Strategy

This test is performed using Next-Generation sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the KSR2 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with isolated obesity and other features which may include childhood hyperphagia, low heart rate, and insulin resistance.


Official Gene Symbol OMIM ID
KSR2 610737
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID


  • Fontaine et al. 2003. PubMed ID: 12517229
  • Gusev et al. 2014. PubMed ID: 25439723
  • Michaud et al. 1997. PubMed ID: 9371754
  • Pearce et al. 2013. PubMed ID: 24209692
  • Pigeyre et al. 2016. PubMed ID: 27154742
  • Roy et al. 2002. PubMed ID: 11850406


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

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View Ordering Instructions

1) Select Test Method (Platform)

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2) Select Additional Test Options

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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