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Primary Immunodeficiency via the IRAK4 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
IRAK4 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8217IRAK481479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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


  • Megan Piazza, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Interleukin-1 receptor-associated kinase (IRAK) 4 deficiency is a rare primary immunodeficiency disorder that results from impaired Toll-like receptor- (TLR) and interleukin1 (IL-1) receptor-mediated immune response (Picard et al. 2010). Patients with IRAK4 deficiency present with severe, recurrent, invasive bacterial infections, particularly Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa (Ku et al. 2007; Picard et al. 2010; Paciolla et al. 2015; Takada et al. 2016). In young children, the infections often lead to fatal pneumococcal meningitis (Ku et al. 2007; Picard et al. 2010; Takada et al. 2016). However, the frequency and severity of infections appears to decrease with age. In the largest patient series reported to date, no deaths were reported in children over 8 years of age and no infections were reported in children over 14 years of age (Picard et al. 2010). Prophylactic treatments, including antibiotics, antipneumococcal vaccinations, and/or IgG infusion, were reported to be beneficial until the teenage years with no apparent benefit thereafter (Picard et al. 2010). Genetic testing is helpful in distinguishing IRAK4 deficiency from chronic granulomatous disease, Hyper IgE syndromes, and other primary immunodeficiencies.


IRAK4 deficiency is inherited in an autosomal recessive fashion and is caused by homozygous or compound heterozygous pathogenic variants in the IRAK4 gene (Ku et al. 2007; Picard et al. 2010; Takada et al. 2016). The majority of pathogenic variants to date are truncating with nonsense, splice site, small insertions/deletions, and gross deletions being reported throughout the IRAK4 gene. Missense changes have also been reported in a few cases (Human Gene Mutation Database). No genotype-phenotype correlations have been reported to date (Ku et al. 2007; Picard et al. 2010; Takada et al. 2016). The IRAK4 gene encodes is a receptor kinase involved in mediating innate immune responses through TLR and IL-1 receptor pathways (Picard et al. 2010).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity cannot be estimated because only a small number of patients have been reported (Ku et al. 2007; Picard et al. 2010; Takada et al. 2016). Analytical sensitivity should be high because the great majority of pathogenic variants reported to date are detectable by this method.

Only a few patients with IRAK4 deletions have been reported (Ku et al. 2007). However, these appear to be a rare cause of IRAK4 deficiency.

Testing Strategy

This test provides full coverage of all coding exons of the IRAK4 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

This test also provides coverage of the c.1188+520A>G variant region.

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Testing for IRAK4 deficiency may be considered in young children with severe, recurrent, invasive bacterial infections, particularly S. pneumoniae, S. aureus, and P. aeruginosa. Targeting testing for known familial variants in family members may also be considered. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in IRAK4.


Official Gene Symbol OMIM ID
IRAK4 606883
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
IRAK4 Deficiency AR 607676


  • Human Gene Mutation Database (Bio-base).
  • Ku C.L. et al. 2007. Journal of Medical Genetics. 44: 16-23. PubMed ID: 16950813
  • Paciolla M. et al. 2015. Genes and Immunity. 16: 239-46. PubMed ID: 24764117
  • Picard C. et al. 2010. Medicine. 89: 403-25. PubMed ID: 21057262
  • Takada H. et al. 2016. Medicine. 95: e2437. PubMed ID: 26825884


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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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View Ordering Instructions

1) Select Test Method (Platform)

1) Select Test Type

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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