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Pseudohypoaldosteronism Type II via the KLHL3 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
KLHL3 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11431KLHL381479 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


  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Pseudohypoaldosteronism type II (PHAII) is a rare monogenic disorder of renal electrolyte handling characterized by hypertension (due to increased renal salt reabsorption), hyperkalaemia (due to reduced renal K+ excretion, despite normal glomerular filtration and aldosterone secretion) and metabolic acidosis (due to reduced renal H+ secretion) (Wilson et al. 2001; Boyden et al. 2012). PHAII has a range of disease severity and age at disease onset. Pseudohypoaldosteronism type IID (OMIM# 614495) is caused by defects in the KLHL3 gene. KLHL3-related PHAII usually develops at an average age of late twenties. The disease severity of KLHL3-related PHAII is more than that caused by WNK defects (WNK1 and WNK4) while much less than that caused by the CUL3 mutations.


In pseudohypoaldosteronism type II (PHAII), the KLHL3-related subtype can be inherited in an autosomal dominant or recessive manner, while the other three subtypes are autosomal dominant disorders caused by defects in WNK1, WNK4 or CUL3 (Wilson et al. 2001; Boyden et al. 2012; Louis-Dit-Picard et al. 2012). KLHL3 has 15 coding exons that encode a BTB-domain-containing kelch protein, which plays a key role in salt, water, potassium, and pH homeostasis. To date, documented pathogenic KLHL3 variants include missense substitutions (majority), splicing and nonsense mutations, and small indels (Human Gene Mutation Database). Recessive KLHL3 mutations are spread throughout the coding regions whereas dominant KLHL3 mutations apparently cluster in short segments within the kelch propeller and BTB domains implicated in substrate and cullin binding.

Clinical Sensitivity - Sequencing with CNV PGxome

In a cohort of 52 pseudohypoaldosteronism type II (PHAII) families, 8 (~15%) and 16 families (~30%) were found to have recessive and dominant KLHL3 mutations, respectively (Boyden et al. 2012).

No large deletions or duplications have been found in KLHL3 (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the KLHL3 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).

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

Candidates for this test are patients with pseudohypoaldosteronism type II. Testing is also indicated for family members of patients who have known KLHL3 mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in KLHL3.


Official Gene Symbol OMIM ID
KLHL3 605775
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Pseudohypoaldosteronism, type IID AR, AD 614495


  • Boyden LM, Choi M, Choate KA, Nelson-Williams CJ, Farhi A, Toka HR, Tikhonova IR, Bjornson R, Mane SM, Colussi G, Lebel M, Gordon RD, et al. 2012. Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities. Nature 482: 98-102. PubMed ID: 22266938
  • Human Gene Mutation Database (Bio-base).
  • Louis-Dit-Picard H, Barc J, Trujillano D, Miserey-Lenkei S, Bouatia-Naji N, Pylypenko O, Beaurain G, Bonnefond A, Sand O, Simian C, Vidal-Petiot E, Soukaseum C, et al. 2012. KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron. Nat. Genet. 44: 456-460, S1-3. PubMed ID: 22406640
  • Wilson FH, Disse-Nicodème S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I, Gunel M, Milford DV, Lipkin GW, Achard JM, Feely MP, Dussol B, et al. 2001. Human hypertension caused by mutations in WNK kinases. Science 293: 1107-1112. PubMed ID: 11498583


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)

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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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