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Molybdenum Cofactor Deficiency via the GPHN 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
GPHN 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11883GPHN81479 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.

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


  • McKenna Kyriss, PhD

Clinical Features and Genetics

Clinical Features

Molybdenum cofactor deficiency is an inborn error in metabolism caused by pathogenic variants in the enzymes responsible for molybdenum cofactor biosynthesis. As a result, several molybdenum cofactor-dependent enzymes (sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase) are nonfunctional. Patients with molybdenum cofactor deficiency excrete elevated levels of sulfite, thiosulfate, S-sulfocysteine, xanthine, and hypoxanthine while uric acid levels are low (Johnson and Duran, 2014). Clinical presentations in molybdenum cofactor deficiencies and isolated sulfite oxidase deficiency are almost indistinguishable. Considerable variability and age of onset for molybdenum cofactor deficiency exists. However, typically presentation will occur shortly after birth with severe convulsions that are difficult to suppress (Reiss et al., 2001. PubMed ID: 11095995; Reiss et al., 2011. PubMed ID: 22040219; Johnson and Duran, 2014). Patients with molybdenum cofactor deficiency also have dysmorphic features that include long face with puffy cheeks, widely spaced eyes, elongated palpebral fissures, thick lips, a long philtrum, and a small nose, which can resemble perinatal asphyxia. Patients also present with psychomotor retardation, ophthalmologic abnormalities such as lens dislocation, peripheral hypertonicity, and axial hypotonia (Johnson and Duran, 2014).


All molybdenum cofactor deficiencies are inherited in an autosomal recessive manner. Reported pathogenic variants in GPHN include a missense variant and a gross deletion of exons 2-3 (Reiss et al., 2001. PubMed ID: 11095995; Reiss et al., 2011. PubMed ID: 22040219). Copy number variants (CNVs) in GPHN in the heterozygous state have been associated with neurodevelopmental disorders such as autism, schizophrenia, and epilepsy (Lionel et al., 2013. PubMed ID: 23393157). However, these variants in the heterozygous state are not causative for molybdenum cofactor deficiency. MOCS1 and MOCS2 pathogenic variants are the more common cause of molybdenum cofactor deficiency (Reiss and Hahnewald, 2011. PubMed ID: 21031595).

The GPHN gene encodes the gephyrin protein which has surprising dual functions in cofactor synthesis as well as synaptic receptor clustering. The gephyrin protein contains two domains (E and G) that are necessary for the activation and insertion of molybdenum into molybdopterin (Reiss et al., 2001. PubMed ID: 11095995). The reported pathogenic variants for molybdenum cofactor deficiency have been observed in both domains. Gephyrin also belongs to a group of cytoskeletal elements that are critical for receptor-associated synaptic localization and organization (Reiss et al., 2001. PubMed ID: 11095995).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity cannot be estimated precisely because only a small number of patients have been reported. However, clinical sensitivity appears to be low.

Testing Strategy

This test provides full coverage of all coding exons of the GPHN 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

Patients with molybdenum cofactor deficiency excrete elevated levels of sulfite, thiosulfate, S-sulfocysteine, xanthine, and hypoxanthine while uric acid levels are low. Patients that biochemically and clinically fit molybdenum cofactor deficiency with no molecular diagnosis after MOCS1 and MOCS2 genetic testing. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GPHN.


Official Gene Symbol OMIM ID
GPHN 603930
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Molybdenum Cofactor Deficiency C AR 615501


  • Johnson and Duran, 2014. Molybdenum Cofactor Deficiency and Isolated Sulfite Oxidase Deficiency. Online Metabolic & Molecular Bases of Inherited Disease, New York, NY: McGraw-Hill.
  • Lionel et al., 2013. PubMed ID: 23393157
  • Reiss and Hahnewald, 2011. PubMed ID: 21031595
  • Reiss et al., 2001. PubMed ID: 11095995
  • Reiss et al., 2011. PubMed ID: 22040219


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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