NR5A1-Related Disorders via the NR5A1 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
15269 NR5A1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15269NR5A181479 81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

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


Genetic Counselors


Clinical Features and Genetics

Clinical Features

Mutations in the NR5A1 gene, which encodes steroidogenic factor 1 (SF1), can cause a wide range of phenotypes, including 46,XY partial or complete gonadal dysgenesis, spermatogenic failure, and 46,XX primary ovarian insufficiency (El-Khairi et al., 2012).

NR5A1-related 46,XY gonadal dysgenesis (OMIM# 612965) can be partial or complete (El-Khairi et al., 2012; Cotinot et al., 2002; Ostrer et al., 2008). 46,XY partial gonadal dysgenesis (also termed 46,XY partial testicular dysgenesis) is the more common condition and is characterized by ambiguous external genitalia with a wide spectrum of genital ambiguity, dysgenetic testis and a mixture of both Wolffian and Mullerian ducts (McElreavey et al., 1996; Domenice et al., 1998; Cotinot et al., 2002).

46,XY complete gonadal dysgenesis (also termed Swyer syndrome or 46,XY pure gonadal dysgenesis) represents the more severe (and rarer) end of the phenotypes. Phenotypically females present in adolescence with absent pubertal development and primary amenorrhea, although they have functional female genitalia and structures. Notably, some patients affected by NR5A1-related 46,XY partial or complete gonadal dysgenesis can have primary adrenal failure (Achermann et al., 1999; Lin et al., 2006; Köhler et al., 2008).

NR5A1-related spermatogenic failure (OMIM# 613957) is a disease of male infertility characterized by azoospermia or oligozoospermia (Bashamboo et al., 2010). Some patients may have elevated gonadotropins and low testosterone. Affected men may be at risk of developing suboptimal testosterone levels in adult life.

NR5A1 defects have also been found in familial 46,XX primary ovarian insufficiency (OMIM# 612964) and sporadic premature ovarian failure (Lourenço et al., 2009). All of these affected women have no evidence of adrenal dysfunction.


The NR5A1 gene has 6 coding exons and encodes steroidogenic factor 1 (SF1), which is a key transcriptional regulator of genes involved in the hypothalamic-pituitary-steroidogenic axis. Genetic aberrations throughout this gene include missense, nonsense, splicing mutations and small deletion/insertions. Large deletions involving the NR5A1 gene have also been reported but are relatively uncommon (Human Gene Mutation Database). In most cases, NR5A1-related disorders are caused by de novo mutations or dominantly inherited mutations (El-Khairi et al., 2012).

In 10-15% of cases, 46,XY complete or partial gonadal dysgenesis is caused by NR5A1 defects (El-Khairi et al., 2012). Haploinsufficiency of NR5A1 is the principle mechanism explaining gonadal phenotypes. The majority of these NR5A1 defects are de novo changes while about one-third of cases have been found transmitted from mothers.

NR5A1 defects have been found in approximately 4% of men with idiopathic spermatogenic failure (Bashamboo et al., 2010). These mutations clustered within the hinge domain of the protein. In some cases, heterozygous NR5A1 mutations can be transmitted from young fathers to their children and an affected child can inherit a NR5A1 mutation from his mosaic father (El-Khairi et al., 2012).

46,XY complete or partial gonadal dysgenesis can be caused by mutations in different genes with different inheritance patterns including autosomal dominant (the WNT4 and NR5A1 genes), autosomal recessive (the DHH gene), X-linked (the NR0B1 gene) or Y-linked (the SRY gene) (Paliwal et al., 2011; Ostrer et al., 2008).

Clinical Sensitivity - Sequencing with CNV PG-Select

NR5A1 mutations have been found in 10-15% of patients with 46,XY complete or partial gonadal dysgenesis (El-Khairi et al., 2012).

In a cohort of 315 men with idiopathic spermatogenic failure, NR5A1 mutations were found in 4% of cases (Bashamboo et al., 2010).

In a limited number of sporadic patients with premature ovarian failure, 8% (2 out of 25) had de novo NR5A1 mutations (Lourenço et al., 2009).

In a limited number of patients with 46,XY gonadal dysgenesis in whom sequencing analyses failed to identify a genetic cause, 5% (1 out of 20) had a partial deletion within NR5A1 (Barbaro et al., 2011). Other large NR5A1 deletions have only been reported in limited individual cases.

Testing Strategy

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

This test provides full coverage of all coding exons of the NR5A1 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.

Indications for Test

Candidates for this test are patients with 46,XY complete or partial gonadal dysgenesis, spermatogenic failure, or ovarian insufficiency (familial or sporadic). Testing is also indicated for family members of patients who have known NR5A1 mutations.


Official Gene Symbol OMIM ID
NR5A1 184757
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


  • Achermann JC, Ito M, Ito M, Hindmarsh PC, Jameson JL. 1999. A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans. Nat. Genet. 22: 125–126. PubMed ID: 10369247
  • Barbaro M, Cools M, Looijenga LHJ, Drop SLS, Wedell A. 2011. Partial deletion of the NR5A1 (SF1) gene detected by synthetic probe MLPA in a patient with XY gonadal disorder of sex development. Sex Dev 5: 181–187. PubMed ID: 21654157
  • Bashamboo A, Ferraz-de-Souza B, Lourenço D, Lin L, Sebire NJ, Montjean D, Bignon-Topalovic J, Mandelbaum J, Siffroi J-P, Christin-Maitre S, Radhakrishna U, Rouba H, et al. 2010. Human male infertility associated with mutations in NR5A1 encoding steroidogenic factor 1. Am. J. Hum. Genet. 87: 505–512. PubMed ID: 20887963
  • Cotinot C, Pailhoux E, Jaubert F, Fellous M. 2002. Molecular genetics of sex determination. Semin. Reprod. Med. 20: 157–168. PubMed ID: 12428196
  • Domenice S, Yumie Nishi M, Correia Billerbeck AE, Latronico AC, Aparecida Medeiros M, Russell AJ, Vass K, Marino Carvalho F, Costa Frade EM, Prado Arnhold IJ, Bilharinho Mendonca B. 1998. A novel missense mutation (S18N) in the 5’ non-HMG box region of the SRY gene in a patient with partial gonadal dysgenesis and his normal male relatives. Hum. Genet. 102: 213–215. PubMed ID: 9521592
  • El-Khairi R, Achermann JC. 2012. Steroidogenic factor-1 and human disease. Semin. Reprod. Med. 30: 374–381. PubMed ID: 23044873
  • Human Gene Mutation Database (Bio-base).
  • Köhler B, Lin L, Ferraz-de-Souza B, Wieacker P, Heidemann P, Schröder V, Biebermann H, Schnabel D, Grüters A, Achermann JC. 2008. Five novel mutations in steroidogenic factor 1 (SF1, NR5A1) in 46,XY patients with severe underandrogenization but without adrenal insufficiency. Hum. Mutat. 29: 59–64. PubMed ID: 17694559
  • Lin L, Gu W-X, Ozisik G, To WS, Owen CJ, Jameson JL, Achermann JC. 2006. Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (NR5A1) in children and adults with primary adrenal failure: ten years’ experience. J. Clin. Endocrinol. Metab. 91: 3048–3054. PubMed ID: 16684822
  • Lourenço D, Brauner R, Lin L, Perdigo A De, Weryha G, Muresan M, Boudjenah R, Guerra-Junior G, Maciel-Guerra AT, Achermann JC, McElreavey K, Bashamboo A. 2009. Mutations in NR5A1 associated with ovarian insufficiency. N. Engl. J. Med. 360: 1200–1210. PubMed ID: 19246354
  • McElreavey K, Vilain E, Barbaux S, Fuqua JS, Fechner PY, Souleyreau N, Doco-Fenzy M, Gabriel R, Quereux C, Fellous M, Berkovitz GD. 1996. Loss of sequences 3’ to the testis-determining gene, SRY, including the Y pseudoautosomal boundary associated with partial testicular determination. Proc. Natl. Acad. Sci. U.S.A. 93: 8590–8594. PubMed ID: 8710915
  • Ostrer H. 1993. 46,XY Disorder of Sex Development and 46,XY Complete Gonadal Dysgenesis. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301714
  • Paliwal P, Sharma A, Birla S, Kriplani A, Khadgawat R, Sharma A. 2011. Identification of novel SRY mutations and SF1 (NR5A1) changes in patients with pure gonadal dysgenesis and 46,XY karyotype. Mol. Hum. Reprod. 17: 372–378. PubMed ID: 21242195


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