Book a test
On this page
⚠ Educational content only Not medical or genetic advice. Speak with a healthcare provider or genetic counsellor before acting on anything here.

NR0B1

nuclear receptor subfamily 0 group B member 1

The NR0B1 gene provides instructions for the DAX1 protein, which is vital for the proper development and function of several hormone-producing tissues, including the adrenal glands and reproductive organs. NR0B1, also known as DAX1, plays a critical role in endocrine system development and hormone regulation.

Chromosome Xp21.2 Various HGNC:7960 Tier C
NR0B1 Xp21.2 p arm q arm X

NR0B1 is located on the short (p) arm of chromosome X, at band Xp21.2. Arm ratio per GRCh38 - banding schematic.

Explore chromosome X in the library →

Available at Jeen Health

Clinical tests that include this

Carrier Screening panel
NR0B1 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions
Newborn Genetic Screening panel
NR0B1 is 1 of 258 genes on this panel
Genomic newborn screening for actionable paediatric conditions

Overview

The NR0B1 gene, formally known as nuclear receptor subfamily 0 group B member 1, contains instructions for producing a protein called DAX1. This protein is essential for the normal formation and function of several endocrine (hormone-producing) tissues within the body. These tissues include the adrenal glands, which sit atop the kidneys, as well as the hypothalamus and pituitary glands in the brain, and the gonads (ovaries in females and testes in males).

What the gene does

The DAX1 protein, encoded by the NR0B1 gene, acts as a regulator of gene expression. Before birth, it helps direct the formation of key endocrine tissues. After these tissues have developed, DAX1 continues to regulate hormone production within them. Its influence is particularly significant in the adrenal glands and reproductive organs, where it helps ensure proper endocrine signalling and development. Pathogenic changes in NR0B1 can disrupt these crucial regulatory processes, leading to various health conditions affecting hormone balance and organ development.

Video: Genetics 101

Chromosome location

The NR0B1 gene is located on the short arm of the X chromosome at position 21.2, a region denoted as Xp21.2. This genomic location means that conditions associated with NR0B1 variants often exhibit an X-linked inheritance pattern.

Protein structure

The DAX1 protein is 470 amino acids long and contains several distinct structural regions. It features four tandem repeats, with the first (Repeat) spanning amino acids 1-67, the second (Repeat) from amino acids 68-133, the third (Repeat) from amino acids 134-200, and a truncated fourth (Repeat) from amino acids 201-253. Within these repeats are three LXXLL motifs: LXXLL motif 1 (amino acids 13-17), LXXLL motif 2 (amino acids 80-84), and LXXLL motif 3 (amino acids 146-150). A significant portion of the protein is dedicated to the NR LBD (Domain), located between amino acids 205-469, which is crucial for its nuclear receptor function. An AF-2 motif (amino acids 461-466) is also present.

Domain map · 470 amino acids
1 (1–67)LXXLL motif 1 (13–17)2 (68–133)LXXLL motif 2 (80–84)3 (134–200)LXXLL motif 3 (146–150)NR LBD (205–469)AF-2 motif (461–466)11–673134–200NR LBD205–4691~235470
Repeat - repeating structural motif
Motif - short conserved sequence
Domain - independent functional unit
🧬 Explore 3D structure on AlphaFold
UniProt:P51843Length:470 aaStructure:AlphaFold

Key variants

Variants in the NR0B1 gene can lead to a range of inherited conditions, often affecting hormone production and sexual development. These genetic changes can involve deletions of entire gene regions or smaller alterations that result in a shortened, non-functional DAX1 protein. The inheritance pattern for conditions linked to NR0B1 is typically X-linked, given its location on the X chromosome.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for NR0B1.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1141C>T
single nucleotide variant
 p.Leu381Phe Pathogenic/Likely pathogenic ★★☆☆ Congenital adrenal hypoplasia, X-linked
c.1168+1_1168+20del
Deletion
 - Pathogenic/Likely pathogenic ★★☆☆ Congenital adrenal hypoplasia, X-linked
c.1273A>G
single nucleotide variant
 p.Arg425Gly Pathogenic/Likely pathogenic ★★☆☆ Differences in sex development
c.327C>A
single nucleotide variant
 p.Cys109Ter Pathogenic ★★☆☆ Congenital adrenal hypoplasia, X-linked
c.516G>A
single nucleotide variant
 p.Trp172Ter Pathogenic ★★☆☆ 46,XY sex reversal 2
c.551_552del
Deletion
 p.Lys184fs Pathogenic ★★☆☆ Congenital adrenal hypoplasia, X-linked
c.708G>A
single nucleotide variant
 p.Trp236Ter Pathogenic ★★☆☆ Congenital adrenal hypoplasia, X-linked
c.754C>T
single nucleotide variant
 p.Gln252Ter Pathogenic ★★☆☆ Congenital adrenal hypoplasia, X-linked
c.773C>A
single nucleotide variant
 p.Ala258Asp Pathogenic/Likely pathogenic ★★☆☆ NR0B1-related disorder
c.919G>T
single nucleotide variant
 p.Glu307Ter Pathogenic ★★☆☆ Congenital adrenal hypoplasia, X-linked

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the NR0B1 gene are associated with several inherited disorders, most notably Congenital adrenal hypoplasia (X-linked). This condition primarily affects the development of the adrenal glands, leading to impaired hormone production. Additionally, NR0B1 variants can be implicated in conditions such as Swyer syndrome and complex glycerol kinase deficiency, which may present with features beyond adrenal dysfunction, including delayed development.

UK clinical status

The NR0B1 gene is included in several NHS Genomic Medicine Service national testing panels. It is evaluated within the Congenital adrenal hypoplasia panel (R150), the Differences in sex development panel (R146), and the Foetal anomalies panel (R21). It is also assessed in the Hypogonadotropic hypogonadism panel.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Congenital adrenal hypoplasia · R150 NHS GMS → Differences in sex development · R146 NHS GMS → Fetal anomalies · R21 NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the function of the NR0B1 gene?

The NR0B1 gene provides instructions for making the DAX1 protein. This protein is essential for the development and proper function of hormone-producing glands such as the adrenal glands, hypothalamus, pituitary, and gonads.

What conditions are associated with variants in NR0B1?

Variants in the NR0B1 gene are primarily associated with X-linked Congenital adrenal hypoplasia, which affects adrenal gland development. They can also be linked to conditions like Swyer syndrome and, in some cases, complex glycerol kinase deficiency.

How is NR0B1 inherited?

Because the NR0B1 gene is located on the X chromosome, conditions caused by its variants typically follow an X-linked inheritance pattern. This means the inheritance and presentation of symptoms can differ between males and females.

References

  1. King TF, Conway GS. Swyer syndrome. Current opinion in endocrinology, diabetes, and obesity. 2014. PMID: 25314337
  2. McCabe ER. DAX1: Increasing complexity in the roles of this novel nuclear receptor. Molecular and cellular endocrinology. 2007. PMID: 17210221
  3. Smyk M, Berg JS, Pursley A. Male-to-female sex reversal associated with an approximately 250 kb deletion upstream of NR0B1 (DAX1). Human genetics. 2007. PMID: 17503084
  4. Barbaro M, Oscarson M, Schoumans J. Isolated 46,XY gonadal dysgenesis in two sisters caused by a Xp21.2 interstitial duplication containing the DAX1 gene. The Journal of clinical endocrinology and metabolism. 2007. PMID: 17504899
  5. Niakan KK, McCabe ER. DAX1 origin, function, and novel role. Molecular genetics and metabolism. 2005. PMID: 16146703
  6. Ludbrook LM, Harley VR. Sex determination: a 'window' of DAX1 activity. Trends in endocrinology and metabolism: TEM. 2004. PMID: 15046740
  7. Iyer AK, McCabe ER. Molecular mechanisms of DAX1 action. Molecular genetics and metabolism. 2004. PMID: 15464421
  8. Lehmann SG, Wurtz JM, Renaud JP. Structure-function analysis reveals the molecular determinants of the impaired biological function of DAX-1 mutants in AHC patients. Human molecular genetics. 2003. PMID: 12700175
  9. Lalli E, Sassone-Corsi P. DAX-1, an unusual orphan receptor at the crossroads of steroidogenic function and sexual differentiation. Molecular endocrinology (Baltimore, Md.). 2003. PMID: 12775766
  10. Clipsham R, McCabe ER. DAX1 and its network partners: exploring complexity in development. Molecular genetics and metabolism. 2003. PMID: 14567960
  11. Lehmann SG, Lalli E, Sassone-Corsi P. X-linked adrenal hypoplasia congenita is caused by abnormal nuclear localization of the DAX-1 protein. Proceedings of the National Academy of Sciences of the United States of America. 2002. PMID: 12034880
  12. Sjarif DR, Ploos van Amstel JK, Duran M. Isolated and contiguous glycerol kinase gene disorders: a review. Journal of inherited metabolic disease. 2000. PMID: 11032329
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 11 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .