NR0B1

Chr X

nuclear receptor subfamily 0 group B member 1

Also known as: AHC, AHCH, AHX, DAX-1, DAX1, DSS, GTD, HHG

NCBI Gene: 190ENSG00000169297UniProt: P51843

This gene encodes a protein that contains a DNA-binding domain. The encoded protein acts as a dominant-negative regulator of transcription which is mediated by the retinoic acid receptor. This protein also functions as an anti-testis gene by acting antagonistically to Sry. Mutations in this gene result in both X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtAdrenal hypoplasia, congenital
UniProt46,XY sex reversal 2
604
ClinVar variants
83
Pathogenic / LP
0.97
pLI score· haploinsufficient
0
Active trials
Clinical Summary— NR0B1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
83 Pathogenic / Likely Pathogenic· 80 VUS of 604 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.28LOEUF
pLI 0.970
Z-score 3.06
OE 0.00 (0.00–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.08Z-score
OE missense 0.78 (0.68–0.89)
150 obs / 192.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.68–0.89)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.11
0≤1.21.6
LoF obs/exp: 0 / 10.9Missense obs/exp: 150 / 192.2Syn Z: -0.84

ClinVar Variant Classifications

604 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic76
Likely Pathogenic7
VUS80
Likely Benign118
Benign11
Conflicting8
76
Pathogenic
7
Likely Pathogenic
80
VUS
118
Likely Benign
11
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
21
0
55
0
76
Likely Pathogenic
4
2
1
0
7
VUS
1
76
3
0
80
Likely Benign
0
8
4
106
118
Benign
0
5
1
5
11
Conflicting
—8
Total269164111300

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NR0B1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

NR0B1-related adrenal hypoplasia, congenital

definitive
Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product
Skin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human disease.
Suntharalingham JP et al.·Best Pract Res Clin Endocrinol Metab
2015Review
Diagnosis and management of non-CAH 46,XX disorders/differences in sex development.
Yavas Abalı Z et al.·Front Endocrinol (Lausanne)
2024Review
46,XY Gonadal Dysgenesis Due to NR0B1 Duplication: A Systematic Review.
Yami Channaiah C et al.·Clin Endocrinol (Oxf)
2026Review
Association of NR0B1 with Malignant Phenotypes in Esophageal Squamous Cell Carcinoma Through Modulation of p53-Independent Cell-Cycle Regulation.
Iizuka A et al.·Ann Surg Oncol
2025
[A Novel Pathogenic variant in NR0B1 gene associated with Congenital Adrenal Hypoplasia].
García-Medina JS et al.·Andes Pediatr
2022Case report
Primary adrenal insufficiency: New genetic causes and their long-term consequences.
Buonocore F et al.·Clin Endocrinol (Oxf)
2020Review
Mutations in NR0B1 (DAX1) and NR5A1 (SF1) responsible for adrenal hypoplasia congenita.
Phelan JK et al.·Hum Mutat
2001Review
Nuclear Receptor Gene Variants Underlying Disorders/Differences of Sex Development through Abnormal Testicular Development.
Hattori A et al.·Biomolecules
2023Review
Nonsense variant of NR0B1 causes hormone disorders associated with congenital adrenal hyperplasia.
Fan DB et al.·Sci Rep
2021
New insights into X-linked adrenal hypoplasia congenita from a novel splice-site variant of NR0B1 and adrenal CT images.
Jiang Y et al.·Mol Genet Genomic Med
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools