NR0B1

Chr XX-linkedXLR

nuclear receptor subfamily 0 group B member 1

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

NCBI Gene: 190ENSG00000169297UniProt: P51843OMIM: 300473

This gene encodes a nuclear receptor corepressor that inhibits transcriptional activity of other nuclear receptors and is essential for development of the hypothalamic-pituitary-adrenal-gonadal axis. Mutations cause X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism, as well as 46,XY sex reversal with dosage sensitivity. The gene shows X-linked recessive inheritance and is highly constrained against loss-of-function variants.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismX-linked/XLRLOEUF 0.282 OMIM phenotypes
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
110 unique Pathogenic / Likely Pathogenic· 107 VUS of 406 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — NR0B1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
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
1.08Z-score
OE missense 0.78 (0.68–0.89)
150 obs / 192.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.28)
0≤0.351.4
Missense OE0.78 (0.68–0.89)
0≤0.61.4
Synonymous OE1.11
0≤1.21.6
LoF obs/exp: 0 / 10.9Missense obs/exp: 150 / 192.2Syn Z: -0.84
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveNR0B1-related adrenal hypoplasia, congenitalLOFXLR
DN
0.2997th %ile
GOF
0.4283th %ile
LOF
0.76top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 48% of P/LP variants are LoF · LOEUF 0.28

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

406 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic97
Likely Pathogenic13
VUS107
Likely Benign149
Benign25
Conflicting11
97
Pathogenic
13
Likely Pathogenic
107
VUS
149
Likely Benign
25
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
46
1
50
0
97
Likely Pathogenic
7
5
1
0
13
VUS
2
102
3
0
107
Likely Benign
0
10
5
134
149
Benign
0
9
2
14
25
Conflicting
—11
Total5512761148402

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients