NR5A1

Chr 9AD

nuclear receptor subfamily 5 group A member 1

Also known as: AD4BP, ELP, FTZ1, FTZF1, POF7, SF-1, SF1, SPGF8

NCBI Gene: 2516ENSG00000136931UniProt: Q13285OMIM: 184757

NR5A1 encodes a transcriptional activator essential for sexual differentiation and formation of primary steroidogenic tissues, binding to promoter regions of steroidogenic genes including CYP11A, CYP11B, and CYP21B. Mutations cause disorders of sex development including 46XX and 46XY sex reversal, adrenocortical insufficiency, premature ovarian failure, and spermatogenic failure with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.99), reflecting its critical role in gonadal and adrenal development.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.265 OMIM phenotypes
Clinical Summary— NR5A1
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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
163 unique Pathogenic / Likely Pathogenic· 121 VUS of 397 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — NR5A1
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
0.26LOEUF
pLI 0.990
Z-score 3.73
OE 0.06 (0.02–0.26)
Highly constrained

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

Missense Constraint
2.34Z-score
OE missense 0.61 (0.54–0.69)
175 obs / 286.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.06 (0.02–0.26)
0≤0.351.4
Missense OE0.61 (0.54–0.69)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 1 / 18.1Missense obs/exp: 175 / 286.2Syn Z: -0.20
DN
0.3991th %ile
GOF
0.3491th %ile
LOF
0.72top 10%

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

LOFprediction above median · 1 literature citation · 39% of P/LP variants are LoF · LOEUF 0.26

Literature Evidence

LOFWe identified a partial NR5A1 deletion affecting exons 2 and 3, leading to NR5A1 haploinsufficiency in 1 patient presenting with female external genitalia with clitoromegaly, absence of a uterus, and mildly dysgenetic testes.PMID:21654157

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

397 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic103
Likely Pathogenic60
VUS121
Likely Benign65
Benign30
Conflicting13
103
Pathogenic
60
Likely Pathogenic
121
VUS
65
Likely Benign
30
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
43
27
33
0
103
Likely Pathogenic
20
35
3
2
60
VUS
2
109
9
1
121
Likely Benign
0
7
22
36
65
Benign
0
2
17
11
30
Conflicting
—13
Total651808450392

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

View in ClinVar →

Protein Context — Lollipop Plot

NR5A1 · 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