NR6A1

Chr 9AD

nuclear receptor subfamily 6 group A member 1

Also known as: CT150, GCNF, GCNF1, NR61, RTR, hGCNF, hRTR

NCBI Gene: 2649ENSG00000148200UniProt: Q15406OMIM: 602778

The protein is an orphan nuclear receptor that binds DNA and regulates embryonic stem cell pluripotency by repressing POU5F1/OCT4 expression during differentiation, and is involved in germ cell development during gametogenesis. Mutations cause oculovertebral syndrome with autosomal dominant inheritance. This condition affects craniofacial and vertebral development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.301 OMIM phenotype
Clinical Summary— NR6A1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
36 unique Pathogenic / Likely Pathogenic· 61 VUS of 118 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.982
Z-score 4.12
OE 0.12 (0.05–0.30)
Highly constrained

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

Missense Constraint
1.83Z-score
OE missense 0.68 (0.60–0.77)
176 obs / 258.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.05–0.30)
0≤0.351.4
Missense OE0.68 (0.60–0.77)
0≤0.61.4
Synonymous OE1.06
0≤1.21.6
LoF obs/exp: 3 / 25.4Missense obs/exp: 176 / 258.6Syn Z: -0.46
DN
0.2599th %ile
GOF
0.2597th %ile
LOF
0.79top 5%

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

LOFprediction above median · LOEUF 0.30

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

118 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic4
VUS61
Likely Benign4
Benign3
32
Pathogenic
4
Likely Pathogenic
61
VUS
4
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
2
28
0
32
Likely Pathogenic
2
1
1
0
4
VUS
0
59
2
0
61
Likely Benign
0
1
1
2
4
Benign
0
1
0
2
3
Total464324104

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

View in ClinVar →

Protein Context — Lollipop Plot

NR6A1 · 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