NCOR1

Chr 17

nuclear receptor corepressor 1

Also known as: N-CoR, N-CoR1, PPP1R109, TRAC1, hN-CoR

NCBI Gene: 9611ENSG00000141027UniProt: O75376OMIM: 600849

The protein mediates transcriptional repression by nuclear receptors and promotes histone deacetylation to form repressive chromatin structures that regulate gene expression. Mutations cause neurodevelopmental disorders with intellectual disability, autism spectrum disorder, and various congenital anomalies, inherited in an autosomal dominant pattern. The gene is extremely constrained against loss-of-function variants, indicating that such mutations are likely to cause severe phenotypes.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.17
Clinical Summary— NCOR1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 270 VUS of 400 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.17LOEUF
pLI 1.000
Z-score 9.44
OE 0.11 (0.07–0.17)
Highly constrained

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

Missense Constraint
3.94Z-score
OE missense 0.70 (0.66–0.74)
940 obs / 1346.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.11 (0.07–0.17)
0≤0.351.4
Missense OE0.70 (0.66–0.74)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 15 / 132.0Missense obs/exp: 940 / 1346.6Syn Z: 0.43
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedNCOR1-related developmental disorderLOFAD
DN
0.2299th %ile
GOF
0.14100th %ile
LOF
0.89top 5%

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

LOFprediction above median · LOEUF 0.17

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

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS270
Likely Benign32
Benign24
16
Pathogenic
1
Likely Pathogenic
270
VUS
32
Likely Benign
24
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
1
0
0
1
VUS
3
246
21
0
270
Likely Benign
0
12
6
14
32
Benign
0
4
3
17
24
Total32634631343

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

View in ClinVar →

Protein Context — Lollipop Plot

NCOR1 · 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