NCOR1

Chr 17

nuclear receptor corepressor 1

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

NCBI Gene: 9611ENSG00000141027UniProt: O75376

This gene encodes a protein that mediates ligand-independent transcription repression of thyroid-hormone and retinoic-acid receptors by promoting chromatin condensation and preventing access of the transcription machinery. It is part of a complex which also includes histone deacetylases and transcriptional regulators similar to the yeast protein Sin3p. This gene is located between the Charcot-Marie-Tooth and Smith-Magenis syndrome critical regions on chromosome 17. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 17 and 20.[provided by RefSeq, Jun 2010]

353
ClinVar variants
26
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
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
26 Pathogenic / Likely Pathogenic· 270 VUS of 353 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.17LOEUF
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?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.
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?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.0.11 (0.07–0.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.66–0.74)
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.0.98
0≤1.21.6
LoF obs/exp: 15 / 132.0Missense obs/exp: 940 / 1346.6Syn Z: 0.43

ClinVar Variant Classifications

353 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic1
VUS270
Likely Benign32
Benign24
Conflicting1
25
Pathogenic
1
Likely Pathogenic
270
VUS
32
Likely Benign
24
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
25
0
25
Likely Pathogenic
0
1
0
0
1
VUS
2
244
24
0
270
Likely Benign
0
12
6
14
32
Benign
0
3
4
17
24
Conflicting
—1
Total22605931353

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.

Gene2Phenotype Curations

NCOR1-related developmental disorder

limited
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
De novo genic mutations among a Chinese autism spectrum disorder cohort.
Wang T et al.·Nat Commun
2016Cohort
p21-activated kinase 4 suppresses fatty acid β-oxidation and ketogenesis by phosphorylating NCoR1.
Shi MY et al.·Nat Commun
2023
Genomic characterization of metastatic breast cancers.
Bertucci F et al.·Nature
2019
Nuclear DEK preserves hematopoietic stem cells potential via NCoR1/HDAC3-Akt1/2-mTOR axis.
Chen Z et al.·J Exp Med
2021
NCoR1 controls immune tolerance in conventional dendritic cells by fine-tuning glycolysis and fatty acid oxidation.
Sen K et al.·Redox Biol
2023
NCoR1 limits angiogenic capacity by altering Notch signaling.
Teichmann T et al.·J Mol Cell Cardiol
2024
Isolation of a tumor neoantigen specific CD8+ TCR from a skin biopsy of a vaccination site.
Roberti MP et al.·Oncoimmunology
2025
Clinical Application of a Customized Gene Panel for Identifying Autism Spectrum Disorder-Associated Variants.
Greco V et al.·Medicina (Kaunas)
2025
Structural Basis of PPARγ-Mediated Transcriptional Repression by the Covalent Inverse Agonist FX-909.
Laughlin ZT et al.·J Med Chem
2025
Racial and sex differences in tumor genomics in urothelial carcinoma.
Nyame YA et al.·Urol Oncol
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
NCOR1 alleviates myocardial infarction by improving lipid peroxidation through PPARG/PINK1-mediated mitophagy.
Liu Z et al.·Biochem Cell Biol
2026
Nsun2-mediated m5C methylation of Ncor1 exacerbates sepsis-induced cardiomyopathy by promoting mitochondrial dysfunction.
Chen C et al.·Free Radic Biol Med
2026
Small molecule disruption of RARα/NCoR1 interaction inhibits chaperone-mediated autophagy in cancer.
McCabe M et al.·EMBO Mol Med
2025🔓 Open Access
An investigative study on the impact of DLK1 and NCoR1 knockdown by siRNA transfection on endometrial cancer proliferation: unveiling notch interactions.
Chandran Manimegalai S et al.·Med Oncol
2025
The transcription factor PPARA mediates SIRT1 regulation of NCOR1 to protect damaged heart cells.
Wang M et al.·Cardiovasc Diagn Ther
2024🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
NCOR Gene MutationsSpironolactoneASD

Spironolactone Improved Children With NCOR Mutations

NOT YET RECRUITING
NCT06678685Phase PHASE2, PHASE3Qilu Hospital of Shandong UniversityStarted 2024-10-30
.spironolactone

External Resources

Links to major genomics databases and tools