NCOR1

Chr 17

nuclear receptor corepressor 1

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

NCBI Gene: 9611 ENSG00000141027 UniProt: O75376 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.17

Clinical Summary— NCOR1

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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.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 251 VUS of 362 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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 OE?0.11 (0.07–0.17)

0≤0.351.4

Missense OE?0.70 (0.66–0.74)

0≤0.61.4

Synonymous OE?0.98

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

This gene — mechanism propensity

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

362 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS251

Likely Benign30

Benign24

Likely Pathogenic

251

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	1	0	0	1
VUS	3	246	2	0	251
Likely Benign	0	12	4	14	30
Benign	0	4	3	17	24
Total	3	263	9	31	306

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

View in ClinVar →

25 pathogenic / likely-pathogenic (of 49) ClinVar copy-number / structural variants overlap NCOR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →