RCOR2

Chr 11

REST corepressor 2

NCBI Gene: 283248 ENSG00000167771 UniProt: Q8IZ40 OMIM: 616019

The protein functions as a transcription corepressor that represses gene expression by acting as a component of histone deacetylase complexes. Mutations cause autosomal recessive neurodevelopmental disorders characterized by intellectual disability, developmental delay, and neurological abnormalities. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.456), suggesting some intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable transcription corepressor activity. Predicted to be involved in negative regulation of DNA-templated transcription and regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of histone deacetylase complex and transcription regulator complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.46

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.46LOEUF

pLI 0.207

Z-score 3.77

OE 0.24 (0.14–0.46)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.65Z-score

OE missense 0.73 (0.65–0.82)

213 obs / 292.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.14–0.46)

0≤0.351.4

Missense OE?0.73 (0.65–0.82)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 7 / 28.8Missense obs/exp: 213 / 292.2Syn Z: 0.45

Background carrier burden — how many people carry a rare variant somewhere in RCOR2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

635 rare PASS variants

Rare truncating (LoF)

1 in 2,400

73 rare PASS variants

Rare synonymous (reference)

1 in 110

310 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RCOR2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 2,000
South Asian	~43k	1 in 92	1 in 3,000
Remaining (unassigned)	~30k	1 in 98	≈ 1 in 6,500
European (Finnish)	~27k	1 in 230	1 in 1,900
Admixed American	~22k	1 in 110	≈ 1 in 6,500
African / African American	~21k	1 in 110	none seen
East Asian	~20k	1 in 120	1 in 1,700
Ashkenazi Jewish	~13k	1 in 240	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 89	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 11 of 12 coding exons well covered in gnomAD exomes; exon 12 marginal. Genomes: 10 of 12 (exons 2, 12 below).? see exons ↓