NCBP2

Chr 3

nuclear cap binding protein subunit 2

Also known as: CBC2, CBP20, NIP1, PIG55

NCBP2 encodes a component of the nuclear cap-binding complex that binds to the 5' cap of pre-mRNAs and regulates pre-mRNA splicing, mRNA export from the nucleus, and nonsense-mediated mRNA decay. Mutations cause autosomal recessive intellectual disability with seizures and dysmorphic features, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.675), suggesting some tolerance to complete protein loss.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
10
Pubs (1 yr)
88
P/LP submissions
P/LP missense
0.68
LOEUF
DN
Mechanism· predicted
Clinical SummaryNCBP2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.21) despite low pLI — interpret in context.
📋
ClinVar Variants
87 unique Pathogenic / Likely Pathogenic· 29 VUS of 127 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.68LOEUF
pLI 0.400
Z-score 2.22
OE 0.21 (0.090.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.15Z-score
OE missense 0.40 (0.310.52)
40 obs / 100.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.21 (0.090.68)
00.351.4
Missense OE0.40 (0.310.52)
00.61.4
Synonymous OE1.33
01.21.6
LoF obs/exp: 2 / 9.3Missense obs/exp: 40 / 100.7Syn Z: -1.58
DN
0.6261th %ile
GOF
0.5660th %ile
LOF
0.53top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

127 submitted variants in ClinVar

Classification Summary

Pathogenic84
Likely Pathogenic3
VUS29
Likely Benign1
Conflicting1
84
Pathogenic
3
Likely Pathogenic
29
VUS
1
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
84
Likely Pathogenic
3
VUS
29
Likely Benign
1
Benign
0
Conflicting
1
Total118

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NCBP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC