NCBP1

Chr 9

nuclear cap binding protein subunit 1

Also known as: CBP80, NCBP, Sto1

The NCBP1 protein is 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 dominant intellectual disability with microcephaly, typically presenting in early childhood. NCBP1 is highly constrained against loss-of-function variants, indicating that proper protein function is critical for normal development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.09
Clinical SummaryNCBP1
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
32 unique Pathogenic / Likely Pathogenic· 75 VUS of 136 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.09LOEUF
pLI 1.000
Z-score 6.44
OE 0.02 (0.010.09)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.52Z-score
OE missense 0.52 (0.470.58)
224 obs / 429.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.02 (0.010.09)
00.351.4
Missense OE0.52 (0.470.58)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 1 / 50.3Missense obs/exp: 224 / 429.5Syn Z: 0.66
DN
0.2997th %ile
GOF
0.4184th %ile
LOF
0.72top 10%

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

LOFprediction above median · LOEUF 0.09

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

136 submitted variants in ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic4
VUS75
Likely Benign1
Benign1
28
Pathogenic
4
Likely Pathogenic
75
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
28
0
28
Likely Pathogenic
0
0
4
0
4
VUS
0
71
4
0
75
Likely Benign
0
0
1
0
1
Benign
0
0
0
1
1
Total071371109

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

View in ClinVar →

Protein Context — Lollipop Plot

NCBP1 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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