NBEA

Chr 13AD

neurobeachin

Also known as: BCL8B, LYST2, NEDEGE

NCBI Gene: 26960ENSG00000172915UniProt: Q8NFP9OMIM: 604889

This protein anchors protein kinase A to specific membrane locations and is involved in neuronal membrane trafficking. Mutations cause neurodevelopmental disorder with or without early-onset generalized epilepsy with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI = 1, LOEUF = 0.074), indicating intolerance to protein disruption.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.071 OMIM phenotype
Clinical Summary— NBEA
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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
13 unique Pathogenic / Likely Pathogenic· 115 VUS of 200 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
0.07LOEUF
pLI 1.000
Z-score 10.66
OE 0.04 (0.02–0.07)
Highly constrained

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

Missense Constraint
5.51Z-score
OE missense 0.60 (0.56–0.63)
875 obs / 1469.5 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.04 (0.02–0.07)
0≤0.351.4
Missense OE0.60 (0.56–0.63)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 5 / 142.1Missense obs/exp: 875 / 1469.5Syn Z: 0.34
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongNBEA-related neurodevelopment disorder with seizuresLOFAD
DN
0.3296th %ile
GOF
0.4184th %ile
LOF
0.73top 10%

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

LOFprediction above median · 1 literature citation · 62% of P/LP variants are LoF · LOEUF 0.07

Literature Evidence

LOFThese findings indicate that Nbea haploinsufficiency leads to various molecular and cellular changes that affect neuroplasticity and behavioral functions in mice, and could thus underlie the ASD symptomatology in NBEA deficient humans.PMID:23153818

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

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic4
VUS115
Likely Benign34
Benign3
Conflicting1
9
Pathogenic
4
Likely Pathogenic
115
VUS
34
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
3
0
9
Likely Pathogenic
2
2
0
0
4
VUS
2
106
7
0
115
Likely Benign
1
12
3
18
34
Benign
0
1
0
2
3
Conflicting
—1
Total111211320166

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

View in ClinVar →

Protein Context — Lollipop Plot

NBEA · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients