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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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NBEA
neurobeachin
Chromosome 13 Β· 13q13.3
NCBI Gene: 26960Ensembl: ENSG00000172915.20HGNC: HGNC:7648UniProt: B3KXQ8
56PubMed Papers
21Diseases
0Drugs
74Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
endomembrane systemsynapse organizationcytosolmembraneneurodevelopmental disorder with or without early-onset generalized epilepsyepilepsy, early-onset, with or without developmental delayIntellectual disabilityGlobal developmental delay
✦AI Summary

NBEA (neurobeachin) is a scaffolding protein that anchors protein kinase A (PKA) regulatory subunits to cellular membranes and organelles, facilitating kinase positioning at specific subcellular locations. 1 At GABAergic synapses, NBEA interacts with the postsynaptic anchor protein gephyrin and regulates GABAA receptor internalization through PKA-dependent mechanisms, thereby modulating inhibitory synaptic strength. 1 NBEA functions in synapse organization and trafficking of ion channels, with its DUF1088 domain being critical for proper neuronal function. 2 NBEA is established as a neurodevelopmental disorder (NDD) gene, with de novo variants identified in 24 patients presenting primarily with early-onset generalized epilepsy characterized by myoclonic and atonic seizure types, often manifesting within the first few years of life. 3 Loss-of-function variants in NBEA result in altered neuronal trafficking and cell fate determination. 2 Beyond neurological disease, NBEA genetic variation predicts individual responsiveness to GLP-1 receptor agonist weight-loss therapy, with specific genetic scores associated with significantly higher likelihood of substantial weight loss on liraglutide and semaglutide. 4 Additionally, circular RNA derived from NBEA (circ-Nbea) participates in diabetic encephalopathy pathogenesis through microRNA-128-3p sponging mechanisms. 5

Sources cited
1
NBEA established as NDD gene with de novo variants; patients present with early-onset generalized epilepsy including myoclonic and atonic seizures
PMID: 30269351
2
NBEA regulates GABAA receptor internalization at inhibitory synapses through PKA-dependent anchoring and gephyrin interaction
PMID: 39668217
3
DUF1088 domain of NBEA is critical for neuronal function including potassium channel trafficking and cell fate determination
PMID: 34412939
4
NBEA genetic variation predicts GLP-1 receptor agonist weight loss response in large real-world cohorts
PMID: 40677145
5
Circular RNA circ-Nbea participates in diabetic encephalopathy through miR-128-3p sponging mechanisms
PMID: 34695392
Disease Associationsβ“˜21
neurodevelopmental disorder with or without early-onset generalized epilepsyOpen Targets
0.64Moderate
epilepsy, early-onset, with or without developmental delayOpen Targets
0.62Moderate
Intellectual disabilityOpen Targets
0.61Moderate
Global developmental delayOpen Targets
0.50Moderate
SeizureOpen Targets
0.50Moderate
cerebellar, ocular, craniofacial, and genital syndromeOpen Targets
0.49Moderate
genetic disorderOpen Targets
0.49Moderate
hepatocellular carcinomaOpen Targets
0.47Moderate
ovarian carcinomaOpen Targets
0.43Moderate
esophageal diseaseOpen Targets
0.39Weak
Abnormal dense granulesOpen Targets
0.37Weak
autosomal dominant non-syndromic intellectual disabilityOpen Targets
0.37Weak
complex neurodevelopmental disorderOpen Targets
0.37Weak
placental retentionOpen Targets
0.35Weak
smoking initiationOpen Targets
0.35Weak
autism spectrum disorderOpen Targets
0.34Weak
Neurodevelopmental delayOpen Targets
0.34Weak
epilepsyOpen Targets
0.34Weak
high grade ovarian serous adenocarcinomaOpen Targets
0.34Weak
alcohol drinkingOpen Targets
0.33Weak
Neurodevelopmental disorder with or without early-onset generalized epilepsyUniProt
Pathogenic Variants74
NM_001385012.1(NBEA):c.3362dup (p.Asn1121fs)Likely pathogenic
Neurodevelopmental disorder with or without early-onset generalized epilepsy
β˜…β˜…β˜†β˜†2024β†’ Residue 1121
NM_001385012.1(NBEA):c.6637C>T (p.Arg2213Ter)Pathogenic
not specified|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 2213
NM_001385012.1(NBEA):c.4477_4478del (p.Arg1493fs)Pathogenic
Inborn genetic diseases|Neurodevelopmental disorder with or without early-onset generalized epilepsy
β˜…β˜…β˜†β˜†2023β†’ Residue 1493
NM_001385012.1(NBEA):c.955G>T (p.Asp319Tyr)Likely pathogenic
NBEA-related complex neurodevelopmental disorder|not specified
β˜…β˜…β˜†β˜†2022β†’ Residue 319
NM_001385012.1(NBEA):c.7765del (p.His2589fs)Pathogenic
Neurodevelopmental disorder with or without early-onset generalized epilepsy
β˜…β˜†β˜†β˜†2026β†’ Residue 2589
NM_001385012.1(NBEA):c.5854A>G (p.Ile1952Val)Likely pathogenic
Neurodevelopmental disorder with or without early-onset generalized epilepsy
β˜…β˜†β˜†β˜†2025β†’ Residue 1952
NM_001385012.1(NBEA):c.8596C>T (p.Arg2866Ter)Pathogenic
Neurodevelopmental disorder with or without early-onset generalized epilepsy
β˜…β˜†β˜†β˜†2025β†’ Residue 2866
NM_001385012.1(NBEA):c.972+1G>TPathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_001385012.1(NBEA):c.6756_6757del (p.Tyr2252_Ser2253delinsTer)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 2252
NM_001385012.1(NBEA):c.6091C>T (p.Arg2031Ter)Likely pathogenic
Neurodevelopmental disorder with or without early-onset generalized epilepsy
β˜…β˜†β˜†β˜†2025β†’ Residue 2031
NM_001385012.1(NBEA):c.6012+2T>CLikely pathogenic
Neurodevelopmental disorder with or without early-onset generalized epilepsy
β˜…β˜†β˜†β˜†2025
NM_001385012.1(NBEA):c.1624C>T (p.Gln542Ter)Likely pathogenic
Neurodevelopmental disorder with or without early-onset generalized epilepsy
β˜…β˜†β˜†β˜†2025β†’ Residue 542
NM_001385012.1(NBEA):c.4662+2dupLikely pathogenic
Neurodevelopmental disorder with or without early-onset generalized epilepsy
β˜…β˜†β˜†β˜†2025
NM_001385012.1(NBEA):c.7616_7617+1delLikely pathogenic
Neurodevelopmental disorder with or without early-onset generalized epilepsy
β˜…β˜†β˜†β˜†2025
NM_001385012.1(NBEA):c.7491G>A (p.Trp2497Ter)Pathogenic
Neurodevelopmental disorder with or without early-onset generalized epilepsy
β˜…β˜†β˜†β˜†2024β†’ Residue 2497
NM_001385012.1(NBEA):c.6564dup (p.Phe2189fs)Pathogenic
Neurodevelopmental disorder with or without early-onset generalized epilepsy
β˜…β˜†β˜†β˜†2024β†’ Residue 2189
NM_001385012.1(NBEA):c.1102_1111dup (p.Leu371fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 371
NM_001385012.1(NBEA):c.8661+1G>APathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_001385012.1(NBEA):c.7928G>A (p.Arg2643Gln)Likely pathogenic
Neurodevelopmental disorder with or without early-onset generalized epilepsy
β˜…β˜†β˜†β˜†2024β†’ Residue 2643
NM_001385012.1(NBEA):c.5904-2A>GPathogenic
Neurodevelopmental disorder with or without early-onset generalized epilepsy|Glioma susceptibility 1
β˜…β˜†β˜†β˜†2024
View on ClinVar β†—
Related Genes
PPFIA4Shared pathway100%PRKACAProtein interaction100%PRKACBProtein interaction100%PRKACGProtein interaction100%DLG3Protein interaction96%NOTCH1Protein interaction91%
Tissue Expression6 tissues
Brain
100%
Heart
76%
Ovary
36%
Bone Marrow
8%
Lung
6%
Liver
3%
Gene Interaction Network
Click a node to explore
NBEAPPFIA4PRKACAPRKACBPRKACGDLG3NOTCH1
PROTEIN STRUCTURE
Preparing viewer…
PDB1MI1 Β· 2.90 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.14Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.10 [0.07–0.14]
RankingsWhere NBEA stands among ~20K protein-coding genes
  • #8,111of 20,598
    Most Researched56
  • #998of 5,498
    Most Pathogenic Variants74 Β· top quartile
  • #157of 17,882
    Most Constrained (LOEUF)0.14 Β· top 1%
Genes detectedNBEA
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
NBEA: Developmental disease gene with early generalized epilepsy phenotypes.
PMID: 30269351
Ann Neurol Β· 2018
1.00
2
Genotypic and phenotypic spectra of NBEA-related neurodevelopmental disorder with epilepsy: a case series and literature review.
PMID: 35852783
World J Pediatr Β· 2022
0.90
3
Synchronized long-read genome, methylome, epigenome and transcriptome profiling resolve a Mendelian condition.
PMID: 39880924
Nat Genet Β· 2025
0.80
4
Functional analysis of a de novo variant in the neurodevelopment and generalized epilepsy disease gene NBEA.
PMID: 34412939
Mol Genet Metab Β· 2021
0.70
5
Neurobeachin regulates receptor downscaling at GABAergic inhibitory synapses in a protein kinase A-dependent manner.
PMID: 39668217
Commun Biol Β· 2024
0.60