NBEA

neurobeachin, the group of BEACH domain containing |WD repeat domain containing|A-kinase anchoring proteins|Armadillo like helical domain containing

Basic information

Region (hg38): 13:34942269-35673022

Links

ENSG00000172915 ∙ NCBI:26960 ∙ OMIM:604889 ∙ HGNC:7648 ∙ Uniprot:Q8NFP9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic intellectual disability (Strong), mode of inheritance: AD
• neurodevelopmental disorder with or without early-onset generalized epilepsy (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with or without early-onset generalized epilepsy	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	28554332; 30269351

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NBEA gene.

• not provided (218 variants)
• Neurodevelopmental disorder with or without early-onset generalized epilepsy (74 variants)
• Inborn genetic diseases (72 variants)
• See cases (12 variants)
• NBEA-related condition (11 variants)
• not specified (10 variants)
• Intellectual disability (3 variants)
• Developmental disorder (2 variants)
• Neurodevelopmental disorder (2 variants)
• Autism spectrum disorder (2 variants)
• NBEA-related intellectual disability (2 variants)
• Seizure (2 variants)
• Global developmental delay (1 variants)
• Hypoplasia of scrotum (1 variants)
• Intellectual disability and seizures (1 variants)
• Neurodevelopmental delay;Epilepsy (1 variants)
• NBEA-related complex neurodevelopmental disorder (1 variants)
• NBEA-related developmental delay and generalized epilepsy (1 variants)
• Intellectual disability;Autistic behavior (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NBEA gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	39	5	45
missense		5	234	27	6	272
nonsense	6	8				14
start loss						0
frameshift	5	5	2			12
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)	5	2	3			10
splice region		1	8	3	2	14
non coding		1	10		2	13
Total	16	21	251	67	13

Variants in NBEA

This is a list of pathogenic ClinVar variants found in the NBEA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
13-34942660-C-T		Abnormal bleeding;Thrombocytopenia	Uncertain significance (May 01, 2020)
13-34942834-A-G		Neurodevelopmental disorder with or without early-onset generalized epilepsy	Uncertain significance (-)
13-34942836-C-T		Neurodevelopmental disorder with or without early-onset generalized epilepsy	Uncertain significance (Feb 04, 2022)
13-34942837-C-A		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
13-34942840-G-A		See cases	Uncertain significance (Aug 19, 2021)
13-34942845-G-T			Uncertain significance (Oct 01, 2023)
13-34942858-A-C		Neurodevelopmental disorder with or without early-onset generalized epilepsy	Uncertain significance (Mar 29, 2024)
13-34942861-C-T		NBEA-related disorder	Uncertain significance (Nov 15, 2023)
13-34942867-C-T		Inborn genetic diseases	Uncertain significance (Jan 09, 2024)
13-34942868-C-G		NBEA-related disorder	Benign/Likely benign (Aug 28, 2019)
13-34942893-G-A		not specified	Conflicting classifications of pathogenicity (Feb 06, 2024)
13-34942906-GCGGGGGCAGCGGTGGTGGCGGCAC-G		NBEA-related disorder	Conflicting classifications of pathogenicity (Jan 02, 2024)
13-34942915-GC-AT		Neurodevelopmental disorder with or without early-onset generalized epilepsy	Uncertain significance (Apr 30, 2021)
13-34942922-T-G			Likely benign (Aug 01, 2023)
13-34942935-G-T			Uncertain significance (Apr 19, 2023)
13-34942936-G-A			Uncertain significance (Dec 09, 2021)
13-34942938-A-C		Inborn genetic diseases	Uncertain significance (Mar 14, 2023)
13-34942938-A-G		Inborn genetic diseases	Likely benign (Aug 01, 2023)
13-34942938-AG-CC		NBEA-related disorder	Uncertain significance (Feb 15, 2024)
13-34942939-G-C		Inborn genetic diseases	Uncertain significance (Mar 14, 2023)
13-34942942-G-A			Uncertain significance (Jul 22, 2019)
13-34942942-G-C		NBEA-related disorder	Uncertain significance (Sep 29, 2023)
13-34942956-A-C			Likely benign (Nov 01, 2023)
13-34942961-G-C		NBEA-related disorder	Likely benign (Feb 27, 2023)
13-34942962-G-A			Uncertain significance (May 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NBEA	protein_coding	protein_coding	ENST00000400445	58	730736

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	5.55e-20	124615	0	11	124626	0.0000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.51	875	1.47e+3	0.595	0.0000746	19241
Missense in Polyphen		194	540.22	0.35911		7330
Synonymous	0.344	505	515	0.981	0.0000264	5628
Loss of Function	10.7	5	142	0.0352	0.00000778	1798

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000192	0.000192
Ashkenazi Jewish	0.00	0.00
East Asian	0.000116	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.0000381	0.0000354
Middle Eastern	0.000116	0.0000556
South Asian	0.0000351	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds to type II regulatory subunits of protein kinase A and anchors/targets them to the membrane. May anchor the kinase to cytoskeletal and/or organelle-associated proteins (By similarity). {ECO:0000250}.

Intolerance Scores

• loftool: 0.362
• rvis_EVS: -1.89
• rvis_percentile_EVS: 1.98

Haploinsufficiency Scores

• pHI: 0.506
• hipred: Y
• hipred_score: 0.761
• ghis: 0.580

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.836

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nbea
• Phenotype: embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: nbeaa
• Affected structure: Mauthner neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: protein localization
• Cellular component: trans-Golgi network;cytosol;plasma membrane;endomembrane system
• Molecular function: protein kinase binding