NEB

nebulin

Basic information

Region (hg38): 2:151485335-151734487

Previous symbols: [ "NEM2" ]

Links

ENSG00000183091 ∙ NCBI:4703 ∙ OMIM:161650 ∙ HGNC:7720 ∙ Uniprot:P20929 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nemaline myopathy 2 (Definitive), mode of inheritance: AR
• nemaline myopathy 2 (Definitive), mode of inheritance: AR
• lethal multiple pterygium syndrome (Supportive), mode of inheritance: AR
• severe congenital nemaline myopathy (Supportive), mode of inheritance: AR
• intermediate nemaline myopathy (Supportive), mode of inheritance: AD
• typical nemaline myopathy (Supportive), mode of inheritance: AD
• childhood-onset nemaline myopathy (Supportive), mode of inheritance: AD
• nemaline myopathy 2 (Limited), mode of inheritance: AD
• nemaline myopathy 2 (Strong), mode of inheritance: AR
• nemaline myopathy 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nemaline myopathy 2, autosomal recessive; Arthrogryposis multiplex congenita 6	AR	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	Craniofacial; Musculoskeletal	10051637; 10619714; 12207937; 15221447; 16917880; 19232495; 19805734; 21798101; 22367672; 23010307; 25205138; 26578207; 27933661; 28336317; 29274205; 33376055

ClinVar

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

• Nemaline myopathy 2 (8409 variants)
• not provided (1601 variants)
• not specified (557 variants)
• Arthrogryposis multiplex congenita 6 (426 variants)
• Inborn genetic diseases (321 variants)
• Nemaline myopathy (82 variants)
• Nemaline myopathy 2;Arthrogryposis multiplex congenita 6 (55 variants)
• Arthrogryposis multiplex congenita 6;Nemaline myopathy 2 (37 variants)
• NEB-related condition (28 variants)
• Nemaline Myopathy, Recessive (12 variants)
• See cases (7 variants)
• Nebulin-related early-onset distal myopathy (3 variants)
• Peripheral neuropathy (2 variants)
• Actin accumulation myopathy (2 variants)
• Congenital muscular dystrophy;Muscle weakness (2 variants)
• Progressive proximal muscle weakness;Limb pain;Muscular dystrophy (2 variants)
• Abnormality of the neck;Dysphagia;Low-set ears (1 variants)
• NEB-related disorder (1 variants)
• Non-immune hydrops fetalis (1 variants)
• Abnormality of the musculature (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NEB 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	2	38	2602	63	2706
missense	2	4	2057	579	60	2702
nonsense	195	197	7			399
start loss						0
frameshift	280	330	2			612
inframe indel		2	87	1		90
splice donor/acceptor (+/-2bp)	34	300	14	1		349
splice region		3	163	432	30	628
non coding		1	111	740	85	937
Total	512	836	2316	3923	208

Highest pathogenic variant AF is 0.0000394

Variants in NEB

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

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

Position	Type	Phenotype	Significance	ClinVar
2-151485444-G-A		Nemaline myopathy 2	Uncertain significance (Jan 13, 2018)
2-151485494-CCT-C		Nemaline Myopathy, Recessive	Likely benign (Jun 14, 2016)
2-151485548-A-G		Nemaline myopathy 2	Conflicting classifications of pathogenicity (Mar 01, 2023)
2-151485559-T-A		Nemaline myopathy 2	Conflicting classifications of pathogenicity (Apr 01, 2023)
2-151485665-C-T		Nemaline myopathy 2	Uncertain significance (Jan 13, 2018)
2-151485703-G-A		Nemaline myopathy 2	Uncertain significance (Jan 13, 2018)
2-151485724-G-A		Nemaline myopathy 2	Uncertain significance (Jan 12, 2018)
2-151485765-T-C		Nemaline myopathy 2	Uncertain significance (Jan 12, 2018)
2-151485773-A-C		Inborn genetic diseases	Uncertain significance (Jan 02, 2024)
2-151485773-A-G		Nemaline myopathy 2 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 29, 2023)
2-151485774-C-A		Nemaline myopathy 2	Uncertain significance (Nov 20, 2020)
2-151485774-C-T		Nemaline myopathy 2 • NEB-related disorder	Conflicting classifications of pathogenicity (Jan 31, 2024)
2-151485775-G-A		Nemaline myopathy 2	Likely benign (Dec 21, 2022)
2-151485783-C-T		Nemaline myopathy 2 • Inborn genetic diseases	Uncertain significance (Oct 04, 2022)
2-151485787-G-A		Nemaline myopathy 2	Likely benign (May 15, 2023)
2-151485793-TC-T		Nemaline myopathy 2	Uncertain significance (May 23, 2017)
2-151485795-C-A		Nemaline myopathy 2	Uncertain significance (May 23, 2017)
2-151485795-C-T		Nemaline myopathy 2 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Feb 27, 2024)
2-151485796-G-A		not specified • Nemaline myopathy 2	Benign (Feb 01, 2024)
2-151485796-G-C		Nemaline myopathy 2	Likely benign (Jul 21, 2021)
2-151485798-T-C		Nemaline myopathy 2	Likely benign (Nov 10, 2023)
2-151485802-G-A		Nemaline myopathy 2	Likely benign (Feb 24, 2023)
2-151485803-C-T		Nemaline myopathy 2	Uncertain significance (May 23, 2023)
2-151485804-C-G		Nemaline myopathy 2 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 25, 2024)
2-151485804-C-T		Nemaline myopathy 2 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NEB	protein_coding	protein_coding	ENST00000397345	180	249152

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.56e-41	1.00	124483	0	365	124848	0.00146

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0409	3782	3.77e+3	1.00	0.000208	56792
Missense in Polyphen		1817	1893.8	0.95943		28149
Synonymous	-0.364	1373	1.36e+3	1.01	0.0000788	14549
Loss of Function	11.6	145	393	0.369	0.0000205	5971

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00297	0.00286
Ashkenazi Jewish	0.000902	0.000795
East Asian	0.00137	0.00134
Finnish	0.000978	0.000974
European (Non-Finnish)	0.00175	0.00167
Middle Eastern	0.00137	0.00134
South Asian	0.00142	0.00137
Other	0.00170	0.00165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This giant muscle protein may be involved in maintaining the structural integrity of sarcomeres and the membrane system associated with the myofibrils. Binds and stabilize F-actin.
• Pathway: Striated Muscle Contraction;Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling;Striated Muscle Contraction;Muscle contraction (Consensus)

Recessive Scores

• pRec: 0.379

Intolerance Scores

• loftool: 0.995
• rvis_EVS: 0.88
• rvis_percentile_EVS: 88.9

Haploinsufficiency Scores

• pHI: 0.149
• hipred: N
• hipred_score: 0.270
• ghis: 0.492

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.744

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Neb
• Phenotype: 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; vision/eye phenotype; muscle phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: neb
• Affected structure: skeletal muscle cell
• Phenotype tag: abnormal
• Phenotype quality: aggregated

Gene ontology

• Biological process: muscle organ development;somatic muscle development;muscle filament sliding;regulation of actin filament length;muscle fiber development;cardiac muscle thin filament assembly
• Cellular component: cytosol;actin cytoskeleton;Z disc;extracellular exosome
• Molecular function: protein binding;structural constituent of muscle;actin filament binding