NEB

nebulin

Basic information

Region (hg38): 2:151485336-151734487

Previous symbols: [ "NEM2" ]

Links

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

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 58.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_001164508.2	NP_001157980.2	180	yes	-
ENST00000397345.8	ENSP00000380505.3	180	yes	-
NM_004543.5	NP_004534.3	148	-	-
NM_001164507.2	NP_001157979.2	180	-	yes

Phenotypes

GenCC

Source: genCC

• nemaline myopathy 2 (Limited), mode of inheritance: AD
• nemaline myopathy 2 (Definitive), mode of inheritance: AR
• autosomal dominant nebulin-related myopathy (Moderate), mode of inheritance: AD
• nemaline myopathy 2 (Strong), 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 (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 (11060 variants)
• not_provided (1963 variants)
• Inborn_genetic_diseases (1078 variants)
• Arthrogryposis_multiplex_congenita_6 (724 variants)
• not_specified (584 variants)
• Nemaline_myopathy (327 variants)
• NEB-related_disorder (218 variants)
• See_cases (7 variants)
• Congenital_structural_myopathy (4 variants)
• Congenital_myopathy (4 variants)
• Limb-girdle_muscular_dystrophy (4 variants)
• Nebulin-related_early-onset_distal_myopathy (3 variants)
• Peripheral_neuropathy (2 variants)
• Progressive_proximal_muscle_weakness (2 variants)
• Distal_myopathy (2 variants)
• Muscle_weakness (2 variants)
• Limb_pain (2 variants)
• Congenital_muscular_dystrophy (2 variants)
• Actin_accumulation_myopathy (2 variants)
• Muscular_dystrophy (2 variants)
• Abnormality_of_the_neck (1 variants)
• Dysphagia (1 variants)
• Abnormality_of_the_musculature (1 variants)
• Non-immune_hydrops_fetalis (1 variants)
• Fetal_anomalies_with_a_likely_genetic_cause (1 variants)
• Low-set_ears (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. These statistics are base on transcript: NM_001164508.2. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	4	10	116	3344	72	3546
missense	4	53	2944	1243	38	4282
nonsense	194	347	10			551
start loss						0
frameshift	331	587	5			923
splice donor/acceptor (+/-2bp)	39	403	27	1		470
Total	572	1400	3102	4588	110

Highest pathogenic variant AF is 0.0011467724

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
		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

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

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