GeneBe

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

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Nemaline myopathy 2, autosomal recessive; Arthrogryposis multiplex congenita 6ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Musculoskeletal10051637; 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 (10710 variants)
  • not_provided (1898 variants)
  • Inborn_genetic_diseases (970 variants)
  • Arthrogryposis_multiplex_congenita_6 (717 variants)
  • not_specified (540 variants)
  • Nemaline_myopathy (323 variants)
  • NEB-related_disorder (218 variants)
  • See_cases (7 variants)
  • Nemaline_Myopathy,_Recessive (5 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)
  • Limb_pain (2 variants)
  • Muscle_weakness (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)
  • 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.

EffectPLPVUSLBBSum
synonymous
4
clinvar
7
clinvar
112
clinvar
3272
clinvar
73
clinvar
 3468
missense
4
clinvar
49
clinvar
2827
clinvar
1236
clinvar
39
clinvar
 4155
nonsense
209
clinvar
291
clinvar
7
clinvar
 507
start loss
0
frameshift
345
clinvar
494
clinvar
4
clinvar
 843
splice donor/acceptor (+/-2bp)
46
clinvar
383
clinvar
23
clinvar
1
clinvar
 453
Total 608 1224 2973 4509 112

Highest pathogenic variant AF is 0.0011467724

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
NEBprotein_codingprotein_codingENST00000397345 180249152
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
4.56e-411.0012448303651248480.00146
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.040937823.77e+31.000.00020856792
Missense in Polyphen18171893.80.9594328149
Synonymous-0.36413731.36e+31.010.000078814549
Loss of Function11.61453930.3690.00002055971

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.002970.00286
Ashkenazi Jewish0.0009020.000795
East Asian0.001370.00134
Finnish0.0009780.000974
European (Non-Finnish)0.001750.00167
Middle Eastern0.001370.00134
South Asian0.001420.00137
Other0.001700.00165

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

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

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