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 (532 variants)
  • not provided (44 variants)
  • Arthrogryposis multiplex congenita 6 (38 variants)
  • Nemaline myopathy (34 variants)
  • Nemaline myopathy 2;Arthrogryposis multiplex congenita 6 (8 variants)
  • NEB-related disorder (7 variants)
  • Arthrogryposis multiplex congenita 6;Nemaline myopathy 2 (2 variants)
  • Inborn genetic diseases (1 variants)
  • Abnormality of the neck;Low-set ears;Dysphagia (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
clinvar
3
clinvar
34
clinvar
3035
clinvar
81
clinvar
 3154
missense
2
clinvar
4
clinvar
2200
clinvar
636
clinvar
55
clinvar
 2897
nonsense
215
clinvar
250
clinvar
7
clinvar
 472
start loss
0
frameshift
321
clinvar
418
clinvar
2
clinvar
 741
inframe indel
1
clinvar
2
clinvar
88
clinvar
1
clinvar
 92
splice donor/acceptor (+/-2bp)
35
clinvar
358
clinvar
17
clinvar
1
clinvar
 411
splice region
1
5
162
546
32
 746
non coding
1
clinvar
4
clinvar
59
clinvar
1458
clinvar
96
clinvar
 1618
Total 576 1039 2407 5130 233

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)892682
2-151485494-CCT-C Nemaline Myopathy, Recessive Likely benign (Jun 14, 2016)331397
2-151485548-A-G Nemaline myopathy 2 Conflicting classifications of pathogenicity (Mar 01, 2023)892683
2-151485559-T-A Nemaline myopathy 2 Conflicting classifications of pathogenicity (Apr 01, 2023)893482
2-151485665-C-T Nemaline myopathy 2 Uncertain significance (Jan 13, 2018)893483
2-151485703-G-A Nemaline myopathy 2 Uncertain significance (Jan 13, 2018)331398
2-151485724-G-A Nemaline myopathy 2 Uncertain significance (Jan 12, 2018)331399
2-151485762-A-C Arthrogryposis multiplex congenita 6;Nemaline myopathy 2 Uncertain significance (Apr 11, 2024)3584395
2-151485765-T-C Nemaline myopathy 2 Uncertain significance (Jan 12, 2018)893484
2-151485773-A-C Inborn genetic diseases Uncertain significance (Jan 02, 2024)3189285
2-151485773-A-G Nemaline myopathy 2 • Inborn genetic diseases Conflicting classifications of pathogenicity (Mar 12, 2024)2202536
2-151485774-C-A Nemaline myopathy 2 Uncertain significance (Nov 20, 2020)1501709
2-151485774-C-T Nemaline myopathy 2 • NEB-related disorder Conflicting classifications of pathogenicity (Jan 20, 2025)331400
2-151485775-G-A Nemaline myopathy 2 Likely benign (Dec 21, 2022)1574459
2-151485783-C-T Nemaline myopathy 2 • Inborn genetic diseases Uncertain significance (Mar 26, 2025)653358
2-151485787-G-A Nemaline myopathy 2 Likely benign (May 15, 2023)2892127
2-151485793-TC-T Nemaline myopathy 2 Uncertain significance (May 23, 2017)552112
2-151485795-C-A Nemaline myopathy 2 Uncertain significance (May 23, 2017)552113
2-151485795-C-T Inborn genetic diseases • Nemaline myopathy 2 Conflicting classifications of pathogenicity (Mar 18, 2024)1366105
2-151485796-G-A not specified • Nemaline myopathy 2 Benign (Feb 03, 2025)194578
2-151485796-G-C Nemaline myopathy 2 Likely benign (Jul 21, 2021)737095
2-151485798-T-C Nemaline myopathy 2 Likely benign (Nov 10, 2023)2960447
2-151485802-G-A Nemaline myopathy 2 Likely benign (Feb 24, 2023)3011312
2-151485803-C-T Nemaline myopathy 2 Uncertain significance (May 23, 2023)1378961
2-151485804-C-G Nemaline myopathy 2 • Inborn genetic diseases Conflicting classifications of pathogenicity (Mar 19, 2024)2078290

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