NEB

Chr 2

nebulin

NCBI Gene: 4703ENSG00000183091UniProt: P20929

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

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNemaline myopathy 2
UniProtArthrogryposis multiplex congenita 6

Clinical highlights

Gene-disease validity (ClinGen)
nemaline myopathy 2 · ARDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
214
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.42
LOEUF
LOF
Mechanism· G2P
📖
GeneReview available — NEB
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.42LOEUF
pLI 0.000
Z-score 11.58
OE 0.37 (0.32–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
-0.04Z-score
OE missense 1.00 (0.97–1.03)
3782 obs / 3774.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.37 (0.32–0.42)
0≤0.351.4
Missense OE?1.00 (0.97–1.03)
0≤0.61.4
Synonymous OE?1.01
0≤1.21.6
LoF obs/exp: 145 / 392.5Missense obs/exp: 3782 / 3774.9Syn Z: -0.36

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

NEB · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

VCEP specificationsCongenital MyopathiesReleased
Panel ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients