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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
KLHL41
kelch like family member 41
Chromosome 2 Β· 2q31.1
NCBI Gene: 10324Ensembl: ENSG00000239474.8HGNC: HGNC:16905UniProt: O60662
28PubMed Papers
21Diseases
0Drugs
32Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingprotein ubiquitinationcytoplasmsarcoplasmic reticulum membranenemaline myopathy 9nemaline myopathytypical nemaline myopathyintermediate nemaline myopathy
✦AI Summary

KLHL41 (kelch like family member 41) is a ubiquitin ligase adaptor protein critical for skeletal muscle sarcomere maintenance and integrity. As a component of the Cul3-RING ubiquitin ligase complex, KLHL41 stabilizes sarcomeric proteins through nonproteolytic ubiquitination, particularly preventing aggregation and degradation of Nebulin, an essential sarcomere component 1. This stabilization function is distinct from canonical protein degradation pathways and represents a unique molecular chaperone-like mechanism for protein preservation 1. KLHL41 also regulates myoblast proliferation and differentiation during skeletal muscle development and participates in myofibril assembly by promoting lateral fusion of thin fibrils into mature myofibrils. Mutations in KLHL41 cause nemaline myopathy 9, a fatal muscle disorder characterized by sarcomere disarray and lethal disruption of muscle structure 1. KLHL41 mutant mice display aberrant expression of muscle structural and contractile proteins mimicking human disease phenotypes 1. Recent evidence indicates KLHL41 is upregulated during beta2-adrenergic-mediated muscle hypertrophy and is required for the anabolic response to beta2-agonists in cultured myotubes 2, suggesting therapeutic potential for muscle wasting conditions. Homozygous KLHL41 mutations have been identified in critically ill neonates with nemaline myopathy 3, confirming its clinical relevance in severe early-onset myopathies.

Sources cited
1
KLHL41 stabilizes sarcomeric Nebulin through nonproteolytic ubiquitination and prevents sarcomere disarray in nemaline myopathy
PMID: 28826497
2
KLHL41 is upregulated during beta2-adrenergic muscle hypertrophy and is required for myotube diameter increase in response to beta2-agonist
PMID: 39366923
3
Homozygous KLHL41 mutations cause nemaline myopathy in critically ill neonates
PMID: 28939701
⚠Limited data available β€” This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
nemaline myopathy 9Open Targets
0.78Strong
nemaline myopathyOpen Targets
0.44Moderate
childhood-onset nemaline myopathyOpen Targets
0.37Weak
intermediate nemaline myopathyOpen Targets
0.37Weak
severe congenital nemaline myopathyOpen Targets
0.37Weak
typical nemaline myopathyOpen Targets
0.37Weak
genetic disorderOpen Targets
0.19Weak
metabolic syndromeOpen Targets
0.07Suggestive
Distal myopathy, Nonaka typeOpen Targets
0.05Suggestive
myopathy, distal, 5Open Targets
0.05Suggestive
autosomal recessive limb-girdle muscular dystrophy type 2LOpen Targets
0.05Suggestive
tibial muscular dystrophyOpen Targets
0.04Suggestive
GNE myopathyOpen Targets
0.04Suggestive
nerve plexus diseaseOpen Targets
0.04Suggestive
arthrogryposis multiplex congenita 2, neurogenic typeOpen Targets
0.04Suggestive
Neurogenic arthrogryposis multiplex congenitaOpen Targets
0.04Suggestive
autosomal dominant limb-girdle muscular dystrophy type 1GOpen Targets
0.04Suggestive
distal myopathy, Welander typeOpen Targets
0.04Suggestive
nebulin-related early-onset distal myopathyOpen Targets
0.03Suggestive
schizophreniaOpen Targets
0.03Suggestive
Nemaline myopathy 9UniProt
Pathogenic Variants32
NM_006063.3(KLHL41):c.1416dup (p.Gly473fs)Pathogenic
Nemaline myopathy 9|KLHL41-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 473
NM_006063.3(KLHL41):c.1027C>T (p.Gln343Ter)Pathogenic
Nemaline myopathy 9
β˜…β˜…β˜†β˜†2024β†’ Residue 343
NM_006063.3(KLHL41):c.215del (p.Lys72fs)Pathogenic
Nemaline myopathy 9
β˜…β˜…β˜†β˜†2022β†’ Residue 72
NM_006063.3(KLHL41):c.678del (p.Leu226_Met227insTer)Pathogenic
Nemaline myopathy 9
β˜…β˜†β˜†β˜†2025β†’ Residue 226
NM_006063.3(KLHL41):c.1561_1562+2delLikely pathogenic
Nemaline myopathy 9
β˜…β˜†β˜†β˜†2025
NM_006063.3(KLHL41):c.446_447insT (p.Arg149fs)Pathogenic
Nemaline myopathy 9
β˜…β˜†β˜†β˜†2025β†’ Residue 149
NM_006063.3(KLHL41):c.1615del (p.Ser539fs)Pathogenic
Nemaline myopathy 9
β˜…β˜†β˜†β˜†2025β†’ Residue 539
NM_006063.3(KLHL41):c.624_628del (p.Glu209fs)Pathogenic
Nemaline myopathy 9
β˜…β˜†β˜†β˜†2024β†’ Residue 209
NM_006063.3(KLHL41):c.613C>T (p.Arg205Ter)Pathogenic
Nemaline myopathy 9
β˜…β˜†β˜†β˜†2024β†’ Residue 205
NM_006063.3(KLHL41):c.1093C>T (p.Gln365Ter)Pathogenic
Nemaline myopathy 9
β˜…β˜†β˜†β˜†2024β†’ Residue 365
NM_006063.3(KLHL41):c.468dup (p.Phe157fs)Pathogenic
Nemaline myopathy 9
β˜…β˜†β˜†β˜†2024β†’ Residue 157
NM_006063.3(KLHL41):c.667C>T (p.Arg223Cys)Likely pathogenic
Nemaline myopathy 9
β˜…β˜†β˜†β˜†2023β†’ Residue 223
NM_006063.3(KLHL41):c.1690G>T (p.Glu564Ter)Pathogenic
Nemaline myopathy 9
β˜…β˜†β˜†β˜†2023β†’ Residue 564
NM_006063.3(KLHL41):c.881_890del (p.Asp294fs)Likely pathogenic
Nemaline myopathy 9
β˜…β˜†β˜†β˜†2023β†’ Residue 294
NM_006063.3(KLHL41):c.1425G>A (p.Trp475Ter)Pathogenic
Nemaline myopathy 9
β˜…β˜†β˜†β˜†2023β†’ Residue 475
NM_006063.3(KLHL41):c.1044T>G (p.Tyr348Ter)Pathogenic
Nemaline myopathy 9
β˜…β˜†β˜†β˜†2022β†’ Residue 348
NM_006063.3(KLHL41):c.155_159del (p.Ser52fs)Pathogenic
Nemaline myopathy 9
β˜…β˜†β˜†β˜†2022β†’ Residue 52
NM_006063.3(KLHL41):c.756_757insT (p.Lys253Ter)Pathogenic
Nemaline myopathy 9
β˜…β˜†β˜†β˜†2022β†’ Residue 253
NM_006063.3(KLHL41):c.1632_1633del (p.Tyr545fs)Pathogenic
Nemaline myopathy 9
β˜…β˜†β˜†β˜†2022β†’ Residue 545
NM_006063.3(KLHL41):c.1566G>A (p.Trp522Ter)Pathogenic
Nemaline myopathy 9
β˜…β˜†β˜†β˜†2022β†’ Residue 522
View on ClinVar β†—
Related Genes
RBX1Protein interaction99%KLHL22Protein interaction93%KLHL42Protein interaction92%KLHL9Protein interaction92%KBTBD8Protein interaction92%KCTD13Protein interaction92%
Tissue Expression6 tissues
Heart
100%
Lung
2%
Brain
1%
Ovary
1%
Liver
1%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
KLHL41RBX1KLHL22KLHL42KLHL9KBTBD8KCTD13
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O60662
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.83LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.59 [0.42–0.83]
RankingsWhere KLHL41 stands among ~20K protein-coding genes
  • #12,375of 20,598
    Most Researched28
  • #1,765of 5,498
    Most Pathogenic Variants32
  • #7,083of 17,882
    Most Constrained (LOEUF)0.83
Genes detectedKLHL41
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis Β· 2022
1.00
2
KLHL41 stabilizes skeletal muscle sarcomeres by nonproteolytic ubiquitination.
PMID: 28826497
Elife Β· 2017
0.90
3
Molecular autopsy in maternal-fetal medicine.
PMID: 28749478
Genet Med Β· 2018
0.80
4
Critical genes in human photoaged skin identified using weighted gene co-expression network analysis.
PMID: 37454939
Genomics Β· 2023
0.70
5
A prognostic gene signature for gastric cancer and the immune infiltration-associated mechanism underlying the signature gene, PLG.
PMID: 36376702
Clin Transl Oncol Β· 2023
0.60