| HGNC Family | BTB (POZ) domain containing (BTBD), Kelch-like (KLHL) |
| Name | kelch-like family member 40 |
| Description | This gene encodes a protein containing a BACK domain, a BTB/POZ domain, and 5 Kelch repeats, however, its exact function is not known. The gene and the multi-domain protein structure are conserved across different taxa, including primates, rodents, chicken and zebrafish. [provided by RefSeq, Dec 2012] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Kelch‐like family member 40 (KLHL40) is a muscle‐specific adaptor protein that plays a critical role in skeletal muscle development and sarcomere integrity. Rather than targeting its substrates for degradation as seen for many BTB‐Kelch proteins, KLHL40 uniquely stabilizes key thin filament components—including nebulin and leiomodin 3—to preserve proper sarcomere assembly and thin filament organization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Loss‐of‐function mutations in KLHL40 lead to severe congenital myopathies such as nemaline myopathy, a disorder characterized by fetal akinesia, joint contractures, respiratory failure, and pronounced muscle weakness."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " In addition, KLHL40 has been implicated in regulating myogenic differentiation by modulating the activity of transcriptional regulators such as the E2F1–DP1 complex, thereby influencing muscle cell survival and fiber size."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Together, these studies establish KLHL40 as essential for maintaining the stability of sarcomeric proteins and for proper muscle development; disruptions in KLHL40 function compromise thin filament architecture and muscle contractility, underscoring its importance in both muscle physiology and disease.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gianina Ravenscroft, Satoko Miyatake, Vilma-Lotta Lehtokari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2013.05.004"}], "href": "https://doi.org/10.1016/j.ajhg.2013.05.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23746549"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23746549"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ankit Garg, Jason O'Rourke, Chengzu Long, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KLHL40 deficiency destabilizes thin filament proteins and promotes nemaline myopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI74994"}], "href": "https://doi.org/10.1172/JCI74994"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24960163"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24960163"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tai-Heng Chen, Xia Tian, Pao-Lin Kuo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of KLHL40 mutations by targeted next-generation sequencing facilitated a prenatal diagnosis in a family with three consecutive affected fetuses with fetal akinesia deformation sequence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prenat Diagn (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pd.4949"}], "href": "https://doi.org/10.1002/pd.4949"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27762439"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27762439"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kit San Yeung, Florrie N Y Yu, Cheuk Wing Fung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The KLHL40 c.1516A>C is a Chinese-specific founder mutation causing nemaline myopathy 8: Report of six patients with pre- and postnatal phenotypes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Genomic Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mgg3.1229"}], "href": "https://doi.org/10.1002/mgg3.1229"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32352246"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32352246"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Haiming Yuan, Qingming Wang, Xiumei Zeng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical and molecular analysis of four unrelated Chinese families with pathogenic KLHL40 variants causing nemaline myopathy 8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Orphanet J Rare Dis (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13023-022-02306-9"}], "href": "https://doi.org/10.1186/s13023-022-02306-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35379254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35379254"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Wuming Gong, Rachel M Gohla, Kathy M Bowlin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kelch Repeat and BTB Domain Containing Protein 5 (Kbtbd5) Regulates Skeletal Muscle Myogenesis through the E2F1-DP1 Complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.629956"}], "href": "https://doi.org/10.1074/jbc.M114.629956"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25940086"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25940086"}]}]}]}
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| Synonyms | KBTBD5, NEM8, SRYP, SYRP |
| Proteins | KLH40_HUMAN |
| NCBI Gene ID | 131377 |
| API | |
| Download Associations | |
| Predicted Functions |
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| Co-expressed Genes |
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| Expression in Tissues and Cell Lines |
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KLHL40 has 2,605 functional associations with biological entities spanning 7 categories (molecular profile, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 80 datasets.
Click the + buttons to view associations for KLHL40 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles | tissues with high or low expression of KLHL40 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset. | |
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of KLHL40 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray | tissue samples with high or low expression of KLHL40 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
| Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of KLHL40 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset. | |
| BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of KLHL40 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of KLHL40 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
| CCLE Cell Line Gene Expression Profiles | cell lines with high or low expression of KLHL40 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
| ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of KLHL40 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of KLHL40 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset. | |
| ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of KLHL40 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| ClinVar Gene-Phenotype Associations | phenotypes associated with KLHL40 gene from the curated ClinVar Gene-Phenotype Associations dataset. | |
| ClinVar Gene-Phenotype Associations 2025 | phenotypes associated with KLHL40 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing KLHL40 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores 2025 | cellular components containing KLHL40 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores | cellular components co-occuring with KLHL40 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with KLHL40 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with KLHL40 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by KLHL40 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Curated Gene-Disease Association Evidence Scores | diseases involving KLHL40 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset. | |
| DISEASES Curated Gene-Disease Association Evidence Scores 2025 | diseases involving KLHL40 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with KLHL40 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DisGeNET Gene-Disease Associations | diseases associated with KLHL40 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with KLHL40 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at KLHL40 gene from the ENCODE Histone Modification Site Profiles dataset. | |
| ENCODE Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of KLHL40 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of KLHL40 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| ESCAPE Omics Signatures of Genes and Proteins for Stem Cells | PubMedIDs of publications reporting gene signatures containing KLHL40 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset. | |
| GeneRIF Biological Term Annotations | biological terms co-occuring with KLHL40 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing KLHL40 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of KLHL40 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of KLHL40 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of KLHL40 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of KLHL40 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving KLHL40 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Biological Process Annotations 2023 | biological processes involving KLHL40 gene from the curated GO Biological Process Annotations 2023 dataset. | |
| GO Biological Process Annotations 2025 | biological processes involving KLHL40 gene from the curated GO Biological Process Annotations2025 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing KLHL40 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Cellular Component Annotations 2023 | cellular components containing KLHL40 protein from the curated GO Cellular Component Annotations 2023 dataset. | |
| GO Cellular Component Annotations 2025 | cellular components containing KLHL40 protein from the curated GO Cellular Component Annotations 2025 dataset. | |
| GO Molecular Function Annotations 2025 | molecular functions performed by KLHL40 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of KLHL40 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of KLHL40 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GTEx Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of KLHL40 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with KLHL40 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| GWASdb SNP-Disease Associations | diseases associated with KLHL40 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset. | |
| GWASdb SNP-Phenotype Associations | phenotypes associated with KLHL40 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset. | |
| HPA Tissue Gene Expression Profiles | tissues with high or low expression of KLHL40 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
| HPA Tissue Protein Expression Profiles | tissues with high or low expression of KLHL40 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset. | |
| IMPC Knockout Mouse Phenotypes | phenotypes of mice caused by KLHL40 gene knockout from the IMPC Knockout Mouse Phenotypes dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for KLHL40 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of KLHL40 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Mouse Transcription Factor Targets 2025 | transcription factors regulating expression of KLHL40 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of KLHL40 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of KLHL40 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain KLHL40 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by KLHL40 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of KLHL40 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| MoTrPAC Rat Endurance Exercise Training | tissue samples with high or low expression of KLHL40 gene relative to other tissue samples from the MoTrPAC Rat Endurance Exercise Training dataset. | |
| NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles | drug perturbations changing expression of KLHL40 gene from the NIBR DRUG-seq U2OS MoA Box dataset. | |
| NURSA Protein Complexes | protein complexs containing KLHL40 protein recovered by IP-MS from the NURSA Protein Complexes dataset. | |
| OMIM Gene-Disease Associations | phenotypes associated with KLHL40 gene from the curated OMIM Gene-Disease Associations dataset. | |
| Pathway Commons Protein-Protein Interactions | interacting proteins for KLHL40 from the Pathway Commons Protein-Protein Interactions dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of KLHL40 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations | gene perturbations changing expression of KLHL40 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving KLHL40 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving KLHL40 protein from the Wikipathways PFOCR 2024 dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at KLHL40 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of KLHL40 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of KLHL40 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| Sanger Dependency Map Cancer Cell Line Proteomics | cell lines associated with KLHL40 protein from the Sanger Dependency Map Cancer Cell Line Proteomics dataset. | |
| Tabula Sapiens Gene-Cell Associations | cell types with high or low expression of KLHL40 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset. | |
| TargetScan Predicted Conserved microRNA Targets | microRNAs regulating expression of KLHL40 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of KLHL40 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of KLHL40 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores | tissues with high expression of KLHL40 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of KLHL40 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores | tissues with high expression of KLHL40 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of KLHL40 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with KLHL40 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with KLHL40 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
