KLHL18 Gene

HGNC Family Kelch-like (KLHL), BTB (POZ) domain containing (BTBD)
Name kelch-like family member 18
Description Predicted to enable ubiquitin-like ligase-substrate adaptor activity. Involved in positive regulation of mitotic cell cycle phase transition and protein ubiquitination. Predicted to be part of Cul3-RING ubiquitin ligase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Mar 2025]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Kelch‐like protein 18 (KLHL18) is a BTB domain‐containing adaptor that functions as part of cullin‐3 (CUL3) E3 ubiquitin ligase complexes to mediate the ubiquitination and degradation of specific protein substrates, thereby regulating key cellular processes. For example, studies in mutant mice have demonstrated that disruption of Klhl18 leads to progressive, predominantly low‐frequency hearing impairment associated with abnormal tapering of inner hair cell stereocilia, indicating a crucial role for Klhl18 in maintaining inner hair cell structure and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In human non‐small cell lung cancer, KLHL18 is markedly downregulated compared to normal lung tissue, and its overexpression inhibits cell proliferation, migration, and invasion through enhanced ubiquitination and degradation of the p85α subunit of phosphatidylinositol 3‐kinase (PI3K) as well as suppression of PD‐L1 expression, suggesting that KLHL18 acts as a tumor suppressor by thwarting tumor cell immune escape."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Furthermore, depletion of KLHL18 delays mitotic entry by impairing centrosomal activation of the mitotic kinase Aurora‐A, while overexpression of KLHL18 (together with CUL3) promotes Aurora‐A ubiquitination in vivo and in vitro, underscoring its important role in timely cell cycle progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Neil J Ingham, Navid Banafshe, Clarisse Panganiban, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inner hair cell dysfunction in Klhl18 mutant mice leads to low frequency progressive hearing loss."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0258158"}], "href": "https://doi.org/10.1371/journal.pone.0258158"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34597341"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34597341"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xizi Jiang, Yitong Xu, Hongjiu Ren, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KLHL18 inhibits the proliferation, migration, and invasion of non-small cell lung cancer by inhibiting PI3K/PD-L1 axis activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biosci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13578-020-00499-9"}], "href": "https://doi.org/10.1186/s13578-020-00499-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33292627"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33292627"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Saili Moghe, Fei Jiang, Yoshie Miura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The CUL3-KLHL18 ligase regulates mitotic entry and ubiquitylates Aurora-A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Open (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/bio.2011018"}], "href": "https://doi.org/10.1242/bio.2011018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23213400"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23213400"}]}]}]}
Proteins KLH18_HUMAN
NCBI Gene ID 23276
API
Download Associations
Predicted Functions View KLHL18's ARCHS4 Predicted Functions.
Co-expressed Genes View KLHL18's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View KLHL18's ARCHS4 Predicted Functions.

Functional Associations

KLHL18 has 5,374 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 95 datasets.

Click the + buttons to view associations for KLHL18 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles tissues with high or low expression of KLHL18 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles tissues with high or low expression of KLHL18 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 KLHL18 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 KLHL18 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq tissue samples with high or low expression of KLHL18 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles tissues with high or low expression of KLHL18 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
BioGPS Cell Line Gene Expression Profiles cell lines with high or low expression of KLHL18 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
BioGPS Human Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of KLHL18 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
BioGPS Mouse Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of KLHL18 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of KLHL18 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 KLHL18 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
CellMarker Gene-Cell Type Associations cell types associated with KLHL18 gene from the CellMarker Gene-Cell Type Associations dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of KLHL18 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of KLHL18 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 KLHL18 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
CMAP Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of KLHL18 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing KLHL18 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Experimental Protein Localization Evidence Scores cellular components containing KLHL18 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores cellular components co-occuring with KLHL18 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 KLHL18 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
COSMIC Cell Line Gene CNV Profiles cell lines with high or low copy number of KLHL18 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with KLHL18 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Disease Associations diseases associated with KLHL18 gene/protein from the curated CTD Gene-Disease Associations dataset.
DeepCoverMOA Drug Mechanisms of Action small molecule perturbations with high or low expression of KLHL18 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by KLHL18 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores diseases co-occuring with KLHL18 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with KLHL18 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
ENCODE Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at KLHL18 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 KLHL18 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of KLHL18 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 KLHL18 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
GDSC Cell Line Gene Expression Profiles cell lines with high or low expression of KLHL18 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
GeneSigDB Published Gene Signatures PubMedIDs of publications reporting gene signatures containing KLHL18 from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of KLHL18 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
GEO Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of KLHL18 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 KLHL18 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 KLHL18 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 KLHL18 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of KLHL18 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2023 biological processes involving KLHL18 gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving KLHL18 gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2025 cellular components containing KLHL18 protein from the curated GO Cellular Component Annotations 2025 dataset.
GO Molecular Function Annotations 2015 molecular functions performed by KLHL18 gene from the curated GO Molecular Function Annotations 2015 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by KLHL18 gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of KLHL18 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 KLHL18 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 KLHL18 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset.
GTEx Tissue-Specific Aging Signatures tissue samples with high or low expression of KLHL18 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset.
GWAS Catalog SNP-Phenotype Associations 2025 phenotypes associated with KLHL18 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.
GWASdb SNP-Phenotype Associations phenotypes associated with KLHL18 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset.
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles cell lines with high or low expression of KLHL18 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset.
HPA Cell Line Gene Expression Profiles cell lines with high or low expression of KLHL18 gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of KLHL18 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 KLHL18 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset.
HPA Tissue Sample Gene Expression Profiles tissue samples with high or low expression of KLHL18 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset.
Hub Proteins Protein-Protein Interactions interacting hub proteins for KLHL18 from the curated Hub Proteins Protein-Protein Interactions dataset.
IMPC Knockout Mouse Phenotypes phenotypes of mice caused by KLHL18 gene knockout from the IMPC Knockout Mouse Phenotypes dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for KLHL18 protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Human Transcription Factor Targets 2025 transcription factors regulating expression of KLHL18 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 KLHL18 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 KLHL18 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 KLHL18 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles cell lines with high or low expression of KLHL18 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles cell lines with KLHL18 gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset.
KnockTF Gene Expression Profiles with Transcription Factor Perturbations transcription factor perturbations changing expression of KLHL18 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures small molecule perturbations changing expression of KLHL18 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset.
LOCATE Curated Protein Localization Annotations cellular components containing KLHL18 protein in low- or high-throughput protein localization assays from the LOCATE Curated Protein Localization Annotations dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain KLHL18 protein from the LOCATE Predicted Protein Localization Annotations dataset.
MGI Mouse Phenotype Associations 2023 phenotypes of transgenic mice caused by KLHL18 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset.
MiRTarBase microRNA Targets microRNAs targeting KLHL18 gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset.
MotifMap Predicted Transcription Factor Targets transcription factors regulating expression of KLHL18 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 KLHL18 gene relative to other tissue samples from the MoTrPAC Rat Endurance Exercise Training dataset.
MPO Gene-Phenotype Associations phenotypes of transgenic mice caused by KLHL18 gene mutations from the MPO Gene-Phenotype Associations dataset.
MSigDB Cancer Gene Co-expression Modules co-expressed genes for KLHL18 from the MSigDB Cancer Gene Co-expression Modules dataset.
NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles drug perturbations changing expression of KLHL18 gene from the NIBR DRUG-seq U2OS MoA Box dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for KLHL18 from the Pathway Commons Protein-Protein Interactions dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of KLHL18 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 KLHL18 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of KLHL18 gene from the Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures dataset.
Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of KLHL18 gene from the Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures dataset.
Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of KLHL18 gene from the Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures dataset.
Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles cell types and tissues with high or low DNA methylation of KLHL18 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset.
Roadmap Epigenomics Cell and Tissue Gene Expression Profiles cell types and tissues with high or low expression of KLHL18 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue Gene Expression Profiles dataset.
Roadmap Epigenomics Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at KLHL18 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of KLHL18 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of KLHL18 gene from the RummaGEO Gene Perturbation Signatures dataset.
Sci-Plex Drug Perturbation Signatures drug perturbations changing expression of KLHL18 gene from the Sci-Plex Drug Perturbation Signatures dataset.
Tahoe Therapeutics Tahoe 100M Perturbation Atlas drug perturbations changing expression of KLHL18 gene from the Tahoe Therapeutics Tahoe 100M Perturbation Atlas dataset.
TargetScan Predicted Conserved microRNA Targets microRNAs regulating expression of KLHL18 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of KLHL18 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 KLHL18 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of KLHL18 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores tissues with high expression of KLHL18 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with KLHL18 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 KLHL18 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.