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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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KLHL9
kelch like family member 9
Chromosome 9 · 9p21.3
NCBI Gene: 55958Ensembl: ENSG00000198642.8HGNC: HGNC:18732UniProt: Q58EZ4
53PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
ubiquitin-protein transferase activityprotein bindingcullin family protein bindingprotein ubiquitinationKLHL9-related childhood-onset distal myopathyKLHL9-related early-onset distal myopathygenetic disordertype 2 diabetes mellitus
✦AI Summary

KLHL9 (kelch like family member 9) functions as a substrate-specific adapter protein in BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes with diverse cellular roles. The protein forms complexes with KLHL13 and CUL3 to regulate multiple cellular processes through targeted protein ubiquitination 1. In mitotic regulation, KLHL9 mediates ubiquitination of AURKB, controlling its dynamic behavior on mitotic chr9 and coordinating faithful mitotic progression and cytokinesis completion. The KLHL9-KLHL13-CUL3 complex also regulates mTORC1 signaling by ubiquitinating Rheb at the lysosome, supporting amino acid-induced mTORC1 activation 2. Additionally, this complex targets IRS1 for proteasomal degradation, linking autophagy deficiency to insulin resistance 3. KLHL9 plays roles in host-pathogen interactions, where bacterial pathogens like Burkholderia pseudomallei hijack the KLHL9-KLHL13-CUL3 complex to promote mitophagy through IMMT ubiquitination, facilitating pathogen survival 14. The complex is also required for interferon-γ-induced immunity against intracellular pathogens 5. Clinically, KLHL9 deletions are found in over 50% of mesenchymal glioblastoma cases and correlate with poor survival across multiple cancer types 67.

Sources cited
1
KLHL9 forms complexes with KLHL13 and CUL3, and is hijacked by bacterial pathogens for mitophagy regulation
PMID: 38834545
2
CUL3-RBX1-KLHL9 complex ubiquitinates Rheb and supports amino acid-induced mTORC1 activation
PMID: 39708321
3
KLHL9-KLHL13-CUL3 complex targets IRS1 for proteasomal degradation, linking autophagy deficiency to insulin resistance
PMID: 31515271
4
BipD hijacks KLHL9-KLHL13-CUL3 complex to promote K63-linked ubiquitination of IMMT for mitophagy
PMID: 39265641
5
KLHL9 and CUL3 are required for interferon-γ-induced inhibition of intracellular pathogen replication
PMID: 37905813
6
KLHL9 deletions are found in over 50% of mesenchymal glioblastoma cases and regulate C/EBP protein degradation
PMID: 25303533
7
KLHL9 deletions and altered expression correlate with poor survival across multiple cancer types
PMID: 36288884
Disease Associationsⓘ20
KLHL9-related childhood-onset distal myopathyOpen Targets
0.37Weak
KLHL9-related early-onset distal myopathyOpen Targets
0.37Weak
genetic disorderOpen Targets
0.12Weak
type 2 diabetes mellitusOpen Targets
0.09Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.05Suggestive
Familial drusenOpen Targets
0.04Suggestive
exudative vitreoretinopathy 4Open Targets
0.04Suggestive
exudative vitreoretinopathyOpen Targets
0.04Suggestive
melorheostosisOpen Targets
0.04Suggestive
X-linked retinoschisisOpen Targets
0.03Suggestive
Liberfarb syndromeOpen Targets
0.03Suggestive
pyknoachondrogenesisOpen Targets
0.03Suggestive
hyperostosis corticalis generalisataOpen Targets
0.03Suggestive
attention deficit hyperactivity disorderOpen Targets
0.03Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.03Suggestive
X-linked retinal dysplasiaOpen Targets
0.03Suggestive
infectionOpen Targets
0.02Suggestive
distal myopathyOpen Targets
0.02Suggestive
melanomaOpen Targets
0.02Suggestive
ataxia telangiectasiaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RHOBTB1Protein interaction100%RHOBTB2Protein interaction100%RBX1Protein interaction99%GLMNProtein interaction97%KLHL21Protein interaction95%AURKBProtein interaction93%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
79%
Heart
76%
Ovary
69%
Liver
54%
Lung
52%
Gene Interaction Network
Click a node to explore
KLHL9RHOBTB1RHOBTB2RBX1GLMNKLHL21AURKB
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q58EZ4
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.83LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.61 [0.45–0.83]
RankingsWhere KLHL9 stands among ~20K protein-coding genes
  • #8,448of 20,598
    Most Researched53
  • #7,155of 17,882
    Most Constrained (LOEUF)0.83
Genes detectedKLHL9
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Burkholderia pseudomallei BipD modulates host mitophagy to evade killing.
PMID: 38834545
Nat Commun · 2024
1.00
2
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis · 2022
0.90
3
PMID: 39265641
Autophagy · 2024
0.80
4
The Cullin3-Rbx1-KLHL9 E3 ubiquitin ligase complex ubiquitinates Rheb and supports amino acid-induced mTORC1 activation.
PMID: 39708321
Cell Rep · 2025
0.70
5
Identification of causal genetic drivers of human disease through systems-level analysis of regulatory networks.
PMID: 25303533
Cell · 2014
0.60