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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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KBTBD7
kelch repeat and BTB domain containing 7
Chromosome 13 · 13q14.11
NCBI Gene: 84078Ensembl: ENSG00000120696.9HGNC: HGNC:25266UniProt: Q8WVZ9
56PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingregulation of Rac protein signal transductionproteasome-mediated ubiquitin-dependent protein catabolic processprotein K48-linked ubiquitinationhypothyroidismnon-small cell lung carcinomaglomerulonephritisPain
✦AI Summary

KBTBD7 functions as a substrate adapter protein within the CUL3-RING ubiquitin ligase complex, mediating K48-linked ubiquitination and proteasomal degradation of multiple target proteins 1. The protein's primary mechanism involves its BTB domain and kelch repeats, which facilitate substrate recognition and transcriptional activation 2. KBTBD7 controls RAC1 signaling by targeting the guanine exchange factor TIAM1 for degradation, thereby regulating cytoskeleton organization, cell migration, and proliferation 1. This ubiquitination process requires cooperation with GABARAP proteins for membrane-restricted activity 1. KBTBD7 demonstrates significant disease relevance across multiple pathologies. In pituitary adenomas, it regulates dopamine receptor DRD2 degradation, with high KBTBD7 expression correlating with dopamine agonist resistance 3. In non-small cell lung cancer, KBTBD7 promotes tumor progression by enhancing PTEN degradation and activating EGFR/PI3K/AKT signaling 4. Additionally, KBTBD7 contributes to septic lung injury by promoting ferroptosis and mitochondrial dysfunction 5. The protein also participates in inflammatory responses, as its knockdown reduces inflammation in dental pulp fibroblasts through the miR-21/KBTBD7 axis and NF-κB pathway modulation 6. These findings establish KBTBD7 as a potential therapeutic target across multiple disease contexts.

Sources cited
1
KBTBD7 functions as substrate adapter in CUL3 complex mediating TIAM1 ubiquitination and RAC1 signaling regulation
PMID: 25684205
2
KBTBD7 contains BTB domain and kelch repeats that facilitate transcriptional activation
PMID: 20132730
3
KBTBD7 regulates DRD2 degradation and correlates with dopamine agonist resistance in pituitary adenomas
PMID: 32572597
4
KBTBD7 promotes NSCLC progression by enhancing PTEN degradation and activating EGFR/PI3K/AKT signaling
PMID: 35499228
5
KBTBD7 contributes to septic lung injury by promoting ferroptosis and mitochondrial dysfunction
PMID: 38652964
6
KBTBD7 participates in inflammatory responses through miR-21/KBTBD7 axis and NF-κB pathway
PMID: 31837588
Disease Associationsⓘ20
hypothyroidismOpen Targets
0.27Weak
non-small cell lung carcinomaOpen Targets
0.07Suggestive
glomerulonephritisOpen Targets
0.06Suggestive
PainOpen Targets
0.06Suggestive
attention deficit hyperactivity disorderOpen Targets
0.03Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.03Suggestive
hypercholanemia, familial, 2Open Targets
0.03Suggestive
myocardial infarctionOpen Targets
0.03Suggestive
ProptosisOpen Targets
0.03Suggestive
breast cancerOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.01Suggestive
colorectal cancerOpen Targets
0.01Suggestive
breast carcinomaOpen Targets
0.01Suggestive
ischemiaOpen Targets
0.01Suggestive
hepatocellular carcinomaOpen Targets
0.01Suggestive
lung cancerOpen Targets
0.00Suggestive
pulpitisOpen Targets
0.00Suggestive
Neurodevelopmental delayOpen Targets
0.00Suggestive
triple-negative breast cancerOpen Targets
0.00Suggestive
chronic kidney diseaseOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
UBE2MProtein interaction100%RBX1Protein interaction99%KLHL22Protein interaction93%KBTBD8Protein interaction92%KCTD13Protein interaction92%SPOPLProtein interaction92%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
76%
Heart
64%
Liver
58%
Ovary
25%
Lung
19%
Gene Interaction Network
Click a node to explore
KBTBD7UBE2MRBX1KLHL22KBTBD8KCTD13SPOPL
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q8WVZ9
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.66LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.47 [0.34–0.66]
RankingsWhere KBTBD7 stands among ~20K protein-coding genes
  • #8,087of 20,598
    Most Researched56
  • #4,832of 17,882
    Most Constrained (LOEUF)0.66
Genes detectedKBTBD7
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Linear ubiquitination at damaged lysosomes induces local NFKB activation and controls cell survival.
PMID: 39744815
Autophagy · 2025
1.00
2
KBTBD7, a novel human BTB-kelch protein, activates transcriptional activities of SRE and AP-1.
PMID: 20132730
BMB Rep · 2010
0.90
3
The KBTBD6/7-DRD2 axis regulates pituitary adenoma sensitivity to dopamine agonist treatment.
PMID: 32572597
Acta Neuropathol · 2020
0.80
4
KBTBD7 promotes non-small cell lung carcinoma progression by enhancing ubiquitin-dependent degradation of PTEN.
PMID: 35499228
Cancer Med · 2022
0.70
5
CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP proteins to spatially restrict TIAM1-RAC1 signaling.
PMID: 25684205
Mol Cell · 2015
0.60