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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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BBOX1
gamma-butyrobetaine hydroxylase 1
Chromosome 11 · 11p14.2
NCBI Gene: 8424Ensembl: ENSG00000129151.10HGNC: HGNC:964UniProt: O75936
32PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
carnitine biosynthetic processzinc ion bindingextracellular exosomegamma-butyrobetaine dioxygenase activityAbnormality of the skeletal systemAbnormality of the gastrointestinal tractneurodegenerative diseaseankylosing spondylitis
✦AI Summary

BBOX1 (gamma-butyrobetaine hydroxylase 1) is a cytosolic dioxygenase that catalyzes the final step of L-carnitine biosynthesis from gamma-butyrobetaine 1. The enzyme is predominantly expressed in kidney, liver, and brain tissue, with tissue-specific transcription patterns regulated by multiple promoters and alternative polyadenylation mechanisms 1. BBOX1 functions as a metabolic checkpoint with context-dependent roles in cancer biology. In hepatocellular carcinoma, CRIP1 suppresses BBOX1 through ubiquitin-proteasomal degradation, reducing carnitine availability and promoting cancer stemness via altered β-catenin signaling 2. Conversely, in clear cell renal cell carcinoma, BBOX1 acts as a tumor suppressor by restraining TBK1-mTORC1 oncogenic signaling through disruption of TBK1-DCLK2 interaction 3. In metastatic cancer, BBOX1-produced carnitine suppresses NK cell cytotoxicity by inhibiting RhoA and preventing immunological synapse formation, enabling immune evasion 4. Beyond cancer, BBOX1 expression is upregulated in psoriasis through the α-KG-H3K9me3 regulatory axis, promoting carnitine metabolism and oxidative phosphorylation 5. Clinically, BBOX1-AS1 (an antisense lncRNA) is upregulated in multiple cancers and recurrent pregnancy loss, associated with poor prognosis and lymph node metastasis 67.

Sources cited
1
BBOX1 is a cytosolic dimeric dioxygenase responsible for L-carnitine biosynthesis, predominantly expressed in kidney, liver, and brain with tissue-specific transcription patterns
PMID: 17110165
2
CRIP1 promotes HCC stemness by targeting BBOX1 for ubiquitin-proteasomal degradation at K240, suppressing carnitine metabolism and altering β-catenin signaling
PMID: 35775648
3
BBOX1 acts as a tumor suppressor in ccRCC by restraining TBK1-mTORC1 signaling through disruption of TBK1-DCLK2 interaction
PMID: 39934163
4
BBOX1-produced carnitine mediates metastatic cancer immune evasion by suppressing NK cell RhoA activation and immunological synapse formation
PMID: 40742308
5
BBOX1 expression is upregulated in psoriasis through the α-KG-H3K9me3 axis, promoting carnitine-dependent metabolic reprogramming
PMID: 37303600
6
High BBOX1-AS1 expression is associated with poor overall survival, disease-free survival, lymph node metastasis, and advanced tumor stage across multiple cancers
PMID: 37636267
7
BBOX1-AS1 is upregulated in recurrent pregnancy loss and mediates trophoblast dysfunction via the hnRNPK/GADD45A axis
PMID: 36617174
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.50Moderate
Abnormality of the gastrointestinal tractOpen Targets
0.29Weak
neurodegenerative diseaseOpen Targets
0.28Weak
ankylosing spondylitisOpen Targets
0.13Weak
androgenetic alopeciaOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.11Weak
hypothyroidismOpen Targets
0.11Weak
thyroid cancerOpen Targets
0.11Weak
retinitis pigmentosaOpen Targets
0.10Weak
stomach diseaseOpen Targets
0.10Weak
neoplasmOpen Targets
0.10Weak
hypertensionOpen Targets
0.10Suggestive
colorectal carcinomaOpen Targets
0.09Suggestive
age-related macular degenerationOpen Targets
0.09Suggestive
azoospermiaOpen Targets
0.09Suggestive
gastric cancerOpen Targets
0.08Suggestive
X-linked retinal dysplasiaOpen Targets
0.08Suggestive
nasopharyngeal carcinomaOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.08Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TMLHEShared pathway100%TRIM24Protein interaction96%ALDH2Protein interaction92%ALDH1B1Protein interaction92%ALDH3A2Protein interaction92%ALDH7A1Protein interaction92%
Tissue Expression6 tissues
Liver
100%
Brain
37%
Bone Marrow
0%
Lung
0%
Ovary
0%
Heart
0%
Gene Interaction Network
Click a node to explore
BBOX1TMLHETRIM24ALDH2ALDH1B1ALDH3A2ALDH7A1
PROTEIN STRUCTURE
Preparing viewer…
PDB4C5W · 1.70 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.98LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.71 [0.53–0.98]
RankingsWhere BBOX1 stands among ~20K protein-coding genes
  • #11,472of 20,598
    Most Researched32
  • #9,391of 17,882
    Most Constrained (LOEUF)0.98
Genes detectedBBOX1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
CRIP1 suppresses BBOX1-mediated carnitine metabolism to promote stemness in hepatocellular carcinoma.
PMID: 35775648
EMBO J · 2022
1.00
2
BBOX1 Is a Metabolic Checkpoint That Mediates Metastatic Cancer Cell Evasion from Immunosurveillance by NK Cells.
PMID: 40742308
Cancer Res · 2025
0.90
3
BBOX1 restrains TBK1-mTORC1 oncogenic signaling in clear cell renal cell carcinoma.
PMID: 39934163
Nat Commun · 2025
0.80
4
BBOX1-AS1: A novel oncogenic long non-coding RNA in human cancers.
PMID: 37696243
Pathol Res Pract · 2023
0.70
5
Prognostic effect of lncRNA BBOX1-AS1 in malignancies: a meta-analysis.
PMID: 37636267
Front Genet · 2023
0.60