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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TBCC
tubulin folding cofactor C
Chromosome 6 · 6p21.1
NCBI Gene: 6903Ensembl: ENSG00000124659.7HGNC: HGNC:11580UniProt: Q15814
21PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
GTPase activityGTPase activator activityprotein bindingpost-chaperonin tubulin folding pathwayneurodegenerative diseaseRomano-Ward syndromefamilial atrial fibrillationFamilial short QT syndrome
✦AI Summary

TBCC (tubulin folding cofactor C) is a tubulin-specific chaperone that completes the final step of αβ-tubulin heterodimer assembly 1. Structurally, TBCC functions as a molecular clamp within a cage-like complex with TBCD, TBCE, and the Arl2 GTPase, engaging multiple domains of the αβ-tubulin intradimer interface to promote proper heterodimer maturation 2. This process is essential for microtubule polymerization competency and cytoskeletal proteostasis 1. Clinically, TBCC dysfunction impacts cancer and neurological disorders. In breast cancer, TBCC overexpression reduces polymerizable tubulin pools and microtubule dynamics, leading to G2-M cell cycle arrest, reduced tumor growth, and enhanced chemosensitivity to antimicrotubule agents 3. In ovarian cancer, miR-1251-5p suppresses TBCC expression, promoting cell proliferation and autophagy through altered tubulin and CDK4 levels 4. Additionally, rare damaging variants in TBCC are associated with ADHD, potentially contributing to abnormal late-infancy cerebellar development and immune dysfunction 5. TBCC variants are also implicated in Progressive Encephalopathy with Brain Atrophy and Thin Corpus Callosum (PEBAT), a severe neurodevelopmental disorder featuring neurodegeneration and seizures, with phenotypic severity potentially modified by genetic background 6.

Sources cited
1
TBCC overexpression reduces polymerizable tubulin dimers and microtubule dynamics, delays tumor growth, and enhances chemosensitivity in breast cancer
PMID: 20384997
2
miR-1251-5p promotes ovarian cancer through TBCC downregulation, affecting cell cycle and autophagy via altered tubulin and CDK4 expression
PMID: 31278033
3
TBCC acts as a molecular clamp completing αβ-tubulin heterodimer assembly within a TBC complex, ensuring proper tubulin biogenesis and GTP-dependent checkpoint
PMID: 41166473
4
TBCC engages the αβ-tubulin intradimer interface and Arl2-GTP to regulate tubulin cofactor assembly and catalyze biogenesis/degradation for microtubule polymerization
PMID: 41461644
5
Rare damaging variants in TBCC are associated with ADHD, linked to late-infancy cerebellar development and immune processes
PMID: 40542392
6
TBCC variants in tubulin cofactor family are implicated in Progressive Encephalopathy with Brain Atrophy and Thin Corpus Callosum, a severe neurodevelopmental disorder
PMID: 39853547
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.54Moderate
Romano-Ward syndromeOpen Targets
0.08Suggestive
familial atrial fibrillationOpen Targets
0.08Suggestive
Familial short QT syndromeOpen Targets
0.07Suggestive
Brugada syndromeOpen Targets
0.07Suggestive
atrial fibrillationOpen Targets
0.07Suggestive
Familial progressive cardiac conduction defectOpen Targets
0.07Suggestive
catecholaminergic polymorphic ventricular tachycardiaOpen Targets
0.07Suggestive
Arrhythmogenic right ventricular dysplasiaOpen Targets
0.07Suggestive
Idiopathic ventricular fibrillation, not Brugada typeOpen Targets
0.06Suggestive
long QT syndrome 11Open Targets
0.05Suggestive
sinoatrial node dysfunction and deafnessOpen Targets
0.05Suggestive
hypertrophic cardiomyopathyOpen Targets
0.05Suggestive
Rare familial disorder with hypertrophic cardiomyopathyOpen Targets
0.05Suggestive
Brugada syndrome 9Open Targets
0.05Suggestive
long QT syndrome 9Open Targets
0.05Suggestive
sick sinus syndrome 1Open Targets
0.05Suggestive
long QT syndrome 5Open Targets
0.05Suggestive
long QT syndrome 10Open Targets
0.05Suggestive
ventricular fibrillation, paroxysmal familial, type 1Open Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TBCAShared pathway100%ARL3Protein interaction87%TBCDProtein interaction68%TBCBProtein interaction65%TBCEShared pathway60%TBCELShared pathway50%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
76%
Heart
59%
Lung
42%
Liver
37%
Ovary
29%
Gene Interaction Network
Click a node to explore
TBCCTBCAARL3TBCDTBCBTBCETBCEL
PROTEIN STRUCTURE
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PDB2L3L · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.80LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.99 [0.51–1.80]
RankingsWhere TBCC stands among ~20K protein-coding genes
  • #14,033of 20,598
    Most Researched21
  • #16,586of 17,882
    Most Constrained (LOEUF)1.80
Genes detectedTBCC
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Tubulin binding cofactor C (TBCC) suppresses tumor growth and enhances chemosensitivity in human breast cancer cells.
PMID: 20384997
BMC Cancer · 2010
1.00
2
MicroRNA-1251-5p Promotes Carcinogenesis and Autophagy via Targeting the Tumor Suppressor TBCC in Ovarian Cancer Cells.
PMID: 31278033
Mol Ther · 2019
0.90
3
Structural dissection of αβ-tubulin heterodimer assembly and disassembly by human tubulin-specific chaperones.
PMID: 41166473
Science · 2025
0.80
4
Trichoblastoma: is a clinical or dermoscopic diagnosis possible?
PMID: 27439654
J Eur Acad Dermatol Venereol · 2016
0.70
5
Respiratory stabilization before umbilical cord clamping in preterm neonates: a systematic review and network meta-analysis.
PMID: 40819818
Resuscitation · 2025
0.60