On this page
TBCE
tubulin folding cofactor E
TBCE is located on the long (q) arm of chromosome 1, at band 1q42.3. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 1 in the library →Available at Jeen Health
Clinical tests that include this
Overview
TBCE is located on chromosome 1 at band 1q42.3 and encodes a 527-amino-acid protein known as tubulin folding cofactor E. This protein plays a specialised role in the biogenesis of microtubules, the tubular structures that underpin cellular architecture and enable critical functions such as chromosome segregation and intracellular cargo transport.
Pathogenic variants in TBCE follow an autosomal recessive inheritance pattern, meaning that affected individuals typically inherit one altered copy from each parent. TBCE-related conditions are included on multiple NHS Genomic Medicine Service gene panels, reflecting the gene's importance in developmental pathways affecting the nervous system, skeleton, and endocrine organs.
What the gene does
Tubulin folding cofactor E works alongside other cofactors in a coordinated pathway that assembles α-tubulin and β-tubulin subunits into stable heterodimers, the building blocks of microtubules. This assembly process requires precise chaperone activity to ensure correct folding and pairing of tubulin monomers.
The TBCE protein recognises and binds β-tubulin, facilitating its incorporation into functional dimers. Without effective TBCE activity, cells struggle to maintain adequate pools of polymerisation-competent tubulin, impairing microtubule dynamics. Because microtubules are essential for mitotic spindle formation, axonal transport in neurons, and maintenance of cell polarity, disruption of TBCE function has wide-ranging consequences for tissue development and homeostasis.
The protein's activity is particularly critical during periods of rapid cell division and differentiation, such as embryonic development and early postnatal growth, when demand for new microtubules is high.
Video: Genetics 101
Chromosome location
TBCE is situated on the long arm of chromosome 1 at cytogenetic band 1q42.3. This region lies near the telomeric end of chromosome 1. The gene spans multiple exons encoding the 527-amino-acid protein product, though detailed exon-intron architecture varies across transcript isoforms.
Protein structure
The TBCE protein comprises 527 amino acids organised into several functional regions. The N-terminal portion contains a CAP-Gly domain spanning amino acids 27 to 71, a motif commonly found in proteins that interact with microtubules and their components.
The central region of TBCE features seven leucine-rich repeat (LRR) motifs: LRR 1 (amino acids 154-175), LRR 2 (180-200), LRR 3 (205-226), LRR 4 (230-252), LRR 5 (253-274), LRR 6 (278-299), and LRR 7 (308-329). Leucine-rich repeats typically mediate protein-protein interactions, and in TBCE they likely contribute to recognition and binding of tubulin substrates.
The C-terminal region includes an LRRCT domain (amino acids 342-384), which caps the leucine-rich repeat array and may stabilise the overall fold of the protein. Together, these domains enable TBCE to recognise β-tubulin and coordinate its folding and assembly into heterodimers.
Key variants
Pathogenic variants in TBCE are relatively rare and typically result in loss of protein function. Most disease-causing changes are inherited in an autosomal recessive manner, requiring variants on both gene copies to produce clinical manifestations. The variant spectrum includes missense substitutions that disrupt protein folding or tubulin binding, as well as nonsense and frameshift mutations that lead to truncated, nonfunctional protein products.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.100+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Encephalopathy, progressive, with amyotrophy and optic atrophy |
c.1063C>T | p.Arg355Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Hypoparathyroidism-retardation-dysmorphism syndrome |
c.143_144del | p.Lys48fs | Pathogenic/Likely pathogenic | ★★☆☆ | TBCE-related disorder |
c.355_356del | p.Ile119fs | Pathogenic/Likely pathogenic | ★★☆☆ | Hypoparathyroidism-retardation-dysmorphism syndrome |
c.367C>T | p.Gln123Ter | Pathogenic/Likely pathogenic | ★★☆☆ | TBCE-related disorder |
c.433A>T | p.Lys145Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal recessive Kenny-Caffey syndrome |
c.464T>A | p.Ile155Asn | Pathogenic/Likely pathogenic | ★★☆☆ | TBCE-related disorder |
c.636_639del | p.Asn212fs | Pathogenic/Likely pathogenic | ★★☆☆ | See cases |
c.700del | p.Leu234fs | Pathogenic/Likely pathogenic | ★★☆☆ | TBCE-related disorder |
c.924del | p.Ser308_Leu309insTer | Pathogenic | ★★☆☆ | TBCE-related disorder |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Autosomal recessive variants in TBCE are associated with a range of developmental disorders affecting multiple organ systems. Clinical features commonly include hypoparathyroidism, intellectual disability, and skeletal abnormalities, reflecting the widespread role of microtubules in tissue development. Some affected individuals present with neurological features such as hereditary neuropathy, whilst others exhibit intrauterine growth restriction or congenital anomalies detectable during foetal development. The clinical spectrum reflects variable disruption of microtubule-dependent processes across different tissues and developmental stages.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic TBCE variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
TBCE is classified with green confidence ratings on several NHS Genomic Medicine Service gene panels, indicating strong evidence supporting its clinical validity. These panels include DDG2P, Familial hypoparathyroidism (R153), Fetal anomalies (R21), Hereditary neuropathy or pain disorder (R78), Intellectual disability (R29), IUGR and IGF abnormalities, and Skeletal dysplasia (R104). Green status signifies that the gene-disease relationship is well established and that diagnostic testing for TBCE variants may be clinically indicated in individuals presenting with relevant features within these pathways.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the TBCE gene do?
TBCE provides instructions for making tubulin folding cofactor E, a protein that helps assemble tubulin subunits into microtubules. Microtubules form the structural framework of cells and are essential for processes such as cell division, intracellular transport, and maintaining cell shape.
How are TBCE variants inherited?
Pathogenic variants in TBCE are inherited in an autosomal recessive pattern. This means an individual must inherit one altered copy of the gene from each parent to be affected. Carriers, who have one working copy and one altered copy, typically do not show symptoms.
Why is TBCE on multiple NHS gene panels?
TBCE appears on several NHS Genomic Medicine Service panels because variants in this gene can affect multiple developmental systems, including the nervous system, skeleton, and parathyroid glands. The gene's inclusion on panels such as Intellectual disability, Skeletal dysplasia, and Fetal anomalies reflects the diverse clinical presentations associated with disrupted microtubule function.