CLTC and Associated Diseases
A Summary of CLTC Gene and Associated Protein
Clathrin heavy chain (CLTC) is a protein-coding gene located on the human chromosome 17 and mouse chromosome 11, respectively. Cathrin, a protein encoded by the CLTC gene, is a main protein component of the cytoplasmic face of intracellular organelles. Those organelles participate in the intracellular trafficking of receptors and endocytosis of multifarious macromolecules. As shown in Figure 1, the clathrin consists of three heavy chains and three light chains. The whole polymer forms a triskelion that is involved in the transport function of membranes. The clathrin lattice to the trans-Golgi network and the plasma membrane were linked by two different adapter protein complexes. This unique structure prompts the formation of curved envelopes that cover the cytoplasmic surface of clathrin-coated vesicles. As an essential component of the TACC3/ch-TOG/clathrin complex, the clathrin serves as an inter-microtubule bridge to help stabilize the kinetochore fibers of the mitotic spindle.
Fig.1 The architecture of clathrin. (Edeling,2006)
CLTC and Associated Diseases
Clathrin is of vital importance in endocytosis and intracellular trafficking of receptors. Different types of CLTC mutations can lead to distinct clinical manifestations. Truncating variants give rise to a loss-of-function effect resulting in milder clinical manifestations, while missense and in-frame variants may bring about a dominant-negative effect resulting in more severe clinical features.
- Intellectual Developmental Disorder (Autosomal Dominant 56)
Clathrin heavy chain 1 (CHC1) has been verified to exert a crucial role in the process of vesicle recycling and neurotransmitter release at pre-synaptic nerve terminals in the human brain. Moreover, the correlation between CHC1 and the natural development of the placenta has also been proven. As reported (Nabais Sá, 2020), a de novo missense variant of CLTC would lead to the disorder of biogenic amine trafficking, further leading to an intellectual developmental disorder. Patients with this disease present with intellectual disability, hypoplasia of the corpus callosum, epilepsy, poor speech, vision abnormalities, movement disorder, gastrointestinal problems, and some other symptoms.
- Cancers and Tumors
As an important functional protein that is expressed prevailing in humans, clathrin has three heavy chains and three light chains. Two clathrin heavy chain genes exist in humans: CHC22 (CLTCL1 at 22q11.21) and CHC17 (CLTC at 17q11-qter). Among them, CHC17 was found to be involved in two different types of gene fusion in human cancers. CHC-anaplastic lymphoma kinase (CHC-ALK), a fusion protein, has been reported in many types of tumors, such as ALK+ diffuse large B-cell lymphoma, anaplastic null/T-cell lymphoma, and inflammatory myofibroblastic tumor. In addition, CLTC can also fuse with the C-terminal region of transcription factor binding to IGHM enhancer 3 to form a fusion protein CHC-transcription factor binding to IGHM enhancer 3 (CHC-TFE3). CHC-TFE3 has been found in pediatric renal cell carcinoma (Blixt, 2011).
Creative Biolabs is a renowned biotechnology company that is dedicated to helping you solve your intractable problems. If you have any confusion about the CLTC gene, please contact us in time.
References
- Nabais Sá, M.J., et al. De novo CLTC variants are associated with a variable phenotype from mild to severe intellectual disability, microcephaly, hypoplasia of the corpus callosum, and epilepsy. Genetics in Medicine. 2020, 22(4): 797-802.
- Blixt, M.K.E., Royle, S.J. Clathrin heavy chain gene fusions expressed in human cancers: analysis of cellular functions. Traffic. 2011, 12(6): 754-61.
