CLTCL1 Gene (Clathrin Heavy Chain Like 1)
A clathrin-related gene implicated in vesicle trafficking and neurodevelopmental disorders
Gene Information Card
| Symbol | CLTCL1 |
|---|---|
| Full Name | Clathrin Heavy Chain Like 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q11.21 |
| NCBI Gene ID | 8218 ncbi.nlm.nih.gov/gene/8218 |
| Ensembl ID | ENSG00000100226 |
| UniProt ID | P53675 |
| OMIM ID | 601273 |
| HGNC ID | 2093 |
| Aliases | CHC22, CLTCL, CLH22, CLTCL2 |
Description
CLTCL1 (clathrin heavy chain like 1) encodes a clathrin heavy chain isoform (CHC22) that functions in intracellular vesicle trafficking, particularly in the formation of clathrin-coated vesicles involved in endocytosis and Golgi-to-lysosome transport. Unlike the ubiquitously expressed clathrin heavy chain (CHC17), CHC22 is enriched in skeletal muscle and brain. Mutations in CLTCL1 are associated with neurodevelopmental disorder with seizures and intellectual disability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with seizures and intellectual disability (NEDSI) | Loss-of-function mutations impair clathrin-mediated vesicle trafficking in neurons, disrupting synaptic function and brain development. | ClinVar, OMIM |
| 22q11.2 deletion syndrome (DiGeorge syndrome) | CLTCL1 lies within the common 22q11.2 deletion region; haploinsufficiency may contribute to neurodevelopmental features. | OMIM, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 12.5 | Medium |
| Brain (cerebellum) | 8.3 | Low |
| Brain (cortex) | 6.1 | Low |
| Heart | 5.4 | Low |
| Testis | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| U-2 OS (osteosarcoma) | 10.1 | Moderate expression |
| SH-SY5Y (neuroblastoma) | 7.8 | Low expression |
| HeLa (cervical carcinoma) | 6.5 | Low expression |
| HepG2 (hepatocellular carcinoma) | 4.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1579C>T (p.Arg527*) | Nonsense | Rare | Loss of function; associated with NEDSI |
| c.2263C>T (p.Arg755Trp) | Missense | Rare | Likely damaging; disrupts clathrin triskelion assembly |
| c.3346G>A (p.Gly1116Arg) | Missense | Rare | Uncertain significance; reported in neurodevelopmental cases |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to premature stop codons or nonsense-mediated decay, resulting in haploinsufficiency.
Gain of Function (GOF)
No gain-of-function mutations reported for CLTCL1.
Dominant Negative (DN)
Missense mutations in the heavy chain domain may interfere with clathrin lattice formation, acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Clathrin-mediated endocytosis (KEGG hsa04144)
• Vesicle-mediated transport (Reactome R-HSA-5653656)
• Membrane trafficking (Reactome R-HSA-199991)
Protein Summary
The CLTCL1 gene encodes clathrin heavy chain like 1 (CHC22), a 1647-amino acid protein that forms triskelion structures essential for clathrin-coated vesicle formation. CHC22 is specifically involved in the trafficking of GLUT4 and other cargoes in muscle and brain. It interacts with clathrin light chains and adaptor proteins to mediate endocytosis and intracellular sorting. Mutations in CLTCL1 lead to impaired vesicle trafficking, particularly in neurons, resulting in neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLTCL1 Knockout HEK293 Cell Line | EDJ-KQ2806 | Human | 8218 | Details Get a Quote |
| CLTCL1 Knockout HeLa Cell Line | EDJ-KQ22383 | Human | 8218 | Details Get a Quote |
| CLTCL1 Knockout A-549 Cell Line | EDJ-KQ23749 | Human | 8218 | Details Get a Quote |
| CLTCL1 Knockout HCT 116 Cell Line | EDJ-KQ23750 | Human | 8218 | Details Get a Quote |
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