CLIP3: CAP-Gly Domain Containing Linker Protein 3
A microtubule-associated protein involved in vesicular transport and linked to neurodegenerative and metabolic disorders.
Gene Information Card
| Symbol | CLIP3 |
|---|---|
| Full Name | CAP-Gly domain containing linker protein 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.12 |
| NCBI Gene ID | 25923 ncbi.nlm.nih.gov/gene/25923 |
| Ensembl ID | ENSG00000105270 |
| UniProt ID | Q96DZ5 |
| OMIM ID | 605178 |
| HGNC ID | 20636 |
| Aliases | CLIP-170-related protein, CLIPR-59, GTRAP3-18, RSNL1 |
Description
CLIP3 encodes a member of the CAP-Gly domain-containing family of microtubule-associated proteins. The protein localizes to the Golgi apparatus and cytoplasmic vesicles, where it regulates microtubule dynamics and vesicular transport. It is also known as GTRAP3-18, a negative regulator of the excitatory amino acid transporter EAAT3 (SLC1A1), and has been implicated in neuronal glutamate homeostasis, insulin secretion, and lipid metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodegenerative disorders (e.g., Alzheimer's disease) | CLIP3 modulates EAAT3 activity, affecting glutamate clearance and excitotoxicity; altered expression linked to synaptic dysfunction. | NCBI Gene, OMIM |
| Type 2 diabetes | CLIP3 regulates insulin granule exocytosis in pancreatic beta-cells via interaction with Rab3A and microtubule network. | UniProt, PubMed |
| Obesity | CLIP3 expression in adipose tissue influences lipid droplet formation and energy metabolism. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Pancreas | 8.3 | Low |
| Adipose tissue | 6.1 | Low |
| Testis | 15.2 | Medium |
| Kidney | 9.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.7 | Neuronal model; high expression |
| HeLa (cervical carcinoma) | 7.2 | Moderate expression |
| HepG2 (hepatocellular carcinoma) | 5.4 | Low expression |
| MIN6 (mouse pancreatic beta-cell) | N/A | Used in functional studies of insulin secretion |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | <0.01% | Unknown; rare variant in population databases |
| c.457G>A (p.Val153Ile) | Missense | <0.01% | Potential impact on protein stability (in silico prediction) |
| c.1234_1235del (p.Lys412Glufs*5) | Frameshift | <0.01% | Predicted loss-of-function; not validated in disease |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., p.Lys412Glufs*5) are predicted to truncate the protein, likely impairing microtubule binding and vesicle transport.
Gain of Function (GOF)
No gain-of-function mutations reported in CLIP3.
Dominant Negative (DN)
No dominant-negative mutations documented; potential if mutant protein interferes with wild-type CLIP3 or EAAT3 regulation.
View complete mutation data：
Gene Ontology (GO)
| • microtubule binding | • Golgi apparatus |
| • cytoplasmic vesicle | • protein transport |
| • negative regulation of glutamate uptake | • insulin secretion |
Pathways
• Glutamatergic synapse (EAAT3 regulation)
• Insulin secretion (Rab3A-mediated exocytosis)
• Microtubule-dependent vesicle transport
Protein Summary
CLIP3 is a 59 kDa protein containing an N-terminal CAP-Gly domain that mediates microtubule binding and a C-terminal region involved in Golgi/vesicle localization. It interacts with the small GTPase Rab3A to regulate insulin granule exocytosis and with EAAT3 to control glutamate transport. The protein is widely expressed, with highest levels in brain and testis, and plays roles in neuronal signaling, metabolic homeostasis, and intracellular trafficking.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLIP3 Knockout HEK293 Cell Line | EDJ-KQ8347 | Human | 25999 | Details Get a Quote |
| CLIP3 Knockout HeLa Cell Line | EDJ-KQ55861 | Human | 25999 | Details Get a Quote |
| CLIP3 Knockout A-549 Cell Line | EDJ-KQ64353 | Human | 25999 | Details Get a Quote |
| CLIP3 Knockout HCT 116 Cell Line | EDJ-KQ72801 | Human | 25999 | Details Get a Quote |
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