HOOK3: Microtubule Tethering Protein and Oncogene in Thyroid Cancer
Comprehensive genomic and functional analysis of HOOK3, a key component of the FHF complex implicated in thyroid carcinogenesis and cellular trafficking.
Gene Information Card
| Symbol | HOOK3 |
|---|---|
| Full Name | Hook microtubule tethering protein 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 8p11.21 |
| NCBI Gene ID | 84376 ncbi.nlm.nih.gov/gene/84376 |
| Ensembl ID | ENSG00000168172 |
| UniProt ID | Q86VS8 |
| OMIM ID | 607825 |
| HGNC ID | 23484 |
| Aliases | HK3, h-hook3, FLJ20291 |
Description
HOOK3 encodes a member of the hook family of proteins, which function as microtubule-tethering factors. HOOK3 is a component of the FHF complex (FTS/Hook/FHIP), which links cargo vesicles to microtubules for intracellular transport. The protein contains an N-terminal microtubule-binding domain and a C-terminal cargo-binding domain. HOOK3 is recurrently fused to the RET tyrosine kinase domain in papillary thyroid carcinoma (PTC), resulting in a constitutively active oncoprotein.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Papillary thyroid carcinoma | HOOK3-RET fusion (fusion of HOOK3 N-terminus to RET kinase domain) leads to ligand-independent dimerization and constitutive activation of RET, driving MAPK/ERK signaling. | PMID: 9242372; COSMIC; ClinVar |
| Thyroid cancer (general) | HOOK3 rearrangements (e.g., with RET) are recurrent in radiation-associated and sporadic PTC. | PMID: 9242372; COSMIC |
| Colorectal cancer | HOOK3 overexpression and copy number gains observed in some colorectal tumors; functional role unclear. | COSMIC; PMID: 23535966 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 14.2 | Medium |
| Thyroid | 11.8 | Medium |
| Testis | 10.5 | Medium |
| Lung | 8.3 | Low |
| Kidney | 7.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 12.1 | Cervical adenocarcinoma |
| A549 | 9.4 | Lung carcinoma |
| MCF7 | 8.7 | Breast adenocarcinoma |
| K562 | 7.2 | Leukemia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| HOOK3-RET fusion (PTC) | Gene fusion | Recurrent in PTC (~5-10% of RET fusions) | Constitutive RET kinase activation; oncogenic |
| Missense (p.Arg123Cys) | Missense | <0.1% (gnomAD) | Unknown; likely benign |
| Frameshift (p.Glu456fs) | Frameshift | <0.01% | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense variants that truncate the C-terminal cargo-binding domain are predicted to impair microtubule tethering and vesicle transport.
Gain of Function (GOF)
HOOK3-RET fusions result in gain-of-function by constitutive activation of RET tyrosine kinase, promoting cell proliferation and survival.
Dominant Negative (DN)
No dominant-negative mutations have been reported for HOOK3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Microtubule-dependent transport (FHF complex)
• RET signaling (via HOOK3-RET fusion)
• MAPK/ERK cascade (downstream of RET)
Protein Summary
HOOK3 is a 718-amino acid protein (UniProt Q86VS8) that localizes to the Golgi apparatus and endosomes. It contains an N-terminal hook domain for microtubule binding and a C-terminal domain for cargo recognition. As part of the FHF complex, HOOK3 facilitates the tethering of endocytic vesicles to microtubules for retrograde transport. In cancer, the N-terminal region of HOOK3 fuses to the RET kinase domain, creating a potent oncogene that drives papillary thyroid carcinoma.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HOOK3 Knockout HEK293 Cell Line | EDJ-KQ10077 | Human | 84376 | Details Get a Quote |
| HOOK3 Knockout A-549 Cell Line | EDJ-KQ37146 | Human | 84376 | Details Get a Quote |
| HOOK3 Knockout HCT 116 Cell Line | EDJ-KQ37147 | Human | 84376 | Details Get a Quote |
| HOOK3 Knockout HeLa Cell Line | EDJ-KQ37148 | Human | 84376 | Details Get a Quote |
