HAP1 (Huntingtin-Associated Protein 1)
A key regulator of intracellular trafficking and neuronal survival, implicated in Huntington disease and other neurodegenerative disorders.
Gene Information Card
| Symbol | HAP1 |
|---|---|
| Full Name | Huntingtin-Associated Protein 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 17q21.2 |
| NCBI Gene ID | 9001 ncbi.nlm.nih.gov/gene/9001 |
| Ensembl ID | ENSG00000108798 |
| UniProt ID | P54257 |
| OMIM ID | 600947 |
| HGNC ID | 4730 |
| Aliases | HIP5, HAP1A, HAP1B, HAP1-1, HAP1-2 |
Description
HAP1 (Huntingtin-Associated Protein 1) encodes a protein that interacts with huntingtin, the protein mutated in Huntington disease. HAP1 is involved in intracellular trafficking, vesicle transport, and neuronal survival. It is predominantly expressed in the brain and plays a role in the pathogenesis of Huntington disease and other neurodegenerative conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Huntington disease | HAP1 interacts with mutant huntingtin; altered trafficking and aggregation contribute to neuronal dysfunction. | PMID: 7596436; OMIM #600947 |
| Spinocerebellar ataxia type 17 | HAP1 binds TBP (TATA-box binding protein); expanded polyglutamine tracts may disrupt HAP1 function. | PMID: 11528394 |
| Alzheimer disease | HAP1 modulates amyloid precursor protein (APP) trafficking and processing. | PMID: 17690110 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Testis | 3.2 | Medium |
| Spinal cord | 8.1 | High |
| Heart | 1.0 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | High expression; used in neurodegeneration studies |
| HeLa (cervical carcinoma) | 2.1 | Low expression |
| HEK293 (embryonic kidney) | 4.5 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.214C>T (p.Arg72Cys) | Missense | <0.01% | Alters huntingtin binding affinity; potential modifier of Huntington disease onset |
| c.487_489del (p.Lys163del) | In-frame deletion | <0.01% | Disrupts HAP1 dimerization and trafficking function |
| c.1024G>A (p.Gly342Ser) | Missense | <0.01% | Reduced stability; associated with altered neuronal survival in vitro |
Mutation functional classification
Loss of Function (LOF)
Decreased HAP1 expression or impaired huntingtin binding leads to disrupted vesicle transport and increased neuronal vulnerability.
Gain of Function (GOF)
Not well characterized; some missense variants may enhance aggregation of mutant huntingtin.
Dominant Negative (DN)
Truncating or dimerization-disrupting mutations may interfere with wild-type HAP1 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Huntington disease (KEGG: hsa05016)
• Vesicle-mediated transport (Reactome: R-HSA-5653656)
• Clathrin-mediated endocytosis (Reactome: R-HSA-199991)
Protein Summary
HAP1 is a 75-85 kDa protein that forms homodimers and interacts with huntingtin via a coiled-coil domain. It functions as an adaptor in intracellular trafficking, linking cargo to dynein/dynactin motor complexes. HAP1 is enriched in neurons and is essential for neurotrophic factor transport, autophagy, and protection against excitotoxicity. Alternative splicing generates two major isoforms: HAP1A and HAP1B.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| THAP12 Knockout HEK293 Cell Line | EDJ-KQ5539 | Human | 5612 | Details Get a Quote |
| HAP1 Knockout HEK293 Cell Line | EDJ-KQ6426 | Human | 9001 | Details Get a Quote |
| THAP10 Knockout HEK293 Cell Line | EDJ-KQ15717 | Human | 56906 | Details Get a Quote |
| THAP12 Knockout A-549 Cell Line | EDJ-KQ28795 | Human | 5612 | Details Get a Quote |
| THAP12 Knockout HCT 116 Cell Line | EDJ-KQ28796 | Human | 5612 | Details Get a Quote |
| THAP12 Knockout HeLa Cell Line | EDJ-KQ28797 | Human | 5612 | Details Get a Quote |
| HAP1 Knockout A-549 Cell Line | EDJ-KQ30480 | Human | 9001 | Details Get a Quote |
| HAP1 Knockout HCT 116 Cell Line | EDJ-KQ30481 | Human | 9001 | Details Get a Quote |
| THAP10 Knockout A-549 Cell Line | EDJ-KQ46632 | Human | 56906 | Details Get a Quote |
| THAP10 Knockout HCT 116 Cell Line | EDJ-KQ46633 | Human | 56906 | Details Get a Quote |
| THAP10 Knockout HeLa Cell Line | EDJ-KQ46634 | Human | 56906 | Details Get a Quote |
| HAP1 Knockout HeLa Cell Line | EDJ-KQ55054 | Human | 9001 | Details Get a Quote |
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