GAN
Gigaxonin Gene
Gene Information Card
| Symbol | GAN |
|---|---|
| Full Name | Gigaxonin |
| Gene Type | Protein coding |
| Chromosomal Location | 16q23.2 |
| NCBI Gene ID | 8139 ncbi.nlm.nih.gov/gene/8139 |
| Ensembl ID | ENSG00000103510 |
| UniProt ID | Q9H2C0 |
| OMIM ID | 605379 |
| HGNC ID | 4137 |
| Aliases | GAN1, KLHL16, FLJ20719 |
Description
The GAN gene encodes gigaxonin, a member of the BTB/kelch repeat family of proteins. Gigaxonin is involved in cytoskeletal organization, specifically in the regulation of intermediate filament networks. Mutations in GAN cause giant axonal neuropathy (GAN), a severe autosomal recessive neurodegenerative disorder characterized by progressive motor and sensory neuropathy, central nervous system involvement, and characteristic kinky hair.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Giant axonal neuropathy (GAN) | Loss-of-function mutations in GAN disrupt gigaxonin-mediated degradation of intermediate filament proteins, leading to accumulation of neurofilaments and other intermediate filaments in neurons and other cells. | ClinVar, OMIM |
| Giant axonal neuropathy 1 (GAN1) | Same mechanism as above; GAN1 is an allelic variant of GAN. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 6.5 | Low |
| Spinal cord | 4.2 | Low |
| Peripheral nerve | 3.8 | Low |
| Testis | 2.1 | Not detected |
| Skeletal muscle | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 5.0 | Neuronal model |
| HeLa (cervical carcinoma) | 2.3 | Low expression |
| HEK293 (embryonic kidney) | 1.8 | Low expression |
| U-87 MG (glioblastoma) | 4.1 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.529C>T (p.Arg177*) | Nonsense | Rare | Loss of function; truncation of gigaxonin |
| c.1390C>T (p.Arg464*) | Nonsense | Rare | Loss of function; premature stop codon |
| c.1078G>A (p.Gly360Arg) | Missense | Rare | Loss of function; disrupts kelch domain |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no protein produced |
Mutation functional classification
Loss of Function (LOF)
Most GAN mutations are loss-of-function, leading to impaired degradation of intermediate filament proteins and subsequent neurofilament accumulation.
Gain of Function (GOF)
No gain-of-function mutations reported for GAN.
Dominant Negative (DN)
No dominant-negative mutations reported; GAN-associated giant axonal neuropathy is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Intermediate filament organization
• Ubiquitin-proteasome pathway
• Protein degradation via CUL3 ubiquitin ligase complex
Protein Summary
Gigaxonin is a 597-amino acid protein containing an N-terminal BTB/POZ domain and six C-terminal kelch repeats. It functions as a substrate-specific adaptor for the CUL3-based E3 ubiquitin ligase complex, targeting intermediate filament proteins (e.g., GFAP, vimentin, peripherin) for proteasomal degradation. Loss of gigaxonin function leads to abnormal accumulation of intermediate filaments, causing the neurodegenerative phenotype of giant axonal neuropathy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GANC Knockout HEK293 Cell Line | EDJ-KQ2165 | Human | 2595 | Details Get a Quote |
| GANAB Knockout HEK293 Cell Line | EDJ-KQ2622 | Human | 23193 | Details Get a Quote |
| GAN Knockout HEK293 Cell Line | EDJ-KQ3739 | Human | 8139 | Details Get a Quote |
| GANC Knockout HeLa Cell Line | EDJ-KQ21061 | Human | 2595 | Details Get a Quote |
| GANAB Knockout HCT 116 Cell Line | EDJ-KQ21990 | Human | 23193 | Details Get a Quote |
| GANC Knockout A-549 Cell Line | EDJ-KQ22370 | Human | 2595 | Details Get a Quote |
| GANC Knockout HCT 116 Cell Line | EDJ-KQ22371 | Human | 2595 | Details Get a Quote |
| GANAB Knockout A-549 Cell Line | EDJ-KQ23354 | Human | 23193 | Details Get a Quote |
| GANAB Knockout HeLa Cell Line | EDJ-KQ23355 | Human | 23193 | Details Get a Quote |
| GAN Knockout A-549 Cell Line | EDJ-KQ25792 | Human | 8139 | Details Get a Quote |
| GAN Knockout HCT 116 Cell Line | EDJ-KQ25793 | Human | 8139 | Details Get a Quote |
| GAN Knockout HeLa Cell Line | EDJ-KQ25794 | Human | 8139 | Details Get a Quote |
