SLC33A1: Acetyl-CoA Transporter and SPG42 Link
Solute Carrier Family 33 Member 1 – Key in Acetylation, Axonal Integrity, and Hereditary Spastic Paraplegia
Gene Information Card
| Symbol | SLC33A1 |
|---|---|
| Full Name | Solute Carrier Family 33 Member 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q25.31 |
| NCBI Gene ID | 9197 ncbi.nlm.nih.gov/gene/9197 |
| Ensembl ID | ENSG00000169359 |
| UniProt ID | O00400 |
| OMIM ID | 603690 |
| HGNC ID | 10962 |
| Aliases | AT-1, ACATN, SPG42 |
Description
SLC33A1 encodes the acetyl-CoA transporter 1 (AT-1), a multi-pass transmembrane protein localized to the endoplasmic reticulum and Golgi apparatus. It transports acetyl-CoA from the cytosol into the lumen of these organelles, providing the substrate for N-epsilon-acetylation of proteins, including those involved in axonal maintenance and myelin formation. Loss-of-function mutations in SLC33A1 cause autosomal dominant hereditary spastic paraplegia type 42 (SPG42), characterized by progressive lower limb spasticity and weakness.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Spastic Paraplegia 42 (SPG42) | Dominant-negative or haploinsufficiency of acetyl-CoA transport reduces luminal acetylation, impairing axonal transport and leading to corticospinal tract degeneration. | OMIM #612539; multiple missense mutations (e.g., p.Ser113Arg, p.Pro317Leu) reported in families. |
| Developmental and Epileptic Encephalopathy (DEE) | Biallelic loss-of-function variants cause severe neurodevelopmental disorder with seizures, likely due to global acetylation defects. | ClinVar; rare homozygous/compound heterozygous variants. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Kidney | 7.1 | Medium |
| Heart | 6.4 | Low |
| Lung | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression; relevant for neuronal studies |
| HepG2 (hepatocellular carcinoma) | 9.8 | Moderate expression |
| HEK293 (embryonic kidney) | 7.5 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.337A>G (p.Ser113Arg) | Missense | Unknown | Dominant; reduces acetyl-CoA transport; associated with SPG42 |
| c.950C>T (p.Pro317Leu) | Missense | Unknown | Dominant; impairs transporter function; SPG42 |
| c.1A>G (p.Met1?) | Start loss | Rare | Likely loss-of-function; DEE |
Mutation functional classification
Loss of Function (LOF)
Biallelic null variants (e.g., start loss, frameshift) cause severe DEE due to complete loss of acetyl-CoA transport.
Gain of Function (GOF)
Not reported for SLC33A1.
Dominant Negative (DN)
Missense mutations (e.g., p.Ser113Arg) act via dominant-negative effect, reducing overall transporter activity in the ER/Golgi.
View complete mutation data：
Gene Ontology (GO)
| • GO:0015870 – acetyl-CoA transport | • GO:0016021 – integral component of membrane |
| • GO:0005783 – endoplasmic reticulum | • GO:0005794 – Golgi apparatus |
| • GO:0016740 – transferase activity (acetyl group) |
Pathways
• Acetyl-CoA transport (Reactome: R-HSA-8873719)
• Protein acetylation in ER/Golgi (Reactome: R-HSA-381038)
Protein Summary
The SLC33A1 protein (AT-1) is a 549-amino acid transmembrane transporter with 6-8 predicted membrane-spanning domains. It resides in the ER and Golgi membranes, where it mediates the import of cytosolic acetyl-CoA into the lumen. This acetyl-CoA is used for N-epsilon-acetylation of nascent proteins, a modification critical for proper folding, stability, and function of secreted and membrane proteins. In neurons, AT-1 is essential for axonal integrity; its dysfunction leads to spastic paraplegia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC33A1 Knockout HEK293 Cell Line | EDJ-KQ6493 | Human | 9197 | Details Get a Quote |
| SLC33A1 Knockout HeLa Cell Line | EDJ-KQ29277 | Human | 9197 | Details Get a Quote |
| SLC33A1 Knockout HCT 116 Cell Line | EDC07721 | Human | 9197 | Details Get a Quote |
| SLC33A1 Knockout A-549 Cell Line | EDJ-KQ63583 | Human | 9197 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
