ST3GAL5 (ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 5)
Key enzyme in ganglioside biosynthesis; mutations cause Amish infantile epilepsy syndrome and related disorders.
Gene Information Card
| Symbol | ST3GAL5 |
|---|---|
| Full Name | ST3 beta-galactoside alpha-2,3-sialyltransferase 5 |
| Gene Type | protein coding |
| Chromosomal Location | 2p11.2 |
| NCBI Gene ID | 8869 ncbi.nlm.nih.gov/gene/8869 |
| Ensembl ID | ENSG00000115525 |
| UniProt ID | Q9UNP4 |
| OMIM ID | 604402 |
| HGNC ID | 10864 |
| Aliases | SIAT9, GM3 synthase, SIATGM3S |
Description
ST3GAL5 encodes a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to lactosylceramide, forming GM3 ganglioside. This is the first step in the biosynthesis of most complex gangliosides, which are essential for neuronal development and function. Mutations in this gene lead to GM3 synthase deficiency, resulting in severe neurological phenotypes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Amish infantile epilepsy syndrome | Loss-of-function mutations cause absence of GM3 synthase activity, leading to accumulation of lactosylceramide and deficiency of downstream gangliosides, disrupting neuronal signaling. | OMIM #609056; multiple homozygous mutations identified in Amish population. |
| Salt-and-pepper syndrome | Biallelic mutations in ST3GAL5 cause this autosomal recessive disorder characterized by intellectual disability, seizures, and distinctive skin pigmentation. | ClinVar entries; case reports in non-Amish populations. |
| GM3 synthase deficiency | Complete loss of enzyme activity due to homozygous or compound heterozygous mutations results in severe developmental delay, epilepsy, and blindness. | UniProt and OMIM; functional assays confirm loss of sialyltransferase activity. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | Highest expression in brain, especially in neurons and glial cells. |
| Testis | Moderate | Detected in testicular tissue. |
| Kidney | Low | Low expression in kidney. |
| Liver | Low | Minimal expression in liver. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High | Neuronal cell line; used for ganglioside studies. |
| HeLa (cervical carcinoma) | Low | Low expression; not a primary site. |
| HepG2 (hepatocellular carcinoma) | Low | Low expression; liver origin. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.862C>T (p.Arg288Ter) | Nonsense | Rare | Premature stop codon; loss of enzyme activity. |
| c.1042G>A (p.Gly348Arg) | Missense | Rare | Amino acid substitution; reduced catalytic activity. |
| c.506T>C (p.Leu169Pro) | Missense | Rare | Structural change; loss of function. |
| c.694C>T (p.Arg232Ter) | Nonsense | Rare | Truncated protein; no activity. |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations are loss-of-function, leading to complete or near-complete loss of GM3 synthase activity.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative effects documented; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • sialyltransferase activity | • ganglioside biosynthetic process |
| • Golgi membrane | • alpha-2 |
| • 3-sialyltransferase activity |
Pathways
• Ganglioside biosynthesis
• Glycosphingolipid metabolism
Protein Summary
ST3GAL5 is a 418-amino acid type II membrane protein localized to the Golgi apparatus. It catalyzes the formation of GM3 ganglioside from lactosylceramide and CMP-N-acetylneuraminic acid. The protein has a short N-terminal cytoplasmic tail, a transmembrane domain, and a large C-terminal catalytic domain. It is critical for the synthesis of a- and b-series gangliosides, which are abundant in the nervous system.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ST3GAL5 Knockout HEK293 Cell Line | EDJ-KQ3838 | Human | 8869 | Details Get a Quote |
| ST3GAL5 Knockout A-549 Cell Line | EDJ-KQ25994 | Human | 8869 | Details Get a Quote |
| ST3GAL5 Knockout HCT 116 Cell Line | EDJ-KQ25995 | Human | 8869 | Details Get a Quote |
| ST3GAL5 Knockout HeLa Cell Line | EDJ-KQ25996 | Human | 8869 | Details Get a Quote |
