SPNS1 (Spinster Homolog 1): Lipid Transporter, Autophagy Regulator, and Disease Implications
A comprehensive biomedical overview of SPNS1, covering gene structure, expression, function, mutations, and clinical relevance.
Gene Information Card
| Symbol | SPNS1 |
|---|---|
| Full Name | Spinster homolog 1 (Drosophila) |
| Gene Type | protein coding |
| Chromosomal Location | 16p13.13 |
| NCBI Gene ID | 83943 ncbi.nlm.nih.gov/gene/83943 |
| Ensembl ID | ENSG00000169683 |
| UniProt ID | Q9H2H9 |
| OMIM ID | 609831 |
| HGNC ID | 28623 |
| Aliases | FLJ10637, MGC126851, MGC126853, spinster homolog 1 |
Description
SPNS1 encodes a multi-pass transmembrane protein that functions as a lysosomal lipid transporter, specifically facilitating the export of sphingolipids and other lipids from lysosomes. It is involved in autophagy regulation, lipid metabolism, and cellular homeostasis. SPNS1 is widely expressed across tissues and has been implicated in various cellular processes including apoptosis, development, and neurodegeneration. Mutations and dysregulation of SPNS1 have been linked to lysosomal storage disorders and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lysosomal storage disorders | Impaired lipid export from lysosomes leads to accumulation of sphingolipids and other lipids, disrupting lysosomal function and cellular homeostasis. | ClinVar: Pathogenic variants in SPNS1 associated with lysosomal storage phenotypes; functional studies in model organisms. |
| Neurodegenerative diseases | Dysregulation of autophagy and lipid metabolism in neurons may contribute to neurodegeneration; SPNS1 deficiency impairs autophagic flux. | PubMed: Studies in Drosophila and mouse models show neuronal defects and autophagic dysfunction. |
| Cancer | Altered SPNS1 expression may affect tumor cell survival and proliferation through modulation of autophagy and lipid signaling. | COSMIC: Somatic mutations and expression changes observed in various cancers; functional studies suggest role in tumor progression. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Liver | 12.8 | Medium |
| Kidney | 10.5 | Medium |
| Heart | 8.9 | Low |
| Lung | 7.3 | Low |
| Spleen | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.4 | Cervical cancer cell line; high expression |
| HepG2 | 15.7 | Liver cancer cell line; moderate-high expression |
| SH-SY5Y | 12.3 | Neuroblastoma cell line; moderate expression |
| A549 | 9.8 | Lung carcinoma cell line; low-moderate expression |
| MCF7 | 8.2 | Breast cancer cell line; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Ter) | Nonsense | Rare (0.01% in gnomAD) | Premature stop codon leading to truncated protein, likely loss of function. |
| c.567_568del (p.Leu190fs) | Frameshift | Not reported in population databases | Frameshift causing protein truncation, loss of function. |
| c.890A>G (p.Asp297Gly) | Missense | 0.05% in gnomAD | Amino acid substitution in transmembrane domain, may affect protein stability or function. |
| c.1456G>A (p.Glu486Lys) | Missense | 0.02% in gnomAD | Substitution in cytoplasmic loop, potential impact on protein interactions. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., nonsense, frameshift) lead to truncated or absent protein, impairing lysosomal lipid transport and autophagy, resulting in lysosomal storage and cellular toxicity.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported for SPNS1. Most pathogenic variants are loss-of-function.
Dominant Negative (DN)
Dominant-negative effects are not well established for SPNS1. However, some missense mutations might interfere with protein oligomerization or function, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • lipid transporter activity | • lysosomal membrane |
| • integral component of membrane | • autophagy |
| • lipid homeostasis | • sphingolipid metabolic process |
| • cellular response to starvation |
Pathways
• Lysosomal lipid transport
• Autophagy
• Sphingolipid metabolism
• mTOR signaling (indirect)
Protein Summary
SPNS1 is a 549-amino acid protein with multiple transmembrane domains, localized to lysosomal membranes. It functions as a lipid transporter, exporting sphingolipids and other lipids from lysosomes to the cytoplasm. This activity is crucial for maintaining lipid homeostasis and proper autophagic flux. SPNS1 interacts with other lysosomal proteins and is regulated by nutrient availability. Defects in SPNS1 lead to lysosomal storage and impaired autophagy, contributing to disease pathogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPNS1 Knockout HEK293 Cell Line | EDJ-KQ9950 | Human | 83985 | Details Get a Quote |
| SPNS1 Knockout HeLa Cell Line | EDJ-KQ18211 | Human | 83985 | Details Get a Quote |
| SPNS1 Knockout A-549 Cell Line | EDJ-KQ36862 | Human | 83985 | Details Get a Quote |
| SPNS1 Knockout HCT 116 Cell Line | EDJ-KQ36863 | Human | 83985 | Details Get a Quote |
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