ORMDL3
ORMDL Sphingolipid Biosynthesis Regulator 3
Gene Information Card
| Symbol | ORMDL3 |
|---|---|
| Full Name | ORMDL sphingolipid biosynthesis regulator 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q21.1 |
| NCBI Gene ID | 94103 ncbi.nlm.nih.gov/gene/94103 |
| Ensembl ID | ENSG00000172057 |
| UniProt ID | Q8N138 |
| OMIM ID | 610075 |
| HGNC ID | 16038 |
| Aliases | ORMDL3, ORMDL3_HUMAN, FLJ22405 |
Description
ORMDL3 encodes a member of the ORMDL family of endoplasmic reticulum membrane proteins that negatively regulate serine palmitoyltransferase (SPT), the first and rate-limiting enzyme in sphingolipid biosynthesis. The gene is located on chromosome 17q21.1, a region strongly associated with asthma susceptibility. ORMDL3 is ubiquitously expressed, with highest levels in immune cells and lung tissue. Its dysregulation contributes to altered sphingolipid metabolism and inflammatory responses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Asthma | ORMDL3 overexpression increases SPT activity and sphingolipid levels, promoting airway hyperresponsiveness and inflammation. | Genome-wide association studies (GWAS) and functional studies in human lung epithelial cells and mouse models. |
| Inflammatory Bowel Disease (IBD) | ORMDL3 variants may alter sphingolipid metabolism in intestinal epithelial cells, affecting barrier function and immune signaling. | GWAS and expression quantitative trait loci (eQTL) analyses in colon tissue. |
| Allergic Rhinitis | Shared genetic risk with asthma at 17q21 locus; ORMDL3 expression correlates with IgE levels. | Population-based genetic studies and transcriptomic data. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 18.5 | Medium |
| Whole Blood | 12.3 | Medium |
| Small Intestine | 15.1 | Medium |
| Spleen | 14.8 | Medium |
| Liver | 8.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 22.1 | High expression; used in asthma studies |
| HEK293 (embryonic kidney) | 16.4 | Moderate expression; common for overexpression |
| HepG2 (hepatocellular carcinoma) | 9.7 | Low expression |
| Jurkat (T-cell leukemia) | 18.9 | High expression; relevant for immune function |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs7216389 | SNP (intronic) | ~50% in European populations | Associated with increased ORMDL3 expression and asthma risk |
| rs12603332 | SNP (intergenic) | ~35% in European populations | Linked to ORMDL3 expression and asthma susceptibility |
| c.128G>A (p.Arg43His) | Missense | Rare (<0.1%) | Unknown functional effect; reported in ClinVar |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in ORMDL3.
Gain of Function (GOF)
rs7216389 is associated with increased ORMDL3 expression, potentially leading to gain-of-function in sphingolipid regulation.
Dominant Negative (DN)
No dominant-negative mutations described.
View complete mutation data：
Gene Ontology (GO)
| • ceramide metabolic process (GO:0006672) | • endoplasmic reticulum (GO:0005783) |
| • integral component of membrane (GO:0016021) | • serine C-palmitoyltransferase activity (GO:0004758) |
| • ceramide biosynthetic process (GO:0046513) |
Pathways
• KEGG: sphingolipid metabolism (hsa00600)
• Reactome: sphingolipid de novo biosynthesis (R-HSA-1660661)
Protein Summary
ORMDL3 is a 153-amino acid transmembrane protein localized to the endoplasmic reticulum. It forms a complex with serine palmitoyltransferase (SPT) to negatively regulate sphingolipid biosynthesis. The protein contains a conserved ORMDL domain and is involved in maintaining sphingolipid homeostasis. Dysregulation of ORMDL3 expression is linked to asthma and other inflammatory diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ORMDL3 Knockout HEK293 Cell Line | EDJ-KQ10598 | Human | 94103 | Details Get a Quote |
| ORMDL3 Knockout A-549 Cell Line | EDJ-KQ39401 | Human | 94103 | Details Get a Quote |
| ORMDL3 Knockout HCT 116 Cell Line | EDJ-KQ39402 | Human | 94103 | Details Get a Quote |
| ORMDL3 Knockout HeLa Cell Line | EDJ-KQ39403 | Human | 94103 | Details Get a Quote |
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