ORMDL3
protein-codingORMDL sphingolipid biosynthesis regulator 3
Gene summary
Involved in ceramide metabolic process. Acts upstream of or within several processes, including negative regulation of B cell apoptotic process; negative regulation of ceramide biosynthetic process; and positive regulation of protein localization to nucleus. Located in endoplasmic reticulum. Part of serine palmitoyltransferase complex. Implicated in allergic asthma; asthma; and childhood-onset asthma. Biomarker of allergic asthma and asthma. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ORMDL3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_139280.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 12 | 12 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 12 | 0 | 0 | 12 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_644809.1 | 3 | MANE Select | |
| Ensembl | ENSP00000304858.2 | 3 | MANE Select | |
| RefSeq | NP_001307730.1 | 3 | Standard | |
| RefSeq | NP_001307731.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neutrophil degranulation
- Metabolism of lipids
- Innate Immune System
- Immune System
- Metabolism
Biological Process
- ceramide metabolic process
- neutrophil degranulation
- cellular sphingolipid homeostasis
- negative regulation of ceramide biosynthetic process
Molecular Function
- protein binding
Cellular Component
- endoplasmic reticulum
- plasma membrane
- integral component of membrane
- secretory granule membrane
- SPOTS complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000394169
- Coding exons
- 3
- Length
- 6561
- Individuals with no LoFs
- 125736
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125741
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.32 | 64 | 101 | 0.632 | 0.00000652 | 1008 |
| Missense (PolyPhen) | 21 | 31.686 | 0.66275 | 375 | ||
| Synonymous | -1.19 | 56 | 45.7 | 1.22 | 0.00000341 | 310 |
| Loss of Function | 2.09 | 0 | 5.06 | 0.00 | 2.16e-7 | 55 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Negative regulator of sphingolipid synthesis. May indirectly regulate endoplasmic reticulum-mediated Ca(+2) signaling. {ECO:0000269|PubMed:20182505}.;
Recessive Scores
- pRec
- 0.135
Intolerance Scores
- LoFtool
- 0.254
- RVIS EVS
- -0.23
- RVIS percentile EVS
- 36.86
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.949
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |