ELANE Gene: Neutrophil Elastase in Innate Immunity and Disease
Explore the ELANE gene, its protein product neutrophil elastase, and its role in severe congenital neutropenia, cyclic neutropenia, and other conditions.
Gene Information Card
| Symbol | ELANE |
|---|---|
| Full Name | Elastase, Neutrophil Expressed |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.3 |
| NCBI Gene ID | 1991 ncbi.nlm.nih.gov/gene/1991 |
| Ensembl ID | ENSG00000197561 |
| UniProt ID | P08246 |
| OMIM ID | 130130 |
| HGNC ID | 3309 |
| Aliases | ELA2, HLE, HNE, NE, PMN-E |
Description
The ELANE gene encodes neutrophil elastase, a serine protease primarily stored in azurophilic granules of neutrophils. This enzyme plays a critical role in the innate immune response by degrading bacterial proteins and extracellular matrix components. Beyond its antimicrobial function, ELANE is essential for the proper maturation of neutrophils in the bone marrow. Mutations in ELANE are the most common cause of severe congenital neutropenia (SCN) and cyclic neutropenia (CyN), leading to disrupted granulopoiesis, increased apoptosis of myeloid progenitors, and a predisposition to infections and leukemia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Severe Congenital Neutropenia (SCN) | Mutations cause misfolded protein accumulation in the endoplasmic reticulum (ER), triggering the unfolded protein response (UPR) and apoptosis of myeloid progenitor cells, leading to a block in neutrophil differentiation. | ClinVar, OMIM, PubMed |
| Cyclic Neutropenia (CyN) | Mutations lead to a similar but less severe ER stress and UPR, causing periodic fluctuations in neutrophil counts with an approximately 21-day cycle. The exact mechanism for periodicity is still under investigation. | ClinVar, OMIM, PubMed |
| Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) | Patients with ELANE mutations and SCN have a significantly increased risk of acquiring additional somatic mutations (e.g., in CSF3R, RUNX1) that can lead to leukemic transformation. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Bone Marrow | High | High |
| Spleen | Low | Low |
| Lung | Low | Low |
| Whole Blood | High | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| HL-60 (Promyeloblast) | High | Differentiates into neutrophil-like cells; high ELANE expression. |
| NB4 (Acute Promyelocytic Leukemia) | High | Represents a myeloid lineage with high ELANE expression. |
| K-562 (Chronic Myelogenous Leukemia) | Low | More erythroid/megakaryocytic lineage; low ELANE expression. |
| HeLa (Cervical Carcinoma) | Not detected | Non-myeloid lineage; no significant expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| p.Ser126Leu (c.377C>T) | Missense | Common in SCN | Causes protein misfolding and ER stress, leading to apoptosis. |
| p.Cys122Ser (c.365G>C) | Missense | Common in SCN | Disrupts disulfide bond, leading to misfolding and loss of function. |
| p.Val72Met (c.214G>A) | Missense | Common in CyN | Associated with cyclic neutropenia; causes milder ER stress. |
| c.597+1G>A | Splice site | Rare | Leads to aberrant splicing and premature termination, causing loss of function. |
Mutation functional classification
Loss of Function (LOF)
Most ELANE mutations are considered loss-of-function in terms of protease activity, but the primary pathogenic mechanism is a dominant-negative effect due to protein misfolding, not a simple loss of enzymatic activity.
Gain of Function (GOF)
No clear gain-of-function mutations have been described for ELANE. The pathogenic effect is not due to increased elastase activity.
Dominant Negative (DN)
The primary mechanism for SCN and CyN is a dominant-negative effect. The misfolded mutant protein accumulates in the ER, triggering the unfolded protein response (UPR) and apoptosis, which overwhelms the normal function of the wild-type allele.
View complete mutation data：
Gene Ontology (GO)
| • serine-type endopeptidase activity | • proteolysis |
| • extracellular matrix disassembly | • innate immune response |
| • defense response to bacterium | • neutrophil degranulation |
| • ER-associated misfolded protein catabolic process | • apoptotic process |
Pathways
• Innate Immune System
• Neutrophil degranulation
• Unfolded Protein Response (UPR) (when mutated)
• Apoptosis (when mutated)
Protein Summary
Neutrophil elastase (NE) is a 29.5 kDa glycoprotein composed of 267 amino acids. It is synthesized as a preproenzyme and processed to an active protease stored in azurophilic granules. NE has broad substrate specificity, cleaving proteins such as elastin, collagen, fibronectin, and various bacterial virulence factors. It is inhibited by alpha-1 antitrypsin (SERPINA1) and other serpins. In addition to its role in pathogen clearance, NE is involved in the regulation of inflammation and tissue remodeling. Dysregulation of NE activity is implicated in chronic inflammatory diseases like COPD and cystic fibrosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ELANE Knockout HEK293 Cell Line | EDJ-KQ4514 | Human | 1991 | Details Get a Quote |
| ELANE Knockout HeLa Cell Line | EDJ-KQ53151 | Human | 1991 | Details Get a Quote |
| ELANE Knockout A-549 Cell Line | EDJ-KQ61625 | Human | 1991 | Details Get a Quote |
| ELANE Knockout HCT 116 Cell Line | EDJ-KQ70110 | Human | 1991 | Details Get a Quote |
