GeneBe

ELANE

protein-coding

elastase, neutrophil expressed, the group of Granule associated serine proteases of immune defence|Complement system regulators and receptors

Gene summary

Elastases form a subfamily of serine proteases that hydrolyze many proteins in addition to elastin. Humans have six elastase genes which encode structurally similar proteins. The encoded preproprotein is proteolytically processed to generate the active protease. Following activation, this protease hydrolyzes proteins within specialized neutrophil lysosomes, called azurophil granules, as well as proteins of the extracellular matrix. The enzyme may play a role in degenerative and inflammatory diseases through proteolysis of collagen-IV and elastin. This protein also degrades the outer membrane protein A (OmpA) of E. coli as well as the virulence factors of such bacteria as Shigella, Salmonella and Yersinia. Mutations in this gene are associated with cyclic neutropenia and severe congenital neutropenia (SCN). This gene is present in a gene cluster on chromosome 19. [provided by RefSeq, Jan 2016]

Previous symbols:
  • ELA2

MANE transcript

NM_001972.4

Inheritance

AD

ClinVar variants

P:118U:408B:294

Top phenotype

Neutropenia, severe congenital 1, autosomal dominant; Neutropenia, cyclic

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr19:851,014-856,247

External References & Databases

Ensembl (ENSG00000197561)NCBI Gene (1991)OMIM (130130)HGNC:3309GenCCUniProt (P08246)AlphaFoldClinVar (ELANE)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~5.2 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neutropeniaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0001475

Submitter: PanelApp Australia

cyclic neutropeniaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008090

Submitter: Labcorp Genetics (formerly Invitae)

neutropeniaDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0001475

Submitter: ClinGen

ELANE related neutropenia disorders include cyclic neutropenia (CyN) and severe congenital neutropenia (SCN). Cyclic neutropenia is usually diagnosed within the first year of life based on oscillation of neutrophils and fever with approximately 21 day periodicity. Congenital neutropenia is generally diagnosed right after birth and my present with omphalitis. Individuals with ELANE-related neutropenia are at risk of developing myelodysplasia syndrome (MDS) or acute myelogenous leukemia (AML). It is inherited in an autosomal dominant manner. Most reported pathogenic variants are missense, splicing defects, small in-frame deletions, frameshift deletions or premature stop codons with dominant negative effect. Full gene deletions leading to haploinsufficiency do not cause neutropenia (PMID: 31427279). At least 100 pathogenic variants have been reported in over 100 individuals from more than 40 families. This curation includes both familial and de novo missense, small deletion and splicing variants in individuals with CyN or SCN from 4 studies (PMID: 11001877, 10581030, 10581030 and 20803142). Three studies (PMID: 15657182, 31176364 and 28754797) were evaluated encompassing biochemical function, protein interaction, functional alteration from patients cells with different variants, and cell models expressing different variants further confirm the gene and disease validity. In summary, ELANE is definitively associated with CyN and SCN. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time.

cyclic neutropeniaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008090

Submitter: Orphanet

autosomal dominant severe congenital neutropeniaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008742

Submitter: Orphanet

Clinical Genomic Database (CGD)

Neutropenia, severe congenital 1, autosomal dominant; Neutropenia, cyclicAD

Manifestation: Allergy/Immunology/Infectious; Oncologic

Intervention: Allergy/Immunology/Infectious; Oncologic

Rationale: Antiinfectious prophylaxis (including GCSF and related therapies) and early and aggressive treatment of infections may be beneficial; Surveillance and early treatment for malignancy may be beneficial; HSCT has been described for severe congenital neutropenia

Refs: 13575153; 6050865; 4319697; 2471075; 2469956; 1282277; 8490166; 7529539; 8541539; 8989458; 8624368; 9116280; 9386665; 10581030; 11001877; 10887102; 17063141; 18028488; 17133096; 18611981; 19036076; 21072829; 22148006; 22080845; 22510773; 22624626; 22758217; 23454784; 23463630Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ELANE variants in ClinVar

13 Conditions Cataloged
Neutropenia, severe congenital, 1, autosomal dominantTotal: 530
Cyclical neutropeniaTotal: 509
Inborn genetic diseasesTotal: 498
not providedTotal: 172
not specifiedTotal: 80
ELANE-related disorderTotal: 45
Autoinflammatory syndromeTotal: 38
ELANE-related disordersTotal: 22

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001972.4. 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
4
clinvar
232
clinvar
 238
missense
21
clinvar
54
clinvar
382
clinvar
61
clinvar
1
clinvar
 519
nonsense
5
clinvar
7
clinvar
3
clinvar
 15
start loss
1
clinvar
3
clinvar
 4
frameshift
6
clinvar
10
clinvar
14
clinvar
 30
splice donor/acceptor (+/-2bp)
4
clinvar
5
clinvar
5
clinvar
 14
Total37814082931820

Highest pathogenic variant AF is 0.000017798588

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001972.4RefSeqNP_001963.15MANE Select
ENST00000263621.2EnsemblENSP00000263621.15MANE Select
ENST00000590230.5EnsemblENSP00000466090.15Standard
ENST00000590230.6EnsemblENSP00000466090.15Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Systemic lupus erythematosus - Homo sapiens (human)
  • Transcriptional misregulation in cancer - Homo sapiens (human)
  • Human Complement System
  • Neutrophil degranulation
  • Collagen degradation

Biological Process

  • negative regulation of transcription by RNA polymerase II
  • response to yeast
  • acute inflammatory response to antigenic stimulus
  • leukocyte migration involved in inflammatory response
  • biosynthetic process of antibacterial peptides active against Gram-negative bacteria

Molecular Function

  • protease binding
  • transcription corepressor activity
  • endopeptidase activity
  • serine-type endopeptidase activity
  • protein binding

Cellular Component

  • extracellular region
  • extracellular space
  • cytoplasm
  • cell surface
  • transcriptional repressor complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000590230
Coding exons
5
Length
5229
Individuals with no LoFs
125533
Homozygous LoFs
0
Heterozygous LoFs
20
Defined
125553
p
0.0000797
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.7181641920.8540.00001501664
Missense (PolyPhen)3965.860.59216647
Synonymous-0.1709592.91.020.00000823597
Loss of Function1.28610.50.5727.15e-782

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000760.000062rare
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish0.000490.00028rare
European (Non-Finnish)0.0000660.000062rare
South Asian0.000200.00020rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis. {ECO:0000269|PubMed:15140022}.;
Disease
DISEASE: Neutropenia, severe congenital 1, autosomal dominant (SCN1) [MIM:202700]: A disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections. {ECO:0000269|PubMed:11001877, ECO:0000269|PubMed:11675333, ECO:0000269|PubMed:12091371, ECO:0000269|PubMed:14962902, ECO:0000269|PubMed:17436313, ECO:0000269|PubMed:18946670, ECO:0000269|PubMed:19036076, ECO:0000269|PubMed:19415009, ECO:0000269|PubMed:19927291, ECO:0000269|PubMed:20220065, ECO:0000269|PubMed:20803142, ECO:0000269|PubMed:21425445, ECO:0000269|PubMed:23463630}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.916

Intolerance Scores

LoFtool
0.0124
RVIS EVS
0.19
RVIS percentile EVS
67.03

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Indispensability pred.
E
Indispensability score
0.698

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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