• 1
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
ELANE (HGNC:3309) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
elastase, neutrophil expressed
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
ELA2
Alias symbols
NE, HNE, HLE, PMN-E
%HI
34.42(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0(Read more about gnomAD pLI score)
LOEUF
1.13(Read more about gnomAD LOEUF score)
Cytoband
19p13.3
Genomic Coordinates
GRCh37/hg19: chr19:852303-856243 NCBI Ensembl UCSC
GRCh38/hg38: chr19:852303-856243 NCBI Ensembl UCSC
MANE Select Transcript
NM_001972.4 ENST00000263621.2 (Read more about MANE Select)
Function
Serine protease that modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis (PubMed:15140022). Promotes cleavage of GSDMB, thereby inhibiting pyroptosis (PubMed:36899106). Capable of killing E.coli but not S.aureus in vitro; digests outer membrane protein A (ompA) in E.coli and K.pneumoniae (PubMed:10947984). {ECO:0000269|PubMed:10947984, ECO:0000269|PubMed:15140022, ECO:0000269|PubMed:36899106}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-5250
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Little Evidence for Haploinsufficiency (1)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
07/13/2022

Haploinsufficiency (HI) Score Details

HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 10581030
    Horwitz et al. (1999). In 2 of 13 families and in a sporadic new mutation case with cyclic neutropenia found a splice donor mutation of intron 4 of the ELANE gene, a transition of the invariant guanine to an adenine at the +1 position. The parents were not affected and did not carry the mutation, and paternity was confirmed.
  • PUBMED: 19415009
    2009. One familial cyclic neutropenia was identified with familial nonsense variant (p.W212X) in ELANE gene in the proband and affected father. This variant was localized to the final exon of the gene, and was expected to yield a transcript and a shortened protein that may act via a dominant negative or loss-of-function mechanism on the genes. Inheritance was suggested to be autosomal dominant.
  • PUBMED: 21425445
    2011. A frameshift variant (p.Arg182LeufsX9) in exon 4 was identified in a four-year-old male with diagnosis of severe congenital neutropenia. Parental studies were unavailable, so unknown inheritance.
  • PUBMED: 23463630
    2013. This group screened CN (n = 395) or CyN (n = 92) patients for ELANE mutations, and found 116 different mutations in 162 (41%) CN patients and 26 in 51 (55%) CyN patients. Most of the disease-causing variants are missense. Nonsense and frame shift mutations were found in 26 seveve congenital neutropenia cases and 2 cyclic neutropenia cases. Those variants disrupting the C-terminus important for correct intracellular localization of NE only occur in the last third of exon 4 and in exon 5.
  • PUBMED: 31427279
    This paper described an individual possessing deletion of the entirety of ELANE, occurring in the context of a 37-gene, chromosome 19p terminal deletion. This patient is not associated with neutropenia. In this paper, the authors also summarized 10 other reported patients known to have ELANE whole gene deletion, just 1 was noted to have neutropenia. In summary, the patient reported in this paper, along with collective observations in the literature, suggests that ELANE deletion does not cause neutropenia.
HI Evidence Comments:
Many of the mutations responsible for SCN are chain-terminating, nonsense, or frame-shift events in the fifth (and final) exon. Because mutations in the last exon should not be subject to nonsense-mediated decay, they are expected to yield a stable transcript resulting in the translation of a shortened protein. The absence of chain-terminating mutations in anything but the final exon, where they would be expected to consequently act as null alleles, indicates a dominant-negative or gain-of-function mechanism and eliminates haploinsufficiency. (PMIDs:17053055,23463630) some other pulications: Mensa-Vilar (2019) J Allergy Clin Immunol 143: 359 PubMed: 30273710 NM_001972.4: c.615_618delCTTG; NP_001963.1: p.(Leu206Serfs*5) Liu (2019) BMC Pediatr 19: 189 PubMed: 31176364 NM_001972.4: c.669_670delCGinsA; NP_001963.1: p.(Cys223*) Carlsson (2012) Br J Haematol 158: 363 PubMed: 22624626 NM_001972.4: c.367-1G>C

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000019.9) (NC_000019.10)