ELANE

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

Basic information

Region (hg38): 19:851014-856247

Previous symbols: [ "ELA2" ]

Links

ENSG00000197561 ∙ NCBI:1991 ∙ OMIM:130130 ∙ HGNC:3309 ∙ Uniprot:P08246 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant severe congenital neutropenia (Supportive), mode of inheritance: AD
• cyclic hematopoiesis (Supportive), mode of inheritance: AD
• cyclic hematopoiesis (Strong), mode of inheritance: AD
• neutropenia (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neutropenia, severe congenital 1, autosomal dominant; Neutropenia, cyclic	AD	Allergy/Immunology/Infectious; Oncologic	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	Allergy/Immunology/Infectious; Oncologic	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; 23463630

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ELANE gene.

• Neutropenia, severe congenital, 1, autosomal dominant;Cyclical neutropenia (15 variants)
• not provided (14 variants)
• Cyclical neutropenia;Neutropenia, severe congenital, 1, autosomal dominant (10 variants)
• Neutropenia, severe congenital, 1, autosomal dominant (9 variants)
• Cyclical neutropenia (8 variants)
• not specified (1 variants)
• ELANE-related disorder (1 variants)
• Neutropenia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ELANE gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	9	83	7	100
missense	17	33	194	10	1	255
nonsense	2	2	2			6
start loss	2					2
frameshift	6	3	9			18
inframe indel	2	1	6			9
splice donor/acceptor (+/-2bp)	2	2	4			8
splice region	3		8	13		24
non coding			1	31	27	59
Total	31	42	225	124	35

Highest pathogenic variant AF is 0.00000657

Variants in ELANE

This is a list of pathogenic ClinVar variants found in the ELANE region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-851457-A-G		ELANE-related disorder	Likely benign (Jun 20, 2022)
19-851482-T-C		ELANE-related disorder	Likely benign (Feb 15, 2022)
19-851976-G-A			Benign (Jun 14, 2018)
19-852033-T-C			Benign (Aug 30, 2018)
19-852044-C-T			Benign (Jun 26, 2018)
19-852104-C-A			Benign (Jun 19, 2018)
19-852167-C-T			Likely benign (Jun 19, 2018)
19-852196-C-T			Benign (Mar 03, 2015)
19-852205-C-T			Benign (Mar 03, 2015)
19-852234-C-T			Benign (Mar 03, 2015)
19-852238-C-G			Benign (Mar 03, 2015)
19-852285-G-C			Benign (Mar 03, 2015)
19-852287-G-A			Benign (Mar 03, 2015)
19-852288-C-A		not specified • Neutropenia, severe congenital, 1, autosomal dominant;Cyclical neutropenia	Benign (Sep 27, 2023)
19-852288-C-T			Benign (Mar 03, 2015)
19-852318-C-T			Benign (Mar 03, 2015)
19-852324-C-T		ELANE-related disorder	Likely benign (Sep 23, 2020)
19-852329-A-G		Cyclical neutropenia;Neutropenia, severe congenital, 1, autosomal dominant	Pathogenic (Nov 17, 2021)
19-852330-T-C			Pathogenic (Feb 23, 2018)
19-852337-C-T		Cyclical neutropenia;Neutropenia, severe congenital, 1, autosomal dominant	Likely benign (May 21, 2018)
19-852338-G-A		Neutropenia, severe congenital, 1, autosomal dominant;Cyclical neutropenia • Neutropenia, severe congenital, 1, autosomal dominant	Uncertain significance (Dec 14, 2023)
19-852338-G-C		ELANE-related disorder	Uncertain significance (Nov 24, 2022)
19-852338-G-GGCC		Neutropenia, severe congenital, 1, autosomal dominant;Cyclical neutropenia	Uncertain significance (Jun 22, 2023)
19-852341-C-G		ELANE-related disorder	Uncertain significance (Aug 02, 2024)
19-852341-C-T		Autoinflammatory syndrome	Uncertain significance (Dec 04, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ELANE	protein_coding	protein_coding	ENST00000590230	5	5229

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00123	0.861	125533	0	20	125553	0.0000797

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.718	164	192	0.854	0.0000150	1664
Missense in Polyphen		39	65.86	0.59216		647
Synonymous	-0.170	95	92.9	1.02	0.00000823	597
Loss of Function	1.28	6	10.5	0.572	7.15e-7	82

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000758	0.0000616
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000492	0.000277
European (Non-Finnish)	0.0000662	0.0000617
Middle Eastern	0.00	0.00
South Asian	0.000199	0.000196
Other	0.00	0.00

dbNSFP

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.
• Pathway: Systemic lupus erythematosus - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Human Complement System;Neutrophil degranulation;Collagen degradation;Extracellular matrix organization;Antimicrobial peptides;Innate Immune System;Immune System;Activation of Matrix Metalloproteinases;Degradation of the extracellular matrix;Regulation of Complement cascade;C-MYB transcription factor network;Complement cascade;Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling (Consensus)

Recessive Scores

• pRec: 0.916

Intolerance Scores

• loftool: 0.0124
• rvis_EVS: 0.19
• rvis_percentile_EVS: 67.03

Haploinsufficiency Scores

• pHI: 0.609
• hipred: Y
• hipred_score: 0.594

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.698

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Elane
• Phenotype: homeostasis/metabolism phenotype; neoplasm; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; immune system phenotype

Gene ontology

• 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;proteolysis;cellular calcium ion homeostasis;phagocytosis;response to UV;antimicrobial humoral response;extracellular matrix disassembly;protein catabolic process;response to lipopolysaccharide;defense response to bacterium;neutrophil degranulation;positive regulation of MAP kinase activity;negative regulation of growth of symbiont in host;negative regulation of chemokine biosynthetic process;negative regulation of interleukin-8 biosynthetic process;positive regulation of interleukin-8 biosynthetic process;positive regulation of smooth muscle cell proliferation;negative regulation of inflammatory response;positive regulation of immune response;negative regulation of chemotaxis;neutrophil mediated killing of gram-negative bacterium;neutrophil mediated killing of fungus;positive regulation of leukocyte tethering or rolling
• Cellular component: extracellular region;extracellular space;cytoplasm;cell surface;transcriptional repressor complex;secretory granule;azurophil granule lumen;specific granule lumen;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: protease binding;transcription corepressor activity;endopeptidase activity;serine-type endopeptidase activity;protein binding;heparin binding;peptidase activity;cytokine binding