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 (464 variants)
• Cyclical_neutropenia (446 variants)
• Inborn_genetic_diseases (351 variants)
• not_provided (154 variants)
• not_specified (44 variants)
• Autoinflammatory_syndrome (38 variants)
• ELANE-related_disorder (33 variants)
• Decreased_total_neutrophil_count (2 variants)
• X-linked_severe_congenital_neutropenia (1 variants)
• Autosomal_dominant_severe_congenital_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. These statistics are base on transcript: NM_000001972.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		2	4	182	2	190
missense	24	44	300	46	1	415
nonsense	4	4	4			12
start loss	1	3				4
frameshift	7	8	10			25
splice donor/acceptor (+/-2bp)	3	5	3			11
Total	39	66	321	228	3

Highest pathogenic variant AF is 0.0000177986

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