ELANE (elastase, neutrophil expressed)

Gene

• Entrez ID: 1991
• Gene name: Elastase, neutrophil expressed
• Gene symbol: ELANE
• Synonyms: ELA2, GE, HLE, HNE, NE, PMN-E, SCN1
• Chromosome: 19
• Chromosome location: 19p13.3
• 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 pr

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28931611	T>C	Pathogenic	Coding sequence variant, missense variant
rs57246956	G>A,T	Pathogenic	Coding sequence variant, missense variant
rs137854445	G>A,C	Pathogenic	Coding sequence variant, missense variant
rs137854446	G>C,T	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs137854447	C>A,G,T	Pathogenic	Coding sequence variant, missense variant
rs137854448	C>T	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs137854449	G>A,T	Pathogenic	Coding sequence variant, missense variant
rs137854450	C>A,T	Conflicting-interpretations-of-pathogenicity, pathogenic, likely-pathogenic	Coding sequence variant, missense variant, stop gained
rs137854451	G>A	Pathogenic	Coding sequence variant, missense variant
rs140880838	G>A	Pathogenic	Missense variant, coding sequence variant
rs199558534	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs199659114	G>A	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs201117839	G>A	Pathogenic, uncertain-significance	Splice acceptor variant
rs267606781	G>A,T	Pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs387906553	G>A,C	Pathogenic	Coding sequence variant, missense variant
rs568474579	A>C,G	Likely-pathogenic	Missense variant, coding sequence variant
rs730880095	C>G	Likely-pathogenic	Intron variant
rs745455816	G>A,T	Likely-pathogenic	Coding sequence variant, missense variant
rs754277797	G>C	Likely-pathogenic	Coding sequence variant, missense variant
rs797045007	G>C	Likely-pathogenic	Missense variant, coding sequence variant
rs797045009	C>A	Pathogenic	Coding sequence variant, stop gained
rs878855315	G>T	Pathogenic	Missense variant, coding sequence variant
rs878855317	C>A	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs878855319	T>C	Pathogenic	Missense variant, coding sequence variant
rs878855320	C>A,T	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs878855321	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs879253882	G>A	Likely-pathogenic, pathogenic	Intron variant
rs879255272	AAACTTGCTCAACGACATCGTGAT>-	Pathogenic	Coding sequence variant, inframe deletion
rs1057518191	->GG	Pathogenic	Coding sequence variant, splice acceptor variant
rs1057520110	C>T	Pathogenic	Coding sequence variant, missense variant
rs1064793108	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1085307717	A>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1131691882	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1468631555	->CCATAACCTCTC	Likely-pathogenic	Coding sequence variant, inframe insertion
rs1555709349	TCCCTG>-	Likely-pathogenic	Coding sequence variant, inframe deletion
rs1555709367	T>G	Likely-pathogenic	Coding sequence variant, missense variant
rs1555710005	G>A,C	Pathogenic	Splice donor variant
rs1555710077	C>G	Likely-pathogenic	Coding sequence variant, missense variant
rs1555710089	G>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1599294750	C>A	Pathogenic	Coding sequence variant, stop gained

Transcription factors

Transcription factor	Regulation	Reference
CEBPA	Activation	19620402
CEBPA	Unknown	16247445
GFI1	Unknown	18328744
LEF1	Activation	14594802;19620402
MYB	Unknown	16247445
RUNX1	Unknown	16247445
RUNX2	Activation	14594802
SPI1	Unknown	14732495;16247445

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IMP	19506020
GO:0001878	Process	Response to yeast	IEA
GO:0002020	Function	Protease binding	IPI	6980881
GO:0002438	Process	Acute inflammatory response to antigenic stimulus	IBA	21873635
GO:0002523	Process	Leukocyte migration involved in inflammatory response	IEA
GO:0002812	Process	Biosynthetic process of antibacterial peptides active against Gram-negative bacteria	IDA	20421939
GO:0003714	Function	Transcription corepressor activity	IMP	19506020
GO:0004175	Function	Endopeptidase activity	IDA	6980881, 12887060
GO:0004252	Function	Serine-type endopeptidase activity	IBA	21873635
GO:0004252	Function	Serine-type endopeptidase activity	TAS
GO:0005515	Function	Protein binding	IPI	12114510, 12223522, 14688365, 19506020, 21979170
GO:0005576	Component	Extracellular region	NAS	12114510
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005615	Component	Extracellular space	IDA	20421939, 25645918
GO:0005737	Component	Cytoplasm	IDA	19506020
GO:0006508	Process	Proteolysis	IBA	21873635
GO:0006508	Process	Proteolysis	IDA	11907569, 20421939
GO:0006874	Process	Cellular calcium ion homeostasis	NAS	15140022
GO:0006909	Process	Phagocytosis	IBA	21873635
GO:0008201	Function	Heparin binding	IDA	11907569
GO:0008233	Function	Peptidase activity	IDA	11907569, 20421939
GO:0009411	Process	Response to UV	IDA	11928814
GO:0009986	Component	Cell surface	IDA	12114510
GO:0017053	Component	Transcription repressor complex	IDA	19506020
GO:0019730	Process	Antimicrobial humoral response	TAS
GO:0019955	Function	Cytokine binding	IPI	12393522
GO:0022617	Process	Extracellular matrix disassembly	TAS
GO:0030141	Component	Secretory granule	IDA	11907569
GO:0030163	Process	Protein catabolic process	NAS	12887060
GO:0032496	Process	Response to lipopolysaccharide	IEA
GO:0032682	Process	Negative regulation of chemokine production	IDA	12223522
GO:0032717	Process	Negative regulation of interleukin-8 production	IDA	12223522
GO:0032757	Process	Positive regulation of interleukin-8 production	IDA	14730209
GO:0035578	Component	Azurophil granule lumen	TAS
GO:0035580	Component	Specific granule lumen	TAS
GO:0042742	Process	Defense response to bacterium	IDA	14705961
GO:0043312	Process	Neutrophil degranulation	TAS
GO:0043406	Process	Positive regulation of MAP kinase activity	NAS	14730209
GO:0045335	Component	Phagocytic vesicle	IEA
GO:0048661	Process	Positive regulation of smooth muscle cell proliferation	IDA	15010259
GO:0050728	Process	Negative regulation of inflammatory response	NAS	15140022
GO:0050778	Process	Positive regulation of immune response	IEA
GO:0050922	Process	Negative regulation of chemotaxis	NAS	15140022
GO:0062023	Component	Collagen-containing extracellular matrix	HDA	25037231, 28344315
GO:0070062	Component	Extracellular exosome	HDA	19056867, 23533145
GO:0070945	Process	Neutrophil-mediated killing of gram-negative bacterium	IDA	20421939
GO:0070947	Process	Neutrophil-mediated killing of fungus	IEA
GO:1903238	Process	Positive regulation of leukocyte tethering or rolling	IEA

Other IDs

• MIM: 130130
• HGNC: 3309
• e!Ensembl: ENSG00000197561

Protein

• UniProt ID: P08246
• Protein name: Neutrophil elastase (EC 3.4.21.37) (Bone marrow serine protease) (Elastase-2) (Human leukocyte elastase) (HLE) (Medullasin) (PMN elastase)
• Protein 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
• PDB: 1B0F, 1H1B, 1HNE, 1PPF, 1PPG, 2RG3, 2Z7F, 3Q76, 3Q77, 4NZL, 4WVP, 5A09, 5A0A, 5A0B, 5A0C, 5A8X, 5A8Y, 5A8Z, 5ABW, 6E69, 6F5M, 6SMA, 7CBK, 7WHU, 8D4Q, 8D4U, 8D7I, 8D7K, 8G24, 8G25, 8G26, 8QGX, 8VK5, 9ASS, 9ASX, 9ATK, 9ATU
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00089	Trypsin	30 → 242	Trypsin	Domain

• Sequence:

  MTLGRRLACLFLACVLPALLLGGTALASEIVGGRRARPHAWPFMVSLQLRGGHFCGATLI
  APNFVMSAAHCVANVNVRAVRVVLGAHNLSRREPTRQVFAVQRIFENGYDPVNLLNDIVI
  LQLNGSATINANVQVAQLPAQGRRLGNGVQCLAMGWGLLGRNRGIASVLQELNVTVVTSL
  CRRSNVCTLVRGRQAGVCFGDSGSPLVCNGLIHGIASFVRGGCASGLYPDAFAPVAQFVN
  WIDSIIQRSEDNPCPHPRDPDPASRTH

• Sequence length: 267

Pathways

KEGG:

Neutrophil extracellular trap formation
Transcriptional misregulation in cancer
Systemic lupus erythematosus

Reactome:

Degradation of the extracellular matrix
Activation of Matrix Metalloproteinases
Neutrophil degranulation
Antimicrobial peptides
Regulation of Complement cascade

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Anemia	Anemia	rs118204044, rs118204045, rs118204046, rs121918330, rs869320719, rs869312029, rs121918332, rs869320724, rs767094129, rs786205058, rs786205059, rs137853119, rs137853120, rs137853121, rs1384933966, rs137853122, rs137853123, rs786205060, rs267607121, rs121908584, rs80338697, rs80338699, rs120074166, rs120074167, rs1050828, rs74575103, rs137852314, rs5030868, rs137852316, rs137852317, rs137852318, rs137852319, rs137852320, rs137852321, rs137852322, rs137852323, rs137852324, rs72554665, rs387906468, rs5030872, rs137852326, rs137852333, rs137852327, rs137852328, rs137852329, rs137852330, rs137852331, rs137852332, rs137852334, rs137852335, rs137852336, rs137852339, rs76645461, rs137852340, rs137852341, rs78478128, rs137852343, rs137852344, rs137852345, rs587776730, rs137852346, rs137852347, rs137852349, rs2070404412, rs2070350038, rs2070350009, rs137852303, rs137852304, rs33946267, rs34378160, rs33933298, rs11549407, rs35724775, rs34598529, rs41469945, rs267607201, rs80338694, rs80338696, rs387907018, rs398123546, rs78365220, rs587777100, rs587777101, rs483352840, rs869312752, rs765487627, rs1557229599, rs1557230040, rs1555524842, rs782090947, rs1358275550, rs1557229736, rs1557230573, rs1556323334, rs1233124208, rs1293528130, rs146864395, rs1595503440, rs1603411214, rs137852325, rs1575247302, rs1603411177, rs1336651679, rs782322505
Aplastic anemia	Aplastic Anemia	rs113993991, rs113993993, rs864309668, rs121908974, rs199422265, rs199422270, rs104894176, rs104894180, rs28933973, rs104894182, rs28933376, rs771552960, rs786205093, rs193302876, rs113993992, rs113993994, rs113993998, rs199422298, rs199422305, rs199422273, rs199422275, rs199422276, rs199422259, rs199422279, rs199422280, rs199422281, rs199422283, rs587780100, rs587781305, rs587781891, rs587781969, rs587782130, rs587782545, rs730881864, rs730881857, rs730881850, rs730881839, rs142301194, rs786201745, rs764884516, rs786202490, rs768378152, rs574673404, rs767215758, rs786205135, rs762664474, rs751161742, rs373730800, rs864622143, rs864622090, rs864622511, rs864622253, rs786201965, rs756363734, rs766044684, rs876659521, rs876659592, rs113993990, rs751247865, rs1057517262, rs1057516668, rs1057516611, rs1057516320, rs1057516772, rs931715719, rs767454740, rs1057519587, rs1060503483, rs1060503467, rs1064795816, rs1064793210, rs1131691842, rs772797192, rs751567476, rs780235686, rs1554562083, rs578092914, rs147035858, rs189650890, rs759232053, rs1554558613, rs1554567892, rs1554564297, rs1554558472, rs1554559083, rs1349928568, rs1178384498, rs1198614767, rs1554558449, rs1554568427, rs752858869, rs147462227, rs748513310, rs1238152597, rs760237820, rs1554562110, rs750375741, rs758708229, rs768849283, rs1563578540, rs1563526747, rs1563559078, rs772005832, rs1563539146, rs778306619, rs771475965, rs1586052851, rs1554559094, rs776571416, rs200430442, rs776299562, rs1584439050, rs1586075907, rs1586101154, rs1586059584, rs1586088924, rs1810540992, rs772411713, rs1812023981
Congenital neutropenia	Congenital neutropenia, Autosomal dominant severe congenital neutropenia	rs118203968, rs118203969, rs118203970, rs118203971, rs267606834, rs28936381, rs137854447, rs137854448, rs137854450, rs28931611, rs137854451, rs200478425, rs587777730, rs606231474, rs606231475, rs606231473, rs775224457, rs769441127, rs148559256, rs797044567, rs796065343, rs797045009, rs878855315, rs1555710005, rs879253750, rs879253882, rs1555354200, rs1555354198, rs1555354750, rs890101650, rs759302795, rs57246956, rs138156467, rs1194477276, rs1570588220, rs757401069, rs745582203, rs1191239079, rs1597905369, rs1599294750, rs1594996301, rs1595004126, rs1595004676, rs756667927, rs34019455	28297620
Hemangioma	Hemangioma	rs119475040, rs121917766
Leukemia	Leukemia, Myelocytic, Acute	rs121909646, rs121913488, rs587776834, rs752746786, rs869312821, rs767454740, rs1554564297, rs11978267, rs4132601
Lymphoblastic leukemia	Precursor Cell Lymphoblastic Leukemia Lymphoma	rs387906351, rs104894562, rs398122513, rs398122840, rs398123063, rs1057524466, rs1064796115, rs1064795660, rs1064793129, rs1064796227, rs1567887558, rs1161194345, rs1597558200, rs1406320425, rs1597566470, rs1597566699, rs1597567692, rs1597567985, rs1438890364, rs1288977950, rs1597552140, rs1597566356, rs1597566726, rs1597568117, rs2069719445, rs2069729948, rs2070018439, rs745708044, rs1169577591
Myelodysplasia	Myelodysplasia	rs141601766, rs1261178797
Myelodysplastic syndrome	MYELODYSPLASTIC SYNDROME	rs193303018, rs387906631, rs1576745225, rs373145711, rs752746786, rs377023736, rs373221034, rs1576749014, rs1600586587
Neutropenia	Neutropenia, Neutropenia, Severe Congenital, X-Linked, Neutropenia, Severe Congenital, Autosomal Dominant 1	rs879253882	17436313, 17436313, 14962902, 10581030, 11675333, 25427142, 20220065, 12091371, 23463630, 19927291, 19036076, 20049848, 17391497, 19415009, 24523240, 17053055, 20803142, 18611981, 21425445, 25703294, 11001877, 18946670
Periodontitis	Periodontitis	rs28937571, rs104894211, rs587777534

Unknown
Disease name	Disease term	dbSNP ID	References
Aphthous ulcer	Recurrent aphthous ulcer
Cyclic neutropenia	Cyclic neutropenia		25703294, 23463630, 10581030, 11675333, 14673143, 25427142, 17391497, 20049848, 18611981, 14962902, 24523240, 11001877, 19036076
Eosinophilia	Eosinophilia
Gingivitis	Gingivitis
Hematopoesis	Cyclic Hematopoesis
Lymphopenia	Lymphopenia
Monocytic leukemia	Acute monocytic leukemia
Monocytosis	Monocytosis
Mouth abnormalities	Mouth Abnormalities
Oral ulcer	Oral Ulcer
Osteopenia	Osteopenia
Pharyngitis	Pharyngitis
Pyoderma gangrenosum	Pyoderma Gangrenosum
Rhinitis	Rhinitis
Thrombocytosis	Thrombocytosis