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MCID: SVR003
MIFTS: 59

Severe Congenital Neutropenia

Categories: Blood diseases, Bone diseases, Cardiovascular diseases, Endocrine diseases, Genetic diseases, Immune diseases, Infectious diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Respiratory diseases
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Aliases & Classifications for Severe Congenital Neutropenia

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MalaCards integrated aliases for Severe Congenital Neutropenia:

Name: Severe Congenital Neutropenia 12 20 43 58 29 6 15 37 70
Congenital Neutropenia 43 29 6
Severe Infantile Genetic Neutropenia 43
Infantile Genetic Agranulocytosis 43
Neutropenia, Severe Congenital 54
Congenital Agranulocytosis 43
Kostmann's Agranulocytosis 43
Kostmann's Syndrome 43
Kostmann Disease 43

Characteristics:

Orphanet epidemiological data:

58
severe congenital neutropenia
Inheritance: Autosomal dominant,Autosomal recessive,X-linked recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Childhood; Age of death: any age;

Classifications:

MalaCards categories:
Global: Rare diseases Genetic diseases Infectious diseases
Anatomical: Blood diseases Neuronal diseases Respiratory diseases Bone diseases Immune diseases Nephrological diseases Cardiovascular diseases Endocrine diseases
See all MalaCards categories (disease lists)
ICD10: 32 33
Orphanet: 58  
Rare immunological diseases


External Ids:

Disease Ontology 12 DOID:0050590
ICD10 32 D70
MESH via Orphanet 45 C537592
ICD10 via Orphanet 33 D70
UMLS via Orphanet 71 C1853118
Orphanet 58 ORPHA42738
UMLS 70 C1853118
Sources

Summaries for Severe Congenital Neutropenia

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GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 42738 Definition Severe congenital neutropenia is an immunodeficiency characterized by low levels of granulocytes (< 200/mm3) without an associated lymphocyte deficit. Epidemiology The prevalence in the general population is estimated at 1-1.7/333,300. Annual incidence is around 1/250,000 births. Clinical description This neutropenia leads to repeated bacterial or mycotic infections in various locations, mostly cutaneo-mucous, ear, nose, and throat, and pulmonary. Stomatological signs are almost always present after 2 years of age and are distinguished by erosive gingivitis, hemorrhage and pain, associated with papilla on the tongue and mucous membranes. Infections may be very severe or even lethal. Around 15% of patients evolve to acute leukemia or a myelodysplastic syndrome. Etiology To date, mutations in four genes have been implicated in severe congenital neutropenia. These include the neutrophil elastase gene ( ELA2 ), the GFI1 gene, the HAX1 gene and activation genes of Wiskott Aldrich disease ( WASP ). The combination of these mutations leads to a deficit in the production of neutrophils. Diagnostic methods The defining characteristic is cytology showing profound neutropenia associated with monocytosis. An isolated blockage at the promyelocyte stage of the myeloid series associated with eosinophilia and monocytosis is seen on myelogram. Differential diagnosis On the discovery of these features a complete biological assessment should be conducted to rule out several differential diagnoses, particularly lymphocytic immune deficiencies and autoimmune neutropenia. Antenatal diagnosis Prenatal diagnosis may be offered if the genotype is known. Genetic counseling The four mutations are transmitted differently: ELA2 and GFI1 are autosomal dominant, HAX1 is autosomal recessive, and WASP is X-linked recessive. Genetic counseling is essential and should take into account family history and the causal mutation. Management and treatment All febrile episodes or infections should be reviewed by a hospital and treated actively. Prophylactic antibiotics are used to prevent infections. If this is ineffective, hematopoietic growth factors (G-CSF in particular) can correct both neutropenia and the susceptibility to infections and can be administered either in response to infections or continuously. The dose of G-CSF required varies greatly. Continuous high dose G-CSF (more than 20?g/kg/day) encourages the onset of leukemia in the long term and therefore, in cases requiring continuous high dose treatment, bone marrow transplant should be considered. Prognosis The prognosis depends heavily on the quality of care and timeliness of treatment of severe infections, but also on the possibility of a bone marrow transplant, particularly in cases with malignant transformation.

MalaCards based summary : Severe Congenital Neutropenia, also known as congenital neutropenia, is related to neutropenia, severe congenital, x-linked and neutropenia, severe congenital, 3, autosomal recessive. An important gene associated with Severe Congenital Neutropenia is CSF3R (Colony Stimulating Factor 3 Receptor), and among its related pathways/superpathways are Akt Signaling and Cytokine Signaling in Immune system. The drugs Fludarabine and Busulfan have been mentioned in the context of this disorder. Affiliated tissues include bone marrow, neutrophil and myeloid, and related phenotypes are Decreased viability and Decreased viability

Disease Ontology : 12 A neutropenia characterized by a maturation arrest of granulopoiesis at the level or promyelocytes and early onset of severe bacterial infections.

MedlinePlus Genetics : 43 Severe congenital neutropenia is a condition that causes affected individuals to be prone to recurrent infections. People with this condition have a shortage (deficiency) of neutrophils, a type of white blood cell that plays a role in inflammation and in fighting infection. The deficiency of neutrophils, called neutropenia, is apparent at birth or soon afterward. It leads to recurrent infections beginning in infancy, including infections of the sinuses, lungs, and liver. Affected individuals can also develop fevers and inflammation of the gums (gingivitis) and skin. Approximately 40 percent of affected people have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture. In people with severe congenital neutropenia, these bone disorders can begin at any time from infancy through adulthood.Approximately 20 percent of people with severe congenital neutropenia develop certain cancerous conditions of the blood, particularly myelodysplastic syndrome or leukemia during adolescence.Some people with severe congenital neutropenia have additional health problems such as seizures, developmental delay, or heart and genital abnormalities.

Wikipedia : 73 Severe congenital neutropenia (SCN), also often known as Kostmann syndrome or disease, is a group of... more...

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Related Diseases for Severe Congenital Neutropenia

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Diseases in the Neutropenia family:

Neutropenia, Chronic Familial Neutropenia, Severe Congenital, 1, Autosomal Dominant
Neutropenia, Severe Congenital, 3, Autosomal Recessive Neutropenia, Severe Congenital, 4, Autosomal Recessive
Neutropenia, Severe Congenital, 2, Autosomal Dominant Neutropenia, Severe Congenital, 5, Autosomal Recessive
Neutropenia, Severe Congenital, 6, Autosomal Recessive Neutropenia, Severe Congenital, 7, Autosomal Recessive
Neutropenia, Severe Congenital, 8, Autosomal Dominant Severe Congenital Neutropenia
Severe Congenital Neutropenia 1 Severe Congenital Neutropenia 7
Autosomal Dominant Severe Congenital Neutropenia Severe Congenital Neutropenia 2
Severe Congenital Neutropenia 5 Severe Congenital Neutropenia 3
Severe Congenital Neutropenia 6 Severe Congenital Neutropenia 8
Severe Congenital Neutropenia 4 Elane-Related Neutropenia
Acquired Neutropenia Autosomal Recessive Severe Congenital Neutropenia

Diseases related to Severe Congenital Neutropenia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 243)
# Related Disease Score Top Affiliating Genes
1 neutropenia, severe congenital, x-linked 33.4 WAS ELANE
2 neutropenia, severe congenital, 3, autosomal recessive 33.0 SRPRA SRP19 JAGN1 IL3 HAX1 FCHO1
3 autosomal dominant severe congenital neutropenia 32.9 TCIRG1 SRP54 GFI1 ELANE
4 autosomal recessive severe congenital neutropenia 32.8 HAX1 G6PC3 ELANE CSF3R
5 neutropenia, severe congenital, 1, autosomal dominant 32.3 TCIRG1 ELANE
6 cohen syndrome 32.3 VPS45 JAGN1 HAX1 GFI1 G6PC3 ELANE
7 cyclic neutropenia 32.1 KITLG JAGN1 IL3 HAX1 GFI1 G6PC3
8 bacterial infectious disease 31.6 IL3 ELANE CSF3 CSF2
9 neutropenia 31.4 WAS VPS45 TCIRG1 SRP54 PTPN11 LEF1
10 leukemia, acute myeloid 31.3 PTPN11 KITLG JAK2 IL3 GFI1 CSF3R
11 myeloid leukemia 31.3 PTPN11 JAK2 IL3 CSF3R CSF3 CSF2
12 myelodysplastic syndrome 31.2 PTPN11 KITLG JAK2 IL3 HAX1 GFI1
13 granulocytopenia 30.9 IL3 CSF3 CSF2
14 acute leukemia 30.8 KITLG JAK2 IL3 CSF3R CSF3 CSF2
15 myelofibrosis 30.8 VPS45 JAK2 IL3 CSF3R CSF3
16 chronic neutrophilic leukemia 30.7 JAK2 CSF3R CSF3
17 shwachman-diamond syndrome 1 30.7 SRPRA SRP54 SRP19 HAX1 GFI1 G6PC3
18 leukemia, acute lymphoblastic 30.7 PTPN11 LEF1 KITLG JAK2 IL3 CSF3R
19 chronic myelomonocytic leukemia 30.6 PTPN11 JAK2 CSF3R CSF3 CSF2
20 whim syndrome 30.5 HAX1 G6PC3 ELANE CSF3
21 ecthyma 30.5 HAX1 CSF3
22 pancytopenia 30.5 IL3 G6PC3 CSF3 CSF2
23 dyskeratosis congenita 30.4 KITLG HAX1 CSF3 CSF2
24 acute megakaryocytic leukemia 30.3 JAK2 IL3 CSF2
25 b-lymphoblastic leukemia/lymphoma 30.3 PTPN11 KITLG IL3
26 deficiency anemia 30.3 KITLG JAK2 IL3 CSF3 CSF2
27 leukemia, chronic myeloid 30.2 PTPN11 KITLG JAK2 IL3 ELANE CSF3R
28 aplastic anemia 30.2 TCIRG1 KITLG IL3 CSF3R CSF3 CSF2
29 hypereosinophilic syndrome 30.1 JAK2 IL3 CSF2
30 thrombocytopenia 30.1 WAS TCIRG1 PTPN11 KITLG JAK2 IL3
31 severe congenital neutropenia 4 11.6
32 neutropenia, severe congenital, 5, autosomal recessive 11.6
33 neutropenia, severe congenital, 4, autosomal recessive 11.6
34 neutropenia, severe congenital, 7, autosomal recessive 11.5
35 severe congenital neutropenia 3 11.5
36 severe congenital neutropenia 1 11.5
37 severe congenital neutropenia 7 11.5
38 severe congenital neutropenia 6 11.5
39 severe congenital neutropenia 8 11.5
40 neutropenia, severe congenital, 6, autosomal recessive 11.4
41 severe congenital neutropenia 2 11.4
42 severe congenital neutropenia 5 11.4
43 neutropenia, severe congenital, 2, autosomal dominant 11.3
44 neutropenia, severe congenital, 8, autosomal dominant 11.3
45 autosomal recessive severe congenital neutropenia due to cxcr2 deficiency 11.2
46 wiskott-aldrich syndrome 11.1
47 reticular dysgenesis 11.1
48 neutropenia, lethal congenital, with eosinophilia 11.0
49 immunodeficiency due to defect in mapbp-interacting protein 10.9
50 g6pc3 deficiency 10.5

Graphical network of the top 20 diseases related to Severe Congenital Neutropenia:



Diseases related to Severe Congenital Neutropenia
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Symptoms & Phenotypes for Severe Congenital Neutropenia

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GenomeRNAi Phenotypes related to Severe Congenital Neutropenia according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-2 9.6 JAK2
2 Decreased viability GR00249-S 9.6 CSF2 CSF3R G6PC3 HAX1
3 Decreased viability GR00381-A-1 9.6 JAGN1 SRPRA
4 Decreased viability GR00386-A-1 9.6 CSF3 JAGN1 KITLG SRP54 SRPRA TCIRG1
5 Decreased viability GR00402-S-2 9.6 G6PC3 IL3 LEF1 SRP54 TCIRG1 VPS45

MGI Mouse Phenotypes related to Severe Congenital Neutropenia:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.06 CSF2 CSF3R GFI1 HAX1 JAGN1 JAK2
2 hematopoietic system MP:0005397 10 CSF2 CSF3 CSF3R ELANE G6PC3 GFI1
3 endocrine/exocrine gland MP:0005379 9.96 CSF2 G6PC3 GFI1 HAX1 JAK2 KITLG
4 immune system MP:0005387 9.8 CSF2 CSF3 CSF3R ELANE G6PC3 GFI1
5 neoplasm MP:0002006 9.1 CSF2 ELANE JAK2 KITLG PTPN11 WAS
Sources

Drugs & Therapeutics for Severe Congenital Neutropenia

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Drugs for Severe Congenital Neutropenia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 41)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Fludarabine Approved Phase 1, Phase 2 21679-14-1, 75607-67-9 30751
2
Busulfan Approved, Investigational Phase 1, Phase 2 55-98-1 2478
3
Methotrexate Approved Phase 2 1959-05-2, 59-05-2 126941
4
Prednisolone acetate Approved, Vet_approved Phase 2 52-21-1
5
Methylprednisolone Approved, Vet_approved Phase 2 83-43-2 6741
6
Prednisolone Approved, Vet_approved Phase 2 50-24-8 5755
7
Methylprednisolone hemisuccinate Approved Phase 2 2921-57-5
8
Levoleucovorin Approved, Investigational Phase 2 68538-85-2 149436
9
Prednisolone phosphate Approved, Vet_approved Phase 2 302-25-0
10
alemtuzumab Approved, Investigational Phase 2 216503-57-0
11
Clotrimazole Approved, Vet_approved Phase 2 23593-75-1 2812
12
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
13
Folic acid Approved, Nutraceutical, Vet_approved Phase 2 59-30-3 6037
14
Prednisolone hemisuccinate Experimental Phase 2 2920-86-7
15 Alkylating Agents Phase 1, Phase 2
16 Immunosuppressive Agents Phase 1, Phase 2
17 Antimetabolites Phase 1, Phase 2
18 Antilymphocyte Serum Phase 1, Phase 2
19 Vitamin B9 Phase 2
20 Gastrointestinal Agents Phase 2
21 Neuroprotective Agents Phase 2
22 Methylprednisolone Acetate Phase 2
23 Antiemetics Phase 2
24 Anti-Infective Agents Phase 2
25 Cyclosporins Phase 2
26 Folic Acid Antagonists Phase 2
27 Antirheumatic Agents Phase 2
28 Hormones Phase 2
29 Vitamin B Complex Phase 2
30 Hormone Antagonists Phase 2
31 Antineoplastic Agents, Immunological Phase 2
32 Folate Phase 2
33 glucocorticoids Phase 2
34 Calcineurin Inhibitors Phase 2
35 Anti-Inflammatory Agents Phase 2
36 Protective Agents Phase 2
37 Antifungal Agents Phase 2
38
Thiotepa Approved, Investigational Phase 1 52-24-4 5453
39
Alefacept Approved, Investigational, Withdrawn 222535-22-0
40 Immunologic Factors
41 Dermatologic Agents

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Phase I/II Trial Of Hematopoietic Stem Cell Transplant (HSCT) For Children With A Genetic Disease Of Blood Cells Without An HLA-Matched Sibling Donor Completed NCT00730314 Phase 1, Phase 2
2 Bone Marrow Stem Cell Transplantation for Children With Stem Cell Defects, Marrow Failure Syndromes, or Myeloid Leukemia in 1Remission Completed NCT00305708 Phase 1, Phase 2 busulfan;fludarabine phosphate
3 Evaluation of Fludarabine, Busulfan and Alemtuzumab as a Reduced Toxicity Ablative Bone Marrow Stem Cell Transplant Regimen for Children With Stem Cell Defects, Marrow Failure Syndromes, or Myelodysplastic Syndrome (MDS)/Leukemia Completed NCT00301834 Phase 2 busulfan;cyclosporine;fludarabine phosphate;methotrexate;methylprednisolone
4 Stem Cell Enriched, T Cell Depleted Haplocompatible Peripheral Blood Transplantation for Children With Myelodysplastic Disease, Leukemia, Marrow Failure Syndromes, or Severe Immunodeficiency Diseases Completed NCT00295971 Phase 1 fludarabine phosphate;thiotepa
5 A Phase 1B, Open-Label, Multicenter Study of Mavorixafor in Patients With Severe Congenital Neutropenia and Chronic Neutropenia Disorders Recruiting NCT04154488 Phase 1 Mavorixafor
6 Identification of the Molecular Bases of Syndromic Congenital Neutropenia With Development Anomalies Completed NCT02866162
7 Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation for Children With Non-Malignant Diseases Who Have Been Multiply Transfused: a Pilot Study Terminated NCT01319851 Alefacept

Search NIH Clinical Center for Severe Congenital Neutropenia

Cell-based therapeutics:


LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database
Read about Severe Congenital Neutropenia cell therapies at LifeMap Discovery.
Stem-cell-based therapeutic approaches for Severe Congenital Neutropenia:
ALD-151, umbilical cord blood cells for hematologic and immunodefeciency diseases
Hematopoietic stem cells for refractory severe aplastic anemia or refractory cytopenias
Embryonic/Adult Cultured Cells Related to Severe Congenital Neutropenia:
Umbilical cord blood ALDH+ cells (ALD-151) PMIDs: 10430905
Peripheral blood-derived hematopoietic stem cells
Sources

Genetic Tests for Severe Congenital Neutropenia

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Genetic tests related to Severe Congenital Neutropenia:

# Genetic test Affiliating Genes
1 Severe Congenital Neutropenia 29
2 Congenital Neutropenia 29
Sources

Anatomical Context for Severe Congenital Neutropenia

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MalaCards organs/tissues related to Severe Congenital Neutropenia:

40
Bone Marrow, Neutrophil, Myeloid, Tongue, Bone, Monocytes, Brain
Sources

Publications for Severe Congenital Neutropenia

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Articles related to Severe Congenital Neutropenia:

(show top 50) (show all 748)
# Title Authors PMID Year
1
Prevalence of mutations in ELANE, GFI1, HAX1, SBDS, WAS and G6PC3 in patients with severe congenital neutropenia. 61 6 54
19775295 2009
2
Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia. 61 54 6
18028488 2008
3
Double de novo mutations of ELA2 in cyclic and severe congenital neutropenia. 54 6 61
17436313 2007
4
Neutrophil elastase in cyclic and severe congenital neutropenia. 54 61 6
17053055 2007
5
Strong evidence for autosomal dominant inheritance of severe congenital neutropenia associated with ELA2 mutations. 54 6 61
16737875 2006
6
Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register. 54 61 6
14962902 2004
7
Mutations in the ELA2 gene encoding neutrophil elastase are present in most patients with sporadic severe congenital neutropenia but only in some patients with the familial form of the disease. 6 54 61
11675333 2001
8
Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia. 61 54 6
11001877 2000
9
Mosaicism of an ELANE Mutation in an Asymptomatic Mother. 61 6
30635825 2019
10
Both Granulocytic and Non-Granulocytic Blood Cells Are Affected in Patients with Severe Congenital Neutropenia and Their Non-Neutropenic Family Members: An Evaluation of Morphology, Function, and Cell Death 61 6
30040071 2018
11
Utility of next-generation sequencing technologies for the efficient genetic resolution of haematological disorders. 61 6
25703294 2016
12
ELANE mutant-specific activation of different UPR pathways in congenital neutropenia. 61 6
26567890 2016
13
The diversity of mutations and clinical outcomes for ELANE-associated neutropenia. 61 6
25427142 2015
14
JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia. 61 6
25129144 2014
15
TCIRG1-associated congenital neutropenia. 61 6
24753205 2014
16
Cooperativity of RUNX1 and CSF3R mutations in severe congenital neutropenia: a unique pathway in myeloid leukemogenesis. 61 6
24523240 2014
17
Different clinical phenotypes in familial severe congenital neutropenia cases with same mutation of the ELANE gene. 6 61
24616599 2014
18
The spectrum of ELANE mutations and their implications in severe congenital and cyclic neutropenia. 6 61
23463630 2013
19
Coexistence of sickle cell disease and severe congenital neutropenia: first impressions can be deceiving. 6 61
22758217 2012
20
Novel ELANE gene mutation in a Korean girl with severe congenital neutropenia. 6 61
22148006 2011
21
Four novel ELANE mutations in patients with congenital neutropenia. 61 6
21425445 2011
22
Cyclic neutropenia and severe congenital neutropenia in patients with a shared ELANE mutation and paternal haplotype: evidence for phenotype determination by modifying genes. 6 61
20582973 2010
23
Resolving a genetic paradox throughout preimplantation genetic diagnosis for autosomal dominant severe congenital neutropenia. 6 61
20049848 2010
24
Homozygous HAX1 mutations in severe congenital neutropenia patients with sporadic disease: a novel mutation in two unrelated British kindreds. 6 61
19036076 2009
25
Neurodevelopmental abnormalities associated with severe congenital neutropenia due to the R86X mutation in the HAX1 gene. 61 6
18611981 2008
26
Low plasma levels of the protein pro-LL-37 as an early indication of severe disease in patients with chronic neutropenia. 6 61
17391497 2007
27
Mutations in neutrophil elastase causing congenital neutropenia lead to cytoplasmic protein accumulation and induction of the unfolded protein response. 6 61
16551967 2006
28
A comparison of the defective granulopoiesis in childhood cyclic neutropenia and in severe congenital neutropenia. 6 61
16079102 2005
29
ELANE-Related Neutropenia 6 61
20301705 2002
30
Whole-genome sequencing of patients with rare diseases in a national health system. 6
32581362 2020
31
Unexpected relevant role of gene mosaicism in patients with primary immunodeficiency diseases. 6
30273710 2019
32
Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis. 6
10581030 1999
33
Neutrophil elastase-processing defect in cyclic hematopoietic dogs. 61 54
19941936 2010
34
Double de novo mutations of ELANE (ELA2) in a patient with severe congenital neutropenia requiring high-dose G-CSF therapy. 61 54
19694719 2009
35
Neutrophil elastase is severely down-regulated in severe congenital neutropenia independent of ELA2 or HAX1 mutations but dependent on LEF-1. 61 54
19620402 2009
36
Severe congenital neutropenia: a negative synergistic effect of multiple mutations of ELANE (ELA2) gene. 61 54
19594744 2009
37
Site-specific ubiquitination determines lysosomal sorting and signal attenuation of the granulocyte colony-stimulating factor receptor. 61 54
19453968 2009
38
A novel mutation Ala57Val of the ELA2 gene in a Korean boy with severe congenital neutropenia. 54 61
18946670 2009
39
Gfi1 integrates progenitor versus granulocytic transcriptional programming. 61 54
19346496 2009
40
Ela2 mutations and clinical manifestations in familial congenital neutropenia. 61 54
19415009 2009
41
Survivin expression in the bone marrow of patients with severe congenital neutropenia. 54 61
18818705 2009
42
Clinical implications of ELA2-, HAX1-, and G-CSF-receptor (CSF3R) mutations in severe congenital neutropenia. 54 61
19120359 2009
43
Genetic and molecular diagnosis of severe congenital neutropenia. 54 61
19057199 2009
44
A patient with glycogen storage disease type Ib presenting with acute myeloid leukemia (AML) bearing monosomy 7 and translocation t(3;8)(q26;q24) after 14 years of treatment with granulocyte colony-stimulating factor (G-CSF): a case report. 54 61
18826620 2008
45
Transformation of severe congenital neutropenia to early acute lymphoblastic leukemia in a patient with HAX1 mutation and without G-CSF administration or receptor mutation. 61 54
18354489 2008
46
Functional interaction between mutations in the granulocyte colony-stimulating factor receptor in severe congenital neutropenia. 54 61
18513286 2008
47
Csf3r mutations in mice confer a strong clonal HSC advantage via activation of Stat5. 61 54
18292815 2008
48
G-CSFR ubiquitination critically regulates myeloid cell survival and proliferation. 54 61
18923646 2008
49
Severe congenital neutropenia and the unfolded protein response. 54 61
18043239 2008
50
Chronic idiopathic neutropenias and severe congenital neutropenia. 54 61
18043240 2008
Sources

Variations for Severe Congenital Neutropenia

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ClinVar genetic disease variations for Severe Congenital Neutropenia:

6 (show top 50) (show all 154)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CSF3R NM_000760.4(CSF3R):c.922C>T (p.Arg308Cys) SNV Pathogenic 161982 rs606231473 GRCh37: 1:36937914-36937914
GRCh38: 1:36472313-36472313
2 CSF3R NM_000760.4(CSF3R):c.948_963del (p.His317fs) Deletion Pathogenic 242629 rs606231475 GRCh37: 1:36937873-36937888
GRCh38: 1:36472272-36472287
3 JAGN1 NM_032492.4(JAGN1):c.59G>A (p.Arg20Gln) SNV Pathogenic 190479 rs777966677 GRCh37: 3:9932465-9932465
GRCh38: 3:9890781-9890781
4 JAGN1 NM_032492.4(JAGN1):c.40G>A (p.Gly14Ser) SNV Pathogenic 190480 rs786205704 GRCh37: 3:9932446-9932446
GRCh38: 3:9890762-9890762
5 JAGN1 NM_032492.4(JAGN1):c.297C>G (p.Tyr99Ter) SNV Pathogenic 190481 rs786205705 GRCh37: 3:9934806-9934806
GRCh38: 3:9893122-9893122
6 FCHO1 NM_001161358.2(FCHO1):c.489+1G>A SNV Pathogenic 805886 GRCh37: 19:17881387-17881387
GRCh38: 19:17770578-17770578
7 FCHO1 NM_001161358.2(FCHO1):c.1948C>T (p.Arg650Ter) SNV Pathogenic 805888 GRCh37: 19:17893836-17893836
GRCh38: 19:17783027-17783027
8 FCHO1 NM_001161358.2(FCHO1):c.2023dup (p.Val675fs) Duplication Pathogenic 805885 GRCh37: 19:17893910-17893911
GRCh38: 19:17783101-17783102
9 FCHO1 NM_001161358.2(FCHO1):c.2036G>C (p.Arg679Pro) SNV Pathogenic 805883 GRCh37: 19:17893924-17893924
GRCh38: 19:17783115-17783115
10 FCHO1 NM_001161358.2(FCHO1):c.100G>C (p.Ala34Pro) SNV Pathogenic 805884 GRCh37: 19:17873643-17873643
GRCh38: 19:17762834-17762834
11 FCHO1 NM_001161358.2(FCHO1):c.195-2A>C SNV Pathogenic 805887 GRCh37: 19:17877476-17877476
GRCh38: 19:17766667-17766667
12 ELANE NM_001972.4(ELANE):c.416C>T (p.Pro139Leu) SNV Pathogenic 16743 rs137854448 GRCh37: 19:855613-855613
GRCh38: 19:855613-855613
13 ELANE NM_001972.4(ELANE):c.214G>A (p.Val72Met) SNV Pathogenic 16744 rs387906553 GRCh37: 19:853022-853022
GRCh38: 19:853022-853022
14 ELANE NM_001972.4(ELANE):c.211T>C (p.Cys71Arg) SNV Pathogenic 16746 rs28931611 GRCh37: 19:853019-853019
GRCh38: 19:853019-853019
15 TCIRG1 NM_006019.4(TCIRG1):c.2206C>A (p.Arg736Ser) SNV Pathogenic 127173 rs587779413 GRCh37: 11:67817691-67817691
GRCh38: 11:68050224-68050224
16 ELANE NM_001972.4(ELANE):c.561C>A (p.Cys187Ter) SNV Pathogenic 208494 rs797045009 GRCh37: 19:855758-855758
GRCh38: 19:855758-855758
17 TCIRG1 NM_006019.4(TCIRG1):c.2206C>A (p.Arg736Ser) SNV Pathogenic 127173 rs587779413 GRCh37: 11:67817691-67817691
GRCh38: 11:68050224-68050224
18 ELANE NM_001972.4(ELANE):c.182C>T (p.Ala61Val) SNV Pathogenic 16740 rs137854447 GRCh37: 19:852990-852990
GRCh38: 19:852990-852990
19 ELANE NM_001972.4(ELANE):c.377C>T (p.Ser126Leu) SNV Pathogenic 16745 rs137854450 GRCh37: 19:855574-855574
GRCh38: 19:855574-855574
20 ELANE NM_001972.4(ELANE):c.597+1G>A SNV Pathogenic 242287 rs1555710005 GRCh37: 19:855795-855795
GRCh38: 19:855795-855795
21 ELANE NM_001972.4(ELANE):c.301G>A (p.Val101Met) SNV Pathogenic 844491 GRCh37: 19:853338-853338
GRCh38: 19:853338-853338
22 ELANE NM_001972.4(ELANE):c.659G>A (p.Arg220Gln) SNV Pathogenic 16738 rs137854445 GRCh37: 19:856019-856019
GRCh38: 19:856019-856019
23 ELANE NM_001972.4(ELANE):c.607G>C (p.Gly203Arg) SNV Pathogenic 939547 GRCh37: 19:855967-855967
GRCh38: 19:855967-855967
24 ELANE NM_001972.4(ELANE):c.597+1G>A SNV Pathogenic 242287 rs1555710005 GRCh37: 19:855795-855795
GRCh38: 19:855795-855795
25 JAGN1 NM_032492.4(JAGN1):c.3G>A (p.Met1Ile) SNV Pathogenic 156113 rs587777727 GRCh37: 3:9932409-9932409
GRCh38: 3:9890725-9890725
26 SRP19 NM_003135.3(SRP19):c.189+5G>A SNV Pathogenic 810839 rs1322282571 GRCh37: 5:112200230-112200230
GRCh38: 5:112864533-112864533
27 SRPRA NM_003139.4(SRPRA):c.1390C>G (p.Gln464Glu) SNV Pathogenic 810840 GRCh37: 11:126134989-126134989
GRCh38: 11:126265094-126265094
28 ELANE NM_001972.4(ELANE):c.292G>T (p.Val98Leu) SNV Pathogenic 16747 rs267606781 GRCh37: 19:853329-853329
GRCh38: 19:853329-853329
29 ELANE NM_001972.4(ELANE):c.640G>A (p.Gly214Arg) SNV Pathogenic 16748 rs137854451 GRCh37: 19:856000-856000
GRCh38: 19:856000-856000
30 JAGN1 NM_032492.4(JAGN1):c.130C>T (p.His44Tyr) SNV Pathogenic 156114 rs587777728 GRCh37: 3:9934639-9934639
GRCh38: 3:9892955-9892955
31 JAGN1 NM_032492.4(JAGN1):c.485A>G (p.Gln162Arg) SNV Pathogenic 156116 rs587777730 GRCh37: 3:9934994-9934994
GRCh38: 3:9893310-9893310
32 JAGN1 NM_032492.4(JAGN1):c.63G>T (p.Glu21Asp) SNV Pathogenic 156115 rs587777729 GRCh37: 3:9932469-9932469
GRCh38: 3:9890785-9890785
33 JAGN1 NM_032492.4(JAGN1):c.35_43del (p.Thr12_Gly14del) Deletion Pathogenic 156117 rs587777731 GRCh37: 3:9932436-9932444
GRCh38: 3:9890752-9890760
34 ELANE NM_001972.4(ELANE):c.452G>A (p.Cys151Tyr) SNV Pathogenic 535843 rs57246956 GRCh37: 19:855649-855649
GRCh38: 19:855649-855649
35 ELANE NM_001972.4(ELANE):c.452G>A (p.Cys151Tyr) SNV Pathogenic 535843 rs57246956 GRCh37: 19:855649-855649
GRCh38: 19:855649-855649
36 ELANE NM_001972.4(ELANE):c.416C>T (p.Pro139Leu) SNV Pathogenic/Likely pathogenic 16743 rs137854448 GRCh37: 19:855613-855613
GRCh38: 19:855613-855613
37 CSF3R NM_000760.4(CSF3R):c.1576+1G>A SNV Likely pathogenic 812884 rs1031224658 GRCh37: 1:36934756-36934756
GRCh38: 1:36469155-36469155
38 CSF3R NM_000760.4(CSF3R):c.340C>T (p.Gln114Ter) SNV Likely pathogenic 812885 rs756667927 GRCh37: 1:36940999-36940999
GRCh38: 1:36475398-36475398
39 ELANE NM_001972.4(ELANE):c.597+5G>A SNV Likely pathogenic 245598 rs879253882 GRCh37: 19:855799-855799
GRCh38: 19:855799-855799
40 ELANE NM_001972.4(ELANE):c.308G>C (p.Arg103Pro) SNV Likely pathogenic 842953 GRCh37: 19:853345-853345
GRCh38: 19:853345-853345
41 ELANE NM_001972.4(ELANE):c.136T>C (p.Ser46Pro) SNV Likely pathogenic 952580 GRCh37: 19:852944-852944
GRCh38: 19:852944-852944
42 ELANE NM_001972.4(ELANE):c.253G>A (p.Gly85Arg) SNV Likely pathogenic 836562 GRCh37: 19:853290-853290
GRCh38: 19:853290-853290
43 ELANE NM_001972.4(ELANE):c.524C>T (p.Thr175Met) SNV Conflicting interpretations of pathogenicity 696438 rs193141883 GRCh37: 19:855721-855721
GRCh38: 19:855721-855721
44 GFI1 NM_005263.5(GFI1):c.925-40CT[17] Microsatellite Conflicting interpretations of pathogenicity 298182 rs35896485 GRCh37: 1:92944315-92944316
GRCh38: 1:92478758-92478759
45 ELANE NM_001972.4(ELANE):c.377C>T (p.Ser126Leu) SNV Conflicting interpretations of pathogenicity 16745 rs137854450 GRCh37: 19:855574-855574
GRCh38: 19:855574-855574
46 GFI1 NM_005263.5(GFI1):c.925-40CT[16] Microsatellite Uncertain significance 298184 rs35896485 GRCh37: 1:92944315-92944318
GRCh38: 1:92478758-92478761
47 GFI1 NM_005263.5(GFI1):c.925-40CT[25] Microsatellite Uncertain significance 298181 rs35896485 GRCh37: 1:92944314-92944315
GRCh38: 1:92478757-92478758
48 GFI1 NM_005263.5(GFI1):c.925-40CT[20] Microsatellite Uncertain significance 298179 rs35896485 GRCh37: 1:92944314-92944315
GRCh38: 1:92478757-92478758
49 GFI1 NM_005263.5(GFI1):c.925-40CT[13] Microsatellite Uncertain significance 298186 rs35896485 GRCh37: 1:92944315-92944324
GRCh38: 1:92478758-92478767
50 GFI1 NM_005263.5(GFI1):c.925-40CT[23] Microsatellite Uncertain significance 298183 rs35896485 GRCh37: 1:92944314-92944315
GRCh38: 1:92478757-92478758
Sources

Expression for Severe Congenital Neutropenia

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Search GEO for disease gene expression data for Severe Congenital Neutropenia.
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Pathways for Severe Congenital Neutropenia

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Pathways related to Severe Congenital Neutropenia according to GeneCards Suite gene sharing:

(show all 18)
# Super pathways Score Top Affiliating Genes
1
Akt Signaling 63
Show member pathways
 13.26 WAS KITLG JAK2 IL3 CSF3R CSF3
2
Cytokine Signaling in Immune system 65
Show member pathways
 13.19 PTPN11 KITLG JAK2 IL3 CSF3R CSF3
3
PAK Pathway 63
Show member pathways
 13.04 WAS PTPN11 LEF1 KITLG JAK2 IL3
4
PI3K-Akt signaling pathway 36
Show member pathways
 12.75 TCIRG1 KITLG JAK2 IL3 G6PC3 CSF3R
5
Pathways in cancer 36
12.67 LEF1 KITLG JAK2 IL3 CSF3R
6
Immune response Role of DAP12 receptors in NK cells 23
Show member pathways
 12.35 WAS PTPN11 IL3 CSF2
7
JAK-STAT signaling pathway 36
Show member pathways
 12.03 PTPN11 JAK2 IL3 CSF3R CSF3 CSF2
8
Kit receptor signaling pathway 1
Show member pathways
 12 PTPN11 KITLG JAK2 IL3
9
G beta-gamma signalling through PI3Kgamma 65
Show member pathways
 11.96 PTPN11 JAK2 IL3 CSF2
10
Cytokine production by Th17 cells in CF (Mouse model) 23
Show member pathways
 11.7 JAK2 CSF3 CSF2
11
Immune response IL-2 activation and signaling pathway 23
Show member pathways
 11.66 PTPN11 JAK2 IL3
12
C-MYB transcription factor network 1
11.59 LEF1 KITLG ELANE
13
Adipocytokine signaling pathway 36
11.53 PTPN11 JAK2 G6PC3
14
Hematopoietic Stem Cell Differentiation Pathways and Lineage-specific Markers 64
11.42 KITLG IL3 CSF3R CSF3 CSF2
15
Hematopoietic Stem Cell Differentiation 1
11.24 KITLG IL3 CSF3 CSF2
16
Cytokines and Inflammatory Response 1
11.07 IL3 CSF3 CSF2
17
Hematopoietic cell lineage 36
11.02 KITLG IL3 CSF3R CSF3 CSF2
18
Protein export 36
10.94 SRPRA SRP54 SRP19
Sources

GO Terms for Severe Congenital Neutropenia

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Cellular components related to Severe Congenital Neutropenia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 signal recognition particle, endoplasmic reticulum targeting GO:0005786 9.16 SRP54 SRP19
2 phagocytic vesicle GO:0045335 9.13 WAS TCIRG1 ELANE
3 signal recognition particle GO:0048500 8.62 SRP54 SRP19

Biological processes related to Severe Congenital Neutropenia according to GeneCards Suite gene sharing:

(show all 20)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of cell proliferation GO:0008284 9.87 TCIRG1 LEF1 KITLG JAK2 IL3 CSF3
2 MAPK cascade GO:0000165 9.85 KITLG JAK2 IL3 CSF2
3 cytokine-mediated signaling pathway GO:0019221 9.73 PTPN11 JAK2 IL3 CSF3R CSF3 CSF2
4 positive regulation of phosphatidylinositol 3-kinase signaling GO:0014068 9.71 JAK2 HAX1 CSF3
5 positive regulation of protein kinase B signaling GO:0051897 9.71 PTPN11 KITLG HAX1 CSF3
6 SRP-dependent cotranslational protein targeting to membrane GO:0006614 9.7 SRPRA SRP54 SRP19
7 positive regulation of tyrosine phosphorylation of STAT protein GO:0042531 9.61 JAK2 IL3 CSF2
8 positive regulation of actin cytoskeleton reorganization GO:2000251 9.59 HAX1 CSF3
9 interleukin-6-mediated signaling pathway GO:0070102 9.58 PTPN11 JAK2
10 embryonic hemopoiesis GO:0035162 9.58 KITLG IL3
11 negative regulation of cell-cell adhesion GO:0022408 9.57 LEF1 JAK2
12 protein targeting to ER GO:0045047 9.56 SRPRA SRP54
13 regulation of myeloid cell differentiation GO:0045637 9.51 CSF3R CSF2
14 SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition GO:0006617 9.49 SRP54 SRP19
15 granulocyte differentiation GO:0030851 9.48 SRP54 CSF3
16 cotranslational protein targeting to membrane GO:0006613 9.46 SRPRA SRP19
17 positive regulation of granulocyte differentiation GO:0030854 9.37 LEF1 HAX1
18 cellular response to cytokine stimulus GO:0071345 9.35 TCIRG1 PTPN11 LEF1 HAX1 CSF3
19 neutrophil differentiation GO:0030223 9.33 LEF1 JAGN1 CSF2
20 positive regulation of peptidyl-tyrosine phosphorylation GO:0050731 9.1 PTPN11 KITLG JAK2 IL3 HAX1 CSF3

Molecular functions related to Severe Congenital Neutropenia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytokine activity GO:0005125 9.56 KITLG IL3 CSF3 CSF2
2 phospholipase binding GO:0043274 9.37 WAS PTPN11
3 insulin receptor substrate binding GO:0043560 9.32 PTPN11 JAK2
4 peptide hormone receptor binding GO:0051428 9.16 PTPN11 JAK2
5 7S RNA binding GO:0008312 8.96 SRP54 SRP19
6 growth factor activity GO:0008083 8.92 KITLG IL3 CSF3 CSF2
Sources

Sources for Severe Congenital Neutropenia

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3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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