MCID: SVR003
MIFTS: 58

Severe Congenital Neutropenia

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

MalaCards integrated aliases for Severe Congenital Neutropenia:

Name: Severe Congenital Neutropenia 11 19 42 58 28 5 14 36 71 75
Congenital Neutropenia 42 28 5
Neutropenia, Severe Congenital 53 38
Severe Infantile Genetic Neutropenia 42
Infantile Genetic Agranulocytosis 42
Congenital Agranulocytosis 42
Kostmann's Agranulocytosis 42
Kostmann's Syndrome 42
Kostmann Disease 42

Characteristics:


Inheritance:

Autosomal dominant,Autosomal recessive,X-linked recessive 58

Prevelance:

1-9/1000000 (Europe, Europe, France) 1-9/100000 (Sweden) <1/1000000 (Iran, Islamic Republic of) 1-5/10000 (China) 58

Age Of Onset:

Childhood 58

Classifications:

Orphanet: 58  
Rare immunological diseases


External Ids:

Disease Ontology 11 DOID:0050590
ICD10 31 D70
MESH via Orphanet 44 C537592
ICD10 via Orphanet 32 D70
UMLS via Orphanet 72 C1853118
Orphanet 58 ORPHA42738
UMLS 71 C1853118

Summaries for Severe Congenital Neutropenia

MedlinePlus Genetics: 42 Severe congenital neutropenia is a condition that increases the risk of repeated infections in affected individuals. People with this condition have an abnormally low level (deficiency) of neutrophils, a type of white blood cell that plays a role in inflammation and in fighting infection. The shortage of neutrophils, called neutropenia, is apparent at birth or soon afterward. It leads to frequent 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 likely to fracture. In people with severe congenital neutropenia, 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.

MalaCards based summary: Severe Congenital Neutropenia, also known as congenital neutropenia, is related to severe congenital neutropenia 7 and severe congenital neutropenia 4. 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 Vidarabine and Lenograstim have been mentioned in the context of this disorder. Affiliated tissues include bone, liver and heart, and related phenotypes are Reduced mammosphere formation and Increased transferrin (TF) endocytosis (mild increase), increased transferrin (TF) endosome elongation

Orphanet: 58 Severe congenital neutropenia is an immunodeficiency characterized by low levels of granulocytes (< 200/mm3) without an associated lymphocyte deficit.

Disease Ontology: 11 A neutropenia characterized by a maturation arrest of granulopoiesis at the level or promyelocytes and early onset of severe bacterial infections.

Wikipedia: 75 Severe congenital neutropenia (SCN), also often known as Kostmann syndrome or disease, is a group of... more...

Related Diseases for Severe Congenital Neutropenia

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 Neutropenia, Severe Congenital, 9, 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 293)
# Related Disease Score Top Affiliating Genes
1 severe congenital neutropenia 7 33.3 SRP54 JAGN1 HAX1 GFI1 G6PC3 CSF3R
2 severe congenital neutropenia 4 33.2 HAX1 G6PC3
3 severe congenital neutropenia 6 33.2 JAGN1 G6PC3
4 neutropenia, severe congenital, 3, autosomal recessive 33.2 IL3 HAX1 ELANE CSF3R CSF3 CSF2
5 severe congenital neutropenia 3 33.2 JAGN1 HAX1 GFI1 G6PC3 ELANE CSF3R
6 severe congenital neutropenia 5 33.1 JAGN1 HAX1 GFI1 G6PC3
7 autosomal dominant severe congenital neutropenia 33.1 TCIRG1 SRP54 JAGN1 HAX1 GFI1 G6PC3
8 autosomal recessive severe congenital neutropenia 32.9 HAX1 G6PC3
9 neutropenia, severe congenital, 1, autosomal dominant 32.5 TCIRG1 ELANE
10 cohen syndrome 32.3 JAGN1 HAX1 G6PC3
11 cyclic neutropenia 32.3 KITLG JAGN1 IL3 HAX1 GFI1 G6PC3
12 neutropenia 32.0 SRP54 PTPN11 LEF1 KITLG JAK2 JAGN1
13 leukemia, acute myeloid 31.5 PTPN11 KITLG JAK2 IL3 GFI1 CSF3R
14 myelodysplastic syndrome 31.4 PTPN11 KITLG JAK2 IL3 CSF3R CSF3
15 leukemia 31.3 PTPN11 JAK2 IL3 CSF3R CSF2 CEBPA
16 myeloid leukemia 31.2 PTPN11 KITLG JAK2 IL3 CSF3R CSF3
17 granulocytopenia 31.0 IL3 CSF3 CSF2
18 acute leukemia 30.8 KITLG JAK2 IL3 CSF3R CSF3 CSF2
19 leukemia, acute lymphoblastic 30.8 PTPN11 LEF1 KITLG JAK2 IL3 CSF3R
20 chronic neutrophilic leukemia 30.7 JAK2 CSF3R CSF3
21 myelofibrosis 30.7 JAK2 IL3 CSF3R CSF3
22 shwachman-diamond syndrome 1 30.7 SRPRA SRP54 SRP19 HAX1 GFI1 G6PC3
23 bacterial infectious disease 30.6 IL3 ELANE CSF3 CSF2
24 deficiency anemia 30.6 KITLG JAK2 IL3 CSF3R CSF3 CSF2
25 chronic myelomonocytic leukemia 30.5 PTPN11 KITLG JAK2 IL3 CSF3R CSF3
26 whim syndrome 1 30.5 HAX1 G6PC3 ELANE CSF3R CSF3
27 thrombocytopenia 30.5 TCIRG1 PTPN11 KITLG JAK2 IL3 CSF3
28 neutrophilia, hereditary 30.5 JAK2 IL3 CSF3R CSF3 CSF2
29 bacterial pneumonia 30.5 ELANE CSF3 CSF2
30 acute megakaryocytic leukemia 30.4 JAK2 IL3 CSF2 CEBPA
31 pancytopenia 30.4 IL3 G6PC3 CSF3 CSF2
32 blood platelet disease 30.4 JAK2 IL3 CSF3 CSF2
33 myeloproliferative neoplasm 30.4 PTPN11 KITLG JAK2 IL3 CSF3R CSF3
34 dyskeratosis congenita 30.4 KITLG HAX1 CSF3 CSF2 CEBPA
35 aplastic anemia 30.4 KITLG IL3 CSF3R CSF3 CSF2
36 hematologic cancer 30.4 PTPN11 KITLG JAK2 IL3 CSF3 CSF2
37 leukemia, chronic myeloid 30.2 PTPN11 LEF1 KITLG JAK2 IL3 ELANE
38 diamond-blackfan anemia 30.2 KITLG JAK2 IL3 CSF3 CEBPA
39 hypereosinophilic syndrome 29.9 JAK2 IL3 CSF2
40 neutropenia, severe congenital, x-linked 11.8
41 neutropenia, severe congenital, 2, autosomal dominant 11.6
42 severe congenital neutropenia 8 11.6
43 severe congenital neutropenia 1 11.5
44 severe congenital neutropenia 2 11.5
45 neutropenia, severe congenital, 5, autosomal recessive 11.5
46 autosomal recessive severe congenital neutropenia due to cxcr2 deficiency 11.4
47 neutropenia, severe congenital, 7, autosomal recessive 11.3
48 neutropenia, severe congenital, 8, autosomal dominant 11.3
49 neutropenia, severe congenital, 9, autosomal dominant 11.3
50 neutropenia, severe congenital, 4, autosomal recessive 11.3

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



Diseases related to Severe Congenital Neutropenia

Symptoms & Phenotypes for Severe Congenital Neutropenia

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

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 no effect GR00402-S-1 10.15 BIRC5 CEBPA CSF2 CSF3 CSF3R ELANE
2 no effect GR00402-S-2 10.15 CEBPA CSF2 CSF3 CSF3R ELANE FCHO1
3 Reduced mammosphere formation GR00396-S 9.5 BIRC5 CEBPA CSF3 CSF3R PTPN11 SRP54
4 Increased transferrin (TF) endocytosis (mild increase), increased transferrin (TF) endosome elongation GR00363-A 8.85 LEF1

MGI Mouse Phenotypes related to Severe Congenital Neutropenia:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 10.13 BIRC5 CEBPA CSF2 CSF3R G6PC3 GFI1
2 cellular MP:0005384 10.07 BIRC5 CEBPA CSF2 CSF3R GFI1 HAX1
3 immune system MP:0005387 10.06 BIRC5 CEBPA CSF2 CSF3 CSF3R ELANE
4 neoplasm MP:0002006 9.91 CEBPA CSF2 ELANE IL3 JAK2 KITLG
5 hematopoietic system MP:0005397 9.86 BIRC5 CEBPA CSF2 CSF3 CSF3R ELANE
6 mortality/aging MP:0010768 9.47 BIRC5 CEBPA CSF2 CSF3R ELANE G6PC3

Drugs & Therapeutics for Severe Congenital Neutropenia

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

(show top 50) (show all 63)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Vidarabine Approved, Investigational Phase 2, Phase 3 24356-66-9 21704
2
Lenograstim Approved, Investigational Phase 2, Phase 3 135968-09-1
3 Antiviral Agents Phase 2, Phase 3
4 Anti-Infective Agents Phase 2, Phase 3
5 Adjuvants, Immunologic Phase 2, Phase 3
6 Antineoplastic Agents, Immunological Phase 2, Phase 3
7
Mycophenolic acid Approved, Investigational Phase 2 24280-93-1 446541
8
Prednisolone phosphate Approved, Vet_approved Phase 2 302-25-0
9
Prednisolone acetate Approved, Vet_approved Phase 2 52-21-1
10
Prednisolone Approved, Vet_approved Phase 2 50-24-8 4894 5755
11
Methylprednisolone hemisuccinate Approved Phase 2 2921-57-5 1875
12
Levoleucovorin Approved, Experimental, Investigational Phase 2 68538-85-2, 58-05-9, 73951-54-9 149436 6006
13
Methylprednisolone Approved, Vet_approved Phase 2 83-43-2 4159 6741
14
Methotrexate Approved Phase 2 1959-05-2, 59-05-2 4112 126941
15
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
16
Clotrimazole Approved, Vet_approved Phase 2 23593-75-1 2812
17
Tacrolimus Approved, Investigational Phase 2 104987-11-3 6473866 445643
18
Mechlorethamine Approved, Investigational Phase 2 51-75-2 4033
19
Melphalan Approved Phase 2 148-82-3 4053 460612
20
Fludarabine Approved Phase 2 75607-67-9, 21679-14-1 30751 657237
21
Cyclophosphamide Approved, Investigational Phase 2 50-18-0, 6055-19-2 2907
22
Rituximab Approved Phase 2 174722-31-7
23
Folic acid Approved, Nutraceutical, Vet_approved Phase 2 59-30-3 6037
24
D-Phenylalanine Approved, Experimental, Investigational, Nutraceutical Phase 2 63-91-2, 673-06-3 6140 71567
25
Prednisolone hemisuccinate Experimental Phase 2 2920-86-7 4897
26 Cyclosporins Phase 2
27 Folic Acid Antagonists Phase 2
28 Folate Phase 2
29 Vitamin B9 Phase 2
30 Neuroprotective Agents Phase 2
31 Hormones Phase 2
32 Calcineurin Inhibitors Phase 2
33 Vitamin B Complex Phase 2
34 Hormone Antagonists Phase 2
35 Antifungal Agents Phase 2
36 Antiemetics Phase 2
37 Anti-Inflammatory Agents Phase 2
38 glucocorticoids Phase 2
39
Methylprednisolone Acetate Phase 2 584547
40 Gastrointestinal Agents Phase 2
41 Protective Agents Phase 2
42 Anti-Bacterial Agents Phase 2
43 Antitubercular Agents Phase 2
44 Antibiotics, Antitubercular Phase 2
45 Antirheumatic Agents Phase 2
46 Immunosuppressive Agents Phase 2
47 Immunologic Factors Phase 2
48 Vaccines Phase 1, Phase 2
49 Alkylating Agents Phase 2
50 Antineoplastic Agents, Alkylating Phase 2

Interventional clinical trials:

(show all 15)
# Name Status NCT ID Phase Drugs
1 Allogeneic Hematopoietic Stem Cell Transplant for Patients With High Risk Hemoglobinopathy Using a Preparative Regimen to Achieve Stable Mixed Chimerism Completed NCT00176852 Phase 2, Phase 3 Busulfan, Fludarabine, ATG, TLI;Busulfan, Cyclophosphamide, ATG, GCSF;Campath, Fludarabine, Cyclophosphamide
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 A Phase II Trial of Reduced Intensity Allogeneic Stem Cell Transplantation With Fludarabine, Melphalan and Low Dose Total Body Irradiation Completed NCT01529827 Phase 2 fludarabine phosphate;melphalan;tacrolimus;mycophenolate mofetil;methotrexate
5 A Phase 1b/2, Open-Label, Multicenter Study of Mavorixafor in Patients With Congenital Neutropenia and Chronic Neutropenia Disorders Recruiting NCT04154488 Phase 1, Phase 2 Mavorixafor
6 CD34+ Stem Cell Selection for Patients Receiving a Matched or Partially Matched Family or Unrelated Adult Donor Allogeneic Stem Cell Transplantation for Non-Malignant Disease Active, not recruiting NCT01966367 Phase 1, Phase 2
7 A Phase II Trial of Haploidentical Allogeneic Stem Cell Transplantation Utilizing Mobilized Peripheral Blood Stem Cells Active, not recruiting NCT03333486 Phase 2 Cyclophosphamide;Fludarabine Phosphate
8 Pilot Prospective Clinical Study of Safety and Efficacy of Conditioning Regimen With Total Lymphoid Irradiation Before Allogeneic Hematopoietic Stem Cell Transplantation With TCRab/CD19 Graft Depletion in Severe Congenital Neutropenia Not yet recruiting NCT04844177 Phase 2
9 Abatacept for Post-Transplant Immune Suppression in Children and Adolescents Receiving Allogeneic Hematopoietic Stem Cell Transplants for Non-Malignant Diseases Completed NCT01917708 Phase 1 Abatacept
10 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
11 A Phase 1 Study of Empagliflozin as Treatment for Severe Congenital Neutropenia Due to G6PC3 Deficiency Recruiting NCT05078879 Phase 1 Empagliflozin
12 Identification of the Molecular Bases of Syndromic Congenital Neutropenia With Development Anomalies Completed NCT02866162
13 Investigation of the Genetics of Hematologic Diseases Recruiting NCT02720679
14 MT2014-10C: Allogeneic Hematopoietic Stem Cell Transplant for Patients With High Risk Hemoglobinopathies and Other Red Cell Transfusion Dependent Disorders Recruiting NCT02179359 Reduced Toxicity Ablative Regimen;Reduced Intensity Preparative Regimen;Myeloablative Preparative Regimen
15 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.

Genetic Tests for Severe Congenital Neutropenia

Genetic tests related to Severe Congenital Neutropenia:

# Genetic test Affiliating Genes
1 Severe Congenital Neutropenia 28
2 Congenital Neutropenia 28

Anatomical Context for Severe Congenital Neutropenia

Organs/tissues related to Severe Congenital Neutropenia:

MalaCards : Bone, Liver, Heart, Skin, Bone Marrow, Myeloid, Neutrophil

Publications for Severe Congenital Neutropenia

Articles related to Severe Congenital Neutropenia:

(show top 50) (show all 896)
# Title Authors PMID Year
1
Ela2 mutations and clinical manifestations in familial congenital neutropenia. 53 62 5
19415009 2009
2
Neutrophil elastase in cyclic and severe congenital neutropenia. 53 62 5
17053055 2007
3
Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register. 53 62 5
14962902 2004
4
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. 53 62 5
11675333 2001
5
Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia. 53 62 5
11001877 2000
6
Homozygous c.130-131 ins A (pW44X) mutation in the HAX1 gene as the most common cause of congenital neutropenia in Turkey: Report from the Turkish Severe Congenital Neutropenia Registry. 62 5
31321910 2019
7
Functional characteristics of circulating granulocytes in severe congenital neutropenia caused by ELANE mutations. 62 5
31176364 2019
8
Successful second hematopoietic cell transplantation in severe congenital neutropenia. 62 5
29076228 2018
9
JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia. 62 5
25129144 2014
10
TCIRG1-associated congenital neutropenia. 62 5
24753205 2014
11
The spectrum of ELANE mutations and their implications in severe congenital and cyclic neutropenia. 62 5
23463630 2013
12
Wnt3a stimulates maturation of impaired neutrophils developed from severe congenital neutropenia patient-derived pluripotent stem cells. 62 5
23382209 2013
13
Heterozygous M1V variant of ELA-2 gene mutation associated with G-CSF refractory severe congenital neutropenia. 62 5
21618407 2011
14
Homozygous HAX1 mutations in severe congenital neutropenia patients with sporadic disease: a novel mutation in two unrelated British kindreds. 62 5
19036076 2009
15
Neurodevelopmental abnormalities associated with severe congenital neutropenia due to the R86X mutation in the HAX1 gene. 62 5
18611981 2008
16
ELANE-Related Neutropenia 62 5
20301705 2002
17
Whole-genome sequencing of patients with rare diseases in a national health system. 5
32581362 2020
18
Neutropenia-associated ELANE mutations disrupting translation initiation produce novel neutrophil elastase isoforms. 5
24184683 2014
19
Neutrophil elastase-processing defect in cyclic hematopoietic dogs. 53 62
19941936 2010
20
Prevalence of mutations in ELANE, GFI1, HAX1, SBDS, WAS and G6PC3 in patients with severe congenital neutropenia. 53 62
19775295 2009
21
Double de novo mutations of ELANE (ELA2) in a patient with severe congenital neutropenia requiring high-dose G-CSF therapy. 53 62
19694719 2009
22
Neutrophil elastase is severely down-regulated in severe congenital neutropenia independent of ELA2 or HAX1 mutations but dependent on LEF-1. 53 62
19620402 2009
23
Severe congenital neutropenia: a negative synergistic effect of multiple mutations of ELANE (ELA2) gene. 53 62
19594744 2009
24
Site-specific ubiquitination determines lysosomal sorting and signal attenuation of the granulocyte colony-stimulating factor receptor. 53 62
19453968 2009
25
A novel mutation Ala57Val of the ELA2 gene in a Korean boy with severe congenital neutropenia. 53 62
18946670 2009
26
Gfi1 integrates progenitor versus granulocytic transcriptional programming. 53 62
19346496 2009
27
Survivin expression in the bone marrow of patients with severe congenital neutropenia. 53 62
18818705 2009
28
Clinical implications of ELA2-, HAX1-, and G-CSF-receptor (CSF3R) mutations in severe congenital neutropenia. 53 62
19120359 2009
29
Genetic and molecular diagnosis of severe congenital neutropenia. 53 62
19057199 2009
30
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. 53 62
18826620 2008
31
Transformation of severe congenital neutropenia to early acute lymphoblastic leukemia in a patient with HAX1 mutation and without G-CSF administration or receptor mutation. 53 62
18354489 2008
32
Functional interaction between mutations in the granulocyte colony-stimulating factor receptor in severe congenital neutropenia. 53 62
18513286 2008
33
Csf3r mutations in mice confer a strong clonal HSC advantage via activation of Stat5. 53 62
18292815 2008
34
G-CSFR ubiquitination critically regulates myeloid cell survival and proliferation. 53 62
18923646 2008
35
Severe congenital neutropenia and the unfolded protein response. 53 62
18043239 2008
36
Chronic idiopathic neutropenias and severe congenital neutropenia. 53 62
18043240 2008
37
Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia. 53 62
18028488 2008
38
Genetic heterogeneity in severe congenital neutropenia: how many aberrant pathways can kill a neutrophil? 53 62
17989524 2007
39
Mutations of the ELA2 gene found in patients with severe congenital neutropenia induce the unfolded protein response and cellular apoptosis. 53 62
17761833 2007
40
Double de novo mutations of ELA2 in cyclic and severe congenital neutropenia. 53 62
17436313 2007
41
G-CSF treatment of severe congenital neutropenia reverses neutropenia but does not correct the underlying functional deficiency of the neutrophil in defending against microorganisms. 53 62
17311988 2007
42
LEF-1 is a decisive transcription factor in neutrophil granulopoiesis. 53 62
17360796 2007
43
Current diagnosis of inherited bone marrow failure syndromes. 53 62
17454774 2007
44
The role of the granulocyte colony-stimulating factor receptor (G-CSF-R) in disease. 53 62
17127322 2007
45
Incidence of CSF3R mutations in severe congenital neutropenia and relevance for leukemogenesis: Results of a long-term survey. 53 62
16985178 2007
46
A family of severe congenital neutropenia with -199C to A substitution in ELA2 promoter. 53 62
16795059 2006
47
Molecular screening of the neutrophil elastase gene in congenital neutropenia. 53 62
17202606 2006
48
Src family kinases are important negative regulators of G-CSF-dependent granulopoiesis. 53 62
16772601 2006
49
Granulocyte colony-stimulating factor preferentially stimulates proliferation of monosomy 7 cells bearing the isoform IV receptor. 53 62
16980411 2006
50
The growth factor independence-1 transcription factor: new functions and new insights. 53 62
16716599 2006

Variations for Severe Congenital Neutropenia

ClinVar genetic disease variations for Severe Congenital Neutropenia:

5 (show top 50) (show all 58)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ELANE NM_001972.4(ELANE):c.214G>A (p.Val72Met) SNV Pathogenic
16744 rs387906553 GRCh37: 19:853022-853022
GRCh38: 19:853022-853022
2 ELANE NM_001972.4(ELANE):c.211T>C (p.Cys71Arg) SNV Pathogenic
16746 rs28931611 GRCh37: 19:853019-853019
GRCh38: 19:853019-853019
3 TCIRG1 NM_006019.4(TCIRG1):c.2206C>A (p.Arg736Ser) SNV Pathogenic
Pathogenic
127173 rs587779413 GRCh37: 11:67817691-67817691
GRCh38: 11:68050224-68050224
4 CSF3R NM_000760.4(CSF3R):c.922C>T (p.Arg308Cys) SNV Pathogenic
161982 rs606231473 GRCh37: 1:36937914-36937914
GRCh38: 1:36472313-36472313
5 CSF3R NM_000760.4(CSF3R):c.948_963del (p.His317fs) DEL Pathogenic
242629 rs606231475 GRCh37: 1:36937873-36937888
GRCh38: 1:36472272-36472287
6 JAGN1 NM_032492.4(JAGN1):c.3G>A (p.Met1Ile) SNV Pathogenic
156113 rs587777727 GRCh37: 3:9932409-9932409
GRCh38: 3:9890725-9890725
7 JAGN1 NM_032492.4(JAGN1):c.59G>A (p.Arg20Gln) SNV Pathogenic
190479 rs777966677 GRCh37: 3:9932465-9932465
GRCh38: 3:9890781-9890781
8 JAGN1 NM_032492.4(JAGN1):c.40G>A (p.Gly14Ser) SNV Pathogenic
190480 rs786205704 GRCh37: 3:9932446-9932446
GRCh38: 3:9890762-9890762
9 JAGN1 NM_032492.4(JAGN1):c.297C>G (p.Tyr99Ter) SNV Pathogenic
190481 rs786205705 GRCh37: 3:9934806-9934806
GRCh38: 3:9893122-9893122
10 JAGN1 NM_032492.4(JAGN1):c.485A>G (p.Gln162Arg) SNV Pathogenic
156116 rs587777730 GRCh37: 3:9934994-9934994
GRCh38: 3:9893310-9893310
11 JAGN1 NM_032492.4(JAGN1):c.63G>T (p.Glu21Asp) SNV Pathogenic
156115 rs587777729 GRCh37: 3:9932469-9932469
GRCh38: 3:9890785-9890785
12 ELANE NM_001972.4(ELANE):c.561C>A (p.Cys187Ter) SNV Pathogenic
208494 rs797045009 GRCh37: 19:855758-855758
GRCh38: 19:855758-855758
13 FCHO1 NM_015122.3(FCHO1):c.2036G>C (p.Arg679Pro) SNV Pathogenic
805883 rs530286781 GRCh37: 19:17893924-17893924
GRCh38: 19:17783115-17783115
14 FCHO1 NM_015122.3(FCHO1):c.100G>C (p.Ala34Pro) SNV Pathogenic
805884 rs2086875746 GRCh37: 19:17873643-17873643
GRCh38: 19:17762834-17762834
15 FCHO1 NM_015122.3(FCHO1):c.2023dup (p.Val675fs) DUP Pathogenic
805885 rs2093571190 GRCh37: 19:17893910-17893911
GRCh38: 19:17783101-17783102
16 FCHO1 NM_015122.3(FCHO1):c.489+1G>A SNV Pathogenic
805886 rs2091196149 GRCh37: 19:17881387-17881387
GRCh38: 19:17770578-17770578
17 FCHO1 NM_015122.3(FCHO1):c.195-2A>C SNV Pathogenic
805887 rs2089298923 GRCh37: 19:17877476-17877476
GRCh38: 19:17766667-17766667
18 FCHO1 NM_015122.3(FCHO1):c.1948C>T (p.Arg650Ter) SNV Pathogenic
805888 rs1336566500 GRCh37: 19:17893836-17893836
GRCh38: 19:17783027-17783027
19 SRP19 NM_003135.3(SRP19):c.189+5G>A SNV Pathogenic
810839 rs1322282571 GRCh37: 5:112200230-112200230
GRCh38: 5:112864533-112864533
20 SRPRA NM_003139.4(SRPRA):c.1390C>G (p.Gln464Glu) SNV Pathogenic
810840 rs1950780024 GRCh37: 11:126134989-126134989
GRCh38: 11:126265094-126265094
21 ELANE NM_001972.4(ELANE):c.669C>A (p.Cys223Ter) SNV Pathogenic
803509 rs1599294750 GRCh37: 19:856029-856029
GRCh38: 19:856029-856029
22 ELANE NM_001972.4(ELANE):c.137C>T (p.Ser46Phe) SNV Pathogenic
372362 rs878855320 GRCh37: 19:852945-852945
GRCh38: 19:852945-852945
23 ELANE NM_001972.4(ELANE):c.722G>A (p.Trp241Ter) SNV Pathogenic
986920 rs2035677025 GRCh37: 19:856082-856082
GRCh38: 19:856082-856082
24 ELANE NM_001972.4(ELANE):c.1A>G (p.Met1Val) SNV Pathogenic
1343367 GRCh37: 19:852329-852329
GRCh38: 19:852329-852329
25 ELANE NM_001972.4(ELANE):c.452G>C (p.Cys151Ser) SNV Pathogenic
1339552 GRCh37: 19:855649-855649
GRCh38: 19:855649-855649
26 ELANE NM_001972.4(ELANE):c.574_583del (p.Gly192fs) DEL Pathogenic
1339651 GRCh37: 19:855768-855777
GRCh38: 19:855768-855777
27 JAGN1 NM_032492.4(JAGN1):c.35_43del (p.Thr12_Gly14del) DEL Pathogenic
156117 rs587777731 GRCh37: 3:9932436-9932444
GRCh38: 3:9890752-9890760
28 JAGN1 NM_032492.4(JAGN1):c.130C>T (p.His44Tyr) SNV Pathogenic
156114 rs587777728 GRCh37: 3:9934639-9934639
GRCh38: 3:9892955-9892955
29 CSF3R NM_000760.4(CSF3R):c.1576+1G>A SNV Likely Pathogenic
812884 rs1031224658 GRCh37: 1:36934756-36934756
GRCh38: 1:36469155-36469155
30 CSF3R NM_000760.4(CSF3R):c.340C>T (p.Gln114Ter) SNV Likely Pathogenic
812885 rs756667927 GRCh37: 1:36940999-36940999
GRCh38: 1:36475398-36475398
31 ELANE NM_001972.4(ELANE):c.368T>C (p.Leu123Pro) SNV Likely Pathogenic
1012306 GRCh37: 19:855565-855565
GRCh38: 19:855565-855565
32 ELANE NM_001972.4(ELANE):c.641G>A (p.Gly214Glu) SNV Likely Pathogenic
1301410 GRCh37: 19:856001-856001
GRCh38: 19:856001-856001
33 GFI1 NM_005263.5(GFI1):c.925-40CT[17] MICROSAT Conflicting Interpretations Of Pathogenicity
298182 rs35896485 GRCh37: 1:92944315-92944316
GRCh38: 1:92478758-92478759
34 GFI1 NM_005263.5(GFI1):c.925-40CT[25] MICROSAT Uncertain Significance
298181 rs35896485 GRCh37: 1:92944314-92944315
GRCh38: 1:92478757-92478758
35 GFI1 NM_005263.5(GFI1):c.925-40CT[20] MICROSAT Uncertain Significance
298179 rs35896485 GRCh37: 1:92944314-92944315
GRCh38: 1:92478757-92478758
36 GFI1 NM_005263.5(GFI1):c.925-40CT[13] MICROSAT Uncertain Significance
298186 rs35896485 GRCh37: 1:92944315-92944324
GRCh38: 1:92478758-92478767
37 GFI1 NM_005263.5(GFI1):c.925-40CT[23] MICROSAT Uncertain Significance
298183 rs35896485 GRCh37: 1:92944314-92944315
GRCh38: 1:92478757-92478758
38 GFI1 NM_005263.5(GFI1):c.925-40CT[22] MICROSAT Uncertain Significance
298180 rs35896485 GRCh37: 1:92944314-92944315
GRCh38: 1:92478757-92478758
39 ELANE NM_001972.4(ELANE):c.284C>G (p.Thr95Ser) SNV Uncertain Significance
1687192 GRCh37: 19:853321-853321
GRCh38: 19:853321-853321
40 ELANE NM_001972.4(ELANE):c.22G>A (p.Ala8Thr) SNV Uncertain Significance
242275 rs759486889 GRCh37: 19:852350-852350
GRCh38: 19:852350-852350
41 GFI1 NM_005263.5(GFI1):c.925-7_925-6insTCTCTT MICROSAT Uncertain Significance
298187 rs766365921 GRCh37: 1:92944316-92944317
GRCh38: 1:92478759-92478760
42 GFI1 NM_005263.5(GFI1):c.925-40CT[16] MICROSAT Uncertain Significance
298184 rs35896485 GRCh37: 1:92944315-92944318
GRCh38: 1:92478758-92478761
43 G6PC3 NM_138387.4(G6PC3):c.*1CTT[1] MICROSAT Uncertain Significance
323471 rs761219348 GRCh37: 17:42153412-42153414
GRCh38: 17:44076044-44076046
44 G6PC3 NM_138387.4(G6PC3):c.-191T>G SNV Uncertain Significance
323455 rs886052984 GRCh37: 17:42148143-42148143
GRCh38: 17:44070775-44070775
45 ELANE NM_001972.4(ELANE):c.772C>T (p.Arg258Trp) SNV Uncertain Significance
1354571 GRCh37: 19:856132-856132
GRCh38: 19:856132-856132
46 ELANE NM_001972.4(ELANE):c.461T>G (p.Met154Arg) SNV Uncertain Significance
1372707 GRCh37: 19:855658-855658
GRCh38: 19:855658-855658
47 ELANE NM_001972.4(ELANE):c.437_457dup (p.Gly146_Leu152dup) DUP Uncertain Significance
1374105 GRCh37: 19:855627-855628
GRCh38: 19:855627-855628
48 ELANE NM_001972.4(ELANE):c.550A>C (p.Ser184Arg) SNV Uncertain Significance
1370846 GRCh37: 19:855747-855747
GRCh38: 19:855747-855747
49 overlap with 26 genes NC_000019.9:g.(?_589946)_(1106571_?)del DEL Uncertain Significance
1421361 GRCh37: 19:589946-1106571
GRCh38:
50 ELANE NM_001972.4(ELANE):c.239T>C (p.Val80Ala) SNV Uncertain Significance
1442303 GRCh37: 19:853276-853276
GRCh38: 19:853276-853276

Expression for Severe Congenital Neutropenia

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

Pathways for Severe Congenital Neutropenia



Pathways directly related to Severe Congenital Neutropenia:

# Pathway Source
1 Severe congenital neutropenia type 4 (G6PC3) Reactome 66

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

(show all 20)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.23 CEBPA CSF2 CSF3 CSF3R IL3 JAK2
2
Show member pathways
13.15 PTPN11 JAK2 IL3 CSF3R CSF3 CSF2
3
Show member pathways
12.99 CSF2 CSF3 CSF3R IL3 JAK2 KITLG
4
Show member pathways
12.69 KITLG JAK2 IL3 G6PC3 CSF3R CSF3
5
Show member pathways
12.46 PTPN11 KITLG JAK2 IL3 CSF3R
6 12.4 KITLG JAK2 IL3 CEBPA
7
Show member pathways
12.1 PTPN11 JAK2 IL3 CSF2
8
Show member pathways
12.08 JAK2 CSF3 CSF2 CEBPA
9
Show member pathways
11.84 PTPN11 KITLG JAK2
10 11.8 PTPN11 JAK2 BIRC5
11
Show member pathways
11.74 PTPN11 KITLG JAK2
12
Show member pathways
11.69 JAK2 CSF3 CSF2
13
Show member pathways
11.64 PTPN11 JAK2 IL3
14 11.46 LEF1 KITLG ELANE CEBPA
15 11.39 BIRC5 LEF1 PTPN11
16
Show member pathways
11.3 PTPN11 JAK2 IL3 CSF2
17 11.28 PTPN11 JAK2 BIRC5
18 11.09 KITLG IL3 CSF3R CSF3 CSF2
19 11.01 IL3 CSF3 CSF2
20
Show member pathways
11 PTPN11 JAK2 CSF3R CSF3

GO Terms for Severe Congenital Neutropenia

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

# Name GO ID Score Top Affiliating Genes
1 signal recognition particle GO:0048500 9.13 SRP54 SRP19
2 granulocyte macrophage colony-stimulating factor receptor complex GO:0030526 8.92 JAK2 CSF2

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

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of cell population proliferation GO:0008284 10.2 TCIRG1 LEF1 KITLG JAK2 IL3 CSF3
2 cytokine-mediated signaling pathway GO:0019221 10.13 PTPN11 JAK2 CSF3R CSF3 CEBPA
3 cellular response to lipopolysaccharide GO:0071222 10.11 JAK2 GFI1 CSF3 CSF2
4 positive regulation of tyrosine phosphorylation of STAT protein GO:0042531 10.01 JAK2 IL3 CSF2
5 granulocyte differentiation GO:0030851 9.88 SRP54 CSF3 CEBPA
6 cellular response to cytokine stimulus GO:0071345 9.86 CSF3 HAX1 LEF1 TCIRG1
7 cotranslational protein targeting to membrane GO:0006613 9.83 SRPRA SRP19
8 positive regulation of granulocyte differentiation GO:0030854 9.8 LEF1 HAX1
9 positive regulation of leukocyte proliferation GO:0070665 9.78 CSF2 JAK2
10 granulocyte-macrophage colony-stimulating factor signaling pathway GO:0038157 9.76 JAK2 CSF2
11 SRP-dependent cotranslational protein targeting to membrane GO:0006614 9.67 SRP19 SRP54 SRPRA
12 neutrophil differentiation GO:0030223 9.63 LEF1 JAGN1 CSF2
13 myeloid cell differentiation GO:0030099 9.43 TCIRG1 JAK2 CSF2 CEBPA
14 positive regulation of peptidyl-tyrosine phosphorylation GO:0050731 9.4 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 growth factor activity GO:0008083 9.56 KITLG IL3 CSF3 CSF2
2 peptide hormone receptor binding GO:0051428 9.46 PTPN11 JAK2
3 7S RNA binding GO:0008312 8.92 SRP54 SRP19

Sources for Severe Congenital Neutropenia

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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