SCN3
MCID: NTR049
MIFTS: 51

Neutropenia, Severe Congenital, 3, Autosomal Recessive (SCN3)

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Aliases & Classifications for Neutropenia, Severe Congenital, 3, Autosomal Recessive

MalaCards integrated aliases for Neutropenia, Severe Congenital, 3, Autosomal Recessive:

Name: Neutropenia, Severe Congenital, 3, Autosomal Recessive 57
Kostmann Disease 57 19 73 5
Scn3 57 19 73
Neutropenia, Severe Congenital 3, Autosomal Recessive 57 73
Agranulocytosis Infantile 19 73
Neutropenia, Congenital, Severe, Type 3, Autosomal Recessive 38
Neutropenia, Severe Congenital, Autosomal Recessive 3 12
Severe Congenital Neutropenia Autosomal Recessive 3 19
Severe Congenital Neutropenia 71
Agranulocytosis, Infantile 57
Kostmanns Syndrome 53

Characteristics:


Inheritance:

Autosomal recessive 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
onset in infancy
only some patients showed neurologic involvement


Classifications:



Summaries for Neutropenia, Severe Congenital, 3, Autosomal Recessive

OMIM®: 57 Severe congenital neutropenia-3 is an autosomal recessive bone marrow failure disorder characterized by low numbers of neutrophils, increased susceptibility to bacterial and fungal infections, and increased risk of developing myelodysplastic syndrome or acute myeloid leukemia. In addition, patients with HAX1 mutations affecting both isoform A and B of the gene develop neurologic abnormalities (summary by Boztug et al., 2010). The Swedish physician Rolf Kostmann (1956) described an autosomal recessive hematologic disorder, termed infantile agranulocytosis, with severe neutropenia with an absolute neutrophil count below 0.5 x 10(9)/l and early onset of severe bacterial infections. The disorder was later termed Kostmann syndrome (Skokowa et al., 2007). Lekstrom-Himes and Gallin (2000) discussed severe congenital neutropenia in a review of immunodeficiencies caused by defects in phagocytes. In addition to Kostmann agranulocytosis, recessively inherited neutropenic syndromes include congenital neutropenia with eosinophilia (257100), Chediak-Higashi syndrome (214500), and Fanconi pancytopenic syndrome (see 227650). For a phenotypic description and a discussion of genetic heterogeneity of severe congenital neutropenia, see SCN1 (202700). (610738) (Updated 08-Dec-2022)

MalaCards based summary: Neutropenia, Severe Congenital, 3, Autosomal Recessive, also known as kostmann disease, is related to severe congenital neutropenia 3 and severe congenital neutropenia. An important gene associated with Neutropenia, Severe Congenital, 3, Autosomal Recessive is HAX1 (HCLS1 Associated Protein X-1), and among its related pathways/superpathways are Innate Immune System and Akt Signaling. The drugs Vidarabine and Lenograstim have been mentioned in the context of this disorder. Affiliated tissues include bone marrow, neutrophil and myeloid, and related phenotypes are intellectual disability and seizure

GARD: 19 Kostmann syndrome is a rare, severe, congenital neutropenia disorder characterized by a lack of mature neutrophils (absolute neutrophil counts less than 500 cells/mm3) associated with frequent, recurrent bacterial infections (e.g. otitis media, pneumonia, sinusitis, urinary tract infections, abscesses of skin and/or liver) and increased promyelocytes in the bone marrow. Periodontal disease, as well as neurological symptoms, such as cognitive impairment, severe neurodegeneration and epilepsy, have been reported in some patients.

UniProtKB/Swiss-Prot: 73 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. Some patients affected by severe congenital neutropenia type 3 have neurological manifestations such as psychomotor retardation and seizures.

Related Diseases for Neutropenia, Severe Congenital, 3, Autosomal Recessive

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 Neutropenia, Severe Congenital, 3, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 101)
# Related Disease Score Top Affiliating Genes
1 severe congenital neutropenia 3 30.8 HAX1 ELANE CSF3R CSF3
2 severe congenital neutropenia 30.1 IL3 HAX1 ELANE CSF3R CSF3 CSF2
3 granulocytopenia 29.8 IL3 CSF3 CSF2
4 deficiency anemia 28.9 IL3 CSF3R CSF3 CSF2
5 myelodysplastic syndrome 28.9 IL3 CSF3R CSF3 CSF2
6 neutropenia 28.9 IL3 HAX1 ELANE CSF3R CSF3 CSF2
7 severe congenital neutropenia 7 10.1 HAX1 CSF3R
8 chronic neutrophilic leukemia 10.0 CSF3R CSF3
9 neutropenia, severe congenital, x-linked 10.0 HAX1 ELANE
10 chronic eosinophilic leukemia 10.0 IL3 CSF3R
11 autosomal dominant severe congenital neutropenia 10.0 HAX1 ELANE
12 hemoglobinopathy 9.9 IL3 CSF3
13 down syndrome 9.9
14 immune deficiency disease 9.9
15 periodontitis, chronic 9.9
16 barth syndrome 9.9
17 acute basophilic leukemia 9.9
18 premature menopause 9.9
19 thrombocytopenia 9.9
20 periodontitis 9.9
21 hypereosinophilic syndrome 9.9
22 elane-related neutropenia 9.9
23 g6pc3 deficiency 9.9
24 splenomegaly 9.9
25 autosomal recessive severe congenital neutropenia 9.9
26 gingivitis 9.9 ELANE CSF3
27 chronic eosinophilic pneumonia 9.9 CSF3 CSF2
28 critical covid-19 9.9 CSF3 CSF2
29 meconium aspiration syndrome 9.9 CSF3 CSF2
30 mucormycosis 9.9 CSF3 CSF2
31 capillary disease 9.9 CSF3 CSF2
32 bacterial sepsis 9.9 CSF3 CSF2
33 hypersplenism 9.9 CSF3 CSF2
34 cellulitis 9.9 CSF3 CSF2
35 eosinophilic pneumonia 9.9 IL3 CSF2
36 opportunistic mycosis 9.9 CSF3 CSF2
37 myelodysplastic/myeloproliferative neoplasm 9.9 CSF3R CSF2
38 fungal infectious disease 9.8 CSF3 CSF2
39 exanthem 9.8 CSF3 CSF2
40 severe covid-19 9.8 CSF3 CSF2
41 smallpox 9.8 CSF3 CSF2
42 chronic asthma 9.8 IL3 CSF2
43 nasal cavity disease 9.8 IL3 CSF2
44 coronavirus infectious disease 9.8 CSF3 CSF2
45 respiratory allergy 9.8 IL3 CSF2
46 parasitic helminthiasis infectious disease 9.8 IL3 CSF2
47 blood coagulation disease 9.8 CSF3 CSF2
48 nose disease 9.8 IL3 CSF2
49 essential thrombocythemia 9.8 IL3 CSF3R CSF3
50 capillary leak syndrome 9.8 ELANE CSF2

Graphical network of the top 20 diseases related to Neutropenia, Severe Congenital, 3, Autosomal Recessive:



Diseases related to Neutropenia, Severe Congenital, 3, Autosomal Recessive

Symptoms & Phenotypes for Neutropenia, Severe Congenital, 3, Autosomal Recessive

Human phenotypes related to Neutropenia, Severe Congenital, 3, Autosomal Recessive:

30 (show all 11)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 30 Very rare (1%) HP:0001249
2 seizure 30 Very rare (1%) HP:0001250
3 global developmental delay 30 Very rare (1%) HP:0001263
4 sensorineural hearing impairment 30 Very rare (1%) HP:0000407
5 myelodysplasia 30 Very rare (1%) HP:0002863
6 conductive hearing impairment 30 Very rare (1%) HP:0000405
7 neutropenia 30 Very rare (1%) HP:0001875
8 impaired vibratory sensation 30 Very rare (1%) HP:0002495
9 acute lymphoblastic leukemia 30 Very rare (1%) HP:0006721
10 clumsiness 30 Very rare (1%) HP:0002312
11 recurrent bacterial infections 30 Very rare (1%) HP:0002718

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Immunology:
neutropenia
recurrent bacterial infections

Neoplasia:
increased risk of leukemia
increased risk of myelodysplastic syndromes

Neurologic Central Nervous System:
seizures (in some patients)
psychomotor retardation (in some patients)

Clinical features from OMIM®:

610738 (Updated 08-Dec-2022)

MGI Mouse Phenotypes related to Neutropenia, Severe Congenital, 3, Autosomal Recessive:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 immune system MP:0005387 9.43 CSF2 CSF3 CSF3R ELANE HAX1 IL3
2 hematopoietic system MP:0005397 9.1 CSF2 CSF3 CSF3R ELANE HAX1 IL3

Drugs & Therapeutics for Neutropenia, Severe Congenital, 3, Autosomal Recessive

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

Interventional clinical trials:

(show all 12)
# 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 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
6 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
7 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
8 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
9 A Phase 1 Study of Empagliflozin as Treatment for Severe Congenital Neutropenia Due to G6PC3 Deficiency Recruiting NCT05078879 Phase 1 Empagliflozin
10 Investigation of the Genetics of Hematologic Diseases Recruiting NCT02720679
11 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
12 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 Neutropenia, Severe Congenital, 3, Autosomal Recessive

Genetic Tests for Neutropenia, Severe Congenital, 3, Autosomal Recessive

Anatomical Context for Neutropenia, Severe Congenital, 3, Autosomal Recessive

Organs/tissues related to Neutropenia, Severe Congenital, 3, Autosomal Recessive:

MalaCards : Bone Marrow, Neutrophil, Myeloid, Bone, Liver, Skin, Brain
ODiseA: Blood And Bone Marrow

Publications for Neutropenia, Severe Congenital, 3, Autosomal Recessive

Articles related to Neutropenia, Severe Congenital, 3, Autosomal Recessive:

(show top 50) (show all 72)
# Title Authors PMID Year
1
Neurodevelopmental abnormalities associated with severe congenital neutropenia due to the R86X mutation in the HAX1 gene. 62 57 5
18611981 2008
2
HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). 62 57 5
17187068 2007
3
Homozygous HAX1 mutations in severe congenital neutropenia patients with sporadic disease: a novel mutation in two unrelated British kindreds. 57 5
19036076 2009
4
Novel HAX1 mutations in patients with severe congenital neutropenia reveal isoform-dependent genotype-phenotype associations. 57 5
18337561 2008
5
Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis. 57 5
10581030 1999
6
Compound heterozygous HAX1 mutations in a Swedish patient with severe congenital neutropenia and no neurodevelopmental abnormalities. 62 5
19499579 2009
7
Central nervous system involvement in severe congenital neutropenia: neurological and neuropsychological abnormalities associated with specific HAX1 mutations. 62 57
18513342 2008
8
Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes. 5
28102861 2017
9
Neurological findings and genetic alterations in patients with Kostmann syndrome and HAX1 mutations. 5
24482108 2014
10
A novel compound heterozygous HAX1 mutation in a Chinese patient with severe congenital neutropenia and chronic myelomonocytic leukemia transformation but without neurodevelopmental abnormalities. 5
22102707 2012
11
HAX1 mutations causing severe congenital neuropenia and neurological disease lead to cerebral microstructural abnormalities documented by quantitative MRI. 57
21108402 2010
12
Digenic mutations in severe congenital neutropenia. 5
20220065 2010
13
Novel HAX1 gene mutations associated to neurodevelopment abnormalities in two Italian patients with severe congenital neutropenia. 5
20065084 2010
14
Severe developmental delay and epilepsy in a Japanese patient with severe congenital neutropenia due to HAX1 deficiency. 5
18055975 2007
15
Association of HAX1 deficiency with neurological disorder. 5
18330843 2007
16
Severe congenital neutropenia: inheritance and pathophysiology. 57
17133096 2007
17
Splicing in action: assessing disease causing sequence changes. 5
16199547 2005
18
Kostmann syndrome: severe congenital neutropenia associated with defective expression of Bcl-2, constitutive mitochondrial release of cytochrome c, and excessive apoptosis of myeloid progenitor cells. 57
14764541 2004
19
Infantile genetic agranulocytosis, morbus Kostmann: presentation of six cases from the original "Kostmann family" and a review. 5
11519978 2001
20
Immunodeficiency diseases caused by defects in phagocytes. 57
11106721 2000
21
Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia. 57
11001877 2000
22
Mutations in the gene for the granulocyte colony-stimulating-factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia. 57
7542747 1995
23
Prenatal diagnosis of congenital dysgranulopoietic neutropenia. 57
7803247 1994
24
Transforming growth factor beta-1 (TGF-beta 1) released by an Epstein-Barr virus (EBV) positive spontaneous lymphoblastoid cell line from a patient with Kostmann's congenital neutropenia inhibits the growth of normal committed haemopoietic progenitors in vitro. 57
7918030 1993
25
Congenital dysgranulopoietic neutropenia in two siblings: clinical, ultrastructural, and in vitro bone marrow culture studies. 57
2701701 1989
26
Bone-marrow transplantation for immunodeficiencies and osteopetrosis: European survey, 1968-1985. 57
2877234 1986
27
Spatial distribution of the gene for infantile genetic agranulocytosis. 57
6510932 1984
28
Granulopoiesis in infantile genetic agranulocytosis. In vitro cloning of marrow cells in agar culture. 57
1082629 1976
29
Infantile genetic agranulocytosis. A review with presentation of ten new cases. 57
1130195 1975
30
Inborn errors of immunity and related microbiome. 62
36177048 2022
31
Kostmann disease and other forms of severe congenital neutropenia. 62
34160857 2021
32
Severe congenital neutropenia-associated JAGN1 mutations unleash a calpain-dependent cell death programme in myeloid cells. 62
33206996 2021
33
What can we learn about functional importance of human antimicrobial peptide LL-37 in the oral environment from severe congenital neutropenia (Kostmann disease)? 62
32278809 2020
34
Reliability of breeding values for feed intake and feed efficiency traits in dairy cattle: When dry matter intake recordings are sparse under different scenarios. 62
31155258 2019
35
Gene correction of HAX1 reversed Kostmann disease phenotype in patient-specific induced pluripotent stem cells. 62
29296734 2017
36
Kostmann's Disease and HCLS1-Associated Protein X-1 (HAX1). 62
27943080 2017
37
How we diagnose and treat neutropenia in adults. 62
26778239 2016
38
Primary immunodeficiencies associated with eosinophilia. 62
27222657 2016
39
CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder. 62
25597510 2015
40
Na+ current properties in islet α- and β-cells reflect cell-specific Scn3a and Scn9a expression. 62
25172946 2014
41
Ovarian failure in HAX1-deficient patients: is there a gender-specific difference in pubertal development in severe congenital neutropenia or Kostmann disease? 62
23050867 2013
42
Hax1 regulates neutrophil adhesion and motility through RhoA. 62
21518791 2011
43
[Kostmann disease in children]. 62
21243803 2010
44
Kostmann disease with developmental delay in three patients. 62
20177699 2010
45
Eponym. Kostmann disease. 62
20165869 2010
46
A novel missense mutation in the HAX1 gene in severe congenital neutropenia patients (Kostmann disease). 62
19796188 2009
47
HAX-1: a multifunctional protein with emerging roles in human disease. 62
19524642 2009
48
Late-onset neutropenia associated with rituximab therapy: evidence for a maturation arrest at the (pro)myelocyte stage of granulopoiesis. 62
18278570 2008
49
Genetic heterogeneity in severe congenital neutropenia: how many aberrant pathways can kill a neutrophil? 62
17989524 2007
50
[Chronic neutropenia - experience from the Department of Immunology, Children's Memorial Health Institute]. 62
17625284 2007

Variations for Neutropenia, Severe Congenital, 3, Autosomal Recessive

ClinVar genetic disease variations for Neutropenia, Severe Congenital, 3, Autosomal Recessive:

5 (show top 50) (show all 224)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 HAX1 NM_006118.4(HAX1):c.383C>G (p.Ser128Ter) SNV Pathogenic
561028 rs1398108109 GRCh37: 1:154246316-154246316
GRCh38: 1:154273840-154273840
2 HAX1 NM_006118.4(HAX1):c.372_373insGATA (p.Leu125fs) INSERT Pathogenic
1339545 GRCh37: 1:154246304-154246305
GRCh38: 1:154273828-154273829
3 HAX1 NM_006118.4(HAX1):c.214_217dup (p.Ile73fs) DUP Pathogenic
1374231 GRCh37: 1:154245968-154245969
GRCh38: 1:154273492-154273493
4 HAX1 NM_006118.4(HAX1):c.166del (p.His56fs) DEL Pathogenic
1410664 GRCh37: 1:154245924-154245924
GRCh38: 1:154273448-154273448
5 HAX1 NM_006118.4(HAX1):c.480G>A (p.Trp160Ter) SNV Pathogenic
1366366 GRCh37: 1:154246413-154246413
GRCh38: 1:154273937-154273937
6 HAX1 NM_006118.4(HAX1):c.556+1del DEL Pathogenic
1453309 GRCh37: 1:154247477-154247477
GRCh38: 1:154275001-154275001
7 HAX1 NM_006118.4(HAX1):c.58dup (p.Arg20fs) DUP Pathogenic
1453573 GRCh37: 1:154245815-154245816
GRCh38: 1:154273339-154273340
8 HAX1 NM_006118.4(HAX1):c.368_381del (p.Gln123fs) DEL Pathogenic
1438742 GRCh37: 1:154246296-154246309
GRCh38: 1:154273820-154273833
9 HAX1 NM_006118.4(HAX1):c.235_236del (p.Phe79fs) DEL Pathogenic
1068848 GRCh37: 1:154245993-154245994
GRCh38: 1:154273517-154273518
10 HAX1 NM_006118.4(HAX1):c.146del (p.Pro49fs) DEL Pathogenic
1071627 GRCh37: 1:154245902-154245902
GRCh38: 1:154273426-154273426
11 HAX1 NM_006118.4(HAX1):c.125dup (p.Ser43fs) DUP Pathogenic
4656 rs745666437 GRCh37: 1:154245878-154245879
GRCh38: 1:154273402-154273403
12 HAX1 NM_006118.4(HAX1):c.407del (p.His136fs) DEL Pathogenic
659562 rs748595772 GRCh37: 1:154246340-154246340
GRCh38: 1:154273864-154273864
13 HAX1 NM_006118.4(HAX1):c.337G>T (p.Glu113Ter) SNV Pathogenic
864562 rs374758765 GRCh37: 1:154246270-154246270
GRCh38: 1:154273794-154273794
14 HAX1 NM_006118.4(HAX1):c.256C>T (p.Arg86Ter) SNV Pathogenic
4654 rs121908165 GRCh37: 1:154246014-154246014
GRCh38: 1:154273538-154273538
15 HAX1 NM_006118.4(HAX1):c.349G>T (p.Glu117Ter) SNV Pathogenic
1072845 GRCh37: 1:154246282-154246282
GRCh38: 1:154273806-154273806
16 HAX1 NM_006118.4(HAX1):c.173_175delinsTT (p.Pro58fs) INDEL Pathogenic
964701 rs1684863942 GRCh37: 1:154245931-154245933
GRCh38: 1:154273455-154273457
17 HAX1 NM_006118.4(HAX1):c.173dup (p.Pro58_Glu59insTer) DUP Pathogenic
4653 rs758657008 GRCh37: 1:154245925-154245926
GRCh38: 1:154273449-154273450
18 HAX1 NM_006118.4(HAX1):c.568C>T (p.Gln190Ter) SNV Pathogenic
4650 rs74315322 GRCh37: 1:154247641-154247641
GRCh38: 1:154275165-154275165
19 HAX1 NM_006118.4(HAX1):c.130_131insA (p.Trp44Ter) INSERT Pathogenic
4651 rs1572018284 GRCh37: 1:154245888-154245889
GRCh38: 1:154273412-154273413
20 HAX1 NM_006118.4(HAX1):c.91del (p.Glu31fs) DEL Pathogenic
419887 rs764082747 GRCh37: 1:154245849-154245849
GRCh38: 1:154273373-154273373
21 HAX1 NM_006118.4(HAX1):c.430dup (p.Val144fs) DUP Pathogenic
578906 rs770288337 GRCh37: 1:154246356-154246357
GRCh38: 1:154273880-154273881
22 HAX1 NM_006118.4(HAX1):c.376_434del (p.Arg126fs) DEL Pathogenic
4655 GRCh37: 1:154246306-154246364
GRCh38: 1:154273830-154273888
23 HAX1 NM_006118.4(HAX1):c.487C>T (p.Gln163Ter) SNV Pathogenic
1395898 GRCh37: 1:154246420-154246420
GRCh38: 1:154273944-154273944
24 HAX1 NM_006118.4(HAX1):c.556+1G>C SNV Likely Pathogenic
834967 rs1684901295 GRCh37: 1:154247478-154247478
GRCh38: 1:154275002-154275002
25 HAX1 NM_006118.4(HAX1):c.504+1G>A SNV Likely Pathogenic
1518892 GRCh37: 1:154246438-154246438
GRCh38: 1:154273962-154273962
26 HAX1 NM_006118.4(HAX1):c.54-2A>T SNV Likely Pathogenic
1492611 GRCh37: 1:154245810-154245810
GRCh38: 1:154273334-154273334
27 HAX1 NM_006118.4(HAX1):c.663+1G>A SNV Likely Pathogenic
944776 rs41313932 GRCh37: 1:154247737-154247737
GRCh38: 1:154275261-154275261
28 HAX1 NC_000001.11:g.(?_154274930)_(154275721_?)del DEL Likely Pathogenic
832624 GRCh37: 1:154247406-154248197
GRCh38:
29 HAX1 NM_006118.4(HAX1):c.317-2A>G SNV Likely Pathogenic
653855 rs371504152 GRCh37: 1:154246248-154246248
GRCh38: 1:154273772-154273772
30 HAX1 NM_006118.4(HAX1):c.557-1G>C SNV Likely Pathogenic
1492255 GRCh37: 1:154247629-154247629
GRCh38: 1:154275153-154275153
31 HAX1 NM_006118.4(HAX1):c.664-1G>T SNV Likely Pathogenic
1525761 GRCh37: 1:154247868-154247868
GRCh38: 1:154275392-154275392
32 HAX1 NM_006118.4(HAX1):c.463dup (p.Gln155fs) DUP Likely Pathogenic
800902 rs1572018886 GRCh37: 1:154246390-154246391
GRCh38: 1:154273914-154273915
33 HAX1 NM_006118.4(HAX1):c.798C>T (p.Ser266=) SNV Conflicting Interpretations Of Pathogenicity
874305 rs762492730 GRCh37: 1:154248135-154248135
GRCh38: 1:154275659-154275659
34 HAX1 NM_006118.4(HAX1):c.593C>T (p.Pro198Leu) SNV Conflicting Interpretations Of Pathogenicity
292707 rs146152769 GRCh37: 1:154247666-154247666
GRCh38: 1:154275190-154275190
35 HAX1 NM_006118.4(HAX1):c.713C>T (p.Thr238Ile) SNV Conflicting Interpretations Of Pathogenicity
874304 rs377331781 GRCh37: 1:154247918-154247918
GRCh38: 1:154275442-154275442
36 HAX1 NM_006118.4(HAX1):c.505-4G>A SNV Conflicting Interpretations Of Pathogenicity
792260 rs186219647 GRCh37: 1:154247422-154247422
GRCh38: 1:154274946-154274946
37 HAX1 NM_006118.4(HAX1):c.117_122dup (p.Glu40_Gly41dup) DUP Uncertain Significance
543082 rs781468690 GRCh37: 1:154245874-154245875
GRCh38: 1:154273398-154273399
38 HAX1 NM_006118.4(HAX1):c.377G>A (p.Arg126Gln) SNV Uncertain Significance
964429 rs147036748 GRCh37: 1:154246310-154246310
GRCh38: 1:154273834-154273834
39 HAX1 NM_006118.4(HAX1):c.820C>T (p.Arg274Cys) SNV Uncertain Significance
961625 rs753078666 GRCh37: 1:154248157-154248157
GRCh38: 1:154275681-154275681
40 HAX1 NM_006118.4(HAX1):c.469G>A (p.Ala157Thr) SNV Uncertain Significance
937888 rs745643366 GRCh37: 1:154246402-154246402
GRCh38: 1:154273926-154273926
41 HAX1 NM_006118.4(HAX1):c.450A>C (p.Arg150Ser) SNV Uncertain Significance
937843 rs1684878785 GRCh37: 1:154246383-154246383
GRCh38: 1:154273907-154273907
42 HAX1 NM_006118.4(HAX1):c.106G>A (p.Glu36Lys) SNV Uncertain Significance
1405106 GRCh37: 1:154245864-154245864
GRCh38: 1:154273388-154273388
43 HAX1 NM_006118.4(HAX1):c.54-9del DEL Uncertain Significance
1475682 GRCh37: 1:154245802-154245802
GRCh38: 1:154273326-154273326
44 HAX1 NM_006118.4(HAX1):c.172C>T (p.Pro58Ser) SNV Uncertain Significance
960900 rs1260994720 GRCh37: 1:154245930-154245930
GRCh38: 1:154273454-154273454
45 HAX1 NM_006118.4(HAX1):c.339G>C (p.Glu113Asp) SNV Uncertain Significance
662545 rs367673863 GRCh37: 1:154246272-154246272
GRCh38: 1:154273796-154273796
46 HAX1 NM_006118.4(HAX1):c.428G>C (p.Gly143Ala) SNV Uncertain Significance
574945 rs755031266 GRCh37: 1:154246361-154246361
GRCh38: 1:154273885-154273885
47 HAX1 NM_006118.4(HAX1):c.829C>T (p.Arg277Trp) SNV Uncertain Significance
543083 rs138296453 GRCh37: 1:154248166-154248166
GRCh38: 1:154275690-154275690
48 HAX1 NM_006118.4(HAX1):c.96TGA[2] (p.Asp34del) MICROSAT Uncertain Significance
543081 rs560912060 GRCh37: 1:154245852-154245854
GRCh38: 1:154273376-154273378
49 HAX1 NM_006118.4(HAX1):c.*47A>G SNV Uncertain Significance
292709 rs183456651 GRCh37: 1:154248224-154248224
GRCh38: 1:154275748-154275748
50 HAX1 NM_006118.4(HAX1):c.137G>C (p.Arg46Pro) SNV Uncertain Significance
292703 rs761500862 GRCh37: 1:154245895-154245895
GRCh38: 1:154273419-154273419

UniProtKB/Swiss-Prot genetic disease variations for Neutropenia, Severe Congenital, 3, Autosomal Recessive:

73
# Symbol AA change Variation ID SNP ID
1 HAX1 p.Phe141Leu VAR_062259 rs179363870
2 HAX1 p.Leu130Arg VAR_064514 rs179363871

Expression for Neutropenia, Severe Congenital, 3, Autosomal Recessive

Search GEO for disease gene expression data for Neutropenia, Severe Congenital, 3, Autosomal Recessive.

Pathways for Neutropenia, Severe Congenital, 3, Autosomal Recessive

Pathways related to Neutropenia, Severe Congenital, 3, Autosomal Recessive according to GeneCards Suite gene sharing:

(show all 15)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.48 IL3 ELANE CSF3R CSF3 CSF2
2
Show member pathways
12.9 IL3 CSF3R CSF3 CSF2
3
Show member pathways
12.75 IL3 CSF3R CSF3 CSF2
4
Show member pathways
12.62 IL3 CSF3R CSF3 CSF2
5
Show member pathways
12.53 IL3 CSF3R CSF3
6
Show member pathways
11.5 CSF3 CSF2
7
Show member pathways
11.34 IL3 CSF2
8
Show member pathways
11.3 IL3 CSF2
9 11.23 CSF2 CSF3
10
Show member pathways
11.14 CSF3R CSF3
11 10.99 CSF3 CSF2
12 10.99 IL3 CSF3R CSF3 CSF2
13 10.59 IL3 CSF3 CSF2
14 10.59 IL3 CSF3 CSF2
15 10.54 CSF3R CSF3

GO Terms for Neutropenia, Severe Congenital, 3, Autosomal Recessive

Biological processes related to Neutropenia, Severe Congenital, 3, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular response to cytokine stimulus GO:0071345 9.46 CSF3 HAX1
2 positive regulation of actin cytoskeleton reorganization GO:2000251 9.26 CSF3 HAX1
3 positive regulation of peptidyl-tyrosine phosphorylation GO:0050731 9.1 IL3 HAX1 CSF3

Molecular functions related to Neutropenia, Severe Congenital, 3, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytokine binding GO:0019955 9.46 ELANE CSF3R
2 cytokine activity GO:0005125 9.43 IL3 CSF3 CSF2
3 growth factor activity GO:0008083 9.1 IL3 CSF3 CSF2

Sources for Neutropenia, Severe Congenital, 3, Autosomal Recessive

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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