SCN3
MCID: NTR049
MIFTS: 51

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

Categories: Blood diseases, Bone diseases, Cardiovascular diseases, Endocrine diseases, Genetic diseases, Immune diseases, Infectious diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Respiratory diseases

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
Neutropenia, Severe Congenital 3, Autosomal Recessive 57 72 13
Kostmann Syndrome 58 29 6
Kostmann Disease 57 20 72
Scn3 57 20 72
Agranulocytosis Infantile 20 72
Neutropenia, Congenital, Severe, Type 3, Autosomal Recessive 39
Severe Congenital Neutropenia Autosomal Recessive 3 20
Severe Congenital Neutropenia Type 3 58
Severe Congenital Neutropenia 70
Agranulocytosis, Infantile 57
Infantile Agranulocytosis 58
Kostmanns Syndrome 54

Characteristics:

Orphanet epidemiological data:

58
kostmann syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
only some patients showed neurologic involvement


HPO:

31
neutropenia, severe congenital, 3, autosomal recessive:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare immunological diseases


External Ids:

OMIM® 57 610738
OMIM Phenotypic Series 57 PS202700
MeSH 44 D009503
ICD10 via Orphanet 33 D70
Orphanet 58 ORPHA99749
UMLS 70 C1853118

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 20-May-2021)

MalaCards based summary : Neutropenia, Severe Congenital, 3, Autosomal Recessive, also known as neutropenia, severe congenital 3, autosomal recessive, is related to autosomal recessive severe congenital neutropenia and granulocytopenia. 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 JAK-STAT signaling pathway and Transcriptional misregulation in cancer. The drugs Methotrexate and Methylprednisolone have been mentioned in the context of this disorder. Affiliated tissues include neutrophil, bone marrow and myeloid, and related phenotypes are global developmental delay and seizure

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 99749 Definition 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 : 72 Neutropenia, severe congenital 3, autosomal recessive: 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 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 99)
# Related Disease Score Top Affiliating Genes
1 autosomal recessive severe congenital neutropenia 29.8 HAX1 ELANE CSF3R
2 granulocytopenia 29.6 IL3 CSF3 CSF2
3 cellulitis 29.6 CSF3 CSF2
4 bacterial infectious disease 29.1 IL3 ELANE CSF3 CSF2
5 leukemia, acute myeloid 29.0 IL3 CSF3R CSF3 CSF2
6 severe congenital neutropenia 28.8 SRPRA SRP19 JAGN1 IL3 HAX1 FCHO1
7 myelodysplastic syndrome 28.7 IL3 HAX1 CSF3R CSF3 CSF2
8 neutropenia 28.6 JAGN1 IL3 HAX1 ELANE CSF3R CSF3
9 dentin dysplasia, type i 11.0
10 severe congenital neutropenia 3 11.0
11 ecthyma 10.1 HAX1 CSF3
12 graft-versus-host disease 10.1
13 amegakaryocytic thrombocytopenia, congenital 10.1 IL3 HAX1
14 chronic neutrophilic leukemia 10.1 CSF3R CSF3
15 retinitis pigmentosa and erythrocytic microcytosis 10.0 IL3 CSF3
16 myelodysplastic/myeloproliferative neoplasm 9.9 CSF3R CSF2
17 down syndrome 9.9
18 periodontitis, chronic 9.9
19 barth syndrome 9.9
20 deficiency anemia 9.9
21 autosomal recessive disease 9.9
22 acute basophilic leukemia 9.9
23 thrombocytopenia 9.9
24 periodontitis 9.9
25 hypereosinophilic syndrome 9.9
26 elane-related neutropenia 9.9
27 g6pc3 deficiency 9.9
28 chromosomal triplication 9.9
29 splenomegaly 9.9
30 otitis media 9.9
31 periodontitis, aggressive, 1 9.9
32 thyroid cancer, nonmedullary, 1 9.9
33 alacrima, achalasia, and mental retardation syndrome 9.9
34 lung abscess 9.9
35 suppurative otitis media 9.9
36 pure red-cell aplasia 9.9
37 epilepsy 9.9
38 dental caries 9.9
39 orchitis 9.9
40 gingivitis 9.9
41 b-cell lymphoma 9.9
42 epididymo-orchitis 9.9
43 stomatitis 9.9
44 chronic graft versus host disease 9.9
45 neurometabolic disease 9.9
46 refractory anemia 9.9
47 thyroid carcinoma 9.9
48 cohen syndrome 9.9 JAGN1 HAX1 ELANE
49 engraftment syndrome 9.9 CSF3 CSF2
50 neutropenia, severe congenital, 1, autosomal dominant 9.9

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:

31 (show all 7)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 occasional (7.5%) HP:0001263
2 seizure 31 occasional (7.5%) HP:0001250
3 psychomotor retardation 31 very rare (1%) HP:0025356
4 myelodysplasia 31 HP:0002863
5 leukemia 31 HP:0001909
6 neutropenia 31 HP:0001875
7 recurrent bacterial infections 31 HP:0002718

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
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 20-May-2021)

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

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 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
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 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
4 A Phase 1B, Open-Label, Multicenter Study of Mavorixafor in Patients With Severe Congenital Neutropenia and Chronic Neutropenia Disorders Recruiting NCT04154488 Phase 1 Mavorixafor
5 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

Genetic tests related to Neutropenia, Severe Congenital, 3, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Kostmann Syndrome 29 HAX1

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

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

40
Neutrophil, Bone Marrow, Myeloid, Bone, Lung, Thyroid

Publications for Neutropenia, Severe Congenital, 3, Autosomal Recessive

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

(show all 50)
# Title Authors PMID Year
1
Neurodevelopmental abnormalities associated with severe congenital neutropenia due to the R86X mutation in the HAX1 gene. 61 57 6
18611981 2008
2
HAX1 mutations causing severe congenital neuropenia and neurological disease lead to cerebral microstructural abnormalities documented by quantitative MRI. 6 57
21108402 2010
3
Homozygous HAX1 mutations in severe congenital neutropenia patients with sporadic disease: a novel mutation in two unrelated British kindreds. 57 6
19036076 2009
4
Novel HAX1 mutations in patients with severe congenital neutropenia reveal isoform-dependent genotype-phenotype associations. 6 57
18337561 2008
5
HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). 57 6
17187068 2007
6
Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis. 57 6
10581030 1999
7
Whole-genome sequencing of patients with rare diseases in a national health system. 6
32581362 2020
8
Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes. 6
28102861 2017
9
JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia. 6
25129144 2014
10
Neurological findings and genetic alterations in patients with Kostmann syndrome and HAX1 mutations. 6
24482108 2014
11
A novel compound heterozygous HAX1 mutation in a Chinese patient with severe congenital neutropenia and chronic myelomonocytic leukemia transformation but without neurodevelopmental abnormalities. 6
22102707 2012
12
Alu-mediated recombination in the HAX1 gene as the molecular basis of severe congenital neutropenia. 6
21344642 2011
13
Digenic mutations in severe congenital neutropenia. 6
20220065 2010
14
Novel HAX1 gene mutations associated to neurodevelopment abnormalities in two Italian patients with severe congenital neutropenia. 6
20065084 2010
15
Compound heterozygous HAX1 mutations in a Swedish patient with severe congenital neutropenia and no neurodevelopmental abnormalities. 6
19499579 2009
16
Central nervous system involvement in severe congenital neutropenia: neurological and neuropsychological abnormalities associated with specific HAX1 mutations. 57
18513342 2008
17
Severe developmental delay and epilepsy in a Japanese patient with severe congenital neutropenia due to HAX1 deficiency. 6
18055975 2007
18
Association of HAX1 deficiency with neurological disorder. 6
18330843 2007
19
Severe congenital neutropenia: inheritance and pathophysiology. 57
17133096 2007
20
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
21
Infantile genetic agranulocytosis, morbus Kostmann: presentation of six cases from the original "Kostmann family" and a review. 6
11519978 2001
22
Immunodeficiency diseases caused by defects in phagocytes. 57
11106721 2000
23
Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia. 57
11001877 2000
24
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
25
Prenatal diagnosis of congenital dysgranulopoietic neutropenia. 57
7803247 1994
26
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
27
Congenital dysgranulopoietic neutropenia in two siblings: clinical, ultrastructural, and in vitro bone marrow culture studies. 57
2701701 1989
28
Bone-marrow transplantation for immunodeficiencies and osteopetrosis: European survey, 1968-1985. 57
2877234 1986
29
Spatial distribution of the gene for infantile genetic agranulocytosis. 57
6510932 1984
30
Granulopoiesis in infantile genetic agranulocytosis. In vitro cloning of marrow cells in agar culture. 57
1082629 1976
31
Reliability of breeding values for feed intake and feed efficiency traits in dairy cattle: When dry matter intake recordings are sparse under different scenarios. 61
31155258 2019
32
Kostmann's Disease and HCLS1-Associated Protein X-1 (HAX1). 61
27943080 2017
33
Na+ current properties in islet α- and β-cells reflect cell-specific Scn3a and Scn9a expression. 61
25172946 2014
34
Malignant myeloid transformation in a child with severe congenital neutropenia (Kostmann's syndrome). 54
16898320 2006
35
Periodontal disease in patients from the original Kostmann family with severe congenital neutropenia. 54
16584360 2006
36
Differential STAT5 signaling by ligand-dependent and constitutively active cytokine receptors. 54
15677477 2005
37
Suppression of a mitotic mutant by tRNA-Ala anticodon mutations that produce a dominant defect in late mitosis. 61
15126629 2004
38
Early expression of sodium channel transcripts and sodium current by cajal-retzius cells in the preplate of the embryonic mouse neocortex. 61
14973256 2004
39
Malignant myeloid transformation in congenital forms of neutropenia. 54
12489493 2002
40
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. 54
11675333 2001
41
Severe osteopenia in a young boy with Kostmann's congenital neutropenia treated with granulocyte colony-stimulating factor: suggested therapeutic approach. 54
11533372 2001
42
Trisomy 21 and isodicentric chromosome 21 in Kostmann syndrome following treatment with G-CSF. 54
11343785 2001
43
Management of Kostmann syndrome in the G-CSF era. 54
10886193 2000
44
Failure of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in a patient with Kostmann syndrome. 54
10770686 1999
45
Hematopoietic growth factors for the treatment of severe chronic neutropenia. 54
7787781 1995
46
Transformation of congenital neutropenia into monosomy 7 and acute nonlymphoblastic leukemia in a child treated with granulocyte colony-stimulating factor. 54
7531241 1995
47
Use of recombinant inbred strains for studying genetic determinants of responses to alcohol. 61
8974318 1994
48
[Clinical applications of cytokines in pediatrics]. 54
8152201 1994
49
Kostmann's syndrome with chronic pneumonia and lymphocytosis: effect of recombinant human G-CSF. 54
7514821 1994
50
Measurement of serum granulocyte colony-stimulating factor in a patient with congenital agranulocytosis (Kostmann's syndrome). 54
1713405 1991

Variations for Neutropenia, Severe Congenital, 3, Autosomal Recessive

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

6 (show top 50) (show all 128)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 HAX1 NM_006118.3(HAX1):c.568C>T (p.Gln190Ter) SNV Pathogenic 4650 rs74315322 GRCh37: 1:154247641-154247641
GRCh38: 1:154275165-154275165
2 HAX1 NM_006118.4(HAX1):c.130_131insA (p.Trp44Ter) Insertion Pathogenic 4651 rs1572018284 GRCh37: 1:154245888-154245889
GRCh38: 1:154273412-154273413
3 HAX1 HAX1, 1-BP INS, 431G Insertion Pathogenic 4652 GRCh37:
GRCh38:
4 HAX1 NM_006118.4(HAX1):c.173dup (p.Pro58_Glu59insTer) Duplication Pathogenic 4653 rs758657008 GRCh37: 1:154245925-154245926
GRCh38: 1:154273449-154273450
5 HAX1 HAX1, 59-BP DEL, NT376 Deletion Pathogenic 4655 GRCh37:
GRCh38:
6 HAX1 HAX1, 1-BP DEL, 91G Deletion Pathogenic 4657 GRCh37:
GRCh38:
7 CSF3R NM_000760.4(CSF3R):c.922C>T (p.Arg308Cys) SNV Pathogenic 161982 rs606231473 GRCh37: 1:36937914-36937914
GRCh38: 1:36472313-36472313
8 CSF3R NM_000760.4(CSF3R):c.948_963del (p.His317fs) Deletion Pathogenic 242629 rs606231475 GRCh37: 1:36937873-36937888
GRCh38: 1:36472272-36472287
9 JAGN1 NM_032492.4(JAGN1):c.3G>A (p.Met1Ile) SNV Pathogenic 156113 rs587777727 GRCh37: 3:9932409-9932409
GRCh38: 3:9890725-9890725
10 JAGN1 NM_032492.4(JAGN1):c.59G>A (p.Arg20Gln) SNV Pathogenic 190479 rs777966677 GRCh37: 3:9932465-9932465
GRCh38: 3:9890781-9890781
11 JAGN1 NM_032492.4(JAGN1):c.130C>T (p.His44Tyr) SNV Pathogenic 156114 rs587777728 GRCh37: 3:9934639-9934639
GRCh38: 3:9892955-9892955
12 JAGN1 NM_032492.4(JAGN1):c.40G>A (p.Gly14Ser) SNV Pathogenic 190480 rs786205704 GRCh37: 3:9932446-9932446
GRCh38: 3:9890762-9890762
13 JAGN1 NM_032492.4(JAGN1):c.297C>G (p.Tyr99Ter) SNV Pathogenic 190481 rs786205705 GRCh37: 3:9934806-9934806
GRCh38: 3:9893122-9893122
14 JAGN1 NM_032492.4(JAGN1):c.485A>G (p.Gln162Arg) SNV Pathogenic 156116 rs587777730 GRCh37: 3:9934994-9934994
GRCh38: 3:9893310-9893310
15 JAGN1 NM_032492.4(JAGN1):c.63G>T (p.Glu21Asp) SNV Pathogenic 156115 rs587777729 GRCh37: 3:9932469-9932469
GRCh38: 3:9890785-9890785
16 JAGN1 NM_032492.4(JAGN1):c.35_43del (p.Thr12_Gly14del) Deletion Pathogenic 156117 rs587777731 GRCh37: 3:9932436-9932444
GRCh38: 3:9890752-9890760
17 HAX1 NM_006118.3(HAX1):c.383C>G (p.Ser128Ter) SNV Pathogenic 561028 rs1398108109 GRCh37: 1:154246316-154246316
GRCh38: 1:154273840-154273840
18 HAX1 NM_006118.4(HAX1):c.407del (p.His136fs) Deletion Pathogenic 659562 rs748595772 GRCh37: 1:154246340-154246340
GRCh38: 1:154273864-154273864
19 HAX1 NM_006118.4(HAX1):c.337G>T (p.Glu113Ter) SNV Pathogenic 864562 GRCh37: 1:154246270-154246270
GRCh38: 1:154273794-154273794
20 FCHO1 NM_001161358.2(FCHO1):c.2036G>C (p.Arg679Pro) SNV Pathogenic 805883 GRCh37: 19:17893924-17893924
GRCh38: 19:17783115-17783115
21 FCHO1 NM_001161358.2(FCHO1):c.100G>C (p.Ala34Pro) SNV Pathogenic 805884 GRCh37: 19:17873643-17873643
GRCh38: 19:17762834-17762834
22 FCHO1 NM_001161358.2(FCHO1):c.2023dup (p.Val675fs) Duplication Pathogenic 805885 GRCh37: 19:17893910-17893911
GRCh38: 19:17783101-17783102
23 FCHO1 NM_001161358.2(FCHO1):c.489+1G>A SNV Pathogenic 805886 GRCh37: 19:17881387-17881387
GRCh38: 19:17770578-17770578
24 FCHO1 NM_001161358.2(FCHO1):c.195-2A>C SNV Pathogenic 805887 GRCh37: 19:17877476-17877476
GRCh38: 19:17766667-17766667
25 FCHO1 NM_001161358.2(FCHO1):c.1948C>T (p.Arg650Ter) SNV Pathogenic 805888 GRCh37: 19:17893836-17893836
GRCh38: 19:17783027-17783027
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 HAX1 NM_006118.4(HAX1):c.173_175delinsTT (p.Pro58fs) Indel Pathogenic 964701 GRCh37: 1:154245931-154245933
GRCh38: 1:154273455-154273457
29 HAX1 NM_006118.3(HAX1):c.256C>T (p.Arg86Ter) SNV Pathogenic 4654 rs121908165 GRCh37: 1:154246014-154246014
GRCh38: 1:154273538-154273538
30 HAX1 NM_006118.4(HAX1):c.125dup (p.Ser43fs) Duplication Pathogenic 4656 rs745666437 GRCh37: 1:154245878-154245879
GRCh38: 1:154273402-154273403
31 HAX1 NM_006118.3(HAX1):c.430dup (p.Val144fs) Duplication Pathogenic 578906 rs770288337 GRCh37: 1:154246356-154246357
GRCh38: 1:154273880-154273881
32 HAX1 NM_006118.4(HAX1):c.91del Deletion Pathogenic 419887 rs764082747 GRCh37: 1:154245849-154245849
GRCh38: 1:154273373-154273373
33 HAX1 NM_006118.3(HAX1):c.317-2A>G SNV Pathogenic/Likely pathogenic 653855 rs371504152 GRCh37: 1:154246248-154246248
GRCh38: 1:154273772-154273772
34 HAX1 NM_006118.4(HAX1):c.663+1G>A SNV Likely pathogenic 944776 GRCh37: 1:154247737-154247737
GRCh38: 1:154275261-154275261
35 HAX1 NM_006118.4(HAX1):c.463dup (p.Gln155fs) Duplication Likely pathogenic 800902 rs1572018886 GRCh37: 1:154246390-154246391
GRCh38: 1:154273914-154273915
36 CSF3R NM_000760.4(CSF3R):c.1576+1G>A SNV Likely pathogenic 812884 rs1031224658 GRCh37: 1:36934756-36934756
GRCh38: 1:36469155-36469155
37 CSF3R NM_000760.4(CSF3R):c.340C>T (p.Gln114Ter) SNV Likely pathogenic 812885 rs756667927 GRCh37: 1:36940999-36940999
GRCh38: 1:36475398-36475398
38 HAX1 NC_000001.11:g.(?_154274930)_(154275721_?)del Deletion Likely pathogenic 832624 GRCh37: 1:154247406-154248197
GRCh38:
39 HAX1 NM_006118.4(HAX1):c.556+1G>C SNV Likely pathogenic 834967 GRCh37: 1:154247478-154247478
GRCh38: 1:154275002-154275002
40 HAX1 NM_006118.3(HAX1):c.593C>T (p.Pro198Leu) SNV Conflicting interpretations of pathogenicity 292707 rs146152769 GRCh37: 1:154247666-154247666
GRCh38: 1:154275190-154275190
41 GFI1 NM_005263.5(GFI1):c.925-40CT[17] Microsatellite Conflicting interpretations of pathogenicity 298182 rs35896485 GRCh37: 1:92944315-92944316
GRCh38: 1:92478758-92478759
42 HAX1 NM_006118.4(HAX1):c.505-4G>A SNV Conflicting interpretations of pathogenicity 792260 rs186219647 GRCh37: 1:154247422-154247422
GRCh38: 1:154274946-154274946
43 HAX1 NM_006118.4(HAX1):c.461C>T (p.Pro154Leu) SNV Uncertain significance 845002 GRCh37: 1:154246394-154246394
GRCh38: 1:154273918-154273918
44 HAX1 NM_006118.4(HAX1):c.15T>A (p.Asp5Glu) SNV Uncertain significance 863374 GRCh37: 1:154245214-154245214
GRCh38: 1:154272738-154272738
45 HAX1 NM_006118.3(HAX1):c.105_110dup (p.Glu39_Glu40dup) Duplication Uncertain significance 642986 rs755700193 GRCh37: 1:154245860-154245861
GRCh38: 1:154273384-154273385
46 HAX1 NM_006118.4(HAX1):c.191G>A (p.Gly64Asp) SNV Uncertain significance 949897 GRCh37: 1:154245949-154245949
GRCh38: 1:154273473-154273473
47 HAX1 NM_006118.4(HAX1):c.110A>C (p.Glu37Ala) SNV Uncertain significance 950107 GRCh37: 1:154245868-154245868
GRCh38: 1:154273392-154273392
48 HAX1 NM_006118.4(HAX1):c.168C>A (p.His56Gln) SNV Uncertain significance 960445 GRCh37: 1:154245926-154245926
GRCh38: 1:154273450-154273450
49 HAX1 NM_006118.4(HAX1):c.172C>T (p.Pro58Ser) SNV Uncertain significance 960900 GRCh37: 1:154245930-154245930
GRCh38: 1:154273454-154273454
50 HAX1 NM_006118.4(HAX1):c.820C>T (p.Arg274Cys) SNV Uncertain significance 961625 GRCh37: 1:154248157-154248157
GRCh38: 1:154275681-154275681

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

72
# 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

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 9.43 HAX1 CSF3
2 defense response to fungus GO:0050832 9.4 JAGN1 ELANE
3 positive regulation of actin cytoskeleton reorganization GO:2000251 9.37 HAX1 CSF3
4 positive regulation of peptidyl-tyrosine phosphorylation GO:0050731 9.33 IL3 HAX1 CSF3
5 regulation of myeloid cell differentiation GO:0045637 9.32 CSF3R CSF2
6 cotranslational protein targeting to membrane GO:0006613 9.26 SRPRA SRP19
7 cytokine-mediated signaling pathway GO:0019221 9.26 IL3 CSF3R CSF3 CSF2
8 neutrophil differentiation GO:0030223 8.62 JAGN1 CSF2

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 9.16 ELANE CSF3R
2 cytokine activity GO:0005125 9.13 IL3 CSF3 CSF2
3 growth factor activity GO:0008083 8.8 IL3 CSF3 CSF2

Sources for Neutropenia, Severe Congenital, 3, Autosomal Recessive

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
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56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
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68 SNOMED-CT via HPO
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71 UMLS via Orphanet
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