MCID: NTR011
MIFTS: 36

Neutrophil-Specific Granule Deficiency

Categories: Blood diseases, Rare diseases

Aliases & Classifications for Neutrophil-Specific Granule Deficiency

MalaCards integrated aliases for Neutrophil-Specific Granule Deficiency:

Name: Neutrophil-Specific Granule Deficiency 20 58
Recurrent Infection Due to Specific Granule Deficiency 20 58
Specific Granule Deficiency 20 71
Neutrophil Secondary Granule Deficiency 71
Neutrophil Specific Granule Deficiency 36
Lactoferrin-Deficient Neutrophils 20
Neutrophil Lactoferrin Deficiency 20

Characteristics:

Orphanet epidemiological data:

58
recurrent infection due to specific granule deficiency
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

Classifications:

Orphanet: 58  
Rare immunological diseases


External Ids:

KEGG 36 H02024
ICD10 via Orphanet 33 D71
Orphanet 58 ORPHA169142
UMLS 71 C0398593 C0398745

Summaries for Neutrophil-Specific Granule Deficiency

KEGG : 36 Neutrophil-specific granule deficiency (SGD) is a rare disorder characterized by recurrent pyogenic infections, defective neutrophil chemotaxis and bactericidal activity, and lack of neutrophil secondary granule proteins. It has been linked to a defect in the transcription factor CCAAT/enhancer binding protein (CEBP) epsilon. Recently, loss-of-function mutations in SMARCD2 were identified from SGD patients. SMARCD2 is chromatin-remodeling factor, that interacts with CEBP epsilon.

MalaCards based summary : Neutrophil-Specific Granule Deficiency, also known as recurrent infection due to specific granule deficiency, is related to specific granule deficiency 1 and specific granule deficiency 2. An important gene associated with Neutrophil-Specific Granule Deficiency is CEBPE (CCAAT Enhancer Binding Protein Epsilon), and among its related pathways/superpathways are Endometrial cancer and BRCA1 Pathway. Affiliated tissues include neutrophil, myeloid and monocytes, and related phenotypes are Decreased TP53 mRNA expression and embryo

Wikipedia : 74 Neutrophil-specific granule deficiency ( previously known as lactoferrin deficiency) is a rare... more...

Related Diseases for Neutrophil-Specific Granule Deficiency

Diseases related to Neutrophil-Specific Granule Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 15)
# Related Disease Score Top Affiliating Genes
1 specific granule deficiency 1 30.9 SMARCD2 CEBPE
2 specific granule deficiency 2 11.8
3 bacterial infectious disease 10.4
4 neutropenia 10.0
5 diarrhea 10.0
6 impetigo 10.0
7 myeloid leukemia 10.0
8 chediak-higashi syndrome 9.9
9 lymphoproliferative syndrome 9.9
10 cellulitis 9.9
11 acute erythroid leukemia 9.9 SPI1 GATA1
12 immunodeficiency 21 9.8 SPI1 GATA1
13 severe congenital neutropenia 9.7 SMARCD2 CEBPE
14 acute promyelocytic leukemia 9.4 SPI1 HDAC1 GATA1
15 leukemia, acute myeloid 9.3 SPI1 HDAC1 GATA1 CEBPE

Graphical network of the top 20 diseases related to Neutrophil-Specific Granule Deficiency:



Diseases related to Neutrophil-Specific Granule Deficiency

Symptoms & Phenotypes for Neutrophil-Specific Granule Deficiency

GenomeRNAi Phenotypes related to Neutrophil-Specific Granule Deficiency according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased TP53 mRNA expression GR00389-S-6 8.62 HDAC1 SMARCD2

MGI Mouse Phenotypes related to Neutrophil-Specific Granule Deficiency:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 embryo MP:0005380 9.65 GATA1 HDAC1 SCARB1 SMARCD2 SPI1
2 hematopoietic system MP:0005397 9.63 CEBPE GATA1 HDAC1 SCARB1 SMARCD2 SPI1
3 liver/biliary system MP:0005370 9.26 GATA1 HDAC1 SCARB1 SPI1
4 mortality/aging MP:0010768 9.1 CEBPE GATA1 HDAC1 SCARB1 SMARCD2 SPI1

Drugs & Therapeutics for Neutrophil-Specific Granule Deficiency

Search Clinical Trials , NIH Clinical Center for Neutrophil-Specific Granule Deficiency

Genetic Tests for Neutrophil-Specific Granule Deficiency

Anatomical Context for Neutrophil-Specific Granule Deficiency

MalaCards organs/tissues related to Neutrophil-Specific Granule Deficiency:

40
Neutrophil, Myeloid, Monocytes

Publications for Neutrophil-Specific Granule Deficiency

Articles related to Neutrophil-Specific Granule Deficiency:

(show top 50) (show all 62)
# Title Authors PMID Year
1
Neutrophil-specific granule deficiency: homozygous recessive inheritance of a frameshift mutation in the gene encoding transcription factor CCAAT/enhancer binding protein--epsilon. 61 6
11313242 2001
2
Neutrophil-specific granule deficiency results from a novel mutation with loss of function of the transcription factor CCAAT/enhancer binding protein epsilon. 61 6
10359588 1999
3
Defective neutrophil development and specific granule deficiency caused by a homozygous splice-site mutation in SMARCD2. 61
33279574 2020
4
Neutrophil Defects and Diagnosis Disorders of Neutrophil Function: An Overview. 61
31728980 2020
5
Brain Abscess as Severe Presentation of Specific Granule Deficiency. 61
32391290 2020
6
Gain-of-function CEBPE mutation causes noncanonical autoinflammatory inflammasomopathy. 61
31201888 2019
7
C/EBPε ΔRS derived from a neutrophil-specific granule deficiency patient interacts with HDAC1 and its dysfunction is restored by trichostatin A. 61
31256937 2019
8
Identification of a novel enhancer of CEBPE essential for granulocytic differentiation. 61
30952671 2019
9
CEBPE-Mutant Specific Granule Deficiency Correlates With Aberrant Granule Organization and Substantial Proteome Alterations in Neutrophils. 61
29651288 2018
10
SMARCD2 subunit of SWI/SNF chromatin-remodeling complexes mediates granulopoiesis through a CEBPɛ dependent mechanism. 61
28369034 2017
11
Chromatin-remodeling factor SMARCD2 regulates transcriptional networks controlling differentiation of neutrophil granulocytes. 61
28369036 2017
12
c-Myb acts in parallel and cooperatively with Cebp1 to regulate neutrophil maturation in zebrafish. 61
27268086 2016
13
Role of the Leucine Zipper Domain of CCAAT/ Enhancer Binding Protein-Epsilon (C/EBPε) in Neutrophil-Specific Granule Deficiency. 61
28322138 2016
14
A Novel In-Frame Deletion in the Leucine Zipper Domain of C/EBPε Leads to Neutrophil-Specific Granule Deficiency. 61
26019275 2015
15
The antimicrobial propeptide hCAP-18 plasma levels in neutropenia of various aetiologies: a prospective study. 61
26119962 2015
16
Clinical course in a patient with neutrophil-specific granule deficiency and rapid detection of neutrophil granules as a screening test. 61
25081842 2014
17
Congenital candidiasis as a subject of research in medicine and human ecology. 61
25281815 2014
18
Human α-defensin expression is not dependent on CCAAT/enhancer binding protein-ε in a murine model. 61
24658030 2014
19
Disorders of neutrophil function: an overview. 61
24504971 2014
20
Impaired neutrophil function in 24p3 null mice contributes to enhanced susceptibility to bacterial infections. 61
23543755 2013
21
Neutrophil-specific granule deficiency. 61
23294125 2013
22
C/EBPε mediates nicotinamide-enhanced clearance of Staphylococcus aureus in mice. 61
22922257 2012
23
C/EBPepsilon directs granulocytic-vs-monocytic lineage determination and confers chemotactic function via Hlx. 61
19925846 2010
24
Stimulus-dependent impairment of the neutrophil oxidative burst response in lactoferrin-deficient mice. 61
18321995 2008
25
Derangement of transcription factor profiles during in vitro differentiation of HL60 and NB4 cells. 61
16942795 2007
26
Expression of bactericidal/permeability-increasing protein requires C/EBP epsilon. 61
17483073 2007
27
Growth factor independence-1 (Gfi-1) plays a role in mediating specific granule deficiency (SGD) in a patient lacking a gene-inactivating mutation in the C/EBPepsilon gene. 61
17244686 2007
28
Disorders of neutrophil function: an overview. 61
18453130 2007
29
Haptoglobin is synthesized during granulocyte differentiation, stored in specific granules, and released by neutrophils in response to activation. 61
16543473 2006
30
All-trans retinoic acid-induced expression of bactericidal/permeability-increasing protein (BPI) in human myeloid cells correlates to binding of C/EBPbeta and C/EBPepsilon to the BPI promoter. 61
16684888 2006
31
Intractable diarrhoea of infancy caused by neutrophil specific granule deficiency and cured by stem cell transplantation. 61
16407388 2006
32
Aberrant expression of neutrophil and macrophage-related genes in a murine model for human neutrophil-specific granule deficiency. 61
16204633 2005
33
Highly glycosylated alpha1-acid glycoprotein is synthesized in myelocytes, stored in secondary granules, and released by activated neutrophils. 61
15941779 2005
34
Phenotypic and functional alterations of peripheral blood monocytes in neutrophil-specific granule deficiency. 61
14576362 2004
35
White blood cell defects: molecular discoveries and clinical management. 61
12165204 2002
36
Neutrophil specific granule deficiency and mutations in the gene encoding transcription factor C/EBP(epsilon). 61
11753076 2002
37
Deficiency of the specific granule proteins, R-binder/transcobalamin I and lactoferrin, in plasma and saliva: a new disorder. 61
11298376 2001
38
The role of C/EBP(epsilon) in the terminal stages of granulocyte differentiation. 61
11239167 2001
39
Inherited Neutrophil Disorders: Molecular Basis and New Therapies. 61
11701548 2000
40
CCAAT/enhancer binding protein epsilon is critical for effective neutrophil-mediated response to inflammatory challenge. 61
10216107 1999
41
CCAAT displacement protein (CDP/cut) recognizes a silencer element within the lactoferrin gene promoter. 61
9326246 1997
42
Heterogeneity of peroxidase positive granules in normal and pathologic human neutrophils. 61
9293701 1997
43
A marked decrease in defensin mRNA in the only case of congenital neutrophil-specific granule deficiency reported in Japan. 61
8018907 1994
44
Neutrophil-specific granule deficiency includes eosinophils. 61
8324226 1993
45
Ultrastructure of neutrophilic phagosome of autologous platelet in vivo in specific granule deficiency. 61
8342544 1993
46
Correlation of messenger RNA levels with protein defects in specific granule deficiency. 61
1327289 1992
47
Unique human neutrophil populations are defined by monoclonal antibody ED12F8C10. 61
1829650 1991
48
Glandular secretion of lactoferrin in a patient with neutrophil lactoferrin deficiency. 61
2600325 1989
49
The molecular biology of selected phagocyte defects. 61
2673450 1989
50
Laminin promotes the oxidative burst in human neutrophils via increased chemoattractant receptor expression. 61
2537868 1989

Variations for Neutrophil-Specific Granule Deficiency

ClinVar genetic disease variations for Neutrophil-Specific Granule Deficiency:

6 (show all 20)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CEBPE CEBPE, 5-BP DEL, NT224 Deletion Pathogenic 8854
2 CEBPE CEBPE, 1-BP INS, 1113A Insertion Pathogenic 8855
3 SMARCD2 NM_001098426.2(SMARCD2):c.414_438dup (p.Gln147delinsGluAspGlyArgTer) Duplication Pathogenic 369730 rs1555580263 17:61914560-61914561 17:63837200-63837201
4 SMARCD2 NM_001098426.2(SMARCD2):c.401+2T>C SNV Pathogenic 369731 rs1057518733 17:61914799-61914799 17:63837439-63837439
5 SMARCD2 NM_001098426.2(SMARCD2):c.1181+1G>A SNV Pathogenic 369729 rs1057518731 17:61911268-61911268 17:63833908-63833908
6 CEBPE NM_001805.3(CEBPE):c.391C>T (p.Arg131Ter) SNV Pathogenic 530667 rs760325316 14:23587910-23587910 14:23118701-23118701
7 CEBPE NM_001805.4(CEBPE):c.653T>C (p.Val218Ala) SNV Likely pathogenic 982783 14:23586889-23586889 14:23117680-23117680
8 CEBPE NM_001805.3(CEBPE):c.496C>G (p.Leu166Val) SNV Uncertain significance 461467 rs1273577069 14:23587805-23587805 14:23118596-23118596
9 CEBPE NM_001805.3(CEBPE):c.487G>A (p.Gly163Ser) SNV Uncertain significance 530666 rs762842144 14:23587814-23587814 14:23118605-23118605
10 CEBPE NM_001805.3(CEBPE):c.662G>A (p.Ser221Asn) SNV Uncertain significance 565423 rs1566773059 14:23586880-23586880 14:23117671-23117671
11 CEBPE NM_001805.3(CEBPE):c.349G>A (p.Ala117Thr) SNV Uncertain significance 582470 rs1566773537 14:23587952-23587952 14:23118743-23118743
12 CEBPE NM_001805.3(CEBPE):c.66G>T (p.Gly22=) SNV Uncertain significance 640081 rs776941005 14:23588235-23588235 14:23119026-23119026
13 CEBPE NM_001805.3(CEBPE):c.64G>A (p.Gly22Arg) SNV Uncertain significance 640442 rs766209986 14:23588237-23588237 14:23119028-23119028
14 CEBPE NM_001805.3(CEBPE):c.404G>A (p.Arg135Gln) SNV Uncertain significance 650956 rs374190826 14:23587897-23587897 14:23118688-23118688
15 CEBPE NM_001805.3(CEBPE):c.611G>C (p.Ser204Thr) SNV Uncertain significance 658176 rs760759078 14:23586931-23586931 14:23117722-23117722
16 CEBPE NM_001805.3(CEBPE):c.499C>T (p.Arg167Cys) SNV Uncertain significance 659768 rs559886851 14:23587802-23587802 14:23118593-23118593
17 CEBPE NM_001805.3(CEBPE):c.223C>A (p.Pro75Thr) SNV Uncertain significance 663169 rs148458866 14:23588078-23588078 14:23118869-23118869
18 CEBPE NM_001805.3(CEBPE):c.551T>C (p.Leu184Pro) SNV Uncertain significance 664942 rs749540911 14:23586991-23586991 14:23117782-23117782
19 CEBPE NM_001805.3(CEBPE):c.357G>T (p.Ala119=) SNV Likely benign 530668 rs202220573 14:23587944-23587944 14:23118735-23118735
20 CEBPE NM_001805.3(CEBPE):c.303G>A (p.Ala101=) SNV Likely benign 461466 rs149752323 14:23587998-23587998 14:23118789-23118789

Expression for Neutrophil-Specific Granule Deficiency

Search GEO for disease gene expression data for Neutrophil-Specific Granule Deficiency.

Pathways for Neutrophil-Specific Granule Deficiency

Pathways related to Neutrophil-Specific Granule Deficiency according to GeneCards Suite gene sharing:

(show all 11)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.42 SPI1 HDAC1 CEBPE
2
Show member pathways
11.4 SMARCD2 HDAC1
3 11.37 SPI1 HDAC1
4 11.32 SPI1 GATA1
5
Show member pathways
11.25 SMARCD2 HDAC1
6 11.19 HDAC1 GATA1
7 11.11 SPI1 HDAC1
8 11.08 SPI1 HDAC1 CEBPE
9 11 SPI1 HDAC1
10 10.84 HDAC1 GATA1
11 10.64 SPI1 GATA1

GO Terms for Neutrophil-Specific Granule Deficiency

Cellular components related to Neutrophil-Specific Granule Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transcriptional repressor complex GO:0017053 9.16 HDAC1 GATA1
2 transcription factor complex GO:0005667 9.13 SPI1 HDAC1 GATA1
3 chromatin GO:0000785 9.02 SPI1 SMARCD2 HDAC1 GATA1 CEBPE

Biological processes related to Neutrophil-Specific Granule Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription, DNA-templated GO:0045893 9.65 SPI1 HDAC1 GATA1
2 regulation of transcription by RNA polymerase II GO:0006357 9.55 SPI1 SMARCD2 HDAC1 GATA1 CEBPE
3 chromatin remodeling GO:0006338 9.46 SMARCD2 HDAC1
4 regulation of megakaryocyte differentiation GO:0045652 9.43 HDAC1 GATA1
5 erythrocyte differentiation GO:0030218 9.4 SPI1 GATA1
6 ATP-dependent chromatin remodeling GO:0043044 9.37 SMARCD2 HDAC1
7 myeloid cell differentiation GO:0030099 9.32 GATA1 CEBPE
8 macrophage differentiation GO:0030225 9.26 SPI1 CEBPE
9 positive regulation of transcription by RNA polymerase II GO:0045944 9.02 SPI1 SMARCD2 HDAC1 GATA1 CEBPE
10 granulocyte differentiation GO:0030851 8.96 SPI1 CEBPE

Molecular functions related to Neutrophil-Specific Granule Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.56 SPI1 HDAC1 GATA1 CEBPE
2 DNA-binding transcription factor activity GO:0003700 9.54 SPI1 GATA1 CEBPE
3 p53 binding GO:0002039 9.32 HDAC1 GATA1
4 DNA-binding transcription activator activity, RNA polymerase II-specific GO:0001228 9.26 SPI1 SMARCD2 GATA1 CEBPE
5 nucleosomal DNA binding GO:0031492 9.16 SMARCD2 HDAC1
6 RNA polymerase II transcription factor binding GO:0001085 8.8 SPI1 HDAC1 GATA1

Sources for Neutrophil-Specific Granule Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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