SCN1
MCID: NTR047
MIFTS: 34

Neutropenia, Severe Congenital, 1, Autosomal Dominant (SCN1)

Categories: Blood diseases, Bone diseases, Cancer diseases, Genetic diseases, Immune diseases, Rare diseases

Aliases & Classifications for Neutropenia, Severe Congenital, 1, Autosomal Dominant

MalaCards integrated aliases for Neutropenia, Severe Congenital, 1, Autosomal Dominant:

Name: Neutropenia, Severe Congenital, 1, Autosomal Dominant 57
Neutropenia, Severe Congenital 1, Autosomal Dominant 57 74 29 13 6
Scn1 57 74
Neutropenia, Severe Congenital, Autosomal Dominant 1 72

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
onset in infancy


HPO:

32
neutropenia, severe congenital, 1, autosomal dominant:
Inheritance autosomal dominant inheritance
Onset and clinical course infantile onset


Classifications:



External Ids:

MeSH 44 D009503
MedGen 42 C1859966
UMLS 72 C1859966

Summaries for Neutropenia, Severe Congenital, 1, Autosomal Dominant

OMIM : 57 Severe congenital neutropenia is a heterogeneous disorder of hematopoiesis characterized by a 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 (Skokowa et al., 2007). About 60% of affected individuals of European and Middle Eastern ancestry have dominant ELANE mutations, resulting in a form of severe congenital neutropenia, which is designated here as SCN1. (202700)

MalaCards based summary : Neutropenia, Severe Congenital, 1, Autosomal Dominant, also known as neutropenia, severe congenital 1, autosomal dominant, is related to neutropenia, severe congenital, 3, autosomal recessive and neutropenia, severe congenital, 5, autosomal recessive. An important gene associated with Neutropenia, Severe Congenital, 1, Autosomal Dominant is ELANE (Elastase, Neutrophil Expressed). Affiliated tissues include neutrophil, monocytes and bone, and related phenotypes are anemia and thrombocytosis

UniProtKB/Swiss-Prot : 74 Neutropenia, severe congenital 1, autosomal dominant: 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.

Related Diseases for Neutropenia, Severe Congenital, 1, Autosomal Dominant

Graphical network of the top 20 diseases related to Neutropenia, Severe Congenital, 1, Autosomal Dominant:



Diseases related to Neutropenia, Severe Congenital, 1, Autosomal Dominant

Symptoms & Phenotypes for Neutropenia, Severe Congenital, 1, Autosomal Dominant

Human phenotypes related to Neutropenia, Severe Congenital, 1, Autosomal Dominant:

32 (show all 10)
# Description HPO Frequency HPO Source Accession
1 anemia 32 HP:0001903
2 thrombocytosis 32 HP:0001894
3 neutropenia 32 HP:0001875
4 recurrent bacterial infections 32 HP:0002718
5 eosinophilia 32 HP:0001880
6 increased antibody level in blood 32 HP:0010702
7 monocytosis 32 HP:0012311
8 acute monocytic leukemia 32 HP:0004845
9 growth abnormality 32 HP:0001507
10 congenital agranulocytosis 32 HP:0005541

Symptoms via clinical synopsis from OMIM:

57
Hematology:
thrombocytosis
eosinophilia
increased absolute neutrophil count (anc) within 0.0-0.2 x 10(9)/l
anemia, mild
increase in blood monocytes (2-3 times normal)
more
Immunology:
recurrent severe infections

Clinical features from OMIM:

202700

Drugs & Therapeutics for Neutropenia, Severe Congenital, 1, Autosomal Dominant

Search Clinical Trials , NIH Clinical Center for Neutropenia, Severe Congenital, 1, Autosomal Dominant

Genetic Tests for Neutropenia, Severe Congenital, 1, Autosomal Dominant

Genetic tests related to Neutropenia, Severe Congenital, 1, Autosomal Dominant:

# Genetic test Affiliating Genes
1 Neutropenia, Severe Congenital 1, Autosomal Dominant 29 ELANE

Anatomical Context for Neutropenia, Severe Congenital, 1, Autosomal Dominant

MalaCards organs/tissues related to Neutropenia, Severe Congenital, 1, Autosomal Dominant:

41
Neutrophil, Monocytes, Bone, Bone Marrow, Myeloid, Lung

Publications for Neutropenia, Severe Congenital, 1, Autosomal Dominant

Articles related to Neutropenia, Severe Congenital, 1, Autosomal Dominant:

(show top 50) (show all 53)
# Title Authors PMID Year
1
Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia. 8 71
18028488 2008
2
Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia. 8 71
11001877 2000
3
Role of CSF3R mutations in the pathomechanism of congenital neutropenia and secondary acute myeloid leukemia. 8
27270496 2016
4
Homozygous HAX1 mutations in severe congenital neutropenia patients with sporadic disease: a novel mutation in two unrelated British kindreds. 8
19036076 2009
5
Neurodevelopmental abnormalities associated with severe congenital neutropenia due to the R86X mutation in the HAX1 gene. 8
18611981 2008
6
Double de novo mutations of ELA2 in cyclic and severe congenital neutropenia. 71
17436313 2007
7
Severe congenital neutropenia: inheritance and pathophysiology. 8
17133096 2007
8
LEF-1 is crucial for neutrophil granulocytopoiesis and its expression is severely reduced in congenital neutropenia. 8
17063141 2006
9
Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register. 71
14962902 2004
10
ELANE-Related Neutropenia 71
20301705 2002
11
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. 71
11675333 2001
12
Immunodeficiency diseases caused by defects in phagocytes. 8
11106721 2000
13
Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital neutropenia receiving G-CSF therapy. 8
10887102 2000
14
Increased granulocyte colony-stimulating factor responsiveness but normal resting granulopoiesis in mice carrying a targeted granulocyte colony-stimulating factor receptor mutation derived from a patient with severe congenital neutropenia. 8
9691084 1998
15
Perturbed granulopoiesis in mice with a targeted mutation in the granulocyte colony-stimulating factor receptor gene associated with severe chronic neutropenia. 8
9639496 1998
16
High incidence of significant bone loss in patients with severe congenital neutropenia (Kostmann's syndrome). 8
9386665 1997
17
Clinical relevance of point mutations in the cytoplasmic domain of the granulocyte colony-stimulating factor receptor gene in patients with severe congenital neutropenia. 8
9116280 1997
18
Pathophysiology and treatment of severe chronic neutropenia. 8
8624368 1996
19
The protein tyrosine kinase JAK2 is activated in neutrophils from patients with severe congenital neutropenia. 8
8541539 1995
20
Mutations in the gene for the granulocyte colony-stimulating-factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia. 8
7542747 1995
21
Long-term safety of treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) in patients with severe congenital neutropenias. 8
7529539 1994
22
Identification of a nonsense mutation in the granulocyte-colony-stimulating factor receptor in severe congenital neutropenia. 8
7514305 1994
23
A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia. 8
8490166 1993
24
Effects of recombinant human granulocyte colony-stimulating factor on neutropenia in patients with congenital agranulocytosis. 8
2471075 1989
25
Congenital agranulocytosis terminating in acute myelomonocytic leukemia. 8
284110 1979
26
Infantile genetic agranulocytosis and acute lymphocytic leukemia in two sibs. 8
275472 1978
27
Congenital neutropenia: in vitro growth of colonies mimicking the disease. 8
4514979 1973
28
In vitro induction of myeloid proliferation and maturation in infantile genetic agranulocytosis. 8
4326838 1971
29
Congenital agranulocytosis: prolonged survival and terminal acute leukemia. 8
4319697 1970
30
Familial neutropenia possibly caused by deficiency of a plasma factor. 8
13971340 1962
31
Lethal congenital neutropenia with eosinophilia occurring in two siblings. 8
13683481 1960
32
Infantile agranulocytosis of probably congenital origin. 8
13626582 1959
33
Reliability of breeding values for feed intake and feed efficiency traits in dairy cattle: When dry matter intake recordings are sparse under different scenarios. 38
31155258 2019
34
Functional characteristics of circulating granulocytes in severe congenital neutropenia caused by ELANE mutations. 38
31176364 2019
35
ß-Cyanoalanine Synthase Action in Root Hair Elongation is Exerted at Early Steps of the Root Hair Elongation Pathway and is Independent of Direct Cyanide Inactivation of NADPH Oxidase. 38
29490083 2018
36
Role of mitochondrial cyanide detoxification in Arabidopsis root hair development. 38
30380363 2018
37
Preclinical Animal Models for Dravet Syndrome: Seizure Phenotypes, Comorbidities and Drug Screening. 38
29915537 2018
38
Arabidopsis PROTEIN S-ACYL TRANSFERASE4 mediates root hair growth. 38
28107768 2017
39
Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome. 38
28073790 2017
40
Cardiac conduction defects and Brugada syndrome: A family with overlap syndrome carrying a nonsense SCN5A mutation. 38
28217227 2017
41
PLURIPETALA mediates ROP2 localization and stability in parallel to SCN1 but synergistically with TIP1 in root hairs. 38
27037800 2016
42
Contribution of Cardiac Sodium Channel β-Subunit Variants to Brugada Syndrome. 38
26179811 2015
43
Very early-onset lone atrial fibrillation patients have a high prevalence of rare variants in genes previously associated with atrial fibrillation. 38
24144883 2014
44
Genomic instability of gold nanoparticle treated human lung fibroblast cells. 38
21543115 2011
45
Loss-of-function mutation of the SCN3B-encoded sodium channel {beta}3 subunit associated with a case of idiopathic ventricular fibrillation. 38
20042427 2010
46
[Association study of the SCN1 gene polymorphism and effective dose of lamotrigine]. 38
20037572 2009
47
A RhoGDP dissociation inhibitor spatially regulates growth in root hair cells. 38
16355224 2005
48
Suppression of a mitotic mutant by tRNA-Ala anticodon mutations that produce a dominant defect in late mitosis. 38
15126629 2004
49
Periodic surfaces of simple and complex topology: comparison of scattering patterns. 38
11497583 2001
50
A sodium channel mutation causing epilepsy in man exhibits subtle defects in fast inactivation and activation in vitro. 38
11118488 2000

Variations for Neutropenia, Severe Congenital, 1, Autosomal Dominant

ClinVar genetic disease variations for Neutropenia, Severe Congenital, 1, Autosomal Dominant:

6 (show top 50) (show all 60)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 ELANE NM_001972.4(ELANE): c.452G> A (p.Cys151Tyr) single nucleotide variant Pathogenic rs57246956 19:855649-855649 19:855649-855649
2 ELANE NM_001972.4(ELANE): c.182C> T (p.Ala61Val) single nucleotide variant Pathogenic rs137854447 19:852990-852990 19:852990-852990
3 ELANE NM_001972.4(ELANE): c.214G> A (p.Val72Met) single nucleotide variant Pathogenic rs387906553 19:853022-853022 19:853022-853022
4 ELANE NM_001972.4(ELANE): c.211T> C (p.Cys71Arg) single nucleotide variant Pathogenic rs28931611 19:853019-853019 19:853019-853019
5 ELANE NM_001972.4(ELANE): c.640G> A (p.Gly214Arg) single nucleotide variant Pathogenic rs137854451 19:856000-856000 19:856000-856000
6 ELANE NM_001972.4(ELANE): c.561C> A (p.Cys187Ter) single nucleotide variant Pathogenic rs797045009 19:855758-855758 19:855758-855758
7 ELANE NM_001972.4(ELANE): c.597+1G> A single nucleotide variant Pathogenic rs1555710005 19:855795-855795 19:855795-855795
8 ELANE NM_001972.4(ELANE): c.597+5G> A single nucleotide variant Pathogenic/Likely pathogenic rs879253882 19:855799-855799 19:855799-855799
9 ELANE NM_001972.4(ELANE): c.377C> T (p.Ser126Leu) single nucleotide variant Pathogenic/Likely pathogenic rs137854450 19:855574-855574 19:855574-855574
10 ELANE NM_001972.4(ELANE): c.416C> T (p.Pro139Leu) single nucleotide variant Pathogenic/Likely pathogenic rs137854448 19:855613-855613 19:855613-855613
11 ELANE NM_001972.4(ELANE): c.428G> A (p.Arg143His) single nucleotide variant Conflicting interpretations of pathogenicity rs200993994 19:855625-855625 19:855625-855625
12 TCIRG1 NM_006019.4(TCIRG1): c.2206C> A (p.Arg736Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs587779413 11:67817691-67817691 11:68050224-68050224
13 ELANE NM_001972.4(ELANE): c.431G> A (p.Arg144His) single nucleotide variant Uncertain significance rs142441575 19:855628-855628 19:855628-855628
14 ELANE NM_001972.4(ELANE): c.490G> C (p.Gly164Arg) single nucleotide variant Uncertain significance rs112990855 19:855687-855687 19:855687-855687
15 ELANE NM_001972.4(ELANE): c.119C> T (p.Ala40Val) single nucleotide variant Uncertain significance rs1555709342 19:852927-852927 19:852927-852927
16 ELANE NM_001972.4(ELANE): c.38C> G (p.Ala13Gly) single nucleotide variant Uncertain significance rs756726256 19:852366-852366 19:852366-852366
17 ELANE NM_001972.4(ELANE): c.172A> C (p.Thr58Pro) single nucleotide variant Uncertain significance rs1555709360 19:852980-852980 19:852980-852980
18 ELANE NM_001972.4(ELANE): c.235G> C (p.Ala79Pro) single nucleotide variant Uncertain significance rs769123461 19:853272-853272 19:853272-853272
19 ELANE NM_001972.4(ELANE): c.378G> A (p.Ser126=) single nucleotide variant Uncertain significance rs202204133 19:855575-855575 19:855575-855575
20 ELANE NM_001972.4(ELANE): c.665G> A (p.Gly222Asp) single nucleotide variant Uncertain significance rs1555710104 19:856025-856025 19:856025-856025
21 ELANE NM_001972.4(ELANE): c.10G> A (p.Gly4Ser) single nucleotide variant Uncertain significance 19:852338-852338 19:852338-852338
22 ELANE NM_001972.4(ELANE): c.12_14CCG[3] (p.Arg6dup) short repeat Uncertain significance 19:852343-852345 19:852343-852345
23 ELANE NM_001972.4(ELANE): c.637C> T (p.His213Tyr) single nucleotide variant Uncertain significance 19:855997-855997 19:855997-855997
24 ELANE NM_001972.4(ELANE): c.364C> T (p.Gln122Ter) single nucleotide variant Uncertain significance 19:853401-853401 19:853401-853401
25 ELANE NM_001972.4(ELANE): c.419C> T (p.Ala140Val) single nucleotide variant Uncertain significance 19:855616-855616 19:855616-855616
26 ELANE NM_001972.4(ELANE): c.342G> T (p.Leu114Phe) single nucleotide variant Uncertain significance 19:853379-853379 19:853379-853379
27 ELANE NM_001972.4(ELANE): c.647C> T (p.Ala216Val) single nucleotide variant Uncertain significance 19:856007-856007 19:856007-856007
28 ELANE NM_001972.4(ELANE): c.748G> A (p.Glu250Lys) single nucleotide variant Uncertain significance 19:856108-856108 19:856108-856108
29 ELANE NM_001972.4(ELANE): c.14G> A (p.Arg5His) single nucleotide variant Uncertain significance 19:852342-852342 19:852342-852342
30 ELANE NM_001972.4(ELANE): c.39C> G (p.Ala13=) single nucleotide variant Uncertain significance 19:852367-852367 19:852367-852367
31 ELANE NM_001972.4(ELANE): c.64G> C (p.Gly22Arg) single nucleotide variant Uncertain significance 19:852392-852392 19:852392-852392
32 ELANE NM_001972.4(ELANE): c.70A> C (p.Thr24Pro) single nucleotide variant Uncertain significance 19:852878-852878 19:852878-852878
33 ELANE NM_001972.4(ELANE): c.256G> T (p.Ala86Ser) single nucleotide variant Uncertain significance 19:853293-853293 19:853293-853293
34 ELANE NM_001972.4(ELANE): c.292G> A (p.Val98Met) single nucleotide variant Uncertain significance 19:853329-853329 19:853329-853329
35 ELANE NM_001972.4(ELANE): c.298G> A (p.Ala100Thr) single nucleotide variant Uncertain significance 19:853335-853335 19:853335-853335
36 ELANE NM_001972.4(ELANE): c.347A> G (p.Asn116Ser) single nucleotide variant Uncertain significance 19:853384-853384 19:853384-853384
37 ELANE NM_001972.4(ELANE): c.353T> A (p.Ile118Asn) single nucleotide variant Uncertain significance 19:853390-853390 19:853390-853390
38 ELANE NM_001972.4(ELANE): c.380_382CCA[1] (p.Thr128del) short repeat Uncertain significance 19:855577-855579 19:855577-855579
39 ELANE NM_001972.4(ELANE): c.430C> T (p.Arg144Cys) single nucleotide variant Uncertain significance 19:855627-855627 19:855627-855627
40 ELANE NM_001972.4(ELANE): c.493A> G (p.Ile165Val) single nucleotide variant Uncertain significance 19:855690-855690 19:855690-855690
41 ELANE NM_001972.4(ELANE): c.567C> G (p.Leu189=) single nucleotide variant Uncertain significance 19:855764-855764 19:855764-855764
42 ELANE NM_001972.4(ELANE): c.589G> A (p.Val197Ile) single nucleotide variant Uncertain significance 19:855786-855786 19:855786-855786
43 ELANE NM_001972.4(ELANE): c.727G> T (p.Asp243Tyr) single nucleotide variant Uncertain significance 19:856087-856087 19:856087-856087
44 ELANE NC_000019.9: g.(?_855938)_(856184_?)dup duplication Uncertain significance 19:855938-856184 19:855938-856184
45 ELANE NM_001972.4(ELANE): c.67+1G> T single nucleotide variant Uncertain significance 19:852396-852396 19:852396-852396
46 ELANE NM_001972.4(ELANE): c.367-1G> C single nucleotide variant Uncertain significance 19:855563-855563 19:855563-855563
47 ELANE NM_001972.4(ELANE): c.784C> T (p.Pro262Ser) single nucleotide variant Likely benign rs138211132 19:856144-856144 19:856144-856144
48 ELANE NM_001972.4(ELANE): c.24G> C (p.Ala8=) single nucleotide variant Likely benign rs199901033 19:852352-852352 19:852352-852352
49 ELANE NM_001972.4(ELANE): c.174C> T (p.Thr58=) single nucleotide variant Likely benign rs199714513 19:852982-852982 19:852982-852982
50 ELANE NM_001972.4(ELANE): c.654C> T (p.Phe218=) single nucleotide variant Benign/Likely benign rs148492780 19:856014-856014 19:856014-856014

UniProtKB/Swiss-Prot genetic disease variations for Neutropenia, Severe Congenital, 1, Autosomal Dominant:

74 (show top 50) (show all 72)
# Symbol AA change Variation ID SNP ID
1 ELANE p.Cys55Tyr VAR_038609
2 ELANE p.Ala57Thr VAR_038610
3 ELANE p.Ile60Thr VAR_038611
4 ELANE p.Cys71Arg VAR_038612 rs28931611
5 ELANE p.Cys71Ser VAR_038613
6 ELANE p.Gly85Glu VAR_038614
7 ELANE p.Val98Leu VAR_038615 rs267606781
8 ELANE p.Val101Leu VAR_038616 rs137854449
9 ELANE p.Val101Met VAR_038617 rs137854449
10 ELANE p.Ser126Leu VAR_038619 rs137854450
11 ELANE p.Pro139Leu VAR_038620 rs137854448
12 ELANE p.Cys151Ser VAR_038621
13 ELANE p.Pro205Arg VAR_038623 rs155571007
14 ELANE p.Gly210Val VAR_038624
15 ELANE p.Gly214Arg VAR_038625 rs137854451
16 ELANE p.Ala25Val VAR_064512 rs139623008
17 ELANE p.Ala166Thr VAR_064513 rs201788817
18 ELANE p.Pro42Leu VAR_070696
19 ELANE p.Phe43Leu VAR_070697
20 ELANE p.Met44Arg VAR_070698
21 ELANE p.Val45Glu VAR_070699
22 ELANE p.Ser46Cys VAR_070701
23 ELANE p.Ser46Phe VAR_070702 rs878855320
24 ELANE p.Leu47Pro VAR_070703 rs878855319
25 ELANE p.Leu47Arg VAR_070704
26 ELANE p.Leu49Pro VAR_070705
27 ELANE p.His53Leu VAR_070706
28 ELANE p.His53Tyr VAR_070708 rs113169188
29 ELANE p.Cys55Ser VAR_070709
30 ELANE p.Gly56Arg VAR_070710
31 ELANE p.Ala57Ser VAR_070711
32 ELANE p.Ala57Val VAR_070712 rs105752011
33 ELANE p.Leu59Pro VAR_070713
34 ELANE p.Ala61Val VAR_070715 rs137854447
35 ELANE p.Ser67Trp VAR_070718
36 ELANE p.Cys71Phe VAR_070719 rs878855315
37 ELANE p.Cys71Tyr VAR_070720
38 ELANE p.Val72Gly VAR_070721
39 ELANE p.Val80Gly VAR_070722
40 ELANE p.Arg81Pro VAR_070723
41 ELANE p.Val82Met VAR_070724
42 ELANE p.Leu84Pro VAR_070725 rs106479310
43 ELANE p.Gly85Arg VAR_070726
44 ELANE p.Val98Met VAR_070728 rs267606781
45 ELANE p.Arg103Leu VAR_070729 rs745455816
46 ELANE p.Arg103Pro VAR_070730
47 ELANE p.Ile120Phe VAR_070733 rs113169152
48 ELANE p.Ile120Asn VAR_070734
49 ELANE p.Ile120Ser VAR_070735
50 ELANE p.Leu121Pro VAR_070736

Expression for Neutropenia, Severe Congenital, 1, Autosomal Dominant

Search GEO for disease gene expression data for Neutropenia, Severe Congenital, 1, Autosomal Dominant.

Pathways for Neutropenia, Severe Congenital, 1, Autosomal Dominant

GO Terms for Neutropenia, Severe Congenital, 1, Autosomal Dominant

Biological processes related to Neutropenia, Severe Congenital, 1, Autosomal Dominant according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 neutrophil degranulation GO:0043312 8.62 TCIRG1 ELANE

Sources for Neutropenia, Severe Congenital, 1, Autosomal Dominant

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