SCN1
MCID: NTR047
MIFTS: 25

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

Categories: Blood diseases, Bone 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 75 13
Scn1 57 75
Neutropenia, Severe Congenital, Autosomal Dominant 1 73

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
onset in infancy


HPO:

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


Classifications:



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). The drugs Anticonvulsants and Stiripentol have been mentioned in the context of this disorder. Affiliated tissues include neutrophil, bone and monocytes, and related phenotypes are anemia and thrombocytosis

UniProtKB/Swiss-Prot : 75 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

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

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

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 acute monocytic leukemia 32 HP:0004845
8 congenital agranulocytosis 32 HP:0005541
9 monocytosis 32 HP:0012311
10 growth abnormality 32 HP:0001507

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

Drugs for Neutropenia, Severe Congenital, 1, Autosomal Dominant (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Anticonvulsants Phase 2
2
Stiripentol Approved 49763-96-4

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-935 (OV935) as an Adjunctive Therapy in Pediatric Patients With Developmental and/or Epileptic Encephalopathies Recruiting NCT03650452 Phase 2 TAK-935;Placebo
2 Genetic Analysis Between Charlotte's Web Responders Versus Non- Responders in a Dravet Population Completed NCT02229032
3 Cardiac Arrhythmias in Dravet Syndrome Completed NCT02415686
4 An Evaluation of an SCCD on the Symptomatology of Painful DPN Recruiting NCT03331614 Not Applicable
5 Expanded Access Use of Stiripentol in Dravet Syndrome or Sodium Channel Mutation Epileptic Encephalopathies Available NCT02239276 Stiripentol
6 Cohorts and Collections: Clinical and Genetic Study of Parkinson's Disease and Epilepsies Terminated NCT00142363

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

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

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

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

41
Neutrophil, Bone, Monocytes, Bone Marrow

Publications for Neutropenia, Severe Congenital, 1, Autosomal Dominant

Variations for Neutropenia, Severe Congenital, 1, Autosomal Dominant

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

75 (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
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
45 ELANE p.Arg103Leu VAR_070729
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

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

6 (show top 50) (show all 76)
# Gene Variation Type Significance SNP ID Assembly Location
1 ELANE NM_001972.3(ELANE): c.182C> T (p.Ala61Val) single nucleotide variant Pathogenic rs137854447 GRCh37 Chromosome 19, 852990: 852990
2 ELANE NM_001972.3(ELANE): c.182C> T (p.Ala61Val) single nucleotide variant Pathogenic rs137854447 GRCh38 Chromosome 19, 852990: 852990
3 ELANE NM_001972.3(ELANE): c.416C> T (p.Pro139Leu) single nucleotide variant Pathogenic rs137854448 GRCh37 Chromosome 19, 855613: 855613
4 ELANE NM_001972.3(ELANE): c.416C> T (p.Pro139Leu) single nucleotide variant Pathogenic rs137854448 GRCh38 Chromosome 19, 855613: 855613
5 ELANE NM_001972.3(ELANE): c.214G> A (p.Val72Met) single nucleotide variant Pathogenic rs387906553 GRCh37 Chromosome 19, 853022: 853022
6 ELANE NM_001972.3(ELANE): c.214G> A (p.Val72Met) single nucleotide variant Pathogenic rs387906553 GRCh38 Chromosome 19, 853022: 853022
7 ELANE NM_001972.3(ELANE): c.377C> T (p.Ser126Leu) single nucleotide variant Pathogenic/Likely pathogenic rs137854450 GRCh37 Chromosome 19, 855574: 855574
8 ELANE NM_001972.3(ELANE): c.377C> T (p.Ser126Leu) single nucleotide variant Pathogenic/Likely pathogenic rs137854450 GRCh38 Chromosome 19, 855574: 855574
9 ELANE NM_001972.3(ELANE): c.211T> C (p.Cys71Arg) single nucleotide variant Pathogenic rs28931611 GRCh37 Chromosome 19, 853019: 853019
10 ELANE NM_001972.3(ELANE): c.211T> C (p.Cys71Arg) single nucleotide variant Pathogenic rs28931611 GRCh38 Chromosome 19, 853019: 853019
11 ELANE NM_001972.3(ELANE): c.292G> T (p.Val98Leu) single nucleotide variant no interpretation for the single variant rs267606781 GRCh37 Chromosome 19, 853329: 853329
12 ELANE NM_001972.3(ELANE): c.292G> T (p.Val98Leu) single nucleotide variant no interpretation for the single variant rs267606781 GRCh38 Chromosome 19, 853329: 853329
13 ELANE NM_001972.3(ELANE): c.640G> A (p.Gly214Arg) single nucleotide variant Pathogenic rs137854451 GRCh37 Chromosome 19, 856000: 856000
14 ELANE NM_001972.3(ELANE): c.640G> A (p.Gly214Arg) single nucleotide variant Pathogenic rs137854451 GRCh38 Chromosome 19, 856000: 856000
15 ELANE NM_001972.3(ELANE): c.301G> T (p.Val101Leu) single nucleotide variant no interpretation for the single variant rs137854449 GRCh37 Chromosome 19, 853338: 853338
16 ELANE NM_001972.3(ELANE): c.301G> T (p.Val101Leu) single nucleotide variant no interpretation for the single variant rs137854449 GRCh38 Chromosome 19, 853338: 853338
17 TCIRG1 NM_006019.3(TCIRG1): c.2206C> A (p.Arg736Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs587779413 GRCh37 Chromosome 11, 67817691: 67817691
18 TCIRG1 NM_006019.3(TCIRG1): c.2206C> A (p.Arg736Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs587779413 GRCh38 Chromosome 11, 68050224: 68050224
19 ELANE NM_001972.3(ELANE): c.606C> T (p.Ser202=) single nucleotide variant Benign/Likely benign rs17216649 GRCh37 Chromosome 19, 855966: 855966
20 ELANE NM_001972.3(ELANE): c.606C> T (p.Ser202=) single nucleotide variant Benign/Likely benign rs17216649 GRCh38 Chromosome 19, 855966: 855966
21 ELANE NM_001972.3(ELANE): c.655G> A (p.Val219Ile) single nucleotide variant Benign/Likely benign rs17216656 GRCh38 Chromosome 19, 856015: 856015
22 ELANE NM_001972.3(ELANE): c.655G> A (p.Val219Ile) single nucleotide variant Benign/Likely benign rs17216656 GRCh37 Chromosome 19, 856015: 856015
23 ELANE NM_001972.3(ELANE): c.785C> T (p.Pro262Leu) single nucleotide variant Benign/Likely benign rs17216670 GRCh38 Chromosome 19, 856145: 856145
24 ELANE NM_001972.3(ELANE): c.785C> T (p.Pro262Leu) single nucleotide variant Benign/Likely benign rs17216670 GRCh37 Chromosome 19, 856145: 856145
25 ELANE NM_001972.3(ELANE): c.561C> A (p.Cys187Ter) single nucleotide variant Pathogenic rs797045009 GRCh38 Chromosome 19, 855758: 855758
26 ELANE NM_001972.3(ELANE): c.561C> A (p.Cys187Ter) single nucleotide variant Pathogenic rs797045009 GRCh37 Chromosome 19, 855758: 855758
27 ELANE NM_001972.3(ELANE): c.597+5G> A single nucleotide variant Pathogenic/Likely pathogenic rs879253882 GRCh38 Chromosome 19, 855799: 855799
28 ELANE NM_001972.3(ELANE): c.597+5G> A single nucleotide variant Pathogenic/Likely pathogenic rs879253882 GRCh37 Chromosome 19, 855799: 855799
29 ELANE NM_001972.3(ELANE): c.99C> T (p.Gly33=) single nucleotide variant Benign rs17216628 GRCh38 Chromosome 19, 852907: 852907
30 ELANE NM_001972.3(ELANE): c.99C> T (p.Gly33=) single nucleotide variant Benign rs17216628 GRCh37 Chromosome 19, 852907: 852907
31 ELANE NM_001972.3(ELANE): c.171C> T (p.Ala57=) single nucleotide variant Benign/Likely benign rs201224981 GRCh38 Chromosome 19, 852979: 852979
32 ELANE NM_001972.3(ELANE): c.171C> T (p.Ala57=) single nucleotide variant Benign/Likely benign rs201224981 GRCh37 Chromosome 19, 852979: 852979
33 ELANE NM_001972.3(ELANE): c.390C> T (p.Asn130=) single nucleotide variant Benign rs17223045 GRCh37 Chromosome 19, 855587: 855587
34 ELANE NM_001972.3(ELANE): c.390C> T (p.Asn130=) single nucleotide variant Benign rs17223045 GRCh38 Chromosome 19, 855587: 855587
35 ELANE NM_001972.3(ELANE): c.654C> T (p.Phe218=) single nucleotide variant Benign/Likely benign rs148492780 GRCh37 Chromosome 19, 856014: 856014
36 ELANE NM_001972.3(ELANE): c.654C> T (p.Phe218=) single nucleotide variant Benign/Likely benign rs148492780 GRCh38 Chromosome 19, 856014: 856014
37 ELANE NM_001972.3(ELANE): c.770C> T (p.Pro257Leu) single nucleotide variant Benign/Likely benign rs17216663 GRCh38 Chromosome 19, 856130: 856130
38 ELANE NM_001972.3(ELANE): c.770C> T (p.Pro257Leu) single nucleotide variant Benign/Likely benign rs17216663 GRCh37 Chromosome 19, 856130: 856130
39 ELANE NM_001972.3(ELANE): c.119C> T (p.Ala40Val) single nucleotide variant Uncertain significance GRCh37 Chromosome 19, 852927: 852927
40 ELANE NM_001972.3(ELANE): c.119C> T (p.Ala40Val) single nucleotide variant Uncertain significance GRCh38 Chromosome 19, 852927: 852927
41 ELANE NM_001972.3(ELANE): c.16C> A (p.Arg6=) single nucleotide variant Benign rs182347433 GRCh37 Chromosome 19, 852344: 852344
42 ELANE NM_001972.3(ELANE): c.16C> A (p.Arg6=) single nucleotide variant Benign rs182347433 GRCh38 Chromosome 19, 852344: 852344
43 ELANE NM_001972.3(ELANE): c.174C> T (p.Thr58=) single nucleotide variant Likely benign rs199714513 GRCh37 Chromosome 19, 852982: 852982
44 ELANE NM_001972.3(ELANE): c.174C> T (p.Thr58=) single nucleotide variant Likely benign rs199714513 GRCh38 Chromosome 19, 852982: 852982
45 ELANE NM_001972.3(ELANE): c.24G> C (p.Ala8=) single nucleotide variant Likely benign rs199901033 GRCh38 Chromosome 19, 852352: 852352
46 ELANE NM_001972.3(ELANE): c.24G> C (p.Ala8=) single nucleotide variant Likely benign rs199901033 GRCh37 Chromosome 19, 852352: 852352
47 ELANE NM_001972.3(ELANE): c.38C> G (p.Ala13Gly) single nucleotide variant Uncertain significance rs756726256 GRCh38 Chromosome 19, 852366: 852366
48 ELANE NM_001972.3(ELANE): c.38C> G (p.Ala13Gly) single nucleotide variant Uncertain significance rs756726256 GRCh37 Chromosome 19, 852366: 852366
49 ELANE NM_001972.3(ELANE): c.172A> C (p.Thr58Pro) single nucleotide variant Uncertain significance GRCh37 Chromosome 19, 852980: 852980
50 ELANE NM_001972.3(ELANE): c.172A> C (p.Thr58Pro) single nucleotide variant Uncertain significance GRCh38 Chromosome 19, 852980: 852980

Expression for Neutropenia, Severe Congenital, 1, Autosomal Dominant

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Pathways for Neutropenia, Severe Congenital, 1, Autosomal Dominant

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

Sources for Neutropenia, Severe Congenital, 1, Autosomal Dominant

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