SCN5
MCID: NTR031
MIFTS: 37

Neutropenia, Severe Congenital, 5, Autosomal Recessive (SCN5)

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

Aliases & Classifications for Neutropenia, Severe Congenital, 5, Autosomal Recessive

MalaCards integrated aliases for Neutropenia, Severe Congenital, 5, Autosomal Recessive:

Name: Neutropenia, Severe Congenital, 5, Autosomal Recessive 58 74
Severe Congenital Neutropenia 5, Autosomal Recessive 30 6
Scn5 58 76
Congenital Neutropenia-Bone Marrow Fibrosis-Nephromegaly Syndrome 60
Neutropenia, Congenital, Severe, Type 5, Autosomal Recessive 41
Congenital Neutropenia-Myelofibrosis-Nephromegaly Syndrome 60
Neutropenia, Severe Congenital 5, Autosomal Recessive 76
Vps45 Deficiency 60

Characteristics:

Orphanet epidemiological data:

60
congenital neutropenia-myelofibrosis-nephromegaly syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
early death from infection may occur


HPO:

33
neutropenia, severe congenital, 5, autosomal recessive:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 60  
Rare immunological diseases


Summaries for Neutropenia, Severe Congenital, 5, Autosomal Recessive

OMIM : 58 Severe congenital neutropenia-5 is an autosomal recessive primary immunodeficiency disorder characterized primarily by neutropenia and neutrophil dysfunction, a lack of response to G-CSF, life-threatening infections, bone marrow fibrosis, and renal extramedullary hematopoiesis (summary by Vilboux et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of severe congenital neutropenia, see SCN1 (202700). (615285)

MalaCards based summary : Neutropenia, Severe Congenital, 5, Autosomal Recessive, is also known as severe congenital neutropenia 5, autosomal recessive. An important gene associated with Neutropenia, Severe Congenital, 5, Autosomal Recessive is VPS45 (Vacuolar Protein Sorting 45 Homolog), and among its related pathways/superpathways are Response to elevated platelet cytosolic Ca2+ and Endocytosis. The drugs Mefloquine and Artemether have been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and neutrophil, and related phenotypes are global developmental delay and failure to thrive

UniProtKB/Swiss-Prot : 76 Neutropenia, severe congenital 5, autosomal recessive: An autosomal recessive primary immunodeficiency disorder characterized primarily by neutropenia and neutrophil dysfunction, a lack of response to G-CSF, life-threatening infections, bone marrow fibrosis, and renal extramedullary hematopoiesis.

Related Diseases for Neutropenia, Severe Congenital, 5, Autosomal Recessive

Symptoms & Phenotypes for Neutropenia, Severe Congenital, 5, Autosomal Recessive

Human phenotypes related to Neutropenia, Severe Congenital, 5, Autosomal Recessive:

33 (show all 11)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 33 occasional (7.5%) HP:0001263
2 failure to thrive 33 HP:0001508
3 splenomegaly 33 HP:0001744
4 hepatomegaly 33 HP:0002240
5 anemia 33 HP:0001903
6 thrombocytopenia 33 HP:0001873
7 recurrent infections 33 HP:0002719
8 neutropenia 33 HP:0001875
9 increased antibody level in blood 33 HP:0010702
10 leukopenia 33 HP:0001882
11 extramedullary hematopoiesis 33 HP:0001978

Symptoms via clinical synopsis from OMIM:

58
Abdomen Spleen:
splenomegaly

Hematology:
anemia
thrombocytopenia
extramedullary hematopoiesis
nucleated red cells in peripheral blood
bone marrow fibrosis
more
Growth Weight:
poor weight gain

Neurologic Central Nervous System:
delayed psychomotor development (in 1 family)

Abdomen Liver:
hepatomegaly

Immunology:
neutropenia
leukopenia
hypergammaglobulinemia
recurrent infections, bacterial and fungal
neutrophil dysfunction

Genitourinary Kidneys:
enlarged kidneys due to extramedullary hematopoiesis

Clinical features from OMIM:

615285

Drugs & Therapeutics for Neutropenia, Severe Congenital, 5, Autosomal Recessive

Drugs for Neutropenia, Severe Congenital, 5, Autosomal Recessive (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 25)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Mefloquine Approved, Investigational Phase 3 53230-10-7 4046
2
Artemether Approved Phase 3 71963-77-4 68911 119380
3
Artesunate Approved, Investigational Phase 3 88495-63-0 5464098 6917864
4
Amodiaquine Approved, Investigational Phase 3 86-42-0 2165
5
Lumefantrine Approved Phase 3 82186-77-4 6437380
6
Piperaquine Experimental, Investigational Phase 3 4085-31-8 5079497
7 Antiviral Agents Phase 3
8 Artemisinins Phase 3
9 Artemisinine Phase 3
10 Antiparasitic Agents Phase 3
11 Anti-Infective Agents Phase 3
12 Antimalarials Phase 3
13 Antiprotozoal Agents Phase 3
14 Artemether, Lumefantrine Drug Combination Phase 3
15 Anthelmintics Phase 3
16
Ajmaline Approved, Experimental Phase 2 4360-12-7 441080
17 Lorajmine Experimental Phase 2 47562-08-3
18 Anti-Arrhythmia Agents Phase 2,Phase 1
19 Diuretics, Potassium Sparing Phase 2,Phase 1
20 Sodium Channel Blockers Phase 2,Phase 1
21
Mexiletine Approved, Investigational Phase 1 31828-71-4 4178
22 Cola Phase 1
23
Digoxin Approved 20830-75-5 2724385 30322
24 Cardiotonic Agents
25 Protective Agents

Interventional clinical trials:

(show all 14)
# Name Status NCT ID Phase Drugs
1 A Trial to Compare the Efficacy, Safety and Tolerability of Combinations of 3 Anti-malarial Drugs Against Combinations of 2 Anti-malarial Drugs (Asia) Not yet recruiting NCT03939104 Phase 3 Artemether-lumefantrine+amodiaquine;Artemether-lumefantrine+placebo;Artesunate-piperaquine+mefloquine;Artesunate-piperaquine+placebo OR Artesunate-mefloquine
2 A Study by the Development of Triple Artemisinin Combination Therapies (DeTACT) Collaboration (Africa) Not yet recruiting NCT03923725 Phase 3 Artemether-lumefantrine+ Amodiaquine (AL+AQ);Artemether-lumefantrine + placebo (AL+PBO);Artesunate-piperaquine+mefloquine (AS-PPQ+MQ);Artesunate-piperaquine+placebo (AS-PPQ+PBO)
3 The Response To Ajmaline Provocation in Healthy Subjects Recruiting NCT02933437 Phase 2 Ajmaline
4 Effects of Mexiletine on Colonic Transit in a Patient With Irritable Bowel Syndrome - Constipation (IBS-C) Completed NCT01717404 Phase 1 Mexiletine
5 Role of SNP and DIGOXIN Response in Atrial Fibrillation Patients Unknown status NCT02167165 Digoxin
6 Identification of Gene Polymorphism in Patients With Sick Sinus Syndrome in Chinese Population in Taiwan Unknown status NCT00314223
7 Sodium Channel Splicing in Heart Failure Trial Completed NCT01185587
8 Sodium Channel Splicing in Obstructive Sleep Apnea (SOCS-OSA) Completed NCT02725632 Not Applicable
9 Genetic Determinants of Sudden Cardiac Death Completed NCT00064558
10 Sodium Channel Splicing in Heart Failure Trial (SOCS-HEFT) Prospective Study Recruiting NCT02738749 Not Applicable
11 Worm Study: Modifier Genes in Sudden Cardiac Death Recruiting NCT02014961 Not Applicable
12 Prospective Identification of Long QT Syndrome in Fetal Life Recruiting NCT02876380
13 Na+ Channel mRNA Regulation in Heart Failure Active, not recruiting NCT03313882
14 Noninvasive Electrocardiographic Imaging for Individuals at Risk for Apparently Idiopathic Ventricular Fibrillation. Enrolling by invitation NCT03963271

Search NIH Clinical Center for Neutropenia, Severe Congenital, 5, Autosomal Recessive

Genetic Tests for Neutropenia, Severe Congenital, 5, Autosomal Recessive

Genetic tests related to Neutropenia, Severe Congenital, 5, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Severe Congenital Neutropenia 5, Autosomal Recessive 30 VPS45

Anatomical Context for Neutropenia, Severe Congenital, 5, Autosomal Recessive

MalaCards organs/tissues related to Neutropenia, Severe Congenital, 5, Autosomal Recessive:

42
Bone, Bone Marrow, Neutrophil, Heart, Kidney, Colon

Publications for Neutropenia, Severe Congenital, 5, Autosomal Recessive

Articles related to Neutropenia, Severe Congenital, 5, Autosomal Recessive:

# Title Authors Year
1
The Thr224Asn mutation in the VPS45 gene is associated with the congenital neutropenia and primary myelofibrosis of infancy. ( 23599270 )
2013
2
A congenital neutrophil defect syndrome associated with mutations in VPS45. ( 23738510 )
2013

Variations for Neutropenia, Severe Congenital, 5, Autosomal Recessive

UniProtKB/Swiss-Prot genetic disease variations for Neutropenia, Severe Congenital, 5, Autosomal Recessive:

76
# Symbol AA change Variation ID SNP ID
1 VPS45 p.Thr224Asn VAR_069865 rs879255237
2 VPS45 p.Glu238Lys VAR_069866 rs782269909

ClinVar genetic disease variations for Neutropenia, Severe Congenital, 5, Autosomal Recessive:

6 (show all 34)
# Gene Variation Type Significance SNP ID Assembly Location
1 VPS45 NM_007259.4(VPS45): c.671C> A (p.Thr224Asn) single nucleotide variant Pathogenic rs879255237 GRCh37 Chromosome 1, 150049841: 150049841
2 VPS45 NM_007259.4(VPS45): c.671C> A (p.Thr224Asn) single nucleotide variant Pathogenic rs879255237 GRCh38 Chromosome 1, 150077763: 150077763
3 VPS45 NM_007259.4(VPS45): c.712G> A (p.Glu238Lys) single nucleotide variant Pathogenic rs782269909 GRCh37 Chromosome 1, 150053448: 150053448
4 VPS45 NM_007259.4(VPS45): c.712G> A (p.Glu238Lys) single nucleotide variant Pathogenic rs782269909 GRCh38 Chromosome 1, 150081366: 150081366
5 VPS45 NM_007259.4(VPS45): c.290-10T> C single nucleotide variant Benign/Likely benign rs192850081 GRCh37 Chromosome 1, 150048301: 150048301
6 VPS45 NM_007259.4(VPS45): c.290-10T> C single nucleotide variant Benign/Likely benign rs192850081 GRCh38 Chromosome 1, 150076223: 150076223
7 VPS45 NM_007259.4(VPS45): c.318C> T (p.Asp106=) single nucleotide variant Benign/Likely benign rs150076399 GRCh37 Chromosome 1, 150048339: 150048339
8 VPS45 NM_007259.4(VPS45): c.318C> T (p.Asp106=) single nucleotide variant Benign/Likely benign rs150076399 GRCh38 Chromosome 1, 150076261: 150076261
9 VPS45 NM_007259.4(VPS45): c.614G> A (p.Arg205His) single nucleotide variant Uncertain significance rs146660821 GRCh37 Chromosome 1, 150049784: 150049784
10 VPS45 NM_007259.4(VPS45): c.614G> A (p.Arg205His) single nucleotide variant Uncertain significance rs146660821 GRCh38 Chromosome 1, 150077706: 150077706
11 VPS45 NM_007259.4(VPS45): c.1032A> G (p.Glu344=) single nucleotide variant Benign rs74127419 GRCh37 Chromosome 1, 150054895: 150054895
12 VPS45 NM_007259.4(VPS45): c.1032A> G (p.Glu344=) single nucleotide variant Benign rs74127419 GRCh38 Chromosome 1, 150082811: 150082811
13 VPS45 NM_007259.4(VPS45): c.246T> G (p.Ile82Met) single nucleotide variant Benign rs62622370 GRCh37 Chromosome 1, 150044250: 150044250
14 VPS45 NM_007259.4(VPS45): c.246T> G (p.Ile82Met) single nucleotide variant Benign rs62622370 GRCh38 Chromosome 1, 150072183: 150072183
15 VPS45 NM_007259.4(VPS45): c.718C> G (p.Leu240Val) single nucleotide variant Uncertain significance rs587716374 GRCh37 Chromosome 1, 150053454: 150053454
16 VPS45 NM_007259.4(VPS45): c.718C> G (p.Leu240Val) single nucleotide variant Uncertain significance rs587716374 GRCh38 Chromosome 1, 150081372: 150081372
17 VPS45 NM_007259.5(VPS45): c.299A> G (p.Asn100Ser) single nucleotide variant Uncertain significance rs139341274 GRCh37 Chromosome 1, 150048320: 150048320
18 VPS45 NM_007259.5(VPS45): c.299A> G (p.Asn100Ser) single nucleotide variant Uncertain significance rs139341274 GRCh38 Chromosome 1, 150076242: 150076242
19 VPS45 NM_007259.5(VPS45): c.1442G> A (p.Arg481Lys) single nucleotide variant Uncertain significance rs151292369 GRCh38 Chromosome 1, 150093597: 150093597
20 VPS45 NM_007259.5(VPS45): c.1442G> A (p.Arg481Lys) single nucleotide variant Uncertain significance rs151292369 GRCh37 Chromosome 1, 150065693: 150065693
21 VPS45 NM_007259.5(VPS45): c.126G> A (p.Ser42=) single nucleotide variant Benign rs148944527 GRCh38 Chromosome 1, 150068662: 150068662
22 VPS45 NM_007259.5(VPS45): c.126G> A (p.Ser42=) single nucleotide variant Benign rs148944527 GRCh37 Chromosome 1, 150040719: 150040719
23 VPS45 NM_007259.5(VPS45): c.514T> C (p.Cys172Arg) single nucleotide variant Uncertain significance rs191692092 GRCh37 Chromosome 1, 150049247: 150049247
24 VPS45 NM_007259.5(VPS45): c.514T> C (p.Cys172Arg) single nucleotide variant Uncertain significance rs191692092 GRCh38 Chromosome 1, 150077169: 150077169
25 VPS45 NM_007259.5(VPS45): c.1494-7A> G single nucleotide variant Likely benign rs1435795274 GRCh38 Chromosome 1, 150110489: 150110489
26 VPS45 NM_007259.5(VPS45): c.1494-7A> G single nucleotide variant Likely benign rs1435795274 GRCh37 Chromosome 1, 150082604: 150082604
27 VPS45 NM_007259.5(VPS45): c.566A> G (p.Glu189Gly) single nucleotide variant Uncertain significance rs144659538 GRCh38 Chromosome 1, 150077221: 150077221
28 VPS45 NM_007259.5(VPS45): c.566A> G (p.Glu189Gly) single nucleotide variant Uncertain significance rs144659538 GRCh37 Chromosome 1, 150049299: 150049299
29 VPS45 NM_007259.5(VPS45): c.570C> T (p.Cys190=) single nucleotide variant Benign rs114087868 GRCh38 Chromosome 1, 150077225: 150077225
30 VPS45 NM_007259.5(VPS45): c.570C> T (p.Cys190=) single nucleotide variant Benign rs114087868 GRCh37 Chromosome 1, 150049303: 150049303
31 VPS45 NM_007259.5(VPS45): c.1418C> A (p.Thr473Asn) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 150065669: 150065669
32 VPS45 NM_007259.5(VPS45): c.1418C> A (p.Thr473Asn) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 150093573: 150093573
33 VPS45 NM_007259.5(VPS45): c.1535A> G (p.Tyr512Cys) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 150082652: 150082652
34 VPS45 NM_007259.5(VPS45): c.1535A> G (p.Tyr512Cys) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 150110537: 150110537

Expression for Neutropenia, Severe Congenital, 5, Autosomal Recessive

Search GEO for disease gene expression data for Neutropenia, Severe Congenital, 5, Autosomal Recessive.

Pathways for Neutropenia, Severe Congenital, 5, Autosomal Recessive

Pathways related to Neutropenia, Severe Congenital, 5, Autosomal Recessive according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.33 RBSN VPS45
2 11.54 RBSN VPS45
3 11.15 RBSN VPS45
4
Show member pathways
10.21 RBSN VPS45

GO Terms for Neutropenia, Severe Congenital, 5, Autosomal Recessive

Cellular components related to Neutropenia, Severe Congenital, 5, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endosome GO:0005768 8.96 RBSN VPS45
2 endosome membrane GO:0010008 8.62 RBSN VPS45

Biological processes related to Neutropenia, Severe Congenital, 5, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein transport GO:0015031 8.96 RBSN VPS45
2 blood coagulation GO:0007596 8.62 RBSN VPS45

Sources for Neutropenia, Severe Congenital, 5, Autosomal Recessive

3 CDC
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10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
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31 HGMD
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34 ICD10
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70 SNOMED-CT via HPO
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