MCID: NTR031
MIFTS: 29

Neutropenia, Severe Congenital, 5, Autosomal Recessive

Categories: Genetic diseases, Blood diseases, Rare diseases, Bone diseases, Immune diseases, Nephrological 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 57 73
Severe Congenital Neutropenia 5, Autosomal Recessive 29 6
Scn5 57 75
Congenital Neutropenia-Bone Marrow Fibrosis-Nephromegaly Syndrome 59
Neutropenia, Congenital, Severe, Type 5, Autosomal Recessive 40
Congenital Neutropenia-Myelofibrosis-Nephromegaly Syndrome 59
Neutropenia, Severe Congenital 5, Autosomal Recessive 75
Vps45 Deficiency 59

Characteristics:

Orphanet epidemiological data:

59
congenital neutropenia-myelofibrosis-nephromegaly syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
early death from infection may occur


HPO:

32
neutropenia, severe congenital, 5, autosomal recessive:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare immunological diseases


Summaries for Neutropenia, Severe Congenital, 5, Autosomal Recessive

OMIM : 57 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). The drugs Ajmaline and Anti-Arrhythmia Agents have been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and neutrophil, and related phenotypes are failure to thrive and global developmental delay

UniProtKB/Swiss-Prot : 75 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

Symptoms via clinical synopsis from OMIM:

57
AbdomenSpleen:
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

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

32 (show all 10)
# Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 global developmental delay 32 occasional (7.5%) HP:0001263
3 splenomegaly 32 HP:0001744
4 hepatomegaly 32 HP:0002240
5 anemia 32 HP:0001903
6 thrombocytopenia 32 HP:0001873
7 neutropenia 32 HP:0001875
8 increased antibody level in blood 32 HP:0010702
9 leukopenia 32 HP:0001882
10 extramedullary hematopoiesis 32 HP:0001978

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 9)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Ajmaline Approved, Investigational, Nutraceutical Phase 2 4360-12-7 441080
2 Anti-Arrhythmia Agents Phase 2,Phase 1
3 Diuretics, Potassium Sparing Phase 2,Phase 1
4 Sodium Channel Blockers Phase 2,Phase 1
5 Lorajmine Phase 2
6
Mexiletine Approved, Investigational Phase 1 31828-71-4 4178
7 Cola Nutraceutical Phase 1
8
Digoxin Approved 20830-75-5 30322 2724385
9 Protective Agents

Interventional clinical trials:

(show all 11)
# Name Status NCT ID Phase Drugs
1 The Response To Ajmaline Provocation in Healthy Subjects Recruiting NCT02933437 Phase 2 Ajmaline
2 Effects of Mexiletine on Colonic Transit in a Patient With Irritable Bowel Syndrome - Constipation (IBS-C) Completed NCT01717404 Phase 1 Mexiletine
3 Role of SNP and DIGOXIN Response in Atrial Fibrillation Patients Unknown status NCT02167165 Digoxin
4 Identification of Gene Polymorphism in Patients With Sick Sinus Syndrome in Chinese Population in Taiwan Unknown status NCT00314223
5 Sodium Channel Splicing in Heart Failure Trial Completed NCT01185587
6 Sodium Channel Splicing in Obstructive Sleep Apnea (SOCS-OSA) Completed NCT02725632 Not Applicable
7 Genetic Determinants of Sudden Cardiac Death Completed NCT00064558
8 Sodium Channel Splicing in Heart Failure Trial (SOCS-HEFT) Prospective Study Recruiting NCT02738749 Not Applicable
9 Worm Study: Modifier Genes in Sudden Cardiac Death Recruiting NCT02014961 Not Applicable
10 Prospective Identification of Long QT Syndrome in Fetal Life Recruiting NCT02876380
11 Na+ Channel mRNA Regulation in Heart Failure Active, not recruiting NCT03313882

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 29 VPS45

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

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

41
Bone, Bone Marrow, Neutrophil, Heart, Kidney, Colon

Publications for Neutropenia, Severe Congenital, 5, Autosomal Recessive

Variations for Neutropenia, Severe Congenital, 5, Autosomal Recessive

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

75
# 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 30)
# 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 GRCh38 Chromosome 1, 150076261: 150076261
8 VPS45 NM_007259.4(VPS45): c.318C> T (p.Asp106=) single nucleotide variant Benign/Likely benign rs150076399 GRCh37 Chromosome 1, 150048339: 150048339
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 GRCh38 Chromosome 1, 150082811: 150082811
12 VPS45 NM_007259.4(VPS45): c.1032A> G (p.Glu344=) single nucleotide variant Benign rs74127419 GRCh37 Chromosome 1, 150054895: 150054895
13 VPS45 NM_007259.4(VPS45): c.246T> G (p.Ile82Met) single nucleotide variant Benign rs62622370 GRCh38 Chromosome 1, 150072183: 150072183
14 VPS45 NM_007259.4(VPS45): c.246T> G (p.Ile82Met) single nucleotide variant Benign rs62622370 GRCh37 Chromosome 1, 150044250: 150044250
15 VPS45 NM_007259.4(VPS45): c.718C> G (p.Leu240Val) single nucleotide variant Uncertain significance rs587716374 GRCh38 Chromosome 1, 150081372: 150081372
16 VPS45 NM_007259.4(VPS45): c.718C> G (p.Leu240Val) single nucleotide variant Uncertain significance rs587716374 GRCh37 Chromosome 1, 150053454: 150053454
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 GRCh38 Chromosome 1, 150110489: 150110489
26 VPS45 NM_007259.5(VPS45): c.1494-7A> G single nucleotide variant Likely benign 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

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

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

Sources for Neutropenia, Severe Congenital, 5, Autosomal Recessive

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69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
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74 UMLS via Orphanet
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