SCN5
MCID: SVR106
MIFTS: 37

Severe Congenital Neutropenia 5 (SCN5)

Categories: Blood diseases, Bone diseases, Cancer diseases, Endocrine diseases, Genetic diseases, Immune diseases, Infectious diseases, Neuronal diseases, Rare diseases, Respiratory diseases
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Aliases & Classifications for Severe Congenital Neutropenia 5

MalaCards integrated aliases for Severe Congenital Neutropenia 5:

Name: Severe Congenital Neutropenia 5 11 14
Congenital Neutropenia-Myelofibrosis-Nephromegaly Syndrome 11 58 28 5
Congenital Neutropenia-Bone Marrow Fibrosis-Nephromegaly Syndrome 11 58
Vps45 Deficiency 11 58
Scn5 11

Characteristics:


Inheritance:

Congenital Neutropenia-Myelofibrosis-Nephromegaly Syndrome: Autosomal recessive 58

Prevelance:

Congenital Neutropenia-Myelofibrosis-Nephromegaly Syndrome: <1/1000000 (Worldwide) 58

Age Of Onset:

Congenital Neutropenia-Myelofibrosis-Nephromegaly Syndrome: Infancy,Neonatal 58

Classifications:

Orphanet: 58  
Rare immunological diseases


External Ids:

Disease Ontology 11 DOID:0112132
ICD10 via Orphanet 32 D70
Orphanet 58 ORPHA369852

Summaries for Severe Congenital Neutropenia 5

Orphanet: 58 Congenital neutropenia-myelofibrosis-nephromegaly syndrome is rare, genetic, primary immunodeficiency disorder characterized by severe congenital neutropenia, bone marrow fibrosis and neutrophil dysfunction which is refractory to granulocyte colony-stimulating factor, manifesting with life-threatening infections and/or deep-seated abscesses, hepato-/splenomegaly, thrombocytopenia, hypergammaglobulinemia, anemia with reticulocytosis and nephromegaly. Other reported features include osteosclerosis and neurological abnormalities (e.g. developmental delay, cortical blindness, hearing loss, thin corpus callosum or dysrhythmia on EEG).

MalaCards based summary: Severe Congenital Neutropenia 5, also known as congenital neutropenia-myelofibrosis-nephromegaly syndrome, is related to severe congenital neutropenia and neutropenia. An important gene associated with Severe Congenital Neutropenia 5 is VPS45 (Vacuolar Protein Sorting 45 Homolog), and among its related pathways/superpathways are wtCFTR and delta508-CFTR traffic / Generic schema (norm and CF) and Antiarrhythmic Pathway, Pharmacodynamics. Affiliated tissues include bone marrow, bone and neutrophil, and related phenotype is mortality/aging.

Disease Ontology: 11 A severe congenital neutropenia characterized by neutropenia and neutrophil dysfunction, a lack of response to G-CSF, life-threatening infections, bone marrow fibrosis, and renal extramedullary hematopoiesis that has material basis in homozygous or compound heterozygous mutation in VPS45 on chromosome 1q21.2.

Related Diseases for Severe Congenital Neutropenia 5

Diseases in the Neutropenia family:

Neutropenia, Chronic Familial Neutropenia, Severe Congenital, 1, Autosomal Dominant
Neutropenia, Severe Congenital, 3, Autosomal Recessive Neutropenia, Severe Congenital, 4, Autosomal Recessive
Neutropenia, Severe Congenital, 2, Autosomal Dominant Neutropenia, Severe Congenital, 5, Autosomal Recessive
Neutropenia, Severe Congenital, 6, Autosomal Recessive Neutropenia, Severe Congenital, 7, Autosomal Recessive
Neutropenia, Severe Congenital, 8, Autosomal Dominant Neutropenia, Severe Congenital, 9, Autosomal Dominant
Severe Congenital Neutropenia Severe Congenital Neutropenia 1
Severe Congenital Neutropenia 7 Autosomal Dominant Severe Congenital Neutropenia
Severe Congenital Neutropenia 2 Severe Congenital Neutropenia 5
Severe Congenital Neutropenia 3 Severe Congenital Neutropenia 6
Severe Congenital Neutropenia 8 Severe Congenital Neutropenia 4
Elane-Related Neutropenia Acquired Neutropenia
Autosomal Recessive Severe Congenital Neutropenia

Diseases related to Severe Congenital Neutropenia 5 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 28)
# Related Disease Score Top Affiliating Genes
1 severe congenital neutropenia 28.7 VPS45 SLC37A4 LAMTOR2 JAGN1 HAX1 GFI1
2 neutropenia 28.7 VPS45 USB1 SLC37A4 JAGN1 HAX1 GFI1
3 neutropenia, severe congenital, 5, autosomal recessive 11.6
4 autosomal recessive severe congenital neutropenia 10.2 HAX1 G6PC3
5 severe congenital neutropenia 6 10.2 JAGN1 G6PC3
6 whim syndrome 1 10.1 HAX1 G6PC3
7 hermansky-pudlak syndrome 10.0 VPS45 LAMTOR2 G6PC3
8 shwachman-diamond syndrome 1 10.0 HAX1 GFI1 G6PC3
9 familial sick sinus syndrome 10.0 SCN5A HCN4
10 sick sinus syndrome 9.9 SCN5A HCN4
11 second-degree atrioventricular block 9.9 SCN5A HCN4
12 atrioventricular block 9.9 SCN5A HCN4
13 progressive familial heart block 9.9 SCN5A HCN4
14 sinoatrial node disease 9.9 SCN5A HCN4
15 long qt syndrome 9 9.9 SCN5A HCN4
16 right bundle branch block 9.8 SCN5A HCN4
17 glycogen storage disease ia 9.8 SLC37A4 G6PC3
18 ebstein anomaly 9.8 SCN5A HCN4
19 severe congenital neutropenia 4 9.8 SLC37A4 HAX1 G6PC3
20 atrial heart septal defect 9.8 SCN5A HCN4 G6PC3
21 cohen syndrome 9.8 VPS45 LAMTOR2 JAGN1 HAX1 G6PC3
22 third-degree atrioventricular block 9.7 SCN5A HCN4
23 poikiloderma with neutropenia 9.7 VPS45 USB1 JAGN1 HAX1 G6PC3
24 long qt syndrome 2 9.6 SCN5A HCN4
25 severe congenital neutropenia 7 9.5 VPS45 USB1 JAGN1 HAX1 GFI1 G6PC3
26 severe congenital neutropenia 3 9.3 VPS45 SLC37A4 JAGN1 HAX1 GFI1 G6PC3
27 autosomal dominant severe congenital neutropenia 9.3 SLC37A4 LAMTOR2 JAGN1 HAX1 GFI1 G6PC3
28 cyclic neutropenia 9.2 USB1 SLC37A4 JAGN1 HAX1 GFI1 G6PC3

Graphical network of the top 20 diseases related to Severe Congenital Neutropenia 5:



Diseases related to Severe Congenital Neutropenia 5

Symptoms & Phenotypes for Severe Congenital Neutropenia 5

MGI Mouse Phenotypes related to Severe Congenital Neutropenia 5:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 9.32 G6PC3 GFI1 HAX1 HCN4 LAMTOR2 RBSN

Drugs & Therapeutics for Severe Congenital Neutropenia 5

Search Clinical Trials, NIH Clinical Center for Severe Congenital Neutropenia 5

Genetic Tests for Severe Congenital Neutropenia 5

Genetic tests related to Severe Congenital Neutropenia 5:

# Genetic test Affiliating Genes
1 Congenital Neutropenia-Myelofibrosis-Nephromegaly Syndrome 28 VPS45

Anatomical Context for Severe Congenital Neutropenia 5

Organs/tissues related to Severe Congenital Neutropenia 5:

MalaCards : Bone Marrow, Bone, Neutrophil, Cardiac Myocytes, Cortex

Publications for Severe Congenital Neutropenia 5

Articles related to Severe Congenital Neutropenia 5:

(show all 16)
# Title Authors PMID Year
1
A rare form of congenital neutropenia: VPS45 deficiency. 62 5
32037586 2020
2
A congenital neutrophil defect syndrome associated with mutations in VPS45. 62 5
23738510 2013
3
Severe congenital neutropenia with neurological impairment due to a homozygous VPS45 p.E238K mutation: A case report suggesting a genotype-phenotype correlation. 5
26358756 2015
4
The Thr224Asn mutation in the VPS45 gene is associated with the congenital neutropenia and primary myelofibrosis of infancy. 5
23599270 2013
5
Full-Length Transcriptional Analysis of the Same Soybean Genotype With Compatible and Incompatible Reactions to Heterodera glycines Reveals Nematode Infection Activating Plant Defense Response. 62
35665156 2022
6
Gene variant effects across sodium channelopathies predict function and guide precision therapy. 62
35037686 2022
7
Mammalian VPS45 orchestrates trafficking through the endosomal system. 62
33512427 2021
8
[Discovery and study on potential effect of herbal pair of Uncariae Ramulus cum Uncis-Eucommiae Cortex on pregnancy hypertension based on network pharmacology and molecular docking]. 62
33350198 2020
9
Periodontal Disease in Two Siblings with VPS45-associated Severe Congenital Neutropenia Type V: A Case Report. 62
33623350 2020
10
Preparation and characterization of chemically TEMPO-oxidized and mechanically disintegrated sacchachitin nanofibers (SCNF) for enhanced diabetic wound healing. 62
31826505 2020
11
Reliability of breeding values for feed intake and feed efficiency traits in dairy cattle: When dry matter intake recordings are sparse under different scenarios. 62
31155258 2019
12
[Adverse reactions analysis of Aconiti Lateralis Radix Praeparata and mechanism prediction of cardiac toxicity by network pharmacology]. 62
30989863 2019
13
Effects of seasonal acclimatization on thermal tolerance of inward currents in roach (Rutilus rutilus) cardiac myocytes. 62
28942482 2018
14
Direct activation of the Mauthner cell by electric field pulses drives ultrarapid escape responses. 62
24848468 2014
15
VPS 45-associated primary infantile myelofibrosis--successful treatment with hematopoietic stem cell transplantation. 62
24164830 2013
16
Pathogenic mechanisms and clinical implications of congenital neutropenia syndromes. 62
24145314 2013

Variations for Severe Congenital Neutropenia 5

ClinVar genetic disease variations for Severe Congenital Neutropenia 5:

5 (show top 50) (show all 289)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 VPS45 NM_007259.5(VPS45):c.671C>A (p.Thr224Asn) SNV Pathogenic
55906 rs879255237 GRCh37: 1:150049841-150049841
GRCh38: 1:150077763-150077763
2 VPS45 NM_007259.5(VPS45):c.712G>A (p.Glu238Lys) SNV Likely Pathogenic
55907 rs782269909 GRCh37: 1:150053448-150053448
GRCh38: 1:150081366-150081366
3 VPS45 NM_007259.5(VPS45):c.758C>T (p.Pro253Leu) SNV Conflicting Interpretations Of Pathogenicity
791006 rs143828923 GRCh37: 1:150053494-150053494
GRCh38: 1:150081412-150081412
4 VPS45 NM_007259.5(VPS45):c.1448A>G (p.Lys483Arg) SNV Uncertain Significance
834669 rs917642055 GRCh37: 1:150065699-150065699
GRCh38: 1:150093603-150093603
5 VPS45 NM_007259.5(VPS45):c.526C>T (p.Arg176Cys) SNV Uncertain Significance
853326 rs782677308 GRCh37: 1:150049259-150049259
GRCh38: 1:150077181-150077181
6 VPS45 NM_007259.5(VPS45):c.1481C>T (p.Thr494Ile) SNV Uncertain Significance
853448 rs1656465946 GRCh37: 1:150065732-150065732
GRCh38: 1:150093636-150093636
7 VPS45 NM_007259.5(VPS45):c.1186G>C (p.Glu396Gln) SNV Uncertain Significance
859122 rs1656350811 GRCh37: 1:150064112-150064112
GRCh38: 1:150092018-150092018
8 VPS45 NM_007259.5(VPS45):c.658G>C (p.Asp220His) SNV Uncertain Significance
937399 rs1175122293 GRCh37: 1:150049828-150049828
GRCh38: 1:150077750-150077750
9 VPS45 NM_007259.5(VPS45):c.1267G>A (p.Val423Met) SNV Uncertain Significance
951733 rs201002467 GRCh37: 1:150064399-150064399
GRCh38: 1:150092305-150092305
10 VPS45 NM_007259.5(VPS45):c.1334C>G (p.Ala445Gly) SNV Uncertain Significance
971292 rs781801888 GRCh37: 1:150064466-150064466
GRCh38: 1:150092372-150092372
11 VPS45 NM_007259.5(VPS45):c.1019G>A (p.Arg340Gln) SNV Uncertain Significance
971734 rs782749137 GRCh37: 1:150054882-150054882
GRCh38: 1:150082798-150082798
12 VPS45 NM_007259.5(VPS45):c.1418C>A (p.Thr473Asn) SNV Uncertain Significance
577348 rs1553802469 GRCh37: 1:150065669-150065669
GRCh38: 1:150093573-150093573
13 VPS45 NM_007259.5(VPS45):c.571G>A (p.Val191Ile) SNV Uncertain Significance
642887 rs200783288 GRCh37: 1:150049304-150049304
GRCh38: 1:150077226-150077226
14 VPS45 NM_007259.5(VPS45):c.1294A>C (p.Lys432Gln) SNV Uncertain Significance
645285 rs1571849671 GRCh37: 1:150064426-150064426
GRCh38: 1:150092332-150092332
15 VPS45 NM_007259.5(VPS45):c.192A>T (p.Lys64Asn) SNV Uncertain Significance
651412 rs1441537795 GRCh37: 1:150040785-150040785
GRCh38: 1:150068728-150068728
16 VPS45 NM_007259.5(VPS45):c.167A>G (p.Asp56Gly) SNV Uncertain Significance
659684 rs1278390607 GRCh37: 1:150040760-150040760
GRCh38: 1:150068703-150068703
17 VPS45 NM_007259.5(VPS45):c.596A>C (p.Tyr199Ser) SNV Uncertain Significance
661964 rs368347807 GRCh37: 1:150049766-150049766
GRCh38: 1:150077688-150077688
18 VPS45 NM_007259.5(VPS45):c.1538A>G (p.Glu513Gly) SNV Uncertain Significance
665696 rs1571879434 GRCh37: 1:150082655-150082655
GRCh38: 1:150110540-150110540
19 VPS45 NM_007259.5(VPS45):c.614G>A (p.Arg205His) SNV Uncertain Significance
474245 rs146660821 GRCh37: 1:150049784-150049784
GRCh38: 1:150077706-150077706
20 VPS45 NM_007259.5(VPS45):c.1535A>G (p.Tyr512Cys) SNV Uncertain Significance
626050 rs782797599 GRCh37: 1:150082652-150082652
GRCh38: 1:150110537-150110537
21 VPS45 NM_007259.5(VPS45):c.319G>A (p.Val107Met) SNV Uncertain Significance
639607 rs782553177 GRCh37: 1:150048340-150048340
GRCh38: 1:150076262-150076262
22 VPS45 NM_007259.5(VPS45):c.1664G>A (p.Arg555Gln) SNV Uncertain Significance
647655 rs142968690 GRCh37: 1:150116925-150116925
GRCh38: 1:150144747-150144747
23 VPS45 NM_007259.5(VPS45):c.170C>A (p.Ser57Tyr) SNV Uncertain Significance
659879 rs782358688 GRCh37: 1:150040763-150040763
GRCh38: 1:150068706-150068706
24 VPS45 NM_007259.5(VPS45):c.1190G>A (p.Arg397Gln) SNV Uncertain Significance
665526 rs373735080 GRCh37: 1:150064116-150064116
GRCh38: 1:150092022-150092022
25 VPS45 NM_007259.5(VPS45):c.1567C>T (p.Arg523Cys) SNV Uncertain Significance
841086 rs782426640 GRCh37: 1:150082684-150082684
GRCh38: 1:150110569-150110569
26 VPS45 NM_007259.5(VPS45):c.778A>G (p.Arg260Gly) SNV Uncertain Significance
850179 rs587646859 GRCh37: 1:150053514-150053514
GRCh38: 1:150081432-150081432
27 VPS45 NM_007259.5(VPS45):c.1162G>A (p.Val388Met) SNV Uncertain Significance
851006 rs782104716 GRCh37: 1:150064088-150064088
GRCh38: 1:150091994-150091994
28 VPS45 NM_007259.5(VPS45):c.257T>C (p.Leu86Pro) SNV Uncertain Significance
863733 rs782513242 GRCh37: 1:150044261-150044261
GRCh38: 1:150072194-150072194
29 VPS45 NM_007259.5(VPS45):c.695_696del (p.Tyr232fs) MICROSAT Uncertain Significance
864158 rs782700993 GRCh37: 1:150053429-150053430
GRCh38: 1:150081347-150081348
30 VPS45 NM_007259.5(VPS45):c.617G>A (p.Arg206Gln) SNV Uncertain Significance
952644 rs782495021 GRCh37: 1:150049787-150049787
GRCh38: 1:150077709-150077709
31 VPS45 NM_007259.5(VPS45):c.481G>A (p.Gly161Arg) SNV Uncertain Significance
960979 rs200134576 GRCh37: 1:150049214-150049214
GRCh38: 1:150077136-150077136
32 VPS45 NM_007259.5(VPS45):c.687G>C (p.Gln229His) SNV Uncertain Significance
966855 rs200019200 GRCh37: 1:150049857-150049857
GRCh38: 1:150077779-150077779
33 VPS45 NM_007259.5(VPS45):c.580G>A (p.Val194Met) SNV Uncertain Significance
970136 rs587713385 GRCh37: 1:150049750-150049750
GRCh38: 1:150077672-150077672
34 VPS45 NM_007259.5(VPS45):c.173A>G (p.Gln58Arg) SNV Uncertain Significance
991391 rs1654862605 GRCh37: 1:150040766-150040766
GRCh38: 1:150068709-150068709
35 VPS45 NM_007259.5(VPS45):c.353T>G (p.Val118Gly) SNV Uncertain Significance
991392 rs1298740891 GRCh37: 1:150048374-150048374
GRCh38: 1:150076296-150076296
36 VPS45 NM_007259.5(VPS45):c.419A>G (p.Asn140Ser) SNV Uncertain Significance
991394 rs782339252 GRCh37: 1:150049043-150049043
GRCh38: 1:150076965-150076965
37 VPS45 NM_007259.5(VPS45):c.443G>A (p.Arg148Gln) SNV Uncertain Significance
991395 rs370166172 GRCh37: 1:150049176-150049176
GRCh38: 1:150077098-150077098
38 VPS45 NM_007259.5(VPS45):c.462G>A (p.Gln154=) SNV Uncertain Significance
991396 rs781792682 GRCh37: 1:150049195-150049195
GRCh38: 1:150077117-150077117
39 VPS45 NM_007259.5(VPS45):c.739A>G (p.Ile247Val) SNV Uncertain Significance
991397 rs1553799320 GRCh37: 1:150053475-150053475
GRCh38: 1:150081393-150081393
40 VPS45 NM_007259.5(VPS45):c.1033C>T (p.Arg345Trp) SNV Uncertain Significance
991398 rs782225422 GRCh37: 1:150054896-150054896
GRCh38: 1:150082812-150082812
41 VPS45 NM_007259.5(VPS45):c.1133A>G (p.Lys378Arg) SNV Uncertain Significance
991399 rs190896405 GRCh37: 1:150064059-150064059
GRCh38: 1:150091965-150091965
42 VPS45 NM_007259.5(VPS45):c.1181A>G (p.His394Arg) SNV Uncertain Significance
991400 rs1486347658 GRCh37: 1:150064107-150064107
GRCh38: 1:150092013-150092013
43 VPS45 NM_007259.5(VPS45):c.613C>T (p.Arg205Cys) SNV Uncertain Significance
1020881 rs908608470 GRCh37: 1:150049783-150049783
GRCh38: 1:150077705-150077705
44 VPS45 NM_007259.5(VPS45):c.223A>G (p.Thr75Ala) SNV Uncertain Significance
1029151 rs782052786 GRCh37: 1:150040816-150040816
GRCh38: 1:150068759-150068759
45 VPS45 NM_007259.5(VPS45):c.312G>C (p.Lys104Asn) SNV Uncertain Significance
1387412 GRCh37: 1:150048333-150048333
GRCh38: 1:150076255-150076255
46 VPS45 NM_007259.5(VPS45):c.1577C>G (p.Pro526Arg) SNV Uncertain Significance
1381171 GRCh37: 1:150082694-150082694
GRCh38: 1:150110579-150110579
47 overlap with 11 genes NC_000001.10:g.(?_150044213)_(150477474_?)dup DUP Uncertain Significance
1411622 GRCh37: 1:150044213-150477474
GRCh38:
48 VPS45 NM_007259.5(VPS45):c.576+4T>C SNV Uncertain Significance
1430772 GRCh37: 1:150049313-150049313
GRCh38: 1:150077235-150077235
49 VPS45 NM_007259.5(VPS45):c.466T>G (p.Ser156Ala) SNV Uncertain Significance
1361830 GRCh37: 1:150049199-150049199
GRCh38: 1:150077121-150077121
50 VPS45 NC_000001.10:g.(?_150048291)_(150082762_?)dup DUP Uncertain Significance
1433409 GRCh37: 1:150048291-150082762
GRCh38:

Expression for Severe Congenital Neutropenia 5

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

Pathways for Severe Congenital Neutropenia 5

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.76 VPS45 STX16 RBSN
2 11.06 SCN5A HCN4
3
Show member pathways
10.99 SLC37A4 G6PC3
4 10.6 VPS45 STX16
5
Show member pathways
10.21 VPS45 RBSN

GO Terms for Severe Congenital Neutropenia 5

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

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 9.7 VPS45 VAMP1 STX16 SLC37A4 SCN5A NUP210L
2 membrane GO:0016021 9.7 VPS45 VAMP1 STX16 SLC37A4 SCN5A NUP210L

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

# Name GO ID Score Top Affiliating Genes
1 vesicle-mediated transport GO:0016192 9.8 VPS45 VAMP1 STX16 JAGN1
2 membrane depolarization during cardiac muscle cell action potential GO:0086012 9.56 SCN5A HCN4
3 glucose-6-phosphate transport GO:0015760 9.46 SLC37A4 G6PC3
4 membrane depolarization during SA node cell action potential GO:0086046 9.26 SCN5A HCN4
5 SA node cell action potential GO:0086015 8.92 SCN5A HCN4

Molecular functions related to Severe Congenital Neutropenia 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 voltage-gated sodium channel activity GO:0005248 9.26 SCN5A HCN4
2 sodium channel activity GO:0005272 8.62 SCN5A HCN4

Sources for Severe Congenital Neutropenia 5

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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