SCN5
MCID: NTR031
MIFTS: 36

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

Categories: Blood diseases, Bone diseases, Cardiovascular diseases, Endocrine diseases, Genetic diseases, Immune diseases, Infectious diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Respiratory 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 70
Severe Congenital Neutropenia 5, Autosomal Recessive 29 6
Scn5 57 72
Congenital Neutropenia-Bone Marrow Fibrosis-Nephromegaly Syndrome 58
Neutropenia, Congenital, Severe, Type 5, Autosomal Recessive 39
Congenital Neutropenia-Myelofibrosis-Nephromegaly Syndrome 58
Neutropenia, Severe Congenital 5, Autosomal Recessive 72
Vps45 Deficiency 58

Characteristics:

Orphanet epidemiological data:

58
congenital neutropenia-myelofibrosis-nephromegaly syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
early death from infection may occur


HPO:

31
neutropenia, severe congenital, 5, autosomal recessive:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare immunological diseases


External Ids:

OMIM® 57 615285
OMIM Phenotypic Series 57 PS202700
ICD10 via Orphanet 33 D70
Orphanet 58 ORPHA369852
UMLS 70 C3809031

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) (Updated 20-May-2021)

MalaCards based summary : Neutropenia, Severe Congenital, 5, Autosomal Recessive, also known as severe congenital neutropenia 5, autosomal recessive, is related to severe congenital neutropenia 5 and severe congenital neutropenia. 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 Delta508-CFTR traffic / ER-to-Golgi in CF. Affiliated tissues include bone marrow, neutrophil and bone, and related phenotypes are global developmental delay and failure to thrive

UniProtKB/Swiss-Prot : 72 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:

31 (show all 11)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 occasional (7.5%) HP:0001263
2 failure to thrive 31 HP:0001508
3 splenomegaly 31 HP:0001744
4 hepatomegaly 31 HP:0002240
5 anemia 31 HP:0001903
6 thrombocytopenia 31 HP:0001873
7 neutropenia 31 HP:0001875
8 recurrent infections 31 HP:0002719
9 leukopenia 31 HP:0001882
10 extramedullary hematopoiesis 31 HP:0001978
11 increased circulating antibody level 31 HP:0010702

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
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 (Updated 20-May-2021)

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

Search Clinical Trials , 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:

40
Bone Marrow, Neutrophil, Bone, Cortex, Cardiac Myocytes

Publications for Neutropenia, Severe Congenital, 5, Autosomal Recessive

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

# Title Authors PMID Year
1
A congenital neutrophil defect syndrome associated with mutations in VPS45. 57 6
23738510 2013
2
The Thr224Asn mutation in the VPS45 gene is associated with the congenital neutropenia and primary myelofibrosis of infancy. 6 57
23599270 2013
3
[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]. 61
33350198 2020
4
Periodontal Disease in Two Siblings with VPS45-associated Severe Congenital Neutropenia Type V: A Case Report. 61
33623350 2020
5
Preparation and characterization of chemically TEMPO-oxidized and mechanically disintegrated sacchachitin nanofibers (SCNF) for enhanced diabetic wound healing. 61
31826505 2020
6
Reliability of breeding values for feed intake and feed efficiency traits in dairy cattle: When dry matter intake recordings are sparse under different scenarios. 61
31155258 2019
7
[Adverse reactions analysis of Aconiti Lateralis Radix Praeparata and mechanism prediction of cardiac toxicity by network pharmacology]. 61
30989863 2019
8
Effects of seasonal acclimatization on thermal tolerance of inward currents in roach (Rutilus rutilus) cardiac myocytes. 61
28942482 2018
9
Direct activation of the Mauthner cell by electric field pulses drives ultrarapid escape responses. 61
24848468 2014

Variations for Neutropenia, Severe Congenital, 5, Autosomal Recessive

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

6 (show top 50) (show all 103)
# 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 Pathogenic 55907 rs782269909 GRCh37: 1:150053448-150053448
GRCh38: 1:150081366-150081366
3 VPS45 NM_007259.5(VPS45):c.1140_1141insC (p.Glu381fs) Insertion Pathogenic 1029150 GRCh37: 1:150064066-150064067
GRCh38: 1:150091972-150091973
4 VPS45 NM_007259.5(VPS45):c.223A>G (p.Thr75Ala) SNV Uncertain significance 1029151 GRCh37: 1:150040816-150040816
GRCh38: 1:150068759-150068759
5 VPS45 NM_007259.5(VPS45):c.898A>G (p.Lys300Glu) SNV Uncertain significance 1039732 GRCh37: 1:150054041-150054041
GRCh38: 1:150081959-150081959
6 VPS45 NM_007259.5(VPS45):c.1157G>A (p.Arg386His) SNV Uncertain significance 1040041 GRCh37: 1:150064083-150064083
GRCh38: 1:150091989-150091989
7 VPS45 NM_007259.5(VPS45):c.123A>G (p.Gln41=) SNV Uncertain significance 1044433 GRCh37: 1:150040716-150040716
GRCh38: 1:150068659-150068659
8 VPS45 NM_007259.5(VPS45):c.192A>T (p.Lys64Asn) SNV Uncertain significance 651412 rs1441537795 GRCh37: 1:150040785-150040785
GRCh38: 1:150068728-150068728
9 VPS45 NM_007259.5(VPS45):c.1481C>T (p.Thr494Ile) SNV Uncertain significance 853448 GRCh37: 1:150065732-150065732
GRCh38: 1:150093636-150093636
10 VPS45 NM_007259.5(VPS45):c.693_694AT[1] (p.Tyr232fs) Microsatellite Uncertain significance 864158 GRCh37: 1:150053429-150053430
GRCh38: 1:150081347-150081348
11 VPS45 NM_007259.5(VPS45):c.1516G>A (p.Val506Ile) SNV Uncertain significance 1064193 GRCh37: 1:150082633-150082633
GRCh38: 1:150110518-150110518
12 VPS45 NM_007259.5(VPS45):c.614G>A (p.Arg205His) SNV Uncertain significance 474245 rs146660821 GRCh37: 1:150049784-150049784
GRCh38: 1:150077706-150077706
13 VPS45 NM_007259.5(VPS45):c.260G>A (p.Arg87Gln) SNV Uncertain significance 973738 GRCh37: 1:150044264-150044264
GRCh38: 1:150072197-150072197
14 VPS45 NM_007259.5(VPS45):c.1676G>C (p.Ser559Thr) SNV Uncertain significance 864694 GRCh37: 1:150116937-150116937
GRCh38: 1:150144759-150144759
15 VPS45 NM_007259.5(VPS45):c.1567C>T (p.Arg523Cys) SNV Uncertain significance 841086 GRCh37: 1:150082684-150082684
GRCh38: 1:150110569-150110569
16 VPS45 NM_007259.5(VPS45):c.1018C>T (p.Arg340Ter) SNV Uncertain significance 835122 GRCh37: 1:150054881-150054881
GRCh38: 1:150082797-150082797
17 VPS45 NM_007259.5(VPS45):c.1626-4T>G SNV Uncertain significance 653424 rs1327671540 GRCh37: 1:150116883-150116883
GRCh38: 1:150144705-150144705
18 VPS45 NM_007259.5(VPS45):c.1294A>C (p.Lys432Gln) SNV Uncertain significance 645285 rs1571849671 GRCh37: 1:150064426-150064426
GRCh38: 1:150092332-150092332
19 VPS45 NM_007259.5(VPS45):c.571G>A (p.Val191Ile) SNV Uncertain significance 642887 rs200783288 GRCh37: 1:150049304-150049304
GRCh38: 1:150077226-150077226
20 VPS45 NM_007259.5(VPS45):c.1418C>A (p.Thr473Asn) SNV Uncertain significance 577348 rs1553802469 GRCh37: 1:150065669-150065669
GRCh38: 1:150093573-150093573
21 VPS45 NM_007259.5(VPS45):c.1442G>A (p.Arg481Lys) SNV Uncertain significance 541272 rs151292369 GRCh37: 1:150065693-150065693
GRCh38: 1:150093597-150093597
22 VPS45 NM_007259.5(VPS45):c.299A>G (p.Asn100Ser) SNV Uncertain significance 541271 rs139341274 GRCh37: 1:150048320-150048320
GRCh38: 1:150076242-150076242
23 VPS45 NM_007259.5(VPS45):c.514T>C (p.Cys172Arg) SNV Uncertain significance 541270 rs191692092 GRCh37: 1:150049247-150049247
GRCh38: 1:150077169-150077169
24 VPS45 NM_007259.5(VPS45):c.718C>G (p.Leu240Val) SNV Uncertain significance 474246 rs587716374 GRCh37: 1:150053454-150053454
GRCh38: 1:150081372-150081372
25 VPS45 NM_007259.5(VPS45):c.1700C>T (p.Ala567Val) SNV Uncertain significance 991401 GRCh37: 1:150116961-150116961
GRCh38: 1:150144783-150144783
26 VPS45 NM_007259.5(VPS45):c.1181A>G (p.His394Arg) SNV Uncertain significance 991400 GRCh37: 1:150064107-150064107
GRCh38: 1:150092013-150092013
27 VPS45 NM_007259.5(VPS45):c.1133A>G (p.Lys378Arg) SNV Uncertain significance 991399 GRCh37: 1:150064059-150064059
GRCh38: 1:150091965-150091965
28 VPS45 NM_007259.5(VPS45):c.1033C>T (p.Arg345Trp) SNV Uncertain significance 991398 GRCh37: 1:150054896-150054896
GRCh38: 1:150082812-150082812
29 VPS45 NM_007259.5(VPS45):c.739A>G (p.Ile247Val) SNV Uncertain significance 991397 GRCh37: 1:150053475-150053475
GRCh38: 1:150081393-150081393
30 VPS45 NM_007259.5(VPS45):c.462G>A (p.Gln154=) SNV Uncertain significance 991396 GRCh37: 1:150049195-150049195
GRCh38: 1:150077117-150077117
31 VPS45 NM_007259.5(VPS45):c.390T>C (p.Ile130=) SNV Uncertain significance 991393 GRCh37: 1:150049014-150049014
GRCh38: 1:150076936-150076936
32 VPS45 NM_007259.5(VPS45):c.353T>G (p.Val118Gly) SNV Uncertain significance 991392 GRCh37: 1:150048374-150048374
GRCh38: 1:150076296-150076296
33 VPS45 NM_007259.5(VPS45):c.173A>G (p.Gln58Arg) SNV Uncertain significance 991391 GRCh37: 1:150040766-150040766
GRCh38: 1:150068709-150068709
34 VPS45 NM_007259.5(VPS45):c.-4C>T SNV Uncertain significance 991390 GRCh37: 1:150039911-150039911
GRCh38: 1:150067854-150067854
35 VPS45 NM_007259.5(VPS45):c.1371+5A>G SNV Uncertain significance 647131 rs369221126 GRCh37: 1:150064508-150064508
GRCh38: 1:150092414-150092414
36 VPS45 NM_007259.5(VPS45):c.1664G>A (p.Arg555Gln) SNV Uncertain significance 647655 rs142968690 GRCh37: 1:150116925-150116925
GRCh38: 1:150144747-150144747
37 VPS45 NM_007259.5(VPS45):c.785T>C (p.Val262Ala) SNV Uncertain significance 651262 rs148174305 GRCh37: 1:150053521-150053521
GRCh38: 1:150081439-150081439
38 VPS45 NM_007259.5(VPS45):c.1174G>A (p.Ala392Thr) SNV Uncertain significance 658240 rs782059726 GRCh37: 1:150064100-150064100
GRCh38: 1:150092006-150092006
39 VPS45 NM_007259.5(VPS45):c.1190G>A (p.Arg397Gln) SNV Uncertain significance 665526 rs373735080 GRCh37: 1:150064116-150064116
GRCh38: 1:150092022-150092022
40 VPS45 NM_007259.5(VPS45):c.1535A>G (p.Tyr512Cys) SNV Uncertain significance 626050 rs782797599 GRCh37: 1:150082652-150082652
GRCh38: 1:150110537-150110537
41 VPS45 NM_007259.5(VPS45):c.319G>A (p.Val107Met) SNV Uncertain significance 639607 rs782553177 GRCh37: 1:150048340-150048340
GRCh38: 1:150076262-150076262
42 VPS45 NM_007259.5(VPS45):c.167A>G (p.Asp56Gly) SNV Uncertain significance 659684 rs1278390607 GRCh37: 1:150040760-150040760
GRCh38: 1:150068703-150068703
43 VPS45 NM_007259.5(VPS45):c.170C>A (p.Ser57Tyr) SNV Uncertain significance 659879 rs782358688 GRCh37: 1:150040763-150040763
GRCh38: 1:150068706-150068706
44 VPS45 NM_007259.5(VPS45):c.596A>C (p.Tyr199Ser) SNV Uncertain significance 661964 rs368347807 GRCh37: 1:150049766-150049766
GRCh38: 1:150077688-150077688
45 VPS45 NM_007259.5(VPS45):c.1538A>G (p.Glu513Gly) SNV Uncertain significance 665696 rs1571879434 GRCh37: 1:150082655-150082655
GRCh38: 1:150110540-150110540
46 VPS45 NM_007259.5(VPS45):c.526C>T (p.Arg176Cys) SNV Uncertain significance 853326 GRCh37: 1:150049259-150049259
GRCh38: 1:150077181-150077181
47 VPS45 NM_007259.5(VPS45):c.617G>A (p.Arg206Gln) SNV Uncertain significance 952644 GRCh37: 1:150049787-150049787
GRCh38: 1:150077709-150077709
48 VPS45 NM_007259.5(VPS45):c.687G>C (p.Gln229His) SNV Uncertain significance 966855 GRCh37: 1:150049857-150049857
GRCh38: 1:150077779-150077779
49 VPS45 NM_007259.5(VPS45):c.580G>A (p.Val194Met) SNV Uncertain significance 970136 GRCh37: 1:150049750-150049750
GRCh38: 1:150077672-150077672
50 VPS45 NM_007259.5(VPS45):c.1019G>A (p.Arg340Gln) SNV Uncertain significance 971734 GRCh37: 1:150054882-150054882
GRCh38: 1:150082798-150082798

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

72
# Symbol AA change Variation ID SNP ID
1 VPS45 p.Thr224Asn VAR_069865 rs879255237
2 VPS45 p.Glu238Lys VAR_069866 rs782269909

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
12.4 VPS45 RBSN
2
Show member pathways
11.68 VPS45 RBSN
3 11.56 VPS45 RBSN
4 11.15 VPS45 RBSN
5
Show member pathways
10.21 VPS45 RBSN

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 VPS45 RBSN
2 endosome membrane GO:0010008 8.62 VPS45 RBSN

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 VPS45 RBSN
2 blood coagulation GO:0007596 8.62 VPS45 RBSN

Sources for Neutropenia, Severe Congenital, 5, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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