SCN4
MCID: NTR050
MIFTS: 36

Neutropenia, Severe Congenital, 4, Autosomal Recessive (SCN4)

Categories: Blood diseases, Bone diseases, Cancer diseases, Endocrine diseases, Genetic diseases, Immune diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Neutropenia, Severe Congenital, 4, Autosomal Recessive

MalaCards integrated aliases for Neutropenia, Severe Congenital, 4, Autosomal Recessive:

Name: Neutropenia, Severe Congenital, 4, Autosomal Recessive 56
Dursun Syndrome 56 73 29 13 6 71
Scn4 56 58 73
Neutropenia, Severe Congenital 4, Autosomal Recessive 56 73
Severe Congenital Neutropenia 4, Autosomal Recessive 29 6
Severe Congenital Neutropenia-Pulmonary Hypertension-Superficial Venous Angiectasis Syndrome 58
Autosomal Recessive Severe Congenital Neutropenia Due to G6pc3 Deficiency 58
Pulmonary Arterial Hypertension Leukopenia and Atrial Septal Defect 73
Neutropenia, Severe Congenital, Type 4, Autosomal Recessive 39
Neutropenia, Severe Congenital, Autosomal Recessive 4 71
Severe Congenital Neutropenia Type 4 58
Durss 73

Characteristics:

Orphanet epidemiological data:

58
autosomal recessive severe congenital neutropenia due to g6pc3 deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
variable phenotype
sepsis, neonatal


HPO:

31
neutropenia, severe congenital, 4, autosomal recessive:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare immunological diseases


Summaries for Neutropenia, Severe Congenital, 4, Autosomal Recessive

UniProtKB/Swiss-Prot : 73 Dursun syndrome: A disease characterized by pulmonary arterial hypertension, cardiac abnormalities including secundum-type atrial septal defect, intermittent neutropenia, lymphopenia, monocytosis and anemia.
Neutropenia, severe congenital 4, autosomal recessive: 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.

MalaCards based summary : Neutropenia, Severe Congenital, 4, Autosomal Recessive, also known as dursun syndrome, is related to albinism, oculocutaneous, type iv and alacrima, achalasia, and mental retardation syndrome. An important gene associated with Neutropenia, Severe Congenital, 4, Autosomal Recessive is G6PC3 (Glucose-6-Phosphatase Catalytic Subunit 3). Affiliated tissues include neutrophil, bone marrow and bone, and related phenotypes are global developmental delay and hydronephrosis

More information from OMIM: 612541 PS202700

Related Diseases for Neutropenia, Severe Congenital, 4, Autosomal Recessive

Graphical network of the top 20 diseases related to Neutropenia, Severe Congenital, 4, Autosomal Recessive:



Diseases related to Neutropenia, Severe Congenital, 4, Autosomal Recessive

Symptoms & Phenotypes for Neutropenia, Severe Congenital, 4, Autosomal Recessive

Human phenotypes related to Neutropenia, Severe Congenital, 4, Autosomal Recessive:

31 (show all 34)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 occasional (7.5%) HP:0001263
2 hydronephrosis 31 occasional (7.5%) HP:0000126
3 hearing impairment 31 HP:0000365
4 splenomegaly 31 HP:0001744
5 hepatomegaly 31 HP:0002240
6 recurrent respiratory infections 31 HP:0002205
7 wide nasal bridge 31 HP:0000431
8 pectus carinatum 31 HP:0000768
9 microcephaly 31 HP:0000252
10 broad thumb 31 HP:0011304
11 failure to thrive 31 HP:0001508
12 anemia 31 HP:0001903
13 cleft palate 31 HP:0000175
14 pulmonary arterial hypertension 31 HP:0002092
15 cryptorchidism 31 HP:0000028
16 growth delay 31 HP:0001510
17 high palate 31 HP:0000218
18 atrial septal defect 31 HP:0001631
19 respiratory insufficiency 31 HP:0002093
20 thrombocytopenia 31 HP:0001873
21 mitral regurgitation 31 HP:0001653
22 lymphopenia 31 HP:0001888
23 patent ductus arteriosus 31 HP:0001643
24 hypoplasia of the thymus 31 HP:0000778
25 varicose veins 31 HP:0002619
26 pulmonic stenosis 31 HP:0001642
27 neutropenia 31 HP:0001875
28 sepsis 31 HP:0100806
29 single transverse palmar crease 31 HP:0000954
30 clinodactyly 31 HP:0030084
31 recurrent bacterial infections 31 HP:0002718
32 erythroid hypoplasia 31 HP:0012133
33 monocytosis 31 HP:0012311
34 cor triatriatum 31 HP:0010774

Symptoms via clinical synopsis from OMIM:

56
Abdomen Spleen:
splenomegaly

Respiratory:
recurrent respiratory infections
respiratory insufficiency

Growth Other:
failure to thrive
poor growth

Genitourinary Internal Genitalia Male:
cryptorchidism

Skin Nails Hair Skin:
varicose veins
prominent superficial venous pattern
venous angiectasia
venous stasis ulcer

Skeletal Hands:
clinodactyly
broad thumbs
simian crease
proximal localization of thumb

Head And Neck Nose:
broad nasal bridge

Genitourinary Kidneys:
hydronephrosis (1 patient)
renal agenesis, unilateral (1 patient)

Head And Neck Ears:
hearing loss (reported in 2 patients)

Endocrine Features:
poor secondary sexual development (1 family)
delayed or incomplete puberty (1 family)
increased serum tsh (2 patients)

Abdomen Liver:
hepatomegaly

Chest Ribs Sternum Clavicles And Scapulae:
pectus carinatum

Hematology:
anemia
thrombocytopenia
lymphopenia
neutropenia
leukopenia
more
Cardiovascular Vascular:
patent ductus arteriosus
pulmonary arterial hypertension (in 3 patients)

Immunology:
neutropenia
thymus hypoplasia
increased susceptibility to bacterial infections
few mature neutrophils in the bone marrow

Cardiovascular Heart:
cor triatriatum
pulmonary valve stenosis
atrial septal defect, secundum type
mitral insufficiency

Head And Neck Mouth:
high-arched palate
cleft palate (reported in 1 patient)

Head And Neck Head:
microcephaly (reported in 2 patients)

Neurologic Central Nervous System:
delayed development (1 family)
learning disabilities (1 family)

Clinical features from OMIM:

612541

Drugs & Therapeutics for Neutropenia, Severe Congenital, 4, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Neutropenia, Severe Congenital, 4, Autosomal Recessive

Genetic Tests for Neutropenia, Severe Congenital, 4, Autosomal Recessive

Genetic tests related to Neutropenia, Severe Congenital, 4, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Dursun Syndrome 29
2 Severe Congenital Neutropenia 4, Autosomal Recessive 29 G6PC3

Anatomical Context for Neutropenia, Severe Congenital, 4, Autosomal Recessive

MalaCards organs/tissues related to Neutropenia, Severe Congenital, 4, Autosomal Recessive:

40
Neutrophil, Bone Marrow, Bone, Thymus, Myeloid

Publications for Neutropenia, Severe Congenital, 4, Autosomal Recessive

Articles related to Neutropenia, Severe Congenital, 4, Autosomal Recessive:

# Title Authors PMID Year
1
Mutations in the G6PC3 gene cause Dursun syndrome. 6 61 56
20799326 2010
2
Further delineation of the phenotype of severe congenital neutropenia type 4 due to mutations in G6PC3. 56 6
20717171 2011
3
Severe congenital neutropenia resulting from G6PC3 deficiency with increased neutrophil CXCR4 expression and myelokathexis. 6 56
20616219 2010
4
A syndrome with congenital neutropenia and mutations in G6PC3. 56 6
19118303 2009
5
Familial pulmonary arterial hypertension, leucopenia, and atrial septal defect: a probable new familial syndrome with multisystem involvement. 6 56
19011569 2009
6
G6PC3 Deficiency 61 6
25879134 2015
7
A novel G6PC3 homozygous 1-bp deletion as a cause of severe congenital neutropenia. 56
19696212 2009
8
Dursun syndrome due to G6PC3 gene defect has a fluctuating pattern in all blood cell lines. 61
24549407 2014
9
A clinical and molecular review of ubiquitous glucose-6-phosphatase deficiency caused by G6PC3 mutations. 61
23758768 2013

Variations for Neutropenia, Severe Congenital, 4, Autosomal Recessive

ClinVar genetic disease variations for Neutropenia, Severe Congenital, 4, Autosomal Recessive:

6 (show top 50) (show all 76) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 G6PC3 NM_138387.3(G6PC3):c.565C>T (p.Arg189Ter)SNV Pathogenic 653016 17:42152707-42152707 17:44075339-44075339
2 G6PC3 NM_138387.3(G6PC3):c.207dup (p.Ile70fs)duplication Pathogenic 691992 17:42148539-42148540 17:44071171-44071172
3 G6PC3 NM_138387.3(G6PC3):c.199_218+1deldeletion Pathogenic 691994 17:42148527-42148547 17:44071159-44071179
4 G6PC3 NM_138387.3(G6PC3):c.758G>A (p.Arg253His)SNV Pathogenic 1037 rs118203968 17:42153128-42153128 17:44075760-44075760
5 G6PC3 NM_138387.3(G6PC3):c.554T>C (p.Leu185Pro)SNV Pathogenic 1038 rs118203969 17:42152696-42152696 17:44075328-44075328
6 G6PC3 NM_138387.3(G6PC3):c.141C>G (p.Tyr47Ter)SNV Pathogenic 1039 rs118203970 17:42148474-42148474 17:44071106-44071106
7 G6PC3 NM_001319945.2(G6PC3):c.*77G>CSNV Pathogenic 1040 rs118203971 17:42153154-42153154 17:44075786-44075786
8 G6PC3 G6PC3, 1-BP DUP, 935Tduplication Pathogenic 1041
9 G6PC3 NM_138387.3(G6PC3):c.346A>G (p.Met116Val)SNV Pathogenic 1042 rs267606834 17:42152068-42152068 17:44074700-44074700
10 G6PC3 NM_138387.3(G6PC3):c.130C>T (p.Pro44Ser)SNV Pathogenic 189781 rs775224457 17:42148463-42148463 17:44071095-44071095
11 G6PC3 NM_001319945.2(G6PC3):c.210del (p.Phe71fs)deletion Pathogenic 189782 rs769441127 17:42148543-42148543 17:44071175-44071175
12 G6PC3 NM_138387.3(G6PC3):c.829C>T (p.Gln277Ter)SNV Pathogenic 189783 rs148559256 17:42153199-42153199 17:44075831-44075831
13 G6PC3 NM_001319945.2(G6PC3):c.*228dupduplication Pathogenic 189784 rs797044567 17:42153301-42153302 17:44075933-44075934
14 G6PC3 NM_138387.3(G6PC3):c.144C>G (p.Tyr48Ter)SNV Likely pathogenic 632283 rs1194477276 17:42148477-42148477 17:44071109-44071109
15 G6PC3 NM_138387.3(G6PC3):c.778G>C (p.Gly260Arg)SNV Conflicting interpretations of pathogenicity 30874 rs200478425 17:42153148-42153148 17:44075780-44075780
16 G6PC3 NM_138387.3(G6PC3):c.201C>T (p.Leu67=)SNV Conflicting interpretations of pathogenicity 323461 rs375273894 17:42148534-42148534 17:44071166-44071166
17 G6PC3 NM_138387.3(G6PC3):c.219-13T>CSNV Uncertain significance 323462 rs773122600 17:42151515-42151515 17:44074147-44074147
18 G6PC3 NM_138387.3(G6PC3):c.668A>C (p.Asp223Ala)SNV Uncertain significance 323468 rs779584053 17:42152810-42152810 17:44075442-44075442
19 G6PC3 NM_138387.3(G6PC3):c.187A>G (p.Ile63Val)SNV Uncertain significance 323460 rs34878178 17:42148520-42148520 17:44071152-44071152
20 G6PC3 NM_138387.3(G6PC3):c.407G>A (p.Arg136Gln)SNV Uncertain significance 323465 rs200050824 17:42152129-42152129 17:44074761-44074761
21 G6PC3 NM_138387.3(G6PC3):c.419G>A (p.Arg140His)SNV Uncertain significance 537188 rs989437299 17:42152339-42152339 17:44074971-44074971
22 G6PC3 NM_138387.3(G6PC3):c.-164G>ASNV Uncertain significance 323456 rs886052985 17:42148170-42148170 17:44070802-44070802
23 G6PC3 NM_138387.3(G6PC3):c.377T>C (p.Met126Thr)SNV Uncertain significance 323463 rs886052986 17:42152099-42152099 17:44074731-44074731
24 G6PC3 NM_138387.3(G6PC3):c.*234C>GSNV Uncertain significance 323473 rs763555878 17:42153645-42153645 17:44076277-44076277
25 G6PC3 NM_138387.3(G6PC3):c.406C>T (p.Arg136Trp)SNV Uncertain significance 323464 rs138557340 17:42152128-42152128 17:44074760-44074760
26 G6PC3 NM_138387.3(G6PC3):c.727G>A (p.Val243Met)SNV Uncertain significance 323469 rs140785361 17:42153097-42153097 17:44075729-44075729
27 G6PC3 NM_138387.3(G6PC3):c.-231A>GSNV Uncertain significance 323453 rs886052983 17:42148103-42148103 17:44070735-44070735
28 G6PC3 NM_138387.3(G6PC3):c.-162G>ASNV Uncertain significance 323457 rs536609615 17:42148172-42148172 17:44070804-44070804
29 G6PC3 NM_138387.3(G6PC3):c.175T>C (p.Trp59Arg)SNV Uncertain significance 853860 17:42148508-42148508 17:44071140-44071140
30 G6PC3 NM_138387.3(G6PC3):c.484A>G (p.Ile162Val)SNV Uncertain significance 847646 17:42152404-42152404 17:44075036-44075036
31 G6PC3 NM_138387.3(G6PC3):c.824G>A (p.Arg275Gln)SNV Uncertain significance 850327 17:42153194-42153194 17:44075826-44075826
32 G6PC3 NM_138387.3(G6PC3):c.908C>A (p.Pro303His)SNV Uncertain significance 851336 17:42153278-42153278 17:44075910-44075910
33 G6PC3 NM_138387.3(G6PC3):c.416+3A>GSNV Uncertain significance 849957 17:42152141-42152141 17:44074773-44074773
34 G6PC3 NM_138387.3(G6PC3):c.-178C>ASNV Uncertain significance 891207 17:42148156-42148156 17:44070788-44070788
35 G6PC3 NM_138387.3(G6PC3):c.-155T>ASNV Uncertain significance 891208 17:42148179-42148179 17:44070811-44070811
36 G6PC3 NM_138387.3(G6PC3):c.-149G>ASNV Uncertain significance 892405 17:42148185-42148185 17:44070817-44070817
37 G6PC3 NM_138387.3(G6PC3):c.-48G>ASNV Uncertain significance 892406 17:42148286-42148286 17:44070918-44070918
38 G6PC3 NM_138387.3(G6PC3):c.*67G>ASNV Uncertain significance 889712 17:42153478-42153478 17:44076110-44076110
39 G6PC3 NM_138387.3(G6PC3):c.*97G>CSNV Uncertain significance 889713 17:42153508-42153508 17:44076140-44076140
40 G6PC3 NM_138387.3(G6PC3):c.417-14T>CSNV Uncertain significance 889014 17:42152323-42152323 17:44074955-44074955
41 G6PC3 NM_138387.3(G6PC3):c.417-9T>GSNV Uncertain significance 889015 17:42152328-42152328 17:44074960-44074960
42 G6PC3 NM_138387.3(G6PC3):c.10A>G (p.Thr4Ala)SNV Uncertain significance 665433 17:42148343-42148343 17:44070975-44070975
43 G6PC3 NM_138387.3(G6PC3):c.31A>G (p.Ile11Val)SNV Uncertain significance 652746 17:42148364-42148364 17:44070996-44070996
44 G6PC3 NM_138387.3(G6PC3):c.376A>G (p.Met126Val)SNV Uncertain significance 663027 17:42152098-42152098 17:44074730-44074730
45 G6PC3 NM_138387.3(G6PC3):c.479C>T (p.Ser160Leu)SNV Uncertain significance 651897 17:42152399-42152399 17:44075031-44075031
46 G6PC3 NM_138387.3(G6PC3):c.982G>A (p.Val328Met)SNV Uncertain significance 582332 rs1052762189 17:42153352-42153352 17:44075984-44075984
47 G6PC3 NM_138387.3(G6PC3):c.50A>C (p.Asn17Thr)SNV Uncertain significance 576699 rs375162061 17:42148383-42148383 17:44071015-44071015
48 G6PC3 NM_138387.3(G6PC3):c.580C>T (p.Arg194Trp)SNV Uncertain significance 569633 rs748638373 17:42152722-42152722 17:44075354-44075354
49 G6PC3 NM_138387.3(G6PC3):c.800C>G (p.Ser267Cys)SNV Uncertain significance 570187 rs201700844 17:42153170-42153170 17:44075802-44075802
50 G6PC3 NM_138387.3(G6PC3):c.709C>T (p.Arg237Trp)SNV Uncertain significance 576731 rs763307095 17:42153079-42153079 17:44075711-44075711

UniProtKB/Swiss-Prot genetic disease variations for Neutropenia, Severe Congenital, 4, Autosomal Recessive:

73 (show all 20)
# Symbol AA change Variation ID SNP ID
1 G6PC3 p.Leu185Pro VAR_055156 rs118203969
2 G6PC3 p.Arg253His VAR_055157 rs118203968
3 G6PC3 p.Gly262Arg VAR_055158 rs118203971
4 G6PC3 p.Met116Lys VAR_064508
5 G6PC3 p.Met116Val VAR_064509 rs267606834
6 G6PC3 p.Arg189Gln VAR_064510 rs140294222
7 G6PC3 p.Gly260Arg VAR_064511 rs200478425
8 G6PC3 p.Pro44Ser VAR_072753 rs775224457
9 G6PC3 p.Trp59Arg VAR_072754 rs752966267
10 G6PC3 p.Met116Thr VAR_072756
11 G6PC3 p.Ser139Ile VAR_072757
12 G6PC3 p.Leu154Pro VAR_072758
13 G6PC3 p.Leu208Arg VAR_072759
14 G6PC3 p.Gly260Asp VAR_072760
15 G6PC3 p.Leu325Arg VAR_072761
16 G6PC3 p.Pro44Leu VAR_073174 rs762019955
17 G6PC3 p.Met116Ile VAR_073175 rs137386522
18 G6PC3 p.Thr118Arg VAR_073176 rs766706036
19 G6PC3 p.Arg161Gln VAR_073177 rs148507320
20 G6PC3 p.Arg253Cys VAR_073178 rs765927570

Expression for Neutropenia, Severe Congenital, 4, Autosomal Recessive

Search GEO for disease gene expression data for Neutropenia, Severe Congenital, 4, Autosomal Recessive.

Pathways for Neutropenia, Severe Congenital, 4, Autosomal Recessive

GO Terms for Neutropenia, Severe Congenital, 4, Autosomal Recessive

Sources for Neutropenia, Severe Congenital, 4, Autosomal Recessive

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