PNH1
MCID: PRX094
MIFTS: 30

Paroxysmal Nocturnal Hemoglobinuria 1 (PNH1)

Categories: Blood diseases, Genetic diseases, Immune diseases, Metabolic diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Paroxysmal Nocturnal Hemoglobinuria 1

MalaCards integrated aliases for Paroxysmal Nocturnal Hemoglobinuria 1:

Name: Paroxysmal Nocturnal Hemoglobinuria 1 57 72 29 6 70
Paroxysmal Nocturnal Hemoglobinuria, Somatic 57 13
Pnh1 57 72

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
somatic mutation


HPO:

31
paroxysmal nocturnal hemoglobinuria 1:
Inheritance somatic mutation


Classifications:



External Ids:

OMIM® 57 300818
OMIM Phenotypic Series 57 PS300818
MeSH 44 D006457
SNOMED-CT via HPO 68 124975008 1963002
UMLS 70 C3806670

Summaries for Paroxysmal Nocturnal Hemoglobinuria 1

OMIM® : 57 Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon acquired hemolytic anemia that often manifests with hemoglobinuria, abdominal pain, smooth muscle dystonias, fatigue, and thrombosis. The disease results from the expansion of hematopoietic stem cells harboring a mutation in the PIGA gene, which encodes a protein required for the biosynthesis of glycosylphosphatidylinositol (GPI), a lipid moiety that attaches dozens of proteins to the cell surface. Thus, PNH cells are deficient in cell surface GPI-anchored proteins. This deficiency on erythrocytes leads to intravascular hemolysis, since certain GPI-anchored proteins (i.e., CD55 (125240) and CD59 (107271)) normally function as complement regulators. Free hemoglobin released from intravascular hemolysis leads to circulating nitrous oxide depletion and is responsible for many of the clinical manifestations of PNH, including fatigue, erectile dysfunction, esophageal spasm, and thrombosis (review by Brodsky, 2008). (300818) (Updated 05-Apr-2021)

MalaCards based summary : Paroxysmal Nocturnal Hemoglobinuria 1, also known as paroxysmal nocturnal hemoglobinuria, somatic, is related to hemoglobinuria and bleeding disorder, platelet-type, 9. An important gene associated with Paroxysmal Nocturnal Hemoglobinuria 1 is PIGA (Phosphatidylinositol Glycan Anchor Biosynthesis Class A), and among its related pathways/superpathways are Post-translational modification- synthesis of GPI-anchored proteins and Glycosylphosphatidylinositol (GPI)-anchor biosynthesis. Affiliated tissues include smooth muscle and t cells, and related phenotype is paroxysmal nocturnal hemoglobinuria.

UniProtKB/Swiss-Prot : 72 Paroxysmal nocturnal hemoglobinuria 1: A disorder characterized by hemolytic anemia with hemoglobinuria, thromboses in large vessels, and a deficiency in hematopoiesis. Red blood cell breakdown with release of hemoglobin into the urine is manifested most prominently by dark-colored urine in the morning.

Related Diseases for Paroxysmal Nocturnal Hemoglobinuria 1

Diseases in the Paroxysmal Nocturnal Hemoglobinuria family:

Paroxysmal Nocturnal Hemoglobinuria 1 Paroxysmal Nocturnal Hemoglobinuria 2

Diseases related to Paroxysmal Nocturnal Hemoglobinuria 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hemoglobinuria 9.9 PIGT PIGA
2 bleeding disorder, platelet-type, 9 9.8 PIGT PIGA
3 multiple congenital anomalies-hypotonia-seizures syndrome 2 9.8 PIGT PIGA
4 multiple congenital anomalies-hypotonia-seizures syndrome 9.8 PIGT PIGA
5 hypotonia 9.8 PIGT PIGA
6 anterior segment dysgenesis 4 9.7 PIGT PIGA
7 hemolytic anemia 9.7 PIGT PIGA
8 aplastic anemia 9.4 PIGA LOC110806306
9 paroxysmal nocturnal hemoglobinuria 9.4 PIGT PIGA LOC110806306

Graphical network of the top 20 diseases related to Paroxysmal Nocturnal Hemoglobinuria 1:



Diseases related to Paroxysmal Nocturnal Hemoglobinuria 1

Symptoms & Phenotypes for Paroxysmal Nocturnal Hemoglobinuria 1

Human phenotypes related to Paroxysmal Nocturnal Hemoglobinuria 1:

31
# Description HPO Frequency HPO Source Accession
1 paroxysmal nocturnal hemoglobinuria 31 HP:0004818

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Hematology:
paroxysmal nocturnal hemoglobinuria (pnh)

Laboratory Abnormalities:
defective glcnac-pi synthesis

Clinical features from OMIM®:

300818 (Updated 05-Apr-2021)

Drugs & Therapeutics for Paroxysmal Nocturnal Hemoglobinuria 1

Search Clinical Trials , NIH Clinical Center for Paroxysmal Nocturnal Hemoglobinuria 1

Genetic Tests for Paroxysmal Nocturnal Hemoglobinuria 1

Genetic tests related to Paroxysmal Nocturnal Hemoglobinuria 1:

# Genetic test Affiliating Genes
1 Paroxysmal Nocturnal Hemoglobinuria 1 29 PIGA

Anatomical Context for Paroxysmal Nocturnal Hemoglobinuria 1

MalaCards organs/tissues related to Paroxysmal Nocturnal Hemoglobinuria 1:

40
Smooth Muscle, T Cells

Publications for Paroxysmal Nocturnal Hemoglobinuria 1

Articles related to Paroxysmal Nocturnal Hemoglobinuria 1:

(show all 35)
# Title Authors PMID Year
1
Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals. 6 57
10220445 1999
2
Somatic mutations in paroxysmal nocturnal hemoglobinuria: a blessing in disguise? 6 57
9019395 1997
3
Identification of three novel mutations in the PIG-A gene in paroxysmal nocturnal haemoglobinuria (PNH) patients. 57 6
8557259 1996
4
Genetic defects underlying paroxysmal nocturnal hemoglobinuria that arises out of aplastic anemia. 57 6
8541558 1995
5
Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. 6 57
8500164 1993
6
Eculizumab in Pregnant Patients with Paroxysmal Nocturnal Hemoglobinuria. 57
26352814 2015
7
Deep sequencing reveals stepwise mutation acquisition in paroxysmal nocturnal hemoglobinuria. 57
25244093 2014
8
Genetic variants in C5 and poor response to eculizumab. 57
24521109 2014
9
Advances in the diagnosis and therapy of paroxysmal nocturnal hemoglobinuria. 57
18063459 2008
10
PIG-A mutations in normal hematopoiesis. 57
15687243 2005
11
Childhood paroxysmal nocturnal haemoglobinuria (PNH), a report of 11 cases in the Netherlands. 57
15686469 2005
12
Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. 57
14762182 2004
13
A patient with paroxysmal nocturnal haemoglobinuria in whom granulocyte colony-stimulating factor administration resulted in improvement of recurrent enterocolitis and its associated haemolytic attacks. 57
12437672 2002
14
Frequent detection of T cells with mutations of the hypoxanthine-guanine phosphoribosyl transferase gene in patients with paroxysmal nocturnal hemoglobinuria. 57
11756148 2002
15
Paroxysmal nocturnal hemoglobinuria: An acquired genetic disease. 57
10539884 1999
16
New somatic mutation in the PIG-A gene emerges at relapse of paroxysmal nocturnal hemoglobinuria. 6
9787183 1998
17
Resistance to apoptosis caused by PIG-A gene mutations in paroxysmal nocturnal hemoglobinuria. 57
9238050 1997
18
Recurrent PIG-A mutation (IVS5+1G-->A) in a paediatric case of paroxysmal nocturnal haemoglobinuria: detection by the protein truncation test. 6
9233558 1997
19
Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. French Society of Haematology. 57
8774569 1996
20
Epidemiology of PNH. 57
8774563 1996
21
The dual pathogenesis of paroxysmal nocturnal hemoglobinuria. 57
9372059 1996
22
Natural history of paroxysmal nocturnal hemoglobinuria. 57
7566002 1995
23
Paroxysmal nocturnal hemoglobinuria and the glycosylphosphatidylinositol anchor. 57
8200963 1994
24
Chromosomal assignment of genes involved in glycosylphosphatidylinositol anchor biosynthesis: implications for the pathogenesis of paroxysmal nocturnal hemoglobinuria. 57
8204896 1994
25
Mutations within the Piga gene in patients with paroxysmal nocturnal hemoglobinuria. 6
8167330 1994
26
Somatic mutations and cellular selection in paroxysmal nocturnal haemoglobinuria. 57
7909012 1994
27
Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene. 57
8306954 1994
28
Deficient biosynthesis of N-acetylglucosaminyl-phosphatidylinositol, the first intermediate of glycosyl phosphatidylinositol anchor biosynthesis, in cell lines established from patients with paroxysmal nocturnal hemoglobinuria. 57
8426120 1993
29
Deficient surface expression of glycosylphosphatidylinositol-anchored proteins in B cell lines established from patients with paroxysmal nocturnal hemoglobinuria. 57
1282030 1992
30
Synthesis of mannosylglucosaminylinositol phospholipids in normal but not paroxysmal nocturnal hemoglobinuria cells. 57
1378620 1992
31
Defective glycosylphosphatidylinositol anchor synthesis in paroxysmal nocturnal hemoglobinuria granulocytes. 57
1372185 1992
32
Paroxysmal nocturnal hemoglobinuria: the biochemical defects and the clinical syndrome. 57
2477092 1989
33
Paroxysmal nocturnal haemoglobinuria. 57
2645958 1989
34
A novel multiresistance gene cluster located on a plasmid-borne transposon in Listeria monocytogenes. 61
31971232 2020
35
Three genes specifically expressed during phosphate deficiency in Pholiota nameko strain N2 encode hydrophobins. 61
14608471 2004

Variations for Paroxysmal Nocturnal Hemoglobinuria 1

ClinVar genetic disease variations for Paroxysmal Nocturnal Hemoglobinuria 1:

6 (show all 16)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PIGA NM_002641.3(PIGA):c.1188+2del Deletion Pathogenic 9957 rs587776723 GRCh37: X:15342785-15342785
GRCh38: X:15324663-15324663
2 PIGA NM_020473.3(PIGA):c.13+3864C>A SNV Pathogenic 9958 rs199422232 GRCh37: X:15349759-15349759
GRCh38: X:15331637-15331637
3 PIGA NM_020473.3(PIGA):c.13+4029_13+4030insA Insertion Pathogenic 9959 rs587776724 GRCh37: X:15349593-15349594
GRCh38: X:15331471-15331472
4 PIGA NM_002641.3(PIGA):c.1115del (p.Pro372fs) Deletion Pathogenic 9960 rs587776725 GRCh37: X:15342860-15342860
GRCh38: X:15324738-15324738
5 PIGA NM_020473.3(PIGA):c.13+3733C>T SNV Pathogenic 9961 rs199422233 GRCh37: X:15349890-15349890
GRCh38: X:15331768-15331768
6 PIGA NM_020473.3(PIGA):c.13+3819_13+3820insGT Insertion Pathogenic 9962 rs587776726 GRCh37: X:15349803-15349804
GRCh38: X:15331681-15331682
7 PIGA NM_020473.3(PIGA):c.13+4001del Deletion Pathogenic 9963 rs587776727 GRCh37: X:15349622-15349622
GRCh38: X:15331500-15331500
8 PIGA NM_002641.3(PIGA):c.1323_1324del (p.Leu442fs) Deletion Pathogenic 9964 rs587776728 GRCh37: X:15339759-15339760
GRCh38: X:15321637-15321638
9 PIGA PIGA, IVS5DS, G-A, +1, SOMATIC SNV Pathogenic 9965 GRCh37:
GRCh38:
10 PIGA NM_002641.3(PIGA):c.1355_1356insAATTGAGATGGATGACTCCAGATTCTATCATTGA (p.Asp452delinsGluIleGluMetAspAspSerArgPheTyrHisTer) Insertion Pathogenic 9966 rs786200912 GRCh37: X:15339727-15339728
GRCh38: X:15321605-15321606
11 LOC110806306 NR_001566.1(TERC):n.-100C>G SNV Pathogenic 41400 rs199422256 GRCh37: 3:169482948-169482948
GRCh38: 3:169765160-169765160
12 PIGA NM_002641.4(PIGA):c.1355A>T (p.Asp452Val) SNV Likely pathogenic 973228 GRCh37: X:15339728-15339728
GRCh38: X:15321606-15321606
13 PIGA NM_002641.3(PIGA):c.368C>T (p.Thr123Met) SNV Likely pathogenic 432113 rs1555945480 GRCh37: X:15349685-15349685
GRCh38: X:15331563-15331563
14 PIGA NM_002641.4(PIGA):c.986T>C (p.Val329Ala) SNV Likely pathogenic 1033523 GRCh37: X:15342989-15342989
GRCh38: X:15324867-15324867
15 PIGT NM_015937.6(PIGT):c.602T>C (p.Leu201Pro) SNV Uncertain significance 548620 rs1555876854 GRCh37: 20:44048151-44048151
GRCh38: 20:45419511-45419511
16 PIGA NM_002641.3(PIGA):c.1048C>T (p.Pro350Ser) SNV Uncertain significance 471950 rs372966902 GRCh37: X:15342927-15342927
GRCh38: X:15324805-15324805

UniProtKB/Swiss-Prot genetic disease variations for Paroxysmal Nocturnal Hemoglobinuria 1:

72
# Symbol AA change Variation ID SNP ID
1 PIGA p.Ser155Phe VAR_005531
2 PIGA p.Asn297Asp VAR_005532
3 PIGA p.Asp40His VAR_015436
4 PIGA p.Gly48Ala VAR_015437
5 PIGA p.Gly48Asp VAR_015438
6 PIGA p.Gly48Val VAR_015439
7 PIGA p.His128Arg VAR_015440
8 PIGA p.Gly239Arg VAR_015441
9 PIGA p.Arg19Trp VAR_015442 rs34422225

Expression for Paroxysmal Nocturnal Hemoglobinuria 1

Search GEO for disease gene expression data for Paroxysmal Nocturnal Hemoglobinuria 1.

Pathways for Paroxysmal Nocturnal Hemoglobinuria 1

Pathways related to Paroxysmal Nocturnal Hemoglobinuria 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.95 PIGT PIGA
2
Show member pathways
10.24 PIGT PIGA

GO Terms for Paroxysmal Nocturnal Hemoglobinuria 1

Biological processes related to Paroxysmal Nocturnal Hemoglobinuria 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 GPI anchor biosynthetic process GO:0006506 8.62 PIGT PIGA

Sources for Paroxysmal Nocturnal Hemoglobinuria 1

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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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