MCID: ERY048
MIFTS: 47

Erythrocytosis, Familial, 2

Categories: Genetic diseases, Blood diseases, Rare diseases

Aliases & Classifications for Erythrocytosis, Familial, 2

MalaCards integrated aliases for Erythrocytosis, Familial, 2:

Name: Erythrocytosis, Familial, 2 57 75 29 13 6 73
Chuvash Polycythemia 12 59 15
Autosomal Recessive Benign Erythrocytosis 12 75
Ecyt2 57 75
Erythrocytosis, Autosomal Recessive Benign 57
Von Hippel-Lindau-Dependent Polycythemia 59
Erythrocytosis, Familial, Type 2 40
Polycythemia, Vhl-Dependent 57
Polycythemia, Chuvash Type 57
Vhl-Dependent Polycythemia 75
Chuvash Type Polycythemia 12
Familial Erythrocytosis 2 12
Polycythemia Chuvash Type 75
Chuvash Erythromatosis 12
Chuvash Erythrocytosis 59

Characteristics:

Orphanet epidemiological data:

59
chuvash erythrocytosis
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

57
Miscellaneous:
fatigue
mean age at diagnosis 16 years (range 6 to 22)
see also erythrocytosis 1 (ecyt1, )

Inheritance:
autosomal recessive


HPO:

32
erythrocytosis, familial, 2:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Erythrocytosis, Familial, 2

OMIM : 57 Familial erythrocytosis-2 is an autosomal recessive disorder characterized by increased red blood cell mass, increased serum levels of erythropoietin (EPO; 133170), and normal oxygen affinity. Patients with ECYT2 carry a high risk for peripheral thrombosis and cerebrovascular events (Cario, 2005). Familial erythrocytosis-2 has features of both primary and secondary erythrocytosis. In addition to increased circulating levels of EPO, consistent with a secondary, extrinsic process, erythroid progenitors are also hypersensitive to EPO, consistent with a primary, intrinsic process (Prchal, 2005). (263400)

MalaCards based summary : Erythrocytosis, Familial, 2, also known as chuvash polycythemia, is related to polycythemia and fumarate hydratase deficiency, and has symptoms including fatigue and headache. An important gene associated with Erythrocytosis, Familial, 2 is VHL (Von Hippel-Lindau Tumor Suppressor), and among its related pathways/superpathways are Cellular Senescence (REACTOME) and Pathways in cancer. Affiliated tissues include endothelial, and related phenotypes are hypotension and fatigue

UniProtKB/Swiss-Prot : 75 Erythrocytosis, familial, 2: An autosomal recessive disorder characterized by an increase in serum red blood cell mass, hypersensitivity of erythroid progenitors to erythropoietin, increased erythropoietin serum levels, and normal oxygen affinity. Patients with ECYT2 carry a high risk for peripheral thrombosis and cerebrovascular events.

Related Diseases for Erythrocytosis, Familial, 2

Graphical network of the top 20 diseases related to Erythrocytosis, Familial, 2:



Diseases related to Erythrocytosis, Familial, 2

Symptoms & Phenotypes for Erythrocytosis, Familial, 2

Symptoms via clinical synopsis from OMIM:

57
Cardiovascular Vascular:
hypotension
varicose veins
peripheral thrombosis
vascular abnormalities
vertebral hemangiomas
more
Hematology:
increased hematocrit
erythrocytosis
increased red blood cell mass
increased hemoglobin

Laboratory Abnormalities:
increased serum erythropoietin (epo, )
increased serum vascular endothelial growth factor (vegf, )
increased serum plasminogen activator inhibitor-1 (pai1, )
normal leukocyte and platelet counts

Neurologic Central Nervous System:
headache
cerebral hemorrhage
cerebral vascular events

Skin Nails Hair Skin:
plethora


Clinical features from OMIM:

263400

Human phenotypes related to Erythrocytosis, Familial, 2:

32 (show all 12)
# Description HPO Frequency HPO Source Accession
1 hypotension 32 HP:0002615
2 fatigue 32 HP:0012378
3 varicose veins 32 HP:0002619
4 stroke 32 HP:0001297
5 headache 32 HP:0002315
6 cerebral hemorrhage 32 HP:0001342
7 hemangioma 32 HP:0001028
8 increased hematocrit 32 HP:0001899
9 peripheral thrombosis 32 HP:0002641
10 plethora 32 HP:0001050
11 increased red blood cell mass 32 HP:0001898
12 increased hemoglobin 32 HP:0001900

UMLS symptoms related to Erythrocytosis, Familial, 2:


fatigue, headache

MGI Mouse Phenotypes related to Erythrocytosis, Familial, 2:

46 (show all 11)
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.97 EGLN1 EPOR EPAS1 HIF1A EPO VHL
2 embryo MP:0005380 9.93 EGLN1 EPOR EPAS1 HIF1A EPO VHL
3 hematopoietic system MP:0005397 9.91 VHL EGLN1 EPOR EPAS1 HIF1A EPO
4 cellular MP:0005384 9.88 VHL EPO EGLN1 EPOR HIF1A
5 homeostasis/metabolism MP:0005376 9.88 VHL EPO EGLN1 EPOR EPAS1 HIF1A
6 immune system MP:0005387 9.85 VHL EGLN1 EPOR EPAS1 HIF1A EPO
7 liver/biliary system MP:0005370 9.8 EPOR EPAS1 HIF1A EPO VHL EGLN1
8 mortality/aging MP:0010768 9.73 VHL EPO EGLN1 EPOR EPAS1 HIF1A
9 muscle MP:0005369 9.55 EGLN1 EPAS1 HIF1A EPO VHL
10 respiratory system MP:0005388 9.35 EGLN1 EPOR EPAS1 HIF1A EPO
11 skeleton MP:0005390 9.02 VHL EGLN1 EPAS1 HIF1A EPO

Drugs & Therapeutics for Erythrocytosis, Familial, 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Ruxolitinib for Chuvash Polycythemia No longer available NCT01730755 Ruxolitinib

Search NIH Clinical Center for Erythrocytosis, Familial, 2

Genetic Tests for Erythrocytosis, Familial, 2

Genetic tests related to Erythrocytosis, Familial, 2:

# Genetic test Affiliating Genes
1 Erythrocytosis, Familial, 2 29 VHL

Anatomical Context for Erythrocytosis, Familial, 2

MalaCards organs/tissues related to Erythrocytosis, Familial, 2:

41
Endothelial

Publications for Erythrocytosis, Familial, 2

Articles related to Erythrocytosis, Familial, 2:

(show all 17)
# Title Authors Year
1
Clinical Improvement with JAK2 Inhibition in Chuvash Polycythemia. ( 27518686 )
2016
2
Decreased serum glucose and glycosylated hemoglobin levels in patients with Chuvash polycythemia: a role for HIF in glucose metabolism. ( 23015148 )
2013
3
The phenotype of polycythemia due to Croatian homozygous VHL (571C>G:H191D) mutation is different from that of Chuvash polycythemia (VHL 598C>T:R200W). ( 23403324 )
2013
4
Pulmonary artery pressure and iron deficiency in patients with upregulation of hypoxia sensing due to homozygous VHL(R200W) mutation (Chuvash polycythemia). ( 21993671 )
2012
5
Chuvash polycythemia: diagnosis and management. ( 22252661 )
2011
6
Loss of JAK2 regulation via a heterodimeric VHL-SOCS1 E3 ubiquitin ligase underlies Chuvash polycythemia. ( 21685897 )
2011
7
Chuvash polycythemia VHLR200W mutation is associated with down-regulation of hepcidin expression. ( 21876117 )
2011
8
The heterozygote advantage of the Chuvash polycythemia VHLR200W mutation may be protection against anemia. ( 21606165 )
2011
9
Increased size of solid organs in patients with Chuvash polycythemia and in mice with altered expression of HIF-1alpha and HIF-2alpha. ( 20140661 )
2010
10
Altered cytokine profiles in patients with Chuvash polycythemia. ( 19062180 )
2009
11
Zebrafish mutants in the von Hippel-Lindau tumor suppressor display a hypoxic response and recapitulate key aspects of Chuvash polycythemia. ( 19304954 )
2009
12
Elevated homocysteine, glutathione and cysteinylglycine concentrations in patients homozygous for the Chuvash polycythemia VHL mutation. ( 18223282 )
2008
13
von Hippel-Lindau mutation in mice recapitulates Chuvash polycythemia via hypoxia-inducible factor-2alpha signaling and splenic erythropoiesis. ( 17992257 )
2007
14
Endothelin-1, vascular endothelial growth factor and systolic pulmonary artery pressure in patients with Chuvash polycythemia. ( 16769575 )
2006
15
Vascular complications in Chuvash polycythemia. ( 16673284 )
2006
16
Congenital disorder of oxygen sensing: association of the homozygous Chuvash polycythemia VHL mutation with thrombosis and vascular abnormalities but not tumors. ( 14726398 )
2004
17
Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia. ( 12415268 )
2002

Variations for Erythrocytosis, Familial, 2

UniProtKB/Swiss-Prot genetic disease variations for Erythrocytosis, Familial, 2:

75
# Symbol AA change Variation ID SNP ID
1 VHL p.Val130Leu VAR_005733 rs104893830
2 VHL p.Leu188Val VAR_005777 rs5030824
3 VHL p.Leu198Arg VAR_005778
4 VHL p.Arg200Trp VAR_005779 rs28940298
5 VHL p.Asp126Tyr VAR_034994 rs104893831
6 VHL p.His191Asp VAR_034999 rs28940301
7 VHL p.Pro192Ser VAR_035000 rs28940300

ClinVar genetic disease variations for Erythrocytosis, Familial, 2:

6
(show top 50) (show all 407)
# Gene Variation Type Significance SNP ID Assembly Location
1 VHL NM_000551.3(VHL): c.500G> A (p.Arg167Gln) single nucleotide variant Pathogenic rs5030821 GRCh37 Chromosome 3, 10191507: 10191507
2 VHL NM_000551.3(VHL): c.500G> A (p.Arg167Gln) single nucleotide variant Pathogenic rs5030821 GRCh38 Chromosome 3, 10149823: 10149823
3 VHL NM_000551.3(VHL): c.499C> T (p.Arg167Trp) single nucleotide variant Pathogenic rs5030820 GRCh37 Chromosome 3, 10191506: 10191506
4 VHL NM_000551.3(VHL): c.499C> T (p.Arg167Trp) single nucleotide variant Pathogenic rs5030820 GRCh38 Chromosome 3, 10149822: 10149822
5 VHL NM_000551.3(VHL): c.499C> G (p.Arg167Gly) single nucleotide variant Likely pathogenic rs5030820 GRCh37 Chromosome 3, 10191506: 10191506
6 VHL NM_000551.3(VHL): c.499C> G (p.Arg167Gly) single nucleotide variant Likely pathogenic rs5030820 GRCh38 Chromosome 3, 10149822: 10149822
7 VHL NM_000551.3(VHL): c.191G> C (p.Arg64Pro) single nucleotide variant Pathogenic rs104893826 GRCh37 Chromosome 3, 10183722: 10183722
8 VHL NM_000551.3(VHL): c.191G> C (p.Arg64Pro) single nucleotide variant Pathogenic rs104893826 GRCh38 Chromosome 3, 10142038: 10142038
9 VHL NM_000551.3(VHL): c.388G> C (p.Val130Leu) single nucleotide variant Pathogenic rs104893830 GRCh37 Chromosome 3, 10188245: 10188245
10 VHL NM_000551.3(VHL): c.388G> C (p.Val130Leu) single nucleotide variant Pathogenic rs104893830 GRCh38 Chromosome 3, 10146561: 10146561
11 VHL NM_000551.3(VHL): c.376G> T (p.Asp126Tyr) single nucleotide variant Pathogenic rs104893831 GRCh37 Chromosome 3, 10188233: 10188233
12 VHL NM_000551.3(VHL): c.376G> T (p.Asp126Tyr) single nucleotide variant Pathogenic rs104893831 GRCh38 Chromosome 3, 10146549: 10146549
13 VHL NM_000551.3(VHL): c.571C> G (p.His191Asp) single nucleotide variant Pathogenic rs28940301 GRCh37 Chromosome 3, 10191578: 10191578
14 VHL NM_000551.3(VHL): c.571C> G (p.His191Asp) single nucleotide variant Pathogenic rs28940301 GRCh38 Chromosome 3, 10149894: 10149894
15 VHL NM_000551.3(VHL): c.467A> G (p.Tyr156Cys) single nucleotide variant Pathogenic/Likely pathogenic rs397516441 GRCh37 Chromosome 3, 10191474: 10191474
16 VHL NM_000551.3(VHL): c.467A> G (p.Tyr156Cys) single nucleotide variant Pathogenic/Likely pathogenic rs397516441 GRCh38 Chromosome 3, 10149790: 10149790
17 VHL NM_000551.3(VHL): c.154G> A (p.Glu52Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs373068386 GRCh37 Chromosome 3, 10183685: 10183685
18 VHL NM_000551.3(VHL): c.154G> A (p.Glu52Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs373068386 GRCh38 Chromosome 3, 10142001: 10142001
19 VHL NM_000551.3(VHL): c.235C> T (p.Arg79Cys) single nucleotide variant Uncertain significance rs200885420 GRCh37 Chromosome 3, 10183766: 10183766
20 VHL NM_000551.3(VHL): c.235C> T (p.Arg79Cys) single nucleotide variant Uncertain significance rs200885420 GRCh38 Chromosome 3, 10142082: 10142082
21 VHL NM_000551.3(VHL): c.538A> G (p.Ile180Val) single nucleotide variant Uncertain significance rs377715747 GRCh37 Chromosome 3, 10191545: 10191545
22 VHL NM_000551.3(VHL): c.538A> G (p.Ile180Val) single nucleotide variant Uncertain significance rs377715747 GRCh38 Chromosome 3, 10149861: 10149861
23 VHL NM_000551.3(VHL): c.5C> T (p.Pro2Leu) single nucleotide variant Uncertain significance rs111246617 GRCh38 Chromosome 3, 10141852: 10141852
24 VHL NM_000551.3(VHL): c.5C> T (p.Pro2Leu) single nucleotide variant Uncertain significance rs111246617 GRCh37 Chromosome 3, 10183536: 10183536
25 VHL NM_000551.3(VHL): c.482G> A (p.Arg161Gln) single nucleotide variant Pathogenic rs730882035 GRCh38 Chromosome 3, 10149805: 10149805
26 VHL NM_000551.3(VHL): c.482G> A (p.Arg161Gln) single nucleotide variant Pathogenic rs730882035 GRCh37 Chromosome 3, 10191489: 10191489
27 VHL NM_000551.3(VHL): c.631A> C (p.Met211Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs200019083 GRCh38 Chromosome 3, 10149954: 10149954
28 VHL NM_000551.3(VHL): c.631A> C (p.Met211Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs200019083 GRCh37 Chromosome 3, 10191638: 10191638
29 VHL NM_000551.3(VHL): c.95A> G (p.Glu32Gly) single nucleotide variant Uncertain significance rs786203104 GRCh37 Chromosome 3, 10183626: 10183626
30 VHL NM_000551.3(VHL): c.95A> G (p.Glu32Gly) single nucleotide variant Uncertain significance rs786203104 GRCh38 Chromosome 3, 10141942: 10141942
31 VHL NM_000551.3(VHL): c.209A> G (p.Glu70Gly) single nucleotide variant Uncertain significance rs786202857 GRCh37 Chromosome 3, 10183740: 10183740
32 VHL NM_000551.3(VHL): c.209A> G (p.Glu70Gly) single nucleotide variant Uncertain significance rs786202857 GRCh38 Chromosome 3, 10142056: 10142056
33 VHL NM_000551.3(VHL): c.275A> T (p.Asp92Val) single nucleotide variant Uncertain significance rs749091984 GRCh37 Chromosome 3, 10183806: 10183806
34 VHL NM_000551.3(VHL): c.275A> T (p.Asp92Val) single nucleotide variant Uncertain significance rs749091984 GRCh38 Chromosome 3, 10142122: 10142122
35 VHL NM_000551.3(VHL): c.167C> T (p.Ala56Val) single nucleotide variant Uncertain significance rs752980085 GRCh37 Chromosome 3, 10183698: 10183698
36 VHL NM_000551.3(VHL): c.167C> T (p.Ala56Val) single nucleotide variant Uncertain significance rs752980085 GRCh38 Chromosome 3, 10142014: 10142014
37 VHL NM_000551.3(VHL): c.14C> T (p.Ala5Val) single nucleotide variant Uncertain significance rs755333116 GRCh38 Chromosome 3, 10141861: 10141861
38 VHL NM_000551.3(VHL): c.14C> T (p.Ala5Val) single nucleotide variant Uncertain significance rs755333116 GRCh37 Chromosome 3, 10183545: 10183545
39 VHL NM_000551.3(VHL): c.123_137delAGAGTCCGGCCCGGA (p.Ser43_Glu47del) deletion Uncertain significance rs863224839 GRCh38 Chromosome 3, 10141970: 10141984
40 VHL NM_000551.3(VHL): c.123_137delAGAGTCCGGCCCGGA (p.Ser43_Glu47del) deletion Uncertain significance rs863224839 GRCh37 Chromosome 3, 10183654: 10183668
41 VHL NM_000551.3(VHL): c.135G> A (p.Pro45=) single nucleotide variant Likely benign rs773519476 GRCh38 Chromosome 3, 10141982: 10141982
42 VHL NM_000551.3(VHL): c.135G> A (p.Pro45=) single nucleotide variant Likely benign rs773519476 GRCh37 Chromosome 3, 10183666: 10183666
43 VHL NM_000551.3(VHL): c.213C> T (p.Pro71=) single nucleotide variant Benign/Likely benign rs201663073 GRCh37 Chromosome 3, 10183744: 10183744
44 VHL NM_000551.3(VHL): c.213C> T (p.Pro71=) single nucleotide variant Benign/Likely benign rs201663073 GRCh38 Chromosome 3, 10142060: 10142060
45 VHL NM_000551.3(VHL): c.435G> C (p.Gln145His) single nucleotide variant Uncertain significance rs771727849 GRCh37 Chromosome 3, 10188292: 10188292
46 VHL NM_000551.3(VHL): c.435G> C (p.Gln145His) single nucleotide variant Uncertain significance rs771727849 GRCh38 Chromosome 3, 10146608: 10146608
47 VHL NM_000551.3(VHL): c.552C> T (p.Leu184=) single nucleotide variant Benign/Likely benign rs779157605 GRCh38 Chromosome 3, 10149875: 10149875
48 VHL NM_000551.3(VHL): c.552C> T (p.Leu184=) single nucleotide variant Benign/Likely benign rs779157605 GRCh37 Chromosome 3, 10191559: 10191559
49 VHL NM_000551.3(VHL): c.47A> C (p.Glu16Ala) single nucleotide variant Uncertain significance rs864622379 GRCh37 Chromosome 3, 10183578: 10183578
50 VHL NM_000551.3(VHL): c.47A> C (p.Glu16Ala) single nucleotide variant Uncertain significance rs864622379 GRCh38 Chromosome 3, 10141894: 10141894

Expression for Erythrocytosis, Familial, 2

Search GEO for disease gene expression data for Erythrocytosis, Familial, 2.

Pathways for Erythrocytosis, Familial, 2

Pathways related to Erythrocytosis, Familial, 2 according to GeneCards Suite gene sharing:

(show all 18)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.75 EGLN1 EPAS1 EPO HIF1A VHL
2 12.15 EGLN1 EPAS1 EPO EPOR HIF1A VHL
3
Show member pathways
12.12 EGLN1 EPAS1 HIF1A VHL
4 11.97 EGLN1 EPAS1 HIF1A
5
Show member pathways
11.6 EPAS1 HIF1A VHL
6
Show member pathways
11.56 EPO EPOR
7 11.56 EGLN1 EPO HIF1A VHL
8 11.55 EPO EPOR
9 11.51 EGLN1 HIF1A
10 11.42 EGLN1 EPO HIF1A
11
Show member pathways
11.19 EPO EPOR
12 11.19 EGLN1 EPO HIF1A VHL
13
Show member pathways
11.09 EPAS1 HIF1A
14 11.07 EGLN1 EPO HIF1A
15 10.96 EPO EPOR
16 10.73 EPAS1 VHL
17 10.65 HIF1A VHL
18 10.46 EGLN1 EPAS1 EPO VHL

GO Terms for Erythrocytosis, Familial, 2

Biological processes related to Erythrocytosis, Familial, 2 according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription, DNA-templated GO:0045893 9.7 EPO HIF1A VHL
2 protein ubiquitination GO:0016567 9.69 EPAS1 HIF1A VHL
3 negative regulation of apoptotic process GO:0043066 9.67 EPO HIF1A VHL
4 post-translational protein modification GO:0043687 9.63 EPAS1 HIF1A VHL
5 cellular response to hypoxia GO:0071456 9.54 EPAS1 HIF1A
6 cellular iron ion homeostasis GO:0006879 9.48 EGLN1 HIF1A
7 erythrocyte differentiation GO:0030218 9.43 EPAS1 EPO
8 embryonic placenta development GO:0001892 9.4 EPAS1 HIF1A
9 oxygen homeostasis GO:0032364 9.37 EGLN1 HIF1A
10 regulation of transcription from RNA polymerase II promoter in response to oxidative stress GO:0043619 9.32 EPAS1 HIF1A
11 hemoglobin biosynthetic process GO:0042541 9.26 EPO HIF1A
12 response to hypoxia GO:0001666 9.26 EGLN1 EPAS1 EPO HIF1A
13 erythropoietin-mediated signaling pathway GO:0038162 9.16 EPO EPOR
14 regulation of transcription from RNA polymerase II promoter in response to hypoxia GO:0061418 9.02 EGLN1 EPAS1 EPO HIF1A VHL

Molecular functions related to Erythrocytosis, Familial, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 enzyme binding GO:0019899 9.33 EGLN1 HIF1A VHL
2 transcription factor binding GO:0008134 9.13 EPAS1 HIF1A VHL
3 histone acetyltransferase binding GO:0035035 8.62 EPAS1 HIF1A

Sources for Erythrocytosis, Familial, 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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