MCID: ERY048
MIFTS: 44

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 54 71 29 13 69
Chuvash Polycythemia 12 56 14
Autosomal Recessive Benign Erythrocytosis 12 71
Familial Erythrocytosis 2 12 24
Von Hippel-Lindau-Dependent Polycythemia 56
Polycythemia, Chuvash Type 24
Vhl-Dependent Polycythemia 71
Chuvash Type Polycythemia 12
Polycythemia Chuvash Type 71
Chuvash Erythromatosis 12
Chuvash Erythrocytosis 56
Ecyt2 71

Characteristics:

Orphanet epidemiological data:

56
chuvash erythrocytosis
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal recessive

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


HPO:

32
erythrocytosis, familial, 2:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Erythrocytosis, Familial, 2

OMIM : 54
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 gata1-related x-linked cytopenia, and has symptoms including headache, fatigue and hemangioma. An important gene associated with Erythrocytosis, Familial, 2 is VHL (Von Hippel-Lindau Tumor Suppressor), and among its related pathways/superpathways are Development HGF signaling pathway and Pathways in cancer. Affiliated tissues include endothelial, and related phenotypes are cardiovascular system and embryo

UniProtKB/Swiss-Prot : 71 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

Diseases in the Erythrocytosis, Familial, 2 family:

Erythrocytosis, Familial, 3 Erythrocytosis, Familial, 4

Diseases related to Erythrocytosis, Familial, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 28)
id Related Disease Score Top Affiliating Genes
1 polycythemia 10.5
2 gata1-related x-linked cytopenia 10.1 HIF1A VHL
3 erythropoietin polycythemia 10.1 EPO EPOR
4 disseminated intravascular coagulation 10.1 EPO EPOR
5 hypoxia 10.1
6 exertional headache 10.0 EPO EPOR
7 acute leukemia 10.0 EPO EPOR
8 cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1 10.0 EPO EPOR
9 dic in newborn 9.9 EPO EPOR
10 thrombosis 9.9
11 endotheliitis 9.9
12 isolated delta-storage pool disease 9.9 EGLN1 EPAS1
13 thrombocythemia 3 9.8 EPO EPOR
14 primary oculocerebral lymphoma 9.8 EPAS1 VHL
15 albinism, oculocutaneous, type ia 9.8 EPO HIF1A
16 inflammatory leiomyosarcoma 9.7 EPO EPOR VHL
17 nelson syndrome 9.7 EPO EPOR
18 acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22) 9.7 EGLN1 HIF1A VHL
19 mucinous tubular and spindle renal cell carcinoma 9.5 HIF1A VHL
20 tendinosis 9.5 EPO EPOR HIF1A
21 central nervous system vasculitis 9.3 EPAS1 HIF1A VHL
22 cleft lip palate dysmorphism kumar type 9.3 EPAS1 HIF1A VHL
23 methemoglobinemia 9.3 EGLN1 EPO EPOR VHL
24 ovarian brenner tumor 9.2 EPAS1 HIF1A VHL
25 lupus - neurological sequelae 8.9 EGLN1 EPAS1 HIF1A VHL
26 bernard-soulier syndrome, type c 8.8 EGLN1 EPAS1 HIF1A VHL
27 atrioventricular septal defect 2 7.8 EGLN1 EPAS1 EPO EPOR HIF1A VHL
28 afferent loop syndrome 7.8 EGLN1 EPAS1 EPO EPOR HIF1A VHL

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:

54

Neurologic- Central Nervous System:
headache
cerebral vascular events
cerebral hemorrhage

Cardiovascular- Vascular:
vascular abnormalities
vertebral hemangiomas
varicose veins
peripheral thrombosis
cerebral vascular events
more
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

Hematology:
erythrocytosis
increased red blood cell mass
increased hematocrit
increased hemoglobin

Skin Nails & Hair- Skin:
plethora


Clinical features from OMIM:

263400

Human phenotypes related to Erythrocytosis, Familial, 2:

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

UMLS symptoms related to Erythrocytosis, Familial, 2:


fatigue, headache

MGI Mouse Phenotypes related to Erythrocytosis, Familial, 2:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.95 EGLN1 EPAS1 EPO EPOR HIF1A VHL
2 embryo MP:0005380 9.93 EGLN1 EPAS1 EPO EPOR HIF1A VHL
3 hematopoietic system MP:0005397 9.91 EPAS1 EPO EPOR HIF1A VHL EGLN1
4 homeostasis/metabolism MP:0005376 9.88 EGLN1 EPAS1 EPO EPOR HIF1A VHL
5 immune system MP:0005387 9.85 EGLN1 EPAS1 EPO EPOR HIF1A VHL
6 liver/biliary system MP:0005370 9.8 EGLN1 EPAS1 EPO EPOR HIF1A VHL
7 mortality/aging MP:0010768 9.73 VHL EGLN1 EPAS1 EPO EPOR HIF1A
8 muscle MP:0005369 9.55 EGLN1 EPAS1 EPO HIF1A VHL
9 respiratory system MP:0005388 9.35 EGLN1 EPAS1 EPO EPOR HIF1A
10 skeleton MP:0005390 9.02 EGLN1 EPAS1 EPO HIF1A VHL

Drugs & Therapeutics for Erythrocytosis, Familial, 2

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Ruxolitinib for Chuvash Polycythemia Available NCT01730755 Ruxolitinib

Search NIH Clinical Center for Erythrocytosis, Familial, 2

Genetic Tests for Erythrocytosis, Familial, 2

Genetic tests related to Erythrocytosis, Familial, 2:

id Genetic test Affiliating Genes
1 Erythrocytosis, Familial, 2 29
2 Familial Erythrocytosis 2 24 VHL

Anatomical Context for Erythrocytosis, Familial, 2

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

39
Endothelial

Publications for Erythrocytosis, Familial, 2

Variations for Erythrocytosis, Familial, 2

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

71
id 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 all 19)
id 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.481C> T (p.Arg161Ter) single nucleotide variant Pathogenic/Likely pathogenic rs5030818 GRCh37 Chromosome 3, 10191488: 10191488
3 VHL NM_000551.3(VHL): c.499C> T (p.Arg167Trp) single nucleotide variant Pathogenic/Likely pathogenic rs5030820 GRCh37 Chromosome 3, 10191506: 10191506
4 VHL NM_000551.3(VHL): c.499C> G (p.Arg167Gly) single nucleotide variant Pathogenic/Likely pathogenic rs5030820 GRCh37 Chromosome 3, 10191506: 10191506
5 VHL NM_000551.3(VHL): c.292T> C (p.Tyr98His) single nucleotide variant Pathogenic rs5030809 GRCh37 Chromosome 3, 10183823: 10183823
6 VHL NM_000551.3(VHL): c.191G> C (p.Arg64Pro) single nucleotide variant Pathogenic/Likely pathogenic rs104893826 GRCh37 Chromosome 3, 10183722: 10183722
7 VHL NM_000551.3(VHL): c.388G> C (p.Val130Leu) single nucleotide variant Pathogenic rs104893830 GRCh37 Chromosome 3, 10188245: 10188245
8 VHL NM_000551.3(VHL): c.376G> T (p.Asp126Tyr) single nucleotide variant Pathogenic rs104893831 GRCh37 Chromosome 3, 10188233: 10188233
9 VHL NM_000551.3(VHL): c.571C> G (p.His191Asp) single nucleotide variant Pathogenic rs28940301 GRCh37 Chromosome 3, 10191578: 10191578
10 VHL NM_000551.3(VHL): c.482G> A (p.Arg161Gln) single nucleotide variant Pathogenic rs730882035 GRCh38 Chromosome 3, 10149805: 10149805
11 VHL NM_000551.3(VHL): c.258delC (p.Val87Tyrfs) deletion Pathogenic rs864622545 GRCh38 Chromosome 3, 10142105: 10142105
12 VHL NM_000551.3(VHL): c.337C> T (p.Arg113Ter) single nucleotide variant Pathogenic rs5030810 GRCh38 Chromosome 3, 10142184: 10142184
13 VHL NM_000551.3(VHL): c.227_229delTCT (p.Phe76del) deletion Pathogenic rs5030648 GRCh37 Chromosome 3, 10183758: 10183760
14 VHL NM_000551.3(VHL): c.464-?_*3705del deletion Pathogenic GRCh37 Chromosome 3, 10191471: 10195354
15 VHL NC_000003.12: g.(?_10141635)_(10142187_?)del deletion Pathogenic GRCh37 Chromosome 3, 10183319: 10183871
16 VHL NC_000003.12: g.(?_10146514)_(10146636_?)del deletion Pathogenic GRCh37 Chromosome 3, 10188198: 10188320
17 VHL NM_000551.3(VHL): c.226_227delTT (p.Phe76Leufs) deletion Pathogenic rs1060503552 GRCh38 Chromosome 3, 10142073: 10142074
18 VHL NC_000003.12: g.(?_10141635)_(10153670_?)del deletion Pathogenic GRCh38 Chromosome 3, 10141635: 10153670
19 VHL NM_000551.3(VHL): c.422dupA (p.Asn141Lysfs) duplication Pathogenic GRCh38 Chromosome 3, 10146595: 10146595

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 17)
id Super pathways Score Top Affiliating Genes
1
Show member pathways
12.43 EGLN1 EPAS1 HIF1A VHL
2 12.27 EGLN1 EPAS1 HIF1A VHL
3 11.95 EGLN1 EPAS1 HIF1A
4
Show member pathways
11.55 EPO EPOR
5 11.54 EPO EPOR
6
Show member pathways
11.54 EPAS1 HIF1A VHL
7 11.49 EGLN1 HIF1A
8 11.45 EGLN1 EPO HIF1A VHL
9 11.31 EGLN1 EPO HIF1A
10
Show member pathways
11.18 EPO EPOR
11
Show member pathways
11.08 EPAS1 HIF1A
12 11 EGLN1 EPO HIF1A
13 10.99 EGLN1 EPO HIF1A VHL
14 10.94 EPO EPOR
15 10.71 EPAS1 VHL
16 10.63 HIF1A VHL
17 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)
id Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription, DNA-templated GO:0045893 9.71 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 9.52 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:

id 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
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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