ECYT2
MCID: ERY048
MIFTS: 57

Erythrocytosis, Familial, 2 (ECYT2)

Categories: Blood diseases, Cancer diseases, Genetic diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Erythrocytosis, Familial, 2

MalaCards integrated aliases for Erythrocytosis, Familial, 2:

Name: Erythrocytosis, Familial, 2 57 72 29 13 6 70
Ecyt2 57 12 72
Autosomal Recessive Benign Erythrocytosis 12 72
Familial Erythrocytosis 2 12 15
Chuvash Polycythemia 12 58
Von Hippel-Lindau-Dependent Polycythemia 58
Erythrocytosis, Familial, Type 2 39
Polycythemia, Vhl-Dependent 57
Vhl-Dependent Polycythemia 72
Chuvash Type Polycythemia 12
Polycythemia Chuvash Type 72
Chuvash Erythromatosis 12
Chuvash Erythrocytosis 58

Characteristics:

Orphanet epidemiological data:

58
chuvash erythrocytosis
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 20-May-2021)
Miscellaneous:
fatigue
mean age at diagnosis 16 years (range 6 to 22)
see also erythrocytosis 1 (ecyt1, )

Inheritance:
autosomal recessive


HPO:

31
erythrocytosis, familial, 2:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare haematological diseases


External Ids:

Disease Ontology 12 DOID:0060474
OMIM® 57 263400
OMIM Phenotypic Series 57 PS133100
MeSH 44 D011086
ICD10 32 D75.1
ICD10 via Orphanet 33 D75.1
Orphanet 58 ORPHA238557
MedGen 41 C1837915
UMLS 70 C1837915

Summaries for Erythrocytosis, Familial, 2

OMIM® : 57 Familial erythrocytosis-2 (ECYT2) 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 may be hypersensitive to EPO, consistent with a primary, intrinsic process (Prchal, 2005). For a general phenotypic description and a discussion of genetic heterogeneity of familial erythrocytosis, see ECYT1 (133100). (263400) (Updated 20-May-2021)

MalaCards based summary : Erythrocytosis, Familial, 2, also known as ecyt2, is related to von hippel-lindau syndrome and hemangioblastoma, 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, pancreatic islet and brain, and related phenotypes are hypotension and fatigue

Disease Ontology : 12 A primary polycythemia that has material basis in homozygous or compound heterozygous mutation in the VHL gene (608537) on chromosome 3p25.

UniProtKB/Swiss-Prot : 72 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, 1 Erythrocytosis, Familial, 8
Erythrocytosis, Familial, 3 Erythrocytosis, Familial, 4
Erythrocytosis, Familial, 5 Erythrocytosis, Familial, 6
Erythrocytosis, Familial, 7

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

(show top 50) (show all 80)
# Related Disease Score Top Affiliating Genes
1 von hippel-lindau syndrome 30.1 VHL LOC107303340 HIF1A ELOC ELOB CUL2
2 hemangioblastoma 30.1 VHL LOC107303340 HIF1A EPOR EPO EPAS1
3 polycythemia 29.8 VHL HIF1A HAMP EPOR EPO EPAS1
4 iron metabolism disease 29.2 SLC11A2 HAMP EPO CYBRD1 ACO1
5 pheochromocytoma 28.8 VHL LOC107303340 HIF1A EPOR EPO EPAS1
6 hypoxia 28.5 VHL HIF1AN HIF1A EPAS1 EGLN3 EGLN2
7 renal cell carcinoma, nonpapillary 28.4 VHL LOC107303340 HIF1AN HIF1A EPAS1 ELOC
8 deficiency anemia 28.4 SLC11A2 HIF1A HAMP EPOR EPO EPAS1
9 tumor predisposition syndrome 10.4
10 cutaneous telangiectasia and cancer syndrome, familial 10.4
11 inherited cancer-predisposing syndrome 10.4
12 endolymphatic sac tumor 10.3 VHL LOC107303340
13 congenital myasthenic syndrome with episodic apnea 10.3 VHL LOC107303340
14 fumarate hydratase deficiency 10.3 VHL HIF1A
15 angiomatosis 10.3 VHL LOC107303340
16 sporadic pheochromocytoma/secreting paraganglioma 10.3 VHL EPAS1
17 inflammatory bowel disease 27 10.3 HIF1A EPO
18 progressive myoclonus epilepsy 9 10.3 EPOR EPO
19 thrombosis 10.3
20 acquired color blindness 10.2 EPO EIF5B
21 lumbosacral lipoma 10.2 HIF1A EPOR EPO
22 cerebellar angioblastoma 10.2 VHL LOC107303340
23 erythrocytosis, familial, 1 10.2 EPOR EPO EGLN1
24 plethora of newborn 10.2 EPO EPAS1 EGLN1
25 autosomal dominant secondary polycythemia 10.2 EPO EPAS1 EGLN1
26 duodenal somatostatinoma 10.2 EPAS1 EGLN1
27 varicose veins 10.2
28 hemangioma 10.2
29 folic acid deficiency anemia 10.2 HAMP EPO
30 chronic mountain sickness 10.2 EPO EPAS1 EGLN3
31 esophagus carcinoma in situ 10.2 HIF1A EPO ARNT
32 lung clear cell carcinoma 10.2 HAMP EPO
33 ichthyosis, congenital, autosomal recessive 11 10.1 HIF1A EPAS1 EGLN1
34 acute erythroid leukemia 10.1 EPOR EPO
35 pheochromocytoma-paraganglioma 10.1 VHL LOC107303340 EGLN2 EGLN1
36 neonatal anemia 10.1 EPOR EPO
37 paraganglioma 10.1 VHL HIF1A EPAS1 EGLN1
38 anemia of prematurity 10.1 HAMP EPOR EPO
39 oligohydramnios 10.1
40 erythrocytosis, familial, 4 10.1 VHL EPOR EPAS1 EGLN1
41 asphyxia neonatorum 10.1 HIF1A EPO
42 renal cell carcinoma, papillary, 1 10.1 VHL LOC107303340 HIF1A ELOC
43 pulmonary hypertension 10.0
44 autosomal recessive disease 10.0
45 thrombophilia 10.0
46 tricuspid valve insufficiency 10.0
47 hypoglycemia 10.0
48 cytokine deficiency 10.0
49 splenomegaly 10.0
50 parathyroid gland disease 10.0 HIF1AN EPO EGLN1

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



Diseases related to Erythrocytosis, Familial, 2

Symptoms & Phenotypes for Erythrocytosis, Familial, 2

Human phenotypes related to Erythrocytosis, Familial, 2:

31 (show all 12)
# Description HPO Frequency HPO Source Accession
1 hypotension 31 HP:0002615
2 fatigue 31 HP:0012378
3 varicose veins 31 HP:0002619
4 stroke 31 HP:0001297
5 hemangioma 31 HP:0001028
6 headache 31 HP:0002315
7 cerebral hemorrhage 31 HP:0001342
8 increased hematocrit 31 HP:0001899
9 plethora 31 HP:0001050
10 increased red blood cell mass 31 HP:0001898
11 increased hemoglobin 31 HP:0001900
12 peripheral thrombosis 31 HP:0002641

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Cardiovascular Vascular:
hypotension
varicose veins
peripheral thrombosis
vascular abnormalities
vertebral hemangiomas
more
Hematology:
increased hematocrit
increased red blood cell mass
increased hemoglobin
erythrocytosis

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 (Updated 20-May-2021)

UMLS symptoms related to Erythrocytosis, Familial, 2:


fatigue; headache

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

26 (show all 13)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-130 9.44 ELOB
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-140 9.44 EIF5B
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-144 9.44 VHL
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-159 9.44 VHL
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-163 9.44 ELOB
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-168 9.44 HIF1A
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-181 9.44 EIF5B
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-200 9.44 HIF1A
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-207 9.44 VHL
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-42 9.44 EIF5B
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-43 9.44 ELOB
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-73 9.44 EIF5B
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-79 9.44 HIF1A

MGI Mouse Phenotypes related to Erythrocytosis, Familial, 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.26 ARNT CYBRD1 EGLN1 EGLN2 EGLN3 EPAS1
2 homeostasis/metabolism MP:0005376 10.22 ACO1 ARNT CYBRD1 EGLN1 EGLN2 EGLN3
3 hematopoietic system MP:0005397 10.17 ARNT EGLN1 EGLN2 EGLN3 EPAS1 EPO
4 embryo MP:0005380 10.16 ARNT EGLN1 EGLN2 EGLN3 EIF5B EPAS1
5 immune system MP:0005387 10.11 ARNT EGLN1 EGLN2 EGLN3 EPAS1 EPO
6 liver/biliary system MP:0005370 10.03 ARNT CYBRD1 EGLN1 EGLN2 EGLN3 EPAS1
7 integument MP:0010771 9.97 ARNT EGLN1 EGLN2 EGLN3 EPO HIF1A
8 mortality/aging MP:0010768 9.97 ACO1 ARNT CUL2 EGLN1 EGLN3 EIF5B
9 muscle MP:0005369 9.56 EGLN1 EGLN2 EGLN3 EPAS1 EPO HIF1A
10 normal MP:0002873 9.23 ACO1 ARNT EGLN3 EPO EPOR HIF1A

Drugs & Therapeutics for Erythrocytosis, Familial, 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Pulmonary Hypertension and the Hypoxic Response in SCD Completed NCT00495638
2 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:

40
Endothelial, Pancreatic Islet, Brain, Lung

Publications for Erythrocytosis, Familial, 2

Articles related to Erythrocytosis, Familial, 2:

(show top 50) (show all 244)
# Title Authors PMID Year
1
Effects of Germline VHL Deficiency on Growth, Metabolism, and Mitochondria. 57 6 61
32101665 2020
2
Identification of a new VHL exon and complex splicing alterations in familial erythrocytosis or von Hippel-Lindau disease. 61 57 6
29891534 2018
3
The homozygous VHL(D126N) missense mutation is associated with dramatically elevated erythropoietin levels, consequent polycythemia, and early onset severe pulmonary hypertension. 57 6 61
24729484 2014
4
Novel homozygous VHL mutation in exon 2 is associated with congenital polycythemia but not with cancer. 61 6 57
23538339 2013
5
The phenotype of polycythemia due to Croatian homozygous VHL (571C>G:H191D) mutation is different from that of Chuvash polycythemia (VHL 598C>T:R200W). 61 6 57
23403324 2013
6
Loss of JAK2 regulation via a heterodimeric VHL-SOCS1 E3 ubiquitin ligase underlies Chuvash polycythemia. 6 57 61
21685897 2011
7
von Hippel-Lindau mutation in mice recapitulates Chuvash polycythemia via hypoxia-inducible factor-2alpha signaling and splenic erythropoiesis. 61 6 57
17992257 2007
8
Von Hippel-Lindau-dependent polycythemia is endemic on the island of Ischia: identification of a novel cluster. 61 6 57
16210343 2006
9
Mutations in the von Hippel-Lindau (VHL) tumor suppressor gene and VHL-haplotype analysis in patients with presumable congenital erythrocytosis. 6 57 61
15642664 2005
10
Congenital disorder of oxygen sensing: association of the homozygous Chuvash polycythemia VHL mutation with thrombosis and vascular abnormalities but not tumors. 61 6 57
14726398 2004
11
The worldwide distribution of the VHL 598C>T mutation indicates a single founding event. 61 57 6
14604959 2004
12
Mutations of von Hippel-Lindau tumor-suppressor gene and congenital polycythemia. 6 57 61
12844285 2003
13
Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia. 6 57 61
12415268 2002
14
Endemic polycythemia in Russia: mutation in the VHL gene. 61 57 6
11987242 2002
15
Congenital polycythemia in Chuvashia. 6 57 61
9058738 1997
16
Identification and in silico analysis of novel von Hippel-Lindau (VHL) gene variants from a large population. 6 57
21463266 2011
17
Dysregulation of the HIF pathway due to VHL mutation causing severe erythrocytosis and pulmonary arterial hypertension. 57 6
21454469 2011
18
Chuvash-type congenital polycythemia in 4 families of Asian and Western European ancestry. 6 57
12702509 2003
19
Localization of the gene responsible for familial benign polycythemia to chromosome 11q23. 57 6
10364675 1999
20
Genetic evidence of a precisely tuned dysregulation in the hypoxia signaling pathway during oncogenesis. 61 6
25371412 2014
21
Molecular study of congenital erythrocytosis in 70 unrelated patients revealed a potential causal mutation in less than half of the cases (Where is/are the missing gene(s)?). 6 61
23859443 2013
22
The heterozygote advantage of the Chuvash polycythemia VHLR200W mutation may be protection against anemia. 6 61
21606165 2011
23
Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2alpha gain-of-function mutation. 6 61
21389259 2011
24
Involvement of oxygen-sensing pathways in physiologic and pathologic erythropoiesis. 6 61
19494350 2009
25
Polycythemia vera and other primary polycythemias. 57 61
15725900 2005
26
Mutations in the VHL gene in sporadic apparently congenital polycythemia. 6 61
12393546 2003
27
A novel mutation in the VHL gene in a Chinese family with von Hippel-Lindau disease. 6
30477447 2018
28
Novel genotype-phenotype correlations in five Chinese families with Von Hippel-Lindau disease. 6
29871882 2018
29
Genotype phenotype correlation in Asian Indian von Hippel-Lindau (VHL) syndrome patients with pheochromocytoma/paraganglioma. 6
29124493 2018
30
Identification of a VHL gene mutation in a Chinese family with Von Hippel‑Lindau syndrome. 6
29749453 2018
31
Bilateral Pheochromocytomas in a Patient with Y175C Von Hippel-Lindau Mutation. 6
30105105 2018
32
Interaction between von Hippel-Lindau Protein and Fatty Acid Synthase Modulates Hypoxia Target Gene Expression. 6
28775317 2017
33
Genotype-phenotype correlations in Chinese von Hippel-Lindau disease patients. 6
28388566 2017
34
VHL missense mutations in the p53 binding domain show different effects on p53 signaling and HIFα degradation in clear cell renal cell carcinoma. 6
28052007 2017
35
Genotype-Phenotype Correlation in Patients With Germline Mutations of VHL, RET, SDHB, and SDHD Genes: Thai Experience. 6
28469506 2017
36
Presented Abstracts from the Thirty Fifth Annual Education Conference of the National Society of Genetic Counselors (Seattle, WA, September 2016). 6
27730413 2016
37
Gene panel sequencing improves the diagnostic work-up of patients with idiopathic erythrocytosis and identifies new mutations. 6
27651169 2016
38
Germline mutations and genotype-phenotype correlation in Asian Indian patients with pheochromocytoma and paraganglioma. 6
27539324 2016
39
Coexistence of VHL Disease and CPT2 Deficiency: A Case Report. 6
27034144 2016
40
Difference in CXCR4 expression between sporadic and VHL-related hemangioblastoma. 6
26920352 2016
41
Pulmonary arterial hypertension associated with a von Hippel-Lindau gene mutation. 6
27578599 2016
42
Phosphorylation-dependent cleavage regulates von Hippel Lindau proteostasis and function. 6
26973240 2016
43
Clinical and molecular characteristics of East Asian patients with von Hippel-Lindau syndrome. 6
27527340 2016
44
Characterization of VHL missense mutations in sporadic clear cell renal cell carcinoma: hotspots, affected binding domains, functional impact on pVHL and therapeutic relevance. 6
27530247 2016
45
Genotype-phenotype analysis of von Hippel-Lindau syndrome in Korean families: HIF-α binding site missense mutations elevate age-specific risk for CNS hemangioblastoma. 6
27439424 2016
46
Germline mutations in the VHL gene associated with 3 different renal lesions in a Chinese von Hippel-Lindau disease family. 6
27057652 2016
47
Characterization of endolymphatic sac tumors and von Hippel-Lindau disease in the International Endolymphatic Sac Tumor Registry. 6
25867206 2016
48
Genotype-phenotype analysis of von Hippel-Lindau syndrome in fifteen Indian families. 6
25952756 2015
49
Novel Homozygous Mutation of the Internal Translation Initiation Start Site of VHL is Exclusively Associated with Erythrocytosis: Indications for Distinct Functional Roles of von Hippel-Lindau Tumor Suppressor Isoforms. 6
26224408 2015
50
From arterial hypertension complications to von Hippel-Lindau syndrome diagnosis. 6
26268347 2015

Variations for Erythrocytosis, Familial, 2

ClinVar genetic disease variations for Erythrocytosis, Familial, 2:

6 (show top 50) (show all 728)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 LOC107303340 , VHL NM_000551.3(VHL):c.571C>G (p.His191Asp) SNV Pathogenic 2235 rs28940301 GRCh37: 3:10191578-10191578
GRCh38: 3:10149894-10149894
2 VHL NM_000551.3(VHL):c.258del (p.Val87fs) Deletion Pathogenic 220487 rs864622545 GRCh37: 3:10183787-10183787
GRCh38: 3:10142103-10142103
3 overlap with 2 genes NC_000003.12:g.(?_10141635)_(10153670_?)del Deletion Pathogenic 417800 GRCh37:
GRCh38: 3:10141635-10153670
4 VHL NM_000551.3(VHL):c.337C>T (p.Arg113Ter) SNV Pathogenic 220414 rs5030810 GRCh37: 3:10183868-10183868
GRCh38: 3:10142184-10142184
5 LOC107303340 , VHL NC_000003.12:g.(?_10146514)_(10146636_?)del Deletion Pathogenic 417615 GRCh37: 3:10188198-10188320
GRCh38: 3:10146514-10146636
6 LOC107303340 and overlap with 1 gene(s) NM_000551.3(VHL):c.464-?_*3705del Deletion Pathogenic 238109 GRCh37: 3:10191471-10195354
GRCh38: 3:10149787-10153670
7 VHL NM_000551.3(VHL):c.226_227del (p.Phe76fs) Deletion Pathogenic 411961 rs1060503552 GRCh37: 3:10183757-10183758
GRCh38: 3:10142073-10142074
8 VHL NC_000003.12:g.(?_10141635)_(10142187_?)del Deletion Pathogenic 417616 GRCh37: 3:10183319-10183871
GRCh38: 3:10141635-10142187
9 LOC107303340 , VHL NM_000551.4(VHL):c.414A>G (p.Pro138=) SNV Pathogenic 223206 rs869025648 GRCh37: 3:10188271-10188271
GRCh38: 3:10146587-10146587
10 LOC107303340 , VHL NM_198156.3(VHL):c.341-3192dup Duplication Pathogenic 411979 rs1553619976 GRCh37: 3:10188277-10188278
GRCh38: 3:10146593-10146594
11 LOC107303340 , VHL NM_000551.3(VHL):c.524A>G (p.Tyr175Cys) SNV Pathogenic 36905 rs193922613 GRCh37: 3:10191531-10191531
GRCh38: 3:10149847-10149847
12 VHL NM_000551.3(VHL):c.264G>T (p.Trp88Cys) SNV Pathogenic 223171 rs869025622 GRCh37: 3:10183795-10183795
GRCh38: 3:10142111-10142111
13 LOC107303340 , VHL NM_000551.3(VHL):c.492G>T (p.Gln164His) SNV Pathogenic 456566 rs1352275281 GRCh37: 3:10191499-10191499
GRCh38: 3:10149815-10149815
14 LOC107303340 , VHL NC_000003.12:g.(?_10146508)_(10149971_?)del Deletion Pathogenic 456563 GRCh37:
GRCh38: 3:10146508-10149971
15 overlap with 7 genes NC_000003.12:g.(?_10064723)_(10149971_?)del Deletion Pathogenic 456559 GRCh37:
GRCh38: 3:10064723-10149971
16 VHL NM_000551.3(VHL):c.257C>G (p.Pro86Arg) SNV Pathogenic 223170 rs730882034 GRCh37: 3:10183788-10183788
GRCh38: 3:10142104-10142104
17 VHL NM_000551.3(VHL):c.331A>T (p.Ser111Cys) SNV Pathogenic 565557 rs1559426203 GRCh37: 3:10183862-10183862
GRCh38: 3:10142178-10142178
18 LOC107303340 , VHL NM_198156.3(VHL):c.341-3244AC[2] Microsatellite Pathogenic 223202 rs869025644 GRCh37: 3:10188227-10188228
GRCh38: 3:10146543-10146544
19 LOC107303340 , VHL NM_000551.3(VHL):c.430G>T (p.Gly144Ter) SNV Pathogenic 223208 rs869025650 GRCh37: 3:10188287-10188287
GRCh38: 3:10146603-10146603
20 LOC107303340 , VHL NM_000551.3(VHL):c.472C>G (p.Leu158Val) SNV Pathogenic 567944 rs1559429613 GRCh37: 3:10191479-10191479
GRCh38: 3:10149795-10149795
21 LOC107303340 , VHL NM_000551.3(VHL):c.463+2T>C SNV Pathogenic 569414 rs5030814 GRCh37: 3:10188322-10188322
GRCh38: 3:10146638-10146638
22 VHL NM_000551.3(VHL):c.334T>C (p.Tyr112His) SNV Pathogenic 2222 rs104893824 GRCh37: 3:10183865-10183865
GRCh38: 3:10142181-10142181
23 VHL NM_000551.3(VHL):c.277G>A (p.Gly93Ser) SNV Pathogenic 2237 rs5030808 GRCh37: 3:10183808-10183808
GRCh38: 3:10142124-10142124
24 VHL NM_000551.3(VHL):c.264G>C (p.Trp88Cys) SNV Pathogenic 580847 rs869025622 GRCh37: 3:10183795-10183795
GRCh38: 3:10142111-10142111
25 LOC107303340 , VHL NM_000551.3(VHL):c.452T>C (p.Ile151Thr) SNV Pathogenic 428803 rs869025655 GRCh37: 3:10188309-10188309
GRCh38: 3:10146625-10146625
26 LOC107303340 , VHL NM_000551.3(VHL):c.355T>C (p.Phe119Leu) SNV Pathogenic 496059 rs1553619948 GRCh37: 3:10188212-10188212
GRCh38: 3:10146528-10146528
27 VHL NM_000551.3(VHL):c.262T>C (p.Trp88Arg) SNV Pathogenic 496053 rs1553619431 GRCh37: 3:10183793-10183793
GRCh38: 3:10142109-10142109
28 LOC107303340 , VHL NM_000551.3(VHL):c.533T>C (p.Leu178Pro) SNV Pathogenic 428795 rs5030822 GRCh37: 3:10191540-10191540
GRCh38: 3:10149856-10149856
29 LOC107303340 , VHL NM_000551.3(VHL):c.500G>T (p.Arg167Leu) SNV Pathogenic 526685 rs5030821 GRCh37: 3:10191507-10191507
GRCh38: 3:10149823-10149823
30 LOC107303340 , VHL NM_198156.3(VHL):c.341-3199TC[2] Microsatellite Pathogenic 223207 rs869025649 GRCh37: 3:10188272-10188273
GRCh38: 3:10146588-10146589
31 LOC107303340 , VHL NM_000551.3(VHL):c.463+1G>A SNV Pathogenic 526679 rs869025657 GRCh37: 3:10188321-10188321
GRCh38: 3:10146637-10146637
32 VHL NM_000551.3(VHL):c.245G>T (p.Arg82Leu) SNV Pathogenic 526675 rs794726890 GRCh37: 3:10183776-10183776
GRCh38: 3:10142092-10142092
33 LOC107303340 , VHL NM_198156.3(VHL):c.341-3179_341-3178del Deletion Pathogenic 223210 rs869025652 GRCh37: 3:10188292-10188293
GRCh38: 3:10146608-10146609
34 VHL NM_000551.3(VHL):c.340G>A (p.Gly114Ser) SNV Pathogenic 583094 rs869025636 GRCh37: 3:10183871-10183871
GRCh38: 3:10142187-10142187
35 VHL NM_000551.3(VHL):c.335A>G (p.Tyr112Cys) SNV Pathogenic 223189 rs869025633 GRCh37: 3:10183866-10183866
GRCh38: 3:10142182-10142182
36 VHL NM_000551.3(VHL):c.339_340+5del Deletion Pathogenic 639348 rs1575922562 GRCh37: 3:10183868-10183874
GRCh38: 3:10142184-10142190
37 LOC107303340 , VHL NM_000551.4(VHL):c.449del Deletion Pathogenic 195093 rs794727253 GRCh37: 3:10188305-10188305
GRCh38: 3:10146621-10146621
38 VHL and overlap with 1 gene(s) NC_000003.12:g.(?_10141838)_(10149975_?)del Deletion Pathogenic 640445 GRCh37: 3:10183522-10191659
GRCh38: 3:10141838-10149975
39 LOC107303340 , VHL NM_000551.3(VHL):c.353T>C (p.Leu118Pro) SNV Pathogenic 428807 rs5030830 GRCh37: 3:10188210-10188210
GRCh38: 3:10146526-10146526
40 LOC107303340 , VHL NM_000551.3(VHL):c.461C>T (p.Pro154Leu) SNV Pathogenic 649525 rs1399097617 GRCh37: 3:10188318-10188318
GRCh38: 3:10146634-10146634
41 LOC107303340 , VHL NM_001354723.2(VHL):c.*94_*97del Deletion Pathogenic 223230 rs869025664 GRCh37: 3:10191547-10191550
GRCh38: 3:10149863-10149866
42 LOC107303340 , VHL NC_000003.12:g.(?_10149777)_(10149975_?)del Deletion Pathogenic 651806 GRCh37: 3:10191461-10191659
GRCh38: 3:10149777-10149975
43 VHL NM_000551.3(VHL):c.291_302del (p.Tyr98_Leu101del) Deletion Pathogenic 656391 rs1575922296 GRCh37: 3:10183822-10183833
GRCh38: 3:10142138-10142149
44 VHL NC_000003.12:g.(?_10141838)_(10142197_?)del Deletion Pathogenic 656836 GRCh37: 3:10183522-10183881
GRCh38: 3:10141838-10142197
45 LOC107303340 , VHL NC_000003.12:g.(?_10146504)_(10149975_?)del Deletion Pathogenic 659603 GRCh37: 3:10188188-10191659
GRCh38: 3:10146504-10149975
46 LOC107303340 , VHL NC_000003.12:g.(?_10146504)_(10146646_?)del Deletion Pathogenic 660147 GRCh37: 3:10188188-10188330
GRCh38: 3:10146504-10146646
47 VHL NM_000551.3(VHL):c.266T>C (p.Leu89Pro) SNV Pathogenic 182979 rs5030807 GRCh37: 3:10183797-10183797
GRCh38: 3:10142113-10142113
48 overlap with 7 genes NC_000003.12:g.(?_10052377)_(10149975_?)del Deletion Pathogenic 665653 GRCh37: 3:10094061-10191659
GRCh38: 3:10052377-10149975
49 LOC107303340 , VHL NM_000551.3(VHL):c.464-2A>G SNV Pathogenic 223222 rs5030816 GRCh37: 3:10191469-10191469
GRCh38: 3:10149785-10149785
50 LOC107303340 , VHL NM_000551.4(VHL):c.501_502insTTGTCCGT Insertion Pathogenic 93329 rs398123483 GRCh37: 3:10191508-10191509
GRCh38: 3:10149824-10149825

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

72
# 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

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
13.13 VHL HIF1AN HIF1A EPO EPAS1 ELOC
2 12.87 VHL HIF1A EPOR EPO EPAS1 ELOC
3 12.19 HIF1AN HIF1A EPAS1 EGLN1 ARNT
4 11.99 VHL ELOC ELOB CUL2
5
Show member pathways
11.8 VHL HIF1A EPAS1 ARNT
6 11.79 VHL HIF1A EPAS1 ELOC ELOB EGLN3
7 11.77 HIF1AN HIF1A EGLN1 ARNT
8 11.69 HIF1A EPO EGLN3 EGLN1 ARNT
9 11.69 VHL HIF1A EPO ELOC ELOB EGLN3
10 11.59 VHL HIF1AN HIF1A EPO ELOC ELOB
11 11.42 HIF1AN HIF1A EPO EGLN1 ARNT
12
Show member pathways
11.39 HIF1AN HIF1A EPAS1 EGLN3 ARNT
13 11.04 VHL HIF1AN HIF1A ELOC ELOB CUL2
14 10.9 VHL SLC11A2 HIF1AN EPO EPAS1 ELOC
15 10.81 VHL EPAS1
16 10.75 SLC11A2 HAMP ACO1
17 10.52 HIF1AN HIF1A
18 10.51 ELOC ELOB

GO Terms for Erythrocytosis, Familial, 2

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

# Name GO ID Score Top Affiliating Genes
1 elongin complex GO:0070449 9.16 ELOC ELOB
2 Cul2-RING ubiquitin ligase complex GO:0031462 9.13 ELOC ELOB CUL2
3 VCB complex GO:0030891 8.8 ELOC ELOB CUL2

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

(show all 21)
# Name GO ID Score Top Affiliating Genes
1 protein ubiquitination GO:0016567 10.01 VHL HIF1A EPAS1 ELOC ELOB CUL2
2 post-translational protein modification GO:0043687 9.91 VHL HIF1A EPAS1 ELOC ELOB CUL2
3 cellular response to hypoxia GO:0071456 9.77 HIF1A EPAS1 EGLN3 EGLN2 EGLN1
4 iron ion homeostasis GO:0055072 9.67 SLC11A2 HAMP EPAS1
5 embryonic placenta development GO:0001892 9.63 HIF1A EPAS1 ARNT
6 regulation of neuron apoptotic process GO:0043523 9.6 EGLN3 EGLN2
7 response to vitamin A GO:0033189 9.59 HAMP EPO
8 positive regulation of vascular endothelial growth factor receptor signaling pathway GO:0030949 9.58 HIF1A ARNT
9 oxygen homeostasis GO:0032364 9.58 HIF1A EGLN1
10 peptidyl-proline hydroxylation to 4-hydroxy-L-proline GO:0018401 9.58 EGLN3 EGLN2 EGLN1
11 multicellular organismal iron ion homeostasis GO:0060586 9.57 SLC11A2 HAMP
12 regulation of protein neddylation GO:2000434 9.56 HIF1A EPAS1
13 response to iron ion GO:0010039 9.56 SLC11A2 HIF1A HAMP CYBRD1
14 response to hypoxia GO:0001666 9.56 SLC11A2 HIF1A EPO EPAS1 EGLN3 EGLN2
15 hemoglobin biosynthetic process GO:0042541 9.55 HIF1A EPO
16 cellular iron ion homeostasis GO:0006879 9.55 SLC11A2 HIF1A HAMP CYBRD1 ACO1
17 negative regulation of transcription from RNA polymerase II promoter in response to hypoxia GO:0061428 9.52 VHL HIF1AN
18 erythropoietin-mediated signaling pathway GO:0038162 9.51 EPOR EPO
19 regulation of transcription from RNA polymerase II promoter in response to oxidative stress GO:0043619 9.5 HIF1A EPAS1 ARNT
20 positive regulation of hormone biosynthetic process GO:0046886 9.48 HIF1A ARNT
21 regulation of transcription from RNA polymerase II promoter in response to hypoxia GO:0061418 9.4 VHL HIF1AN HIF1A EPO EPAS1 ELOC

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

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.85 HIF1AN EGLN3 EGLN2 EGLN1 CYBRD1
2 transcription factor binding GO:0008134 9.78 VHL HIF1A EPAS1 ARNT
3 dioxygenase activity GO:0051213 9.62 HIF1AN EGLN3 EGLN2 EGLN1
4 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen GO:0016705 9.61 EGLN3 EGLN2 EGLN1
5 L-ascorbic acid binding GO:0031418 9.54 EGLN3 EGLN2 EGLN1
6 ferrous iron binding GO:0008198 9.46 HIF1AN EGLN3 EGLN2 EGLN1
7 peptidyl-proline dioxygenase activity GO:0031543 9.43 EGLN3 EGLN2 EGLN1
8 oxygen sensor activity GO:0019826 9.4 HIF1AN EGLN2
9 peptidyl-proline 4-dioxygenase activity GO:0031545 9.13 EGLN3 EGLN2 EGLN1
10 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors GO:0016706 8.92 HIF1AN EGLN3 EGLN2 EGLN1

Sources for Erythrocytosis, Familial, 2

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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