ECYT4
MCID: ERY032
MIFTS: 36

Erythrocytosis, Familial, 4 (ECYT4)

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

Aliases & Classifications for Erythrocytosis, Familial, 4

MalaCards integrated aliases for Erythrocytosis, Familial, 4:

Name: Erythrocytosis, Familial, 4 57 72 29 13 6 70
Ecyt4 57 12 72
Familial Erythrocytosis 4 12 15
Erythrocytosis, Familial, Type 4 39

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
age at presentation, 16-23 years


HPO:

31
erythrocytosis, familial, 4:
Inheritance autosomal dominant inheritance
Onset and clinical course young adult onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0080339
OMIM® 57 611783
OMIM Phenotypic Series 57 PS133100
MeSH 44 D011086
MedGen 41 C2673187
SNOMED-CT via HPO 68 131141003 263681008
UMLS 70 C2673187

Summaries for Erythrocytosis, Familial, 4

OMIM® : 57 Familial erythrocytosis-4 (ECYT4) is an autosomal dominant disorder characterized by increased serum red blood cell mass and hemoglobin concentration as well as elevated serum erythropoietin (EPO; 133170). For a general phenotypic description and a discussion of genetic heterogeneity of familial erythrocytosis, see ECYT1 (133100). (611783) (Updated 20-May-2021)

MalaCards based summary : Erythrocytosis, Familial, 4, also known as ecyt4, is related to plethora of newborn and autosomal dominant secondary polycythemia. An important gene associated with Erythrocytosis, Familial, 4 is EPAS1 (Endothelial PAS Domain Protein 1), and among its related pathways/superpathways are Pathways in cancer and HIF-1 signaling pathway. Related phenotypes are increased hematocrit and increased hemoglobin

Disease Ontology : 12 A primary polycythemia that has material basis in autosomal dominant inheritance of gain-of-function mutations in the EPAS1 gene on chromosome 2p21.

UniProtKB/Swiss-Prot : 72 Erythrocytosis, familial, 4: An autosomal dominant disorder characterized by elevated serum hemoglobin and hematocrit, and normal platelet and leukocyte counts.

Related Diseases for Erythrocytosis, Familial, 4

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, 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 24)
# Related Disease Score Top Affiliating Genes
1 plethora of newborn 10.0 EPAS1 EGLN1
2 autosomal dominant secondary polycythemia 10.0 EPAS1 EGLN1
3 duodenal somatostatinoma 10.0 EPAS1 EGLN1
4 sporadic pheochromocytoma/secreting paraganglioma 10.0 VHL EPAS1
5 persistent generalized lymphadenopathy 9.9 EPAS1 EGLN1
6 retinal hemangioblastoma 9.9 VHL EPAS1
7 ichthyosis, congenital, autosomal recessive 11 9.9 EPAS1 EGLN1
8 pheochromocytoma-paraganglioma 9.9 VHL EGLN1
9 acute mountain sickness 9.8 VHL EGLN1
10 erythrocytosis, familial, 8 9.7 EPOR EGLN1 BPGM
11 erythrocytosis, familial, 1 9.7 EPOR EGLN1 BPGM
12 esophagus leiomyoma 9.7 VHL EPAS1 EGLN1
13 familial isolated hypoparathyroidism 9.7 VHL EGLN1
14 hemangioblastoma 9.7 VHL EPOR EPAS1
15 paraganglioma 9.7 VHL EPAS1 EGLN1
16 hypoxia 9.7 VHL EPAS1 EGLN1
17 erythrocytosis, familial, 3 9.6 LINS1 EGLN1 BPGM
18 clear cell renal cell carcinoma 9.6 VHL EPOR EPAS1
19 acquired polycythemia 9.5 EPOR EPAS1 EGLN1 BPGM
20 polycythemia 9.4 VHL EPOR EPAS1 EGLN1
21 erythrocytosis, familial, 2 9.4 VHL EPOR EPAS1 EGLN1
22 pheochromocytoma 9.4 VHL EPOR EPAS1 EGLN1
23 renal cell carcinoma, nonpapillary 9.4 VHL EPAS1 EGLN1
24 primary polycythemia 9.2 VHL EPOR EPAS1 EGLN1 BPGM

Graphical network of the top 20 diseases related to Erythrocytosis, Familial, 4:



Diseases related to Erythrocytosis, Familial, 4

Symptoms & Phenotypes for Erythrocytosis, Familial, 4

Human phenotypes related to Erythrocytosis, Familial, 4:

31
# Description HPO Frequency HPO Source Accession
1 increased hematocrit 31 HP:0001899
2 increased hemoglobin 31 HP:0001900

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
headache

Cardiovascular Vascular:
deep vein thrombosis
mesenteric thrombosis

Hematology:
increased hematocrit
increased red blood cell mass
increased hemoglobin
erythrocytosis
normal platelet count

Laboratory Abnormalities:
increased serum erythropoietin

Clinical features from OMIM®:

611783 (Updated 20-May-2021)

MGI Mouse Phenotypes related to Erythrocytosis, Familial, 4:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 9.65 BPGM EGLN1 EPAS1 EPOR VHL
2 immune system MP:0005387 9.55 BPGM EGLN1 EPAS1 EPOR VHL
3 liver/biliary system MP:0005370 9.26 EGLN1 EPAS1 EPOR VHL
4 mortality/aging MP:0010768 9.1 BPGM EGLN1 EPAS1 EPOR LINS1 VHL

Drugs & Therapeutics for Erythrocytosis, Familial, 4

Search Clinical Trials , NIH Clinical Center for Erythrocytosis, Familial, 4

Genetic Tests for Erythrocytosis, Familial, 4

Genetic tests related to Erythrocytosis, Familial, 4:

# Genetic test Affiliating Genes
1 Erythrocytosis, Familial, 4 29 EPAS1

Anatomical Context for Erythrocytosis, Familial, 4

Publications for Erythrocytosis, Familial, 4

Articles related to Erythrocytosis, Familial, 4:

# Title Authors PMID Year
1
Novel exon 12 mutations in the HIF2A gene associated with erythrocytosis. 57 6
18378852 2008
2
A gain-of-function mutation in the HIF2A gene in familial erythrocytosis. 57 6
18184961 2008
3
Erythrocytosis-associated HIF-2alpha mutations demonstrate a critical role for residues C-terminal to the hydroxylacceptor proline. 6
19208626 2009
4
The HIF2A gene in familial erythrocytosis. 57
18456918 2008

Variations for Erythrocytosis, Familial, 4

ClinVar genetic disease variations for Erythrocytosis, Familial, 4:

6 (show top 50) (show all 133)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 EPAS1 NM_001430.5(EPAS1):c.1609G>T (p.Gly537Trp) SNV Pathogenic 6468 rs137853036 GRCh37: 2:46607420-46607420
GRCh38: 2:46380281-46380281
2 EPAS1 NM_001430.5(EPAS1):c.1609G>A (p.Gly537Arg) SNV Pathogenic 6469 rs137853036 GRCh37: 2:46607420-46607420
GRCh38: 2:46380281-46380281
3 EPAS1 NM_001430.5(EPAS1):c.1603A>G (p.Met535Val) SNV Pathogenic 6470 rs137853037 GRCh37: 2:46607414-46607414
GRCh38: 2:46380275-46380275
4 EPAS1 NM_001430.5(EPAS1):c.1121T>A (p.Phe374Tyr) SNV Conflicting interpretations of pathogenicity 336261 rs150797491 GRCh37: 2:46603764-46603764
GRCh38: 2:46376625-46376625
5 EPAS1 NM_001430.5(EPAS1):c.-231C>G SNV Uncertain significance 336225 rs750848838 GRCh37: 2:46524820-46524820
GRCh38: 2:46297681-46297681
6 EPAS1 NM_001430.5(EPAS1):c.*898C>T SNV Uncertain significance 894840 GRCh37: 2:46612697-46612697
GRCh38: 2:46385558-46385558
7 EPAS1 NM_001430.5(EPAS1):c.*1917G>A SNV Uncertain significance 894907 GRCh37: 2:46613716-46613716
GRCh38: 2:46386577-46386577
8 EPAS1 NM_001430.5(EPAS1):c.-401G>A SNV Uncertain significance 895789 GRCh37: 2:46524650-46524650
GRCh38: 2:46297511-46297511
9 EPAS1 NM_001430.5(EPAS1):c.-357G>C SNV Uncertain significance 895790 GRCh37: 2:46524694-46524694
GRCh38: 2:46297555-46297555
10 EPAS1 NM_001430.5(EPAS1):c.-237C>G SNV Uncertain significance 895791 GRCh37: 2:46524814-46524814
GRCh38: 2:46297675-46297675
11 EPAS1 NM_001430.5(EPAS1):c.591C>A (p.Gly197=) SNV Uncertain significance 895867 GRCh37: 2:46588041-46588041
GRCh38: 2:46360902-46360902
12 EPAS1 NM_001430.5(EPAS1):c.-92G>A SNV Uncertain significance 896076 GRCh37: 2:46524959-46524959
GRCh38: 2:46297820-46297820
13 EPAS1 NM_001430.5(EPAS1):c.*1182G>A SNV Uncertain significance 896277 GRCh37: 2:46612981-46612981
GRCh38: 2:46385842-46385842
14 EPAS1 NM_001430.5(EPAS1):c.192G>T (p.Leu64=) SNV Uncertain significance 897665 GRCh37: 2:46574177-46574177
GRCh38: 2:46347038-46347038
15 EPAS1 NM_001430.5(EPAS1):c.1203C>A (p.Ala401=) SNV Uncertain significance 897741 GRCh37: 2:46603846-46603846
GRCh38: 2:46376707-46376707
16 EPAS1 NM_001430.5(EPAS1):c.1248C>T (p.Phe416=) SNV Uncertain significance 897742 GRCh37: 2:46603891-46603891
GRCh38: 2:46376752-46376752
17 EPAS1 NM_001430.5(EPAS1):c.1281T>C (p.Tyr427=) SNV Uncertain significance 435064 rs947956425 GRCh37: 2:46605064-46605064
GRCh38: 2:46377925-46377925
18 EPAS1 NM_001430.5(EPAS1):c.*150T>G SNV Uncertain significance 897813 GRCh37: 2:46611949-46611949
GRCh38: 2:46384810-46384810
19 EPAS1 NM_001430.5(EPAS1):c.*285C>G SNV Uncertain significance 897815 GRCh37: 2:46612084-46612084
GRCh38: 2:46384945-46384945
20 EPAS1 NM_001430.5(EPAS1):c.*1305G>A SNV Uncertain significance 897892 GRCh37: 2:46613104-46613104
GRCh38: 2:46385965-46385965
21 EPAS1 NM_001430.5(EPAS1):c.*1373C>G SNV Uncertain significance 897893 GRCh37: 2:46613172-46613172
GRCh38: 2:46386033-46386033
22 EPAS1 NM_001430.5(EPAS1):c.*1611A>G SNV Uncertain significance 897895 GRCh37: 2:46613410-46613410
GRCh38: 2:46386271-46386271
23 EPAS1 NM_001430.5(EPAS1):c.1821C>T (p.Ile607=) SNV Uncertain significance 898893 GRCh37: 2:46607632-46607632
GRCh38: 2:46380493-46380493
24 EPAS1 NM_001430.5(EPAS1):c.1960G>A (p.Val654Ile) SNV Uncertain significance 898894 GRCh37: 2:46607771-46607771
GRCh38: 2:46380632-46380632
25 EPAS1 NM_001430.5(EPAS1):c.*408T>C SNV Uncertain significance 898964 GRCh37: 2:46612207-46612207
GRCh38: 2:46385068-46385068
26 EPAS1 NM_001430.5(EPAS1):c.*537T>G SNV Uncertain significance 898966 GRCh37: 2:46612336-46612336
GRCh38: 2:46385197-46385197
27 EPAS1 NM_001430.5(EPAS1):c.*1729T>C SNV Uncertain significance 899031 GRCh37: 2:46613528-46613528
GRCh38: 2:46386389-46386389
28 EPAS1 NM_001430.5(EPAS1):c.*1898C>A SNV Uncertain significance 899032 GRCh37: 2:46613697-46613697
GRCh38: 2:46386558-46386558
29 EPAS1 NM_001430.5(EPAS1):c.2367C>T (p.Ile789=) SNV Uncertain significance 336277 rs755579146 GRCh37: 2:46609643-46609643
GRCh38: 2:46382504-46382504
30 EPAS1 NM_001430.5(EPAS1):c.*594A>G SNV Uncertain significance 336294 rs886056093 GRCh37: 2:46612393-46612393
GRCh38: 2:46385254-46385254
31 EPAS1 NM_001430.5(EPAS1):c.-86C>T SNV Uncertain significance 336231 rs886056083 GRCh37: 2:46524965-46524965
GRCh38: 2:46297826-46297826
32 EPAS1 NM_001430.5(EPAS1):c.26+8G>A SNV Uncertain significance 336234 rs750007571 GRCh37: 2:46525084-46525084
GRCh38: 2:46297945-46297945
33 EPAS1 NM_001430.5(EPAS1):c.861G>A (p.Glu287=) SNV Uncertain significance 336254 rs886056085 GRCh37: 2:46597047-46597047
GRCh38: 2:46369908-46369908
34 EPAS1 NM_001430.5(EPAS1):c.*1278C>T SNV Uncertain significance 336314 rs545916994 GRCh37: 2:46613077-46613077
GRCh38: 2:46385938-46385938
35 EPAS1 NM_001430.5(EPAS1):c.-452A>C SNV Uncertain significance 336220 rs886056076 GRCh37: 2:46524599-46524599
GRCh38: 2:46297460-46297460
36 EPAS1 NM_001430.5(EPAS1):c.2474G>A (p.Arg825Gln) SNV Uncertain significance 336280 rs374829070 GRCh37: 2:46611660-46611660
GRCh38: 2:46384521-46384521
37 EPAS1 NM_001430.5(EPAS1):c.*117T>A SNV Uncertain significance 336286 rs886056089 GRCh37: 2:46611916-46611916
GRCh38: 2:46384777-46384777
38 EPAS1 NM_001430.5(EPAS1):c.-316C>A SNV Uncertain significance 336223 rs886056078 GRCh37: 2:46524735-46524735
GRCh38: 2:46297596-46297596
39 EPAS1 NM_001430.5(EPAS1):c.-111G>C SNV Uncertain significance 336229 rs530436826 GRCh37: 2:46524940-46524940
GRCh38: 2:46297801-46297801
40 EPAS1 NM_001430.5(EPAS1):c.-200A>C SNV Uncertain significance 336226 rs886056080 GRCh37: 2:46524851-46524851
GRCh38: 2:46297712-46297712
41 EPAS1 NM_001430.5(EPAS1):c.2107T>G (p.Ser703Ala) SNV Uncertain significance 336272 rs886056088 GRCh37: 2:46608796-46608796
GRCh38: 2:46381657-46381657
42 EPAS1 NM_001430.5(EPAS1):c.2392A>G (p.Arg798Gly) SNV Uncertain significance 336278 rs541354758 GRCh37: 2:46609668-46609668
GRCh38: 2:46382529-46382529
43 EPAS1 NM_001430.5(EPAS1):c.2496G>C (p.Glu832Asp) SNV Uncertain significance 336281 rs183095352 GRCh37: 2:46611682-46611682
GRCh38: 2:46384543-46384543
44 EPAS1 NM_001430.5(EPAS1):c.*1134T>C SNV Uncertain significance 336306 rs886056100 GRCh37: 2:46612933-46612933
GRCh38: 2:46385794-46385794
45 EPAS1 NM_001430.5(EPAS1):c.882G>C (p.Gln294His) SNV Uncertain significance 336255 rs769949241 GRCh37: 2:46597068-46597068
GRCh38: 2:46369929-46369929
46 EPAS1 NM_001430.5(EPAS1):c.*1290C>T SNV Uncertain significance 336315 rs780890954 GRCh37: 2:46613089-46613089
GRCh38: 2:46385950-46385950
47 EPAS1 NM_001430.5(EPAS1):c.*1790G>A SNV Uncertain significance 336321 rs532892029 GRCh37: 2:46613589-46613589
GRCh38: 2:46386450-46386450
48 EPAS1 NM_001430.5(EPAS1):c.*1620G>C SNV Uncertain significance 336318 rs886056102 GRCh37: 2:46613419-46613419
GRCh38: 2:46386280-46386280
49 EPAS1 NM_001430.5(EPAS1):c.*1916C>A SNV Uncertain significance 336324 rs886056104 GRCh37: 2:46613715-46613715
GRCh38: 2:46386576-46386576
50 EPAS1 NM_001430.5(EPAS1):c.1263C>T (p.Phe421=) SNV Uncertain significance 336264 rs142534349 GRCh37: 2:46605046-46605046
GRCh38: 2:46377907-46377907

UniProtKB/Swiss-Prot genetic disease variations for Erythrocytosis, Familial, 4:

72
# Symbol AA change Variation ID SNP ID
1 EPAS1 p.Gly537Trp VAR_042443 rs137853036
2 EPAS1 p.Pro534Leu VAR_067358
3 EPAS1 p.Met535Thr VAR_067359
4 EPAS1 p.Met535Val VAR_067360 rs137853037
5 EPAS1 p.Gly537Arg VAR_067361 rs137853036
6 EPAS1 p.Phe540Leu VAR_067362

Expression for Erythrocytosis, Familial, 4

Search GEO for disease gene expression data for Erythrocytosis, Familial, 4.

Pathways for Erythrocytosis, Familial, 4

Pathways related to Erythrocytosis, Familial, 4 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 12.18 VHL EPOR EPAS1 EGLN1
2 11.44 VHL EGLN1
3
Show member pathways
11.33 VHL EPAS1
4 11.05 VHL EGLN1
5 10.97 VHL EPAS1 EGLN1
6 10.49 VHL EPAS1
7 10.33 VHL EPAS1 EGLN1

GO Terms for Erythrocytosis, Familial, 4

Biological processes related to Erythrocytosis, Familial, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular response to hypoxia GO:0071456 8.96 EPAS1 EGLN1
2 regulation of transcription from RNA polymerase II promoter in response to hypoxia GO:0061418 8.8 VHL EPAS1 EGLN1

Sources for Erythrocytosis, Familial, 4

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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