EVR4
MCID: EXD004
MIFTS: 42

Exudative Vitreoretinopathy 4 (EVR4)

Categories: Blood diseases, Cardiovascular diseases, Eye diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Exudative Vitreoretinopathy 4

MalaCards integrated aliases for Exudative Vitreoretinopathy 4:

Name: Exudative Vitreoretinopathy 4 57 12 29 13 6 15 71
Evr4 57 12 73
Vitreoretinopathy, Exudative, Type 4 39
Vitreoretinopathy, Exudative 4 73

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
clinical variability
onset in infancy or early childhood
some patients may be asymptomatic
absence of premature birth, low birthweight, and exposure to oxygen
allelic disorder to osteoporosis-pseudoglioma syndrome (oppg, )
genetic heterogeneity, see evr1


HPO:

31
exudative vitreoretinopathy 4:
Inheritance autosomal dominant inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0111411
OMIM® 57 601813
OMIM Phenotypic Series 57 PS133780
MeSH 44 D012164
MedGen 41 C1866176
UMLS 71 C1866176

Summaries for Exudative Vitreoretinopathy 4

OMIM® : 57 Familial exudative vitreoretinopathy (FEVR) is an inherited disorder characterized by the incomplete development of the retinal vasculature. Its clinical appearance varies considerably, even within families, with severely affected patients often registered as blind during infancy, whereas mildly affected patients with few or no visual problems may have such a small area of avascularity in their peripheral retina that it is visible only by fluorescein angiography. It is believed that this peripheral avascularity is the primary anomaly in FEVR and results from defective retinal angiogenesis. The sight-threatening features of the FEVR phenotype are considered secondary to retinal avascularity and develop because of the resulting retinal ischemia; they include the development of hyperpermeable blood vessels, neovascularization, vitreoretinal traction, retinal folds, and retinal detachments (summary by Poulter et al., 2010). For a discussion of genetic heterogeneity of familial exudative vitreoretinopathy, see EVR1 (133780). (601813) (Updated 05-Mar-2021)

MalaCards based summary : Exudative Vitreoretinopathy 4, also known as evr4, is related to exudative vitreoretinopathy 2, x-linked and vitreoretinopathy. An important gene associated with Exudative Vitreoretinopathy 4 is LRP5 (LDL Receptor Related Protein 5), and among its related pathways/superpathways are Signaling by Wnt and Pathways in cancer. Affiliated tissues include retina and bone, and related phenotypes are osteopenia and blindness

Disease Ontology : 12 An exudative vitreoretinopathy that has material basis in homozygous, compound heterozygous, or heterozygous mutation in LRP5 on chromosome 11q13.2.

UniProtKB/Swiss-Prot : 73 Vitreoretinopathy, exudative 4: A disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery.

Related Diseases for Exudative Vitreoretinopathy 4

Graphical network of the top 20 diseases related to Exudative Vitreoretinopathy 4:



Diseases related to Exudative Vitreoretinopathy 4

Symptoms & Phenotypes for Exudative Vitreoretinopathy 4

Human phenotypes related to Exudative Vitreoretinopathy 4:

31 (show all 12)
# Description HPO Frequency HPO Source Accession
1 osteopenia 31 HP:0000938
2 blindness 31 HP:0000618
3 reduced visual acuity 31 HP:0007663
4 vitreous hemorrhage 31 HP:0007902
5 retinal exudate 31 HP:0001147
6 tractional retinal detachment 31 HP:0007917
7 subcapsular cataract 31 HP:0000523
8 horizontal pendular nystagmus 31 HP:0007811
9 exudative vitreoretinopathy 31 HP:0030490
10 peripheral retinal avascularization 31 HP:0007685
11 posterior vitreous detachment 31 HP:0001489
12 falciform retinal fold 31 HP:0001493

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Head And Neck Eyes:
blindness
vitreous hemorrhage
tractional retinal detachment
horizontal pendular nystagmus
peripheral retinal avascularization
more
Skeletal:
decreased bone mineral density

Clinical features from OMIM®:

601813 (Updated 05-Mar-2021)

MGI Mouse Phenotypes related to Exudative Vitreoretinopathy 4:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hearing/vestibular/ear MP:0005377 9.35 FZD3 FZD4 NDP NXN TSPAN12
2 vision/eye MP:0005391 9.17 FZD3 FZD4 LRP5 MYOC NDP NXN

Drugs & Therapeutics for Exudative Vitreoretinopathy 4

Search Clinical Trials , NIH Clinical Center for Exudative Vitreoretinopathy 4

Genetic Tests for Exudative Vitreoretinopathy 4

Genetic tests related to Exudative Vitreoretinopathy 4:

# Genetic test Affiliating Genes
1 Exudative Vitreoretinopathy 4 29 LRP5

Anatomical Context for Exudative Vitreoretinopathy 4

MalaCards organs/tissues related to Exudative Vitreoretinopathy 4:

40
Retina, Bone

Publications for Exudative Vitreoretinopathy 4

Articles related to Exudative Vitreoretinopathy 4:

# Title Authors PMID Year
1
Identification of a fourth locus (EVR4) for familial exudative vitreoretinopathy (FEVR). 57 61
14737064 2004
2
Mutations in TSPAN12 cause autosomal-dominant familial exudative vitreoretinopathy. 57
20159112 2010
3
Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes. 57
15981244 2005
4
Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5. 57
15346351 2004
5
Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q. 57
15024691 2004
6
Autosomal recessive familial exudative vitreoretinopathy: evidence for genetic heterogeneity. 57
9831343 1998
7
Familial exudative vitreoretinopathy: further evidence for genetic heterogeneity. 57
9056564 1997
8
Familial exudative vitreoretinopathy linked to D11S533 in a large Asian family with consanguinity. 57
8832721 1996
9
Biosurfactant mediated bioelectrokinetic remediation of diesel contaminated environment. 61
33017706 2021
10
Further evidence of genetic heterogeneity in familial exudative vitreoretinopathy; exclusion of EVR1, EVR3, and EVR4 in a large autosomal dominant pedigree. 61
15665352 2005

Variations for Exudative Vitreoretinopathy 4

ClinVar genetic disease variations for Exudative Vitreoretinopathy 4:

6
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 LRP5 NM_002335.4(LRP5):c.2737dup (p.Cys913fs) Duplication Pathogenic 287187 rs886043590 11:68181389-68181390 11:68413921-68413922
2 LRP5 NM_002335.4(LRP5):c.917G>A (p.Cys306Tyr) SNV Likely pathogenic 915421 11:68133072-68133072 11:68365604-68365604
3 LRP5 NM_002335.4(LRP5):c.1270G>A (p.Asp424Asn) SNV Likely pathogenic 982389 11:68154038-68154038 11:68386570-68386570
4 LRP5 NM_002335.4(LRP5):c.3361A>G (p.Asn1121Asp) SNV Uncertain significance 225407 rs80358317 11:68192694-68192694 11:68425226-68425226
5 LRP5 NM_002335.4(LRP5):c.883+20C>T SNV Uncertain significance 930443 11:68131431-68131431 11:68363963-68363963
6 LRP5 NM_002335.4(LRP5):c.2581A>T (p.Thr861Ser) SNV Uncertain significance 930787 11:68181234-68181234 11:68413766-68413766
7 LRP5 NM_002335.4(LRP5):c.4328C>A (p.Ser1443Tyr) SNV Uncertain significance 931357 11:68206130-68206130 11:68438662-68438662
8 LRP5 NM_002335.4(LRP5):c.1199C>T (p.Ala400Val) SNV Uncertain significance 520692 rs201320326 11:68153967-68153967 11:68386499-68386499
9 LRP5 NM_002335.4(LRP5):c.3107G>A (p.Arg1036Gln) SNV Uncertain significance 183255 rs61889560 11:68191036-68191036 11:68423568-68423568
10 LRP5 NM_002335.4(LRP5):c.4488G>A (p.Pro1496=) SNV Uncertain significance 635003 rs1565118560 11:68207384-68207384 11:68439916-68439916

UniProtKB/Swiss-Prot genetic disease variations for Exudative Vitreoretinopathy 4:

73 (show all 20)
# Symbol AA change Variation ID SNP ID
1 LRP5 p.Thr173Met VAR_018465 rs80358306
2 LRP5 p.Tyr1168His VAR_018466 rs80358318
3 LRP5 p.Cys1361Gly VAR_018467 rs80358320
4 LRP5 p.Arg570Gln VAR_021222 rs80358312
5 LRP5 p.Arg752Gly VAR_021223 rs121908674
6 LRP5 p.Glu1367Lys VAR_021224 rs28939709
7 LRP5 p.Leu145Phe VAR_063943 rs80358305
8 LRP5 p.Glu441Lys VAR_063956 rs376152274
9 LRP5 p.Arg444Cys VAR_063957 rs80358308
10 LRP5 p.Asp511Ala VAR_063962 rs124562520
11 LRP5 p.Ala522Thr VAR_063964 rs80358309
12 LRP5 p.Thr535Met VAR_063966 rs80358310
13 LRP5 p.Gly550Arg VAR_063967 rs80358311
14 LRP5 p.Gly610Arg VAR_063968 rs80358313
15 LRP5 p.Phe617Cys VAR_063969 rs80358314
16 LRP5 p.Thr798Ala VAR_063972 rs80358316
17 LRP5 p.Arg805Trp VAR_063973 rs765952535
18 LRP5 p.Cys1253Phe VAR_063978 rs768615287
19 LRP5 p.Ala422Thr VAR_071012 rs774342727
20 LRP5 p.Leu540Pro VAR_071013

Expression for Exudative Vitreoretinopathy 4

Search GEO for disease gene expression data for Exudative Vitreoretinopathy 4.

Pathways for Exudative Vitreoretinopathy 4

Pathways related to Exudative Vitreoretinopathy 4 according to GeneCards Suite gene sharing:

(show all 18)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.57 WNT16 LRP5 FZD4 FZD3
2 12.5 WNT16 LRP5 FZD4 FZD3
3
Show member pathways
12.37 WNT16 LRP5 FZD4 FZD3
4
Show member pathways
12.2 WNT16 FZD4 FZD3
5
Show member pathways
12.14 WNT16 FZD4 FZD3
6
Show member pathways
12.14 WNT16 LRP5 FZD4 FZD3
7
Show member pathways
12.03 WNT16 FZD4 FZD3
8 12.01 WNT16 FZD4 FZD3
9 11.96 WNT16 LRP5 FZD4 FZD3
10 11.87 WNT16 FZD4 FZD3
11 11.76 WNT16 FZD4 FZD3
12
Show member pathways
11.71 WNT16 LRP5 FZD4 FZD3
13 11.64 LRP5 FZD4 FZD3
14 11.47 WNT16 LRP5 FZD4 FZD3
15 11.33 WNT16 FZD4 FZD3
16 11.13 WNT16 LRP5 FZD4 FZD3
17
Show member pathways
11.05 LRP5 FZD4
18 10.99 LRP5 FZD4

GO Terms for Exudative Vitreoretinopathy 4

Biological processes related to Exudative Vitreoretinopathy 4 according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.8 WNT16 NXN LRP5 FZD4 FZD3
2 cell surface receptor signaling pathway GO:0007166 9.69 TSPAN12 FZD4 FZD3
3 neuron differentiation GO:0030182 9.63 WNT16 FZD4 FZD3
4 canonical Wnt signaling pathway GO:0060070 9.56 WNT16 LRP5 FZD4 FZD3
5 positive regulation of phosphatidylinositol 3-kinase signaling GO:0014068 9.55 WNT16 MYOC
6 Wnt signaling pathway, planar cell polarity pathway GO:0060071 9.54 FZD4 FZD3
7 positive regulation of DNA-binding transcription factor activity GO:0051091 9.54 NDP LRP5 FZD4
8 bone development GO:0060348 9.52 MYOC LRP5
9 Wnt signaling pathway, calcium modulating pathway GO:0007223 9.49 FZD4 FZD3
10 non-canonical Wnt signaling pathway GO:0035567 9.48 FZD4 FZD3
11 bone remodeling GO:0046849 9.43 WNT16 LRP5
12 retina vasculature morphogenesis in camera-type eye GO:0061299 9.33 NDP LRP5 FZD4
13 retinal blood vessel morphogenesis GO:0061304 9.32 LRP5 FZD4
14 Wnt signaling pathway GO:0016055 9.17 WNT16 TSPAN12 NXN NDP LRP5 FZD4
15 extracellular matrix-cell signaling GO:0035426 9.13 NDP LRP5 FZD4

Molecular functions related to Exudative Vitreoretinopathy 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 frizzled binding GO:0005109 9.33 WNT16 NDP MYOC
2 PDZ domain binding GO:0030165 9.26 FZD4 FZD3
3 Wnt-protein binding GO:0017147 9.13 LRP5 FZD4 FZD3
4 Wnt-activated receptor activity GO:0042813 8.92 TSPAN12 LRP5 FZD4 FZD3

Sources for Exudative Vitreoretinopathy 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 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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