MCID: VNS013
MIFTS: 43

Venous Malformations, Multiple Cutaneous and Mucosal

Categories: Genetic diseases, Cardiovascular diseases, Fetal diseases, Rare diseases

Aliases & Classifications for Venous Malformations, Multiple Cutaneous and Mucosal

MalaCards integrated aliases for Venous Malformations, Multiple Cutaneous and Mucosal:

Name: Venous Malformations, Multiple Cutaneous and Mucosal 57 13 40
Multiple Cutaneous and Mucosal Venous Malformations 12 24 25 29 6 15
Vmcm 57 24 25 59 75
Cutaneous and Mucosal Venous Malformation 59 37
Mucocutaneous Venous Malformations 25 59
Vmcm1 57 25
Dominantly Inherited Venous Malformations 75

Characteristics:

Orphanet epidemiological data:

59
mucocutaneous venous malformations
Inheritance: Autosomal dominant; Age of onset: All ages; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant (9p)


HPO:

32
venous malformations, multiple cutaneous and mucosal:
Inheritance autosomal dominant inheritance


GeneReviews:

24
Penetrance Approximately 90% of individuals who have a germline pathogenic gain-of-function variant in tek develop mucocutaneous venous malformations by age 20 years; conversely, approximately 10% of individuals with a germline gain-of-function tek pathogenic variant are clinically unaffected [boon et al 2004, wouters et al 2010]. reduced penetrance can be explained by the need to acquire a second, somatic pathogenic gain-of-function variant in the wild type or the already mutated tek allele in the target cell(s) to develop a lesion(s) [limaye et al 2009, soblet et al 2017]...

Classifications:



External Ids:

OMIM 57 600195
Disease Ontology 12 DOID:0050792
Orphanet 59 ORPHA2451
UMLS via Orphanet 74 C1838437
ICD10 via Orphanet 34 Q27.8
MedGen 42 C1838437
KEGG 37 H02044

Summaries for Venous Malformations, Multiple Cutaneous and Mucosal

OMIM : 57 Cutaneomucosal venous malformation (VMCM) is an uncommon, heritable form of venous malformation in which lesions tend to be multifocal and small. They are comprised of grossly dilated vascular spaces lined by a single continuous layer of endothelial cells, with areas of relative lack of surrounding mural cells, suggesting a defect in their recruitment. Some VMCM patients have venous malformations located in internal organs, and some have additional anomalies, including cardiac malformations (summary by Wouters et al., 2010). Another form of autosomal dominant venous malformation, blue rubber bleb nevus (112200), is of uncertain relationship to VMCM. Multiple cerebrovenous anomalies without cutaneous lesions are also familial; see cerebral cavernous malformations (116860). Glomuvenous malformations (138000) are similar to but clinically distinguishable from VMCMs. (600195)

MalaCards based summary : Venous Malformations, Multiple Cutaneous and Mucosal, also known as multiple cutaneous and mucosal venous malformations, is related to glomuvenous malformations and gorham's disease. An important gene associated with Venous Malformations, Multiple Cutaneous and Mucosal is TEK (TEK Receptor Tyrosine Kinase), and among its related pathways/superpathways are PI3K-Akt signaling pathway and HIF-1 signaling pathway. Affiliated tissues include endothelial and skin, and related phenotypes are abnormality of the mouth and intestinal bleeding

Disease Ontology : 12 An autosomal dominant disease that is characterized by multiple bluish cutaneous or mucosal venous lesions.

Genetics Home Reference : 25 Multiple cutaneous and mucosal venous malformations (also known as VMCM) are bluish patches (lesions) on the skin (cutaneous) and the mucous membranes, such as the lining of the mouth and nose. These lesions represent areas where the underlying veins and other blood vessels did not develop properly (venous malformations). The lesions can be painful, especially when they extend from the skin into the muscles and joints, or when a calcium deposit forms within the lesion causing inflammation and swelling.

UniProtKB/Swiss-Prot : 75 Dominantly inherited venous malformations: An error of vascular morphogenesis characterized by dilated, serpiginous channels.

GeneReviews: NBK1967

Related Diseases for Venous Malformations, Multiple Cutaneous and Mucosal

Graphical network of the top 20 diseases related to Venous Malformations, Multiple Cutaneous and Mucosal:



Diseases related to Venous Malformations, Multiple Cutaneous and Mucosal

Symptoms & Phenotypes for Venous Malformations, Multiple Cutaneous and Mucosal

Symptoms via clinical synopsis from OMIM:

57
Vascular:
cutaneous and mucosal venous malformations

GI:
variable gastrointestinal bleeding

Mouth:
mucosal bleeding
maxillary and mandibular deformity


Clinical features from OMIM:

600195

Human phenotypes related to Venous Malformations, Multiple Cutaneous and Mucosal:

32
# Description HPO Frequency HPO Source Accession
1 abnormality of the mouth 32 HP:0000153
2 intestinal bleeding 32 HP:0002584
3 venous malformation 32 HP:0012721

GenomeRNAi Phenotypes related to Venous Malformations, Multiple Cutaneous and Mucosal according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased sensitivity to paclitaxel GR00112-A-0 8.96 PTEN SMAD4
2 Increased mitotic index GR00110-A-0 8.8 FLT4 SMAD4 TEK

MGI Mouse Phenotypes related to Venous Malformations, Multiple Cutaneous and Mucosal:

46 (show all 16)
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.45 PDCD10 PTEN RASA1 SMAD4 SOX18 TEK
2 growth/size/body region MP:0005378 10.38 NOTCH4 PDCD10 PTEN RASA1 SMAD4 SOX18
3 embryo MP:0005380 10.34 GLMN KRIT1 NOTCH3 NOTCH4 PDCD10 PTEN
4 mortality/aging MP:0010768 10.32 ACVRL1 AGGF1 CCM2 CDKN2B FLT4 FOXC2
5 cellular MP:0005384 10.28 CCM2 CDKN2B GLMN IKBKG NOTCH3 PDCD10
6 homeostasis/metabolism MP:0005376 10.27 GLMN IKBKG NOTCH3 NOTCH4 PTEN SMAD4
7 behavior/neurological MP:0005386 10.26 ACVRL1 AGGF1 CCM2 IKBKG NOTCH3 PDCD10
8 immune system MP:0005387 10.17 CCM2 CDKN2B FLT4 FOXC2 IKBKG NOTCH3
9 digestive/alimentary MP:0005381 10.11 ACVRL1 FLT4 FOXC2 IKBKG PTEN RASA1
10 integument MP:0010771 10.1 CCM2 CDKN2B FLT4 IKBKG KRIT1 NOTCH3
11 muscle MP:0005369 10.06 ACVRL1 CCM2 FLT4 FOXC2 KRIT1 NOTCH3
12 craniofacial MP:0005382 10 ACVRL1 CCM2 FOXC2 KRIT1 RASA1 SMAD4
13 nervous system MP:0003631 10 ACVRL1 AGGF1 CCM2 FOXC2 GLMN KRIT1
14 neoplasm MP:0002006 9.86 AGGF1 CDKN2B IKBKG KRIT1 NOTCH3 PDCD10
15 normal MP:0002873 9.73 PDCD10 PTEN SMAD4 SOX18 TEK ACVRL1
16 vision/eye MP:0005391 9.23 CCM2 FOXC2 KRIT1 NOTCH3 NOTCH4 PDCD10

Drugs & Therapeutics for Venous Malformations, Multiple Cutaneous and Mucosal

Search Clinical Trials , NIH Clinical Center for Venous Malformations, Multiple Cutaneous and Mucosal

Genetic Tests for Venous Malformations, Multiple Cutaneous and Mucosal

Genetic tests related to Venous Malformations, Multiple Cutaneous and Mucosal:

# Genetic test Affiliating Genes
1 Multiple Cutaneous and Mucosal Venous Malformations 29 TEK

Anatomical Context for Venous Malformations, Multiple Cutaneous and Mucosal

MalaCards organs/tissues related to Venous Malformations, Multiple Cutaneous and Mucosal:

41
Endothelial, Skin

Publications for Venous Malformations, Multiple Cutaneous and Mucosal

Articles related to Venous Malformations, Multiple Cutaneous and Mucosal:

# Title Authors Year
1
Multiple Cutaneous and Mucosal Venous Malformations ( 20301733 )
1993

Variations for Venous Malformations, Multiple Cutaneous and Mucosal

UniProtKB/Swiss-Prot genetic disease variations for Venous Malformations, Multiple Cutaneous and Mucosal:

75
# Symbol AA change Variation ID SNP ID
1 TEK p.Arg849Trp VAR_006352 rs80338908
2 TEK p.Tyr897Ser VAR_008716 rs80338909
3 TEK p.Tyr897Cys VAR_066606 rs80338909
4 TEK p.Arg915His VAR_066607 rs387906745
5 TEK p.Arg918Cys VAR_066608
6 TEK p.Val919Leu VAR_066609
7 TEK p.Ala925Ser VAR_066610
8 TEK p.Lys1100Asn VAR_066611

ClinVar genetic disease variations for Venous Malformations, Multiple Cutaneous and Mucosal:

6
(show top 50) (show all 150)
# Gene Variation Type Significance SNP ID Assembly Location
1 TEK NM_000459.4(TEK): c.2545C> T (p.Arg849Trp) single nucleotide variant Pathogenic rs80338908 GRCh37 Chromosome 9, 27206760: 27206760
2 TEK NM_000459.4(TEK): c.2545C> T (p.Arg849Trp) single nucleotide variant Pathogenic rs80338908 GRCh38 Chromosome 9, 27206762: 27206762
3 TEK NM_000459.4(TEK): c.2690A> C (p.Tyr897Ser) single nucleotide variant Pathogenic rs80338909 GRCh37 Chromosome 9, 27212708: 27212708
4 TEK NM_000459.4(TEK): c.2690A> C (p.Tyr897Ser) single nucleotide variant Pathogenic rs80338909 GRCh38 Chromosome 9, 27212710: 27212710
5 TEK NM_000459.4(TEK): c.2690A> G (p.Tyr897Cys) single nucleotide variant Pathogenic rs80338909 GRCh37 Chromosome 9, 27212708: 27212708
6 TEK NM_000459.4(TEK): c.2690A> G (p.Tyr897Cys) single nucleotide variant Pathogenic rs80338909 GRCh38 Chromosome 9, 27212710: 27212710
7 TEK NM_000459.4(TEK): c.2744G> A (p.Arg915His) single nucleotide variant Pathogenic rs387906745 GRCh37 Chromosome 9, 27212762: 27212762
8 TEK NM_000459.4(TEK): c.2744G> A (p.Arg915His) single nucleotide variant Pathogenic rs387906745 GRCh38 Chromosome 9, 27212764: 27212764
9 TEK NM_000459.4(TEK): c.-96G> A single nucleotide variant Likely benign rs534352362 GRCh38 Chromosome 9, 27109495: 27109495
10 TEK NM_000459.4(TEK): c.-96G> A single nucleotide variant Likely benign rs534352362 GRCh37 Chromosome 9, 27109493: 27109493
11 TEK NM_000459.4(TEK): c.1680T> C (p.Asn560=) single nucleotide variant Benign rs35357088 GRCh37 Chromosome 9, 27197368: 27197368
12 TEK NM_000459.4(TEK): c.1680T> C (p.Asn560=) single nucleotide variant Benign rs35357088 GRCh38 Chromosome 9, 27197370: 27197370
13 TEK NM_000459.4(TEK): c.1798G> T (p.Val600Leu) single nucleotide variant Benign rs35030851 GRCh38 Chromosome 9, 27197488: 27197488
14 TEK NM_000459.4(TEK): c.1798G> T (p.Val600Leu) single nucleotide variant Benign rs35030851 GRCh37 Chromosome 9, 27197486: 27197486
15 TEK NM_000459.4(TEK): c.2170G> A (p.Ala724Thr) single nucleotide variant Benign rs4631561 GRCh37 Chromosome 9, 27203078: 27203078
16 TEK NM_000459.4(TEK): c.2170G> A (p.Ala724Thr) single nucleotide variant Benign rs4631561 GRCh38 Chromosome 9, 27203080: 27203080
17 TEK NM_000459.4(TEK): c.2454G> C (p.Val818=) single nucleotide variant Benign rs55789591 GRCh38 Chromosome 9, 27206671: 27206671
18 TEK NM_000459.4(TEK): c.2454G> C (p.Val818=) single nucleotide variant Benign rs55789591 GRCh37 Chromosome 9, 27206669: 27206669
19 TEK NM_000459.4(TEK): c.3200+12C> G single nucleotide variant Likely benign rs148623971 GRCh37 Chromosome 9, 27220155: 27220155
20 TEK NM_000459.4(TEK): c.3200+12C> G single nucleotide variant Likely benign rs148623971 GRCh38 Chromosome 9, 27220157: 27220157
21 TEK NM_000459.4(TEK): c.*536C> T single nucleotide variant Likely benign rs535524868 GRCh37 Chromosome 9, 27229766: 27229766
22 TEK NM_000459.4(TEK): c.*536C> T single nucleotide variant Likely benign rs535524868 GRCh38 Chromosome 9, 27229768: 27229768
23 TEK NM_000459.4(TEK): c.*788_*789delAT deletion Uncertain significance rs140755654 GRCh38 Chromosome 9, 27230020: 27230021
24 TEK NM_000459.4(TEK): c.*788_*789delAT deletion Uncertain significance rs140755654 GRCh37 Chromosome 9, 27230018: 27230019
25 TEK NM_000459.4(TEK): c.*904T> G single nucleotide variant Uncertain significance rs886063831 GRCh38 Chromosome 9, 27230136: 27230136
26 TEK NM_000459.4(TEK): c.*904T> G single nucleotide variant Uncertain significance rs886063831 GRCh37 Chromosome 9, 27230134: 27230134
27 TEK NM_000459.4(TEK): c.-425A> G single nucleotide variant Likely benign rs149944814 GRCh38 Chromosome 9, 27109166: 27109166
28 TEK NM_000459.4(TEK): c.-425A> G single nucleotide variant Likely benign rs149944814 GRCh37 Chromosome 9, 27109164: 27109164
29 TEK NM_000459.4(TEK): c.138C> T (p.Ala46=) single nucleotide variant Likely benign rs76223779 GRCh38 Chromosome 9, 27157916: 27157916
30 TEK NM_000459.4(TEK): c.138C> T (p.Ala46=) single nucleotide variant Likely benign rs76223779 GRCh37 Chromosome 9, 27157914: 27157914
31 TEK NM_000459.4(TEK): c.1390A> C (p.Asn464His) single nucleotide variant Likely benign rs746069957 GRCh37 Chromosome 9, 27190589: 27190589
32 TEK NM_000459.4(TEK): c.1390A> C (p.Asn464His) single nucleotide variant Likely benign rs746069957 GRCh38 Chromosome 9, 27190591: 27190591
33 TEK NM_000459.4(TEK): c.1456G> A (p.Val486Ile) single nucleotide variant Benign rs1334811 GRCh37 Chromosome 9, 27190655: 27190655
34 TEK NM_000459.4(TEK): c.1456G> A (p.Val486Ile) single nucleotide variant Benign rs1334811 GRCh38 Chromosome 9, 27190657: 27190657
35 TEK NM_000459.4(TEK): c.1565G> T (p.Arg522Leu) single nucleotide variant Likely benign rs138894008 GRCh37 Chromosome 9, 27192562: 27192562
36 TEK NM_000459.4(TEK): c.1565G> T (p.Arg522Leu) single nucleotide variant Likely benign rs138894008 GRCh38 Chromosome 9, 27192564: 27192564
37 TEK NM_000459.4(TEK): c.1834G> A (p.Val612Met) single nucleotide variant Uncertain significance rs764571511 GRCh38 Chromosome 9, 27197524: 27197524
38 TEK NM_000459.4(TEK): c.1834G> A (p.Val612Met) single nucleotide variant Uncertain significance rs764571511 GRCh37 Chromosome 9, 27197522: 27197522
39 TEK NM_000459.4(TEK): c.1973C> A (p.Ser658Tyr) single nucleotide variant Uncertain significance rs886063822 GRCh38 Chromosome 9, 27202883: 27202883
40 TEK NM_000459.4(TEK): c.1973C> A (p.Ser658Tyr) single nucleotide variant Uncertain significance rs886063822 GRCh37 Chromosome 9, 27202881: 27202881
41 TEK NM_000459.4(TEK): c.2052C> T (p.His684=) single nucleotide variant Likely benign rs35818764 GRCh38 Chromosome 9, 27202962: 27202962
42 TEK NM_000459.4(TEK): c.2052C> T (p.His684=) single nucleotide variant Likely benign rs35818764 GRCh37 Chromosome 9, 27202960: 27202960
43 TEK NM_000459.4(TEK): c.2444T> C (p.Ile815Thr) single nucleotide variant Uncertain significance rs777012163 GRCh37 Chromosome 9, 27206659: 27206659
44 TEK NM_000459.4(TEK): c.2444T> C (p.Ile815Thr) single nucleotide variant Uncertain significance rs777012163 GRCh38 Chromosome 9, 27206661: 27206661
45 TEK NM_000459.4(TEK): c.2877+8C> T single nucleotide variant Likely benign rs201140196 GRCh37 Chromosome 9, 27212903: 27212903
46 TEK NM_000459.4(TEK): c.2877+8C> T single nucleotide variant Likely benign rs201140196 GRCh38 Chromosome 9, 27212905: 27212905
47 TEK NM_000459.4(TEK): c.3090G> A (p.Glu1030=) single nucleotide variant Likely benign rs56133834 GRCh37 Chromosome 9, 27218802: 27218802
48 TEK NM_000459.4(TEK): c.3090G> A (p.Glu1030=) single nucleotide variant Likely benign rs56133834 GRCh38 Chromosome 9, 27218804: 27218804
49 TEK NM_000459.4(TEK): c.3104-15C> G single nucleotide variant Likely benign rs766232720 GRCh37 Chromosome 9, 27220032: 27220032
50 TEK NM_000459.4(TEK): c.3104-15C> G single nucleotide variant Likely benign rs766232720 GRCh38 Chromosome 9, 27220034: 27220034

Expression for Venous Malformations, Multiple Cutaneous and Mucosal

Search GEO for disease gene expression data for Venous Malformations, Multiple Cutaneous and Mucosal.

Pathways for Venous Malformations, Multiple Cutaneous and Mucosal

Pathways related to Venous Malformations, Multiple Cutaneous and Mucosal according to KEGG:

37
# Name Kegg Source Accession
1 PI3K-Akt signaling pathway hsa04151
2 HIF-1 signaling pathway hsa04066

GO Terms for Venous Malformations, Multiple Cutaneous and Mucosal

Cellular components related to Venous Malformations, Multiple Cutaneous and Mucosal according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.77 AGGF1 CCM2 CDKN2B FLT4 GLMN IKBKG
2 intrinsic component of the cytoplasmic side of the plasma membrane GO:0031235 8.62 RASA1 SYNGAP1

Biological processes related to Venous Malformations, Multiple Cutaneous and Mucosal according to GeneCards Suite gene sharing:

(show all 27)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of apoptotic process GO:0043066 9.98 FLT4 PDCD10 PTEN RASA1 TEK
2 in utero embryonic development GO:0001701 9.84 ACVRL1 CCM2 SMAD4 SOX18
3 heart development GO:0007507 9.8 CCM2 FOXC2 PTEN SOX18 TEK
4 Notch signaling pathway GO:0007219 9.79 FOXC2 NOTCH3 NOTCH4
5 positive regulation of endothelial cell proliferation GO:0001938 9.67 ACVRL1 AGGF1 FLT4 TEK
6 positive regulation of endothelial cell migration GO:0010595 9.65 FLT4 FOXC2 TEK
7 negative regulation of endothelial cell migration GO:0010596 9.63 ACVRL1 KRIT1
8 negative regulation of axonogenesis GO:0050771 9.63 PTEN SYNGAP1
9 embryonic heart tube development GO:0035050 9.62 FOXC2 SOX18
10 positive regulation of transcription of Notch receptor target GO:0007221 9.62 NOTCH3 NOTCH4
11 blood vessel morphogenesis GO:0048514 9.61 ACVRL1 FLT4 RASA1
12 negative regulation of focal adhesion assembly GO:0051895 9.59 ACVRL1 PTEN
13 negative regulation of endothelial cell differentiation GO:0045602 9.58 ACVRL1 NOTCH4
14 negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle GO:0031658 9.57 CDKN2B PTEN
15 vasculature development GO:0001944 9.56 CCM2 FLT4 NOTCH4 SOX18
16 endothelial tube morphogenesis GO:0061154 9.55 ACVRL1 CCM2
17 lymphatic endothelial cell differentiation GO:0060836 9.52 ACVRL1 SOX18
18 lymph vessel development GO:0001945 9.5 FLT4 FOXC2 SOX18
19 endocardial cell differentiation GO:0060956 9.49 SMAD4 SOX18
20 regulation of developmental process GO:0050793 9.46 NOTCH3 NOTCH4
21 lymphangiogenesis GO:0001946 9.46 ACVRL1 FLT4 FOXC2 SOX18
22 vasculogenesis GO:0001570 9.43 AGGF1 CCM2 FLT4 GLMN RASA1 SOX18
23 angiogenesis GO:0001525 9.23 ACVRL1 AGGF1 FLT4 KRIT1 PDCD10 PTEN
24 multicellular organism development GO:0007275 10.1 AGGF1 CCM2 FLT4 FOXC2 NOTCH3 NOTCH4
25 cell differentiation GO:0030154 10.08 AGGF1 FLT4 FOXC2 NOTCH3 NOTCH4 TEK
26 positive regulation of transcription by RNA polymerase II GO:0045944 10.05 ACVRL1 CDKN2B FOXC2 IKBKG NOTCH3 SMAD4
27 positive regulation of transcription, DNA-templated GO:0045893 10 ACVRL1 FOXC2 NOTCH4 SMAD4 SOX18

Molecular functions related to Venous Malformations, Multiple Cutaneous and Mucosal according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.53 ACVRL1 AGGF1 CCM2 CDKN2B FLT4 FOXC2

Sources for Venous Malformations, Multiple Cutaneous and Mucosal

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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