WSN1
MCID: WHT013
MIFTS: 45

White Sponge Nevus 1 (WSN1)

Categories: Genetic diseases, Rare diseases, Skin diseases

Aliases & Classifications for White Sponge Nevus 1

MalaCards integrated aliases for White Sponge Nevus 1:

Name: White Sponge Nevus 1 58 76 74
White Sponge Nevus of Cannon 58 12 54 26 60 76 30 6 41
White Sponge Nevus 12 77 26 60 38 13
Leukokeratosis, Hereditary Mucosal 58 54 26 45 74
Hereditary Mucosal Leukokeratosis 12 26 60 76 15
Wsn1 58 76
Wsn 54 26
Familial White Folded Mucosal Dysplasia 26
White Folded Gingivostomatosis 26
Leukokeratosis of Oral Mucosa 26
White Sponge Nevus of Mucosa 26
Hereditary Leukokeratosis 26
Hereditary Oral Keratosis 26
White Gingivostomatitis 26
White Sponge Naevus 26
Cannon's Disease 26
Nevus of Cannon 26

Characteristics:

Orphanet epidemiological data:

60
white sponge nevus
Inheritance: Autosomal dominant;

OMIM:

58
Inheritance:
autosomal dominant


HPO:

33
white sponge nevus 1:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 60  
Rare skin diseases


External Ids:

Disease Ontology 12 DOID:0050448
OMIM 58 193900
KEGG 38 H00724
MeSH 45 D053529
NCIt 51 C84760
SNOMED-CT 69 62953009 85388002
ICD10 via Orphanet 35 Q38.6
UMLS via Orphanet 75 C1721005
Orphanet 60 ORPHA171723
SNOMED-CT via HPO 70 263681008 414603003 9187004

Summaries for White Sponge Nevus 1

OMIM : 58 White sponge nevus is a rare autosomal dominant disorder of noncornifying squamous epithelial differentiation that presents clinically as white, soft, thick plaques of the oral mucosa. Less frequently, the mucous membranes of the nose, esophagus, genitalia, and rectum are involved. Histopathologic features, including epithelial thickening, parakeratosis, extensive vacuolization of the suprabasal keratinocytes, and compact aggregates of keratin intermediate filaments in the upper spinus layers resemble those found in epidermal disorders shown to be associated with keratin defects (summary by Richard et al., 1995). (193900)

MalaCards based summary : White Sponge Nevus 1, also known as white sponge nevus of cannon, is related to leukoplakia and pachyonychia congenita 1. An important gene associated with White Sponge Nevus 1 is KRT4 (Keratin 4), and among its related pathways/superpathways are Developmental Biology and Circadian entrainment. Affiliated tissues include skin and tongue, and related phenotypes are abnormality of metabolism/homeostasis and oral leukoplakia

Disease Ontology : 12 A skin disease characterized by a defect in the normal process of keratinization of the mucosa.

Genetics Home Reference : 26 White sponge nevus is a condition characterized by the formation of white patches of tissue called nevi (singular: nevus) that appear as thickened, velvety, sponge-like tissue. The nevi are most commonly found on the moist lining of the mouth (oral mucosa), especially on the inside of the cheeks (buccal mucosa). Affected individuals usually develop multiple nevi. Rarely, white sponge nevi also occur on the mucosae (singular: mucosa) of the nose, esophagus, genitals, or anus. The nevi are caused by a noncancerous (benign) overgrowth of cells.

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 171723Disease definitionWhite sponge nevus (WSN) is a rare and autosomal dominant genetic disease in which the oral mucosa is white or greyish, thickened, folded, and spongy. The onset is early in life, and both sexes are affected equally. Other common sites include the tongue, floor of the mouth, and alveolar mucosa.Visit the Orphanet disease page for more resources.

UniProtKB/Swiss-Prot : 76 White sponge nevus 1: A rare disorder characterized by the presence of soft, white, and spongy plaques in the oral mucosa. The characteristic histopathologic features are epithelial thickening, parakeratosis, and vacuolization of the suprabasal layer of oral epithelial keratinocytes. Less frequently the mucous membranes of the nose, esophagus, genitalia and rectum are involved.

Wikipedia : 77 White sponge nevus (WSN, or white sponge naevus, Cannon''s disease, hereditary leukokeratosis of mucosa,... more...

Related Diseases for White Sponge Nevus 1

Diseases in the White Sponge Nevus 1 family:

White Sponge Nevus 2

Diseases related to White Sponge Nevus 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 105)
# Related Disease Score Top Affiliating Genes
1 leukoplakia 30.3 KRT1 KRT13 KRT4
2 pachyonychia congenita 1 29.7 KRT10 KRT16 KRT2 KRT6A KRT6B
3 white sponge nevus 2 12.8
4 dyskeratosis, hereditary benign intraepithelial 11.7
5 waisman syndrome 11.2
6 early-onset parkinsonism-intellectual disability syndrome 11.1
7 glossitis 10.4 KRT6A KRT6B
8 fissured tongue 10.3 KRT16 KRT6A
9 acanthoma 10.3 KRT1 KRT10
10 epidermolytic acanthoma 10.3 KRT1 KRT10
11 steatocystoma multiplex 10.3 KRT10 KRT16
12 erythroderma, ichthyosiform, congenital reticular 10.3 KRT1 KRT10
13 squamous cell carcinoma of the oral tongue 10.3 KRT10 KRT16
14 ichthyosis, cyclic, with epidermolytic hyperkeratosis 10.3 KRT1 KRT10
15 discoid lupus erythematosus 10.2 KRT10 KRT16
16 palmoplantar keratoderma, nonepidermolytic 10.2 KRT1 KRT16
17 filamentary keratitis 10.2 KRT1 KRT10
18 autosomal dominant epidermolytic ichthyosis 10.2 KRT1 KRT10
19 median rhomboid glossitis 10.2 KRT16 KRT6A KRT6B
20 cholesteatoma of middle ear 10.2 KRT10 KRT13 KRT16
21 lichen planus 10.2 KRT10 KRT13 KRT16
22 influenza 10.2
23 basal cell carcinoma, infundibulocystic 10.2 KRT10 KRT14
24 ichthyosis 10.2 KRT1 KRT10 KRT2
25 ichthyosis bullosa of siemens 10.2 KRT1 KRT10 KRT2
26 breast squamous cell carcinoma 10.1 KRT10 KRT14
27 epidermolysis bullosa simplex with mottled pigmentation 10.1 KRT10 KRT14
28 hard palate cancer 10.1 KRT14 KRT4
29 vulvar disease 10.1 KRT13 KRT7
30 epidermolysis bullosa simplex, dowling-meara type 10.1 KRT10 KRT14
31 chronic cystitis 10.1 KRT13 KRT7
32 predominantly cortical thymoma 10.1 KRT14 KRT19
33 vulvar intraepithelial neoplasia 10.0 KRT10 KRT7
34 hidradenitis suppurativa 10.0 KRT10 KRT14
35 hidradenitis 10.0 KRT10 KRT14
36 nodular hidradenoma 10.0 KRT10 KRT7
37 monilethrix 10.0 KRT16 KRT2 KRT6A KRT86
38 vesiculobullous skin disease 10.0 KRT14 PLEC
39 embryoma 10.0 KRT14 KRT19
40 cervical clear cell adenocarcinoma 10.0 KRT14 KRT19
41 odontoma 10.0 KRT14 KRT19
42 malignant biphasic mesothelioma 10.0 KRT10 KRT7
43 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 1 10.0
44 nevus, epidermal 10.0
45 woolly hair syndrome 10.0
46 gastric squamous cell carcinoma 10.0 KRT10 KRT7
47 skin benign neoplasm 10.0 KRT1 KRT13 KRT14
48 eccrine sweat gland neoplasm 10.0 KRT10 KRT7
49 intrahepatic bile duct adenoma 10.0 KRT19 KRT7
50 anal gland adenocarcinoma 10.0 KRT19 KRT7

Graphical network of the top 20 diseases related to White Sponge Nevus 1:



Diseases related to White Sponge Nevus 1

Symptoms & Phenotypes for White Sponge Nevus 1

Human phenotypes related to White Sponge Nevus 1:

33
# Description HPO Frequency HPO Source Accession
1 abnormality of metabolism/homeostasis 33 HP:0001939
2 oral leukoplakia 33 HP:0002745

Symptoms via clinical synopsis from OMIM:

58
Mouth:
thickened white opalescent spongy-fold mucosa in mouth

Eyes:
no conjunctival involvement

Misc:
alternate periods of remission and exacerbation
? response to penicillin

Skin:
vaginal, rectal and nasal leukokeratosis

Lab:
characteristic cell-within-cell histologic change

Clinical features from OMIM:

193900

MGI Mouse Phenotypes related to White Sponge Nevus 1:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 digestive/alimentary MP:0005381 9.43 CCNE1 KRT14 KRT16 KRT19 KRT4 KRT6B
2 integument MP:0010771 9.23 CCNE1 KRT1 KRT14 KRT16 KRT19 KRT4

Drugs & Therapeutics for White Sponge Nevus 1

Search Clinical Trials , NIH Clinical Center for White Sponge Nevus 1

Cochrane evidence based reviews: leukokeratosis, hereditary mucosal

Genetic Tests for White Sponge Nevus 1

Genetic tests related to White Sponge Nevus 1:

# Genetic test Affiliating Genes
1 White Sponge Nevus of Cannon 30

Anatomical Context for White Sponge Nevus 1

MalaCards organs/tissues related to White Sponge Nevus 1:

42
Skin, Tongue

Publications for White Sponge Nevus 1

Articles related to White Sponge Nevus 1:

(show all 14)
# Title Authors Year
1
Clinical features and molecular genetic analysis in a Turkish family with oral white sponge nevus. ( 29476668 )
2018
2
Keratin 4 regulates the development of human white sponge nevus. ( 29738605 )
2018
3
Mutation of keratin 4 gene causing white sponge nevus in a Japanese family. ( 23182699 )
2013
4
White sponge nevus in a patient with EEC syndrome. ( 20492824 )
2010
5
Woolly hair nevus with an ipsilateral associated epidermal nevus and additional findings of a white sponge nevus. ( 20199427 )
2010
6
Two new mutations in the keratin 4 gene causing oral white sponge nevus in Chinese family. ( 18992023 )
2009
7
Identification of a Keratin 4 mutation in a chemically induced mouse mutant that models white sponge nevus. ( 16858417 )
2007
8
Constitutional mutation of keratin 13 gene in familial white sponge nevus. ( 14600690 )
2003
9
A novel mutation in the keratin 13 gene causing oral white sponge nevus. ( 11379896 )
2001
10
A glutamine insertion in the 1A alpha helical domain of the keratin 4 gene in a familial case of white sponge nevus. ( 10652003 )
2000
11
Keratin 13 point mutation underlies the hereditary mucosal epithelial disorder white sponge nevus. ( 7493031 )
1995
12
A mutation in the mucosal keratin K4 is associated with oral white sponge nevus. ( 7493030 )
1995
13
Expression of keratin 14 and 19 mRNA and protein in normal oral epithelia, hairy leukoplakia, tongue biting and white sponge nevus. ( 7686226 )
1993
14
Four hereditary mucosal syndromes: comparative histology and exfoliative cytology of Darier-White's disease, hereditary benign intraepithelial dyskeratosis, white sponge nevus, and pachyonychia congenita. ( 14007732 )
1961

Variations for White Sponge Nevus 1

UniProtKB/Swiss-Prot genetic disease variations for White Sponge Nevus 1:

76
# Symbol AA change Variation ID SNP ID
1 KRT4 p.Glu449Lys VAR_016038

ClinVar genetic disease variations for White Sponge Nevus 1:

6 (show top 50) (show all 206)
# Gene Variation Type Significance SNP ID Assembly Location
1 KRT4 NM_002272.3(KRT4): c.438_440delCAA (p.Asn146del) deletion Pathogenic rs587776844 GRCh37 Chromosome 12, 53207403: 53207405
2 KRT4 NM_002272.3(KRT4): c.438_440delCAA (p.Asn146del) deletion Pathogenic rs587776844 GRCh38 Chromosome 12, 52813619: 52813621
3 KRT4 NM_002272.3(KRT4): c.419_420insCAA (p.Gln140delinsHisLys) insertion Pathogenic rs587776845 GRCh37 Chromosome 12, 53207423: 53207424
4 KRT4 NM_002272.3(KRT4): c.419_420insCAA (p.Gln140delinsHisLys) insertion Pathogenic rs587776845 GRCh38 Chromosome 12, 52813639: 52813640
5 KRT4 NM_002272.3(KRT4): c.1303G> A (p.Glu435Lys) single nucleotide variant Pathogenic rs62642055 GRCh37 Chromosome 12, 53201471: 53201471
6 KRT4 NM_002272.3(KRT4): c.1303G> A (p.Glu435Lys) single nucleotide variant Pathogenic rs62642055 GRCh38 Chromosome 12, 52807687: 52807687
7 KRT4 NM_002272.3(KRT4): c.*269A> G single nucleotide variant Benign rs2035879 GRCh37 Chromosome 12, 53200584: 53200584
8 KRT4 NM_002272.3(KRT4): c.*269A> G single nucleotide variant Benign rs2035879 GRCh38 Chromosome 12, 52806800: 52806800
9 KRT4 NM_002272.3(KRT4): c.1203C> T (p.Arg401=) single nucleotide variant Likely benign rs199607128 GRCh37 Chromosome 12, 53201571: 53201571
10 KRT4 NM_002272.3(KRT4): c.1203C> T (p.Arg401=) single nucleotide variant Likely benign rs199607128 GRCh38 Chromosome 12, 52807787: 52807787
11 KRT4 NM_002272.3(KRT4): c.870G> A (p.Thr290=) single nucleotide variant Likely benign rs189596654 GRCh37 Chromosome 12, 53202599: 53202599
12 KRT4 NM_002272.3(KRT4): c.870G> A (p.Thr290=) single nucleotide variant Likely benign rs189596654 GRCh38 Chromosome 12, 52808815: 52808815
13 KRT4 NM_002272.3(KRT4): c.726G> A (p.Val242=) single nucleotide variant Uncertain significance rs886049641 GRCh37 Chromosome 12, 53204552: 53204552
14 KRT4 NM_002272.3(KRT4): c.726G> A (p.Val242=) single nucleotide variant Uncertain significance rs886049641 GRCh38 Chromosome 12, 52810768: 52810768
15 KRT4 NM_002272.3(KRT4): c.678-10C> T single nucleotide variant Uncertain significance rs777722293 GRCh38 Chromosome 12, 52810826: 52810826
16 KRT4 NM_002272.3(KRT4): c.678-10C> T single nucleotide variant Uncertain significance rs777722293 GRCh37 Chromosome 12, 53204610: 53204610
17 KRT4 NM_002272.3(KRT4): c.677+4C> T single nucleotide variant Uncertain significance rs886049642 GRCh38 Chromosome 12, 52811759: 52811759
18 KRT4 NM_002272.3(KRT4): c.677+4C> T single nucleotide variant Uncertain significance rs886049642 GRCh37 Chromosome 12, 53205543: 53205543
19 KRT4 NM_002272.3(KRT4): c.548A> G (p.Asn183Ser) single nucleotide variant Likely benign rs199768158 GRCh38 Chromosome 12, 52811892: 52811892
20 KRT4 NM_002272.3(KRT4): c.548A> G (p.Asn183Ser) single nucleotide variant Likely benign rs199768158 GRCh37 Chromosome 12, 53205676: 53205676
21 KRT4 NM_002272.3(KRT4): c.463-9T> C single nucleotide variant Uncertain significance rs886049643 GRCh38 Chromosome 12, 52811986: 52811986
22 KRT4 NM_002272.3(KRT4): c.463-9T> C single nucleotide variant Uncertain significance rs886049643 GRCh37 Chromosome 12, 53205770: 53205770
23 KRT4 NM_002272.3(KRT4): c.457G> A (p.Asp153Asn) single nucleotide variant Uncertain significance rs780754412 GRCh38 Chromosome 12, 52813602: 52813602
24 KRT4 NM_002272.3(KRT4): c.457G> A (p.Asp153Asn) single nucleotide variant Uncertain significance rs780754412 GRCh37 Chromosome 12, 53207386: 53207386
25 KRT4 NM_002272.3(KRT4): c.456C> T (p.Ile152=) single nucleotide variant Likely benign rs140582332 GRCh38 Chromosome 12, 52813603: 52813603
26 KRT4 NM_002272.3(KRT4): c.456C> T (p.Ile152=) single nucleotide variant Likely benign rs140582332 GRCh37 Chromosome 12, 53207387: 53207387
27 KRT4 NM_002272.3(KRT4): c.364C> G (p.Leu122Val) single nucleotide variant Uncertain significance rs758695571 GRCh38 Chromosome 12, 52813695: 52813695
28 KRT4 NM_002272.3(KRT4): c.364C> G (p.Leu122Val) single nucleotide variant Uncertain significance rs758695571 GRCh37 Chromosome 12, 53207479: 53207479
29 KRT4 NM_002272.3(KRT4): c.306C> T (p.Pro102=) single nucleotide variant Uncertain significance rs373594963 GRCh38 Chromosome 12, 52813753: 52813753
30 KRT4 NM_002272.3(KRT4): c.306C> T (p.Pro102=) single nucleotide variant Uncertain significance rs373594963 GRCh37 Chromosome 12, 53207537: 53207537
31 KRT4 NM_002272.3(KRT4): c.-51G> A single nucleotide variant Likely benign rs531951809 GRCh37 Chromosome 12, 53207893: 53207893
32 KRT4 NM_002272.3(KRT4): c.-51G> A single nucleotide variant Likely benign rs531951809 GRCh38 Chromosome 12, 52814109: 52814109
33 KRT4 NM_002272.3(KRT4): c.*405G> A single nucleotide variant Uncertain significance rs886049638 GRCh38 Chromosome 12, 52806664: 52806664
34 KRT4 NM_002272.3(KRT4): c.*405G> A single nucleotide variant Uncertain significance rs886049638 GRCh37 Chromosome 12, 53200448: 53200448
35 KRT4 NM_002272.3(KRT4): c.*126C> A single nucleotide variant Uncertain significance rs886049640 GRCh38 Chromosome 12, 52806943: 52806943
36 KRT4 NM_002272.3(KRT4): c.*126C> A single nucleotide variant Uncertain significance rs886049640 GRCh37 Chromosome 12, 53200727: 53200727
37 KRT4 NM_002272.3(KRT4): c.*81T> A single nucleotide variant Likely benign rs572216995 GRCh38 Chromosome 12, 52806988: 52806988
38 KRT4 NM_002272.3(KRT4): c.*81T> A single nucleotide variant Likely benign rs572216995 GRCh37 Chromosome 12, 53200772: 53200772
39 KRT4 NM_002272.3(KRT4): c.1512C> A (p.Gly504=) single nucleotide variant Likely benign rs573971498 GRCh37 Chromosome 12, 53200904: 53200904
40 KRT4 NM_002272.3(KRT4): c.1512C> A (p.Gly504=) single nucleotide variant Likely benign rs573971498 GRCh38 Chromosome 12, 52807120: 52807120
41 KRT4 NM_002272.3(KRT4): c.1495G> C (p.Gly499Arg) single nucleotide variant Likely benign rs190897990 GRCh37 Chromosome 12, 53200921: 53200921
42 KRT4 NM_002272.3(KRT4): c.1495G> C (p.Gly499Arg) single nucleotide variant Likely benign rs190897990 GRCh38 Chromosome 12, 52807137: 52807137
43 KRT4 NM_002272.3(KRT4): c.1493T> C (p.Phe498Ser) single nucleotide variant Likely benign rs377399080 GRCh37 Chromosome 12, 53200923: 53200923
44 KRT4 NM_002272.3(KRT4): c.1493T> C (p.Phe498Ser) single nucleotide variant Likely benign rs377399080 GRCh38 Chromosome 12, 52807139: 52807139
45 KRT4 NM_002272.3(KRT4): c.1381+15C> T single nucleotide variant Benign rs7952923 GRCh37 Chromosome 12, 53201128: 53201128
46 KRT4 NM_002272.3(KRT4): c.1381+15C> T single nucleotide variant Benign rs7952923 GRCh38 Chromosome 12, 52807344: 52807344
47 KRT4 NM_002272.3(KRT4): c.1346+15A> G single nucleotide variant Benign rs931479 GRCh37 Chromosome 12, 53201413: 53201413
48 KRT4 NM_002272.3(KRT4): c.1346+15A> G single nucleotide variant Benign rs931479 GRCh38 Chromosome 12, 52807629: 52807629
49 KRT4 NM_002272.3(KRT4): c.1259G> A (p.Arg420His) single nucleotide variant Uncertain significance rs377329227 GRCh37 Chromosome 12, 53201515: 53201515
50 KRT4 NM_002272.3(KRT4): c.1259G> A (p.Arg420His) single nucleotide variant Uncertain significance rs377329227 GRCh38 Chromosome 12, 52807731: 52807731

Expression for White Sponge Nevus 1

Search GEO for disease gene expression data for White Sponge Nevus 1.

Pathways for White Sponge Nevus 1

GO Terms for White Sponge Nevus 1

Cellular components related to White Sponge Nevus 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 intermediate filament GO:0005882 9.77 KRT1 KRT10 KRT13 KRT14 KRT16 KRT19
2 cornified envelope GO:0001533 9.54 KRT1 KRT10 KRT2
3 intermediate filament cytoskeleton GO:0045111 9.5 KRT13 KRT4 PLEC
4 costamere GO:0043034 9.4 KRT19 PLEC
5 keratin filament GO:0045095 9.28 KRT1 KRT13 KRT14 KRT2 KRT4 KRT6A
6 extracellular exosome GO:0070062 10 KRT1 KRT10 KRT13 KRT14 KRT16 KRT19
7 cytosol GO:0005829 10 CCNE1 KRT1 KRT10 KRT13 KRT14 KRT16

Biological processes related to White Sponge Nevus 1 according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 cornification GO:0070268 9.73 KRT1 KRT10 KRT13 KRT14 KRT16 KRT19
2 epidermis development GO:0008544 9.61 KRT14 KRT16 KRT2
3 cytoskeleton organization GO:0007010 9.55 KRT13 KRT16 KRT4 KRT6A KRT6B
4 intermediate filament cytoskeleton organization GO:0045104 9.51 KRT16 PLEC
5 peptide cross-linking GO:0018149 9.5 KRT1 KRT10 KRT2
6 morphogenesis of an epithelium GO:0002009 9.49 KRT16 KRT6A
7 establishment of skin barrier GO:0061436 9.48 KRT1 KRT16
8 hair cycle GO:0042633 9.46 KRT14 KRT16
9 hemidesmosome assembly GO:0031581 9.4 KRT14 PLEC
10 keratinization GO:0031424 9.4 KRT1 KRT10 KRT13 KRT14 KRT16 KRT19
11 keratinocyte migration GO:0051546 9.37 KRT16 KRT2
12 positive regulation of epidermis development GO:0045684 9.26 KRT10 KRT2

Molecular functions related to White Sponge Nevus 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 structural constituent of cytoskeleton GO:0005200 9.5 KRT14 KRT16 KRT19 KRT2 KRT6A KRT6B
2 structural constituent of epidermis GO:0030280 9.33 KRT1 KRT10 KRT2
3 structural molecule activity GO:0005198 9.32 KRT1 KRT10 KRT13 KRT16 KRT2 KRT4
4 protein binding GO:0005515 10.07 CCNE1 KRT1 KRT13 KRT14 KRT16 KRT19

Sources for White Sponge Nevus 1

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17 EFO
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63 PubMed
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70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
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75 UMLS via Orphanet
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