NETH
MCID: NTH001
MIFTS: 60

Netherton Syndrome (NETH)

Categories: Blood diseases, Genetic diseases, Immune diseases, Rare diseases, Skin diseases

Aliases & Classifications for Netherton Syndrome

MalaCards integrated aliases for Netherton Syndrome:

Name: Netherton Syndrome 56 12 74 52 25 58 73 36 29 13 54 6 43 15 39
Comel-Netherton Syndrome 56 25 58 73
Netherton Disease 56 52 25 73
Neth 56 52 25 73
Ns 56 25 58 73
Erythroderma, Ichthyosiform, with Hypotrichosis and Hyper-Ige 56 73
Ichthyosis Linearis Circumflexa 25 71
Bamboo Hair Syndrome 25 58
Ichthyosiform Erythroderma with Hypotrichosis and Hyper-Ige 25
N Syndrome 71
Ilc 25
Nts 73

Characteristics:

Orphanet epidemiological data:

58
netherton syndrome
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
some severely affected infants die in the neonatal period


HPO:

31
netherton syndrome:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare skin diseases
Rare immunological diseases


Summaries for Netherton Syndrome

Genetics Home Reference : 25 Netherton syndrome is a disorder that affects the skin, hair, and immune system. Newborns with Netherton syndrome have skin that is red and scaly (ichthyosiform erythroderma), and the skin may leak fluid. Some affected infants are born with a tight, clear sheath covering their skin called a collodion membrane. This membrane is usually shed during the first few weeks of life. Because newborns with this disorder are missing the protection provided by normal skin, they are at risk of becoming dehydrated and developing infections in the skin or throughout the body (sepsis), which can be life-threatening. Affected babies may also fail to grow and gain weight at the expected rate (failure to thrive). The health of older children and adults with Netherton syndrome usually improves, although they often remain underweight and of short stature. After infancy, the severity of the skin abnormalities varies among people with Netherton syndrome and can fluctuate over time. The skin may continue to be red and scaly, especially during the first few years of life. Some affected individuals have intermittent redness or experience outbreaks of a distinctive skin abnormality called ichthyosis linearis circumflexa, involving patches of multiple ring-like lesions. The triggers for the outbreaks are not known, but researchers suggest that stress or infections may be involved. Itchiness is a common problem for affected individuals, and scratching can lead to frequent infections. Dead skin cells are shed at an abnormal rate and often accumulate in the ear canals, which can affect hearing if not removed regularly. The skin is abnormally absorbent of substances such as lotions and ointments, which can result in excessive blood levels of some topical medications. Because the ability of the skin to protect against heat and cold is impaired, affected individuals may have difficulty regulating their body temperature. People with Netherton syndrome have hair that is fragile and breaks easily. Some strands of hair vary in diameter, with thicker and thinner spots. This feature is known as bamboo hair, trichorrhexis nodosa, or trichorrhexis invaginata. In addition to the hair on the scalp, the eyelashes and eyebrows may be affected. The hair abnormality in Netherton syndrome may not be noticed in infancy because babies often have sparse hair. Most people with Netherton syndrome have immune system-related problems such as food allergies, hay fever, asthma, or an inflammatory skin disorder called eczema.

MalaCards based summary : Netherton Syndrome, also known as comel-netherton syndrome, is related to dermatitis, atopic and ichthyosis, and has symptoms including trichorrhexis invaginata An important gene associated with Netherton Syndrome is SPINK5 (Serine Peptidase Inhibitor Kazal Type 5), and among its related pathways/superpathways are Developmental Biology and Collagen chain trimerization. The drugs Pimecrolimus and Adalimumab have been mentioned in the context of this disorder. Affiliated tissues include skin, heart and testes, and related phenotypes are malabsorption and urticaria

Disease Ontology : 12 A skin disease that is characterized by chronic skin inflammation, trichorrhexis invaginata, atopic dermatitis and has material basis in mutations in the SPINK5 gene resulting in reduced capacity to inhibit serine proteases expressed in the skin.

NIH Rare Diseases : 52 Netherton disease is a rare disorder affecting the skin, hair and immune system . Symptoms are present at birth and include red, scaly skin. Other symptoms include outbreaks of red, circular scaly rashes, thin, fragile hair (bamboo hair), and immune reactions such as hay fever, asthma, itchy skin, and eczema. Dehydration and infection are common and can be serious. Babies tend to grow slowly and have poor weight gain. Netherton syndrome is caused by the SPINK5 gene not working correctly. It is inherited in an autosomal recessive pattern. Netherton syndrome is diagnosed based on clinical examination, the symptoms, and genetic testing . Treatment is focused on managing the symptoms.

OMIM : 56 Netherton syndrome is a rare and severe autosomal recessive skin disorder characterized by congenital erythroderma, a specific hair-shaft abnormality, and atopic manifestations with high IgE levels. Generalized scaly erythroderma is apparent at or soon after birth and usually persists. Scalp hair is sparse and brittle with a characteristic 'bamboo' shape under light microscopic examination due to invagination of the distal part of the hair shaft to its proximal part. Atopic manifestations include eczema-like rashes, atopic dermatitis, pruritus, hay fever, angioedema, urticaria, high levels of IgE in the serum, and hypereosinophilia. Life-threatening complications are frequent during the neonatal period, including hypernatremic dehydration, hypothermia, extreme weight loss, bronchopneumonia, and sepsis. During childhood, failure to thrive is common as a result of malnutrition, metabolic disorders, chronic erythroderma, persistent cutaneous infections, or enteropathy (summary by Bitoun et al., 2002). (256500)

KEGG : 36 Netherton syndrome is a rare autosomal recessive genodermatosis consisting of erythroderma, ichthyosis linearis circumflexa, and hair shaft abnormalities with a bamboo shoot appearance (trichorrhexis invaginata). Atopic diathesis is commonly associated with the condition.

UniProtKB/Swiss-Prot : 73 Netherton syndrome: An autosomal recessive congenital ichthyosis associated with hair shaft abnormalities and anomalies of the immune system. Typical features are ichthyosis linearis circumflexa, ichthyosiform erythroderma, trichorrhexis invaginata (bamboo hair), atopic dermatitis, and hayfever. High postnatal mortality is due to failure to thrive, infections and hypernatremic dehydration.

Wikipedia : 74 Netherton syndrome is a severe, autosomal recessive form of ichthyosis associated with mutations in the... more...

Related Diseases for Netherton Syndrome

Diseases related to Netherton Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 537)
# Related Disease Score Top Affiliating Genes
1 dermatitis, atopic 31.3 TGM3 SPINK5 KLK7 KLK5 IGHE FLG
2 ichthyosis 30.9 TGM3 TGM1 SPINK5 KLK7 GBA FLG
3 pustular psoriasis 30.7 PI3 ELANE
4 peeling skin syndrome 30.5 TGM1 DSG1 CDSN
5 ritter's disease 30.3 DSG1 DSC1
6 ichthyosis vulgaris 30.2 TGM1 SPINK5 GBA FLG CDSN
7 dermatitis 30.2 SPINK5 KLK7 IGHE FLG DSG1
8 food allergy 30.1 SPINK5 IGHE FLG
9 psoriasis 29.5 TGM1 PI3 KLK7 KLK6 FLG ELANE
10 skin disease 29.3 TGM3 TGM1 SPINK5 PI3 KLK7 FLG
11 autosomal recessive congenital ichthyosis 28.7 TGM3 TGM1 SPINK5 KLK7 KLK6 KLK5
12 prostate cancer 11.7
13 pancreatic cancer 11.7
14 hypertension, essential 11.6
15 body mass index quantitative trait locus 11 11.5
16 psychotic disorder 11.5
17 colorectal cancer 11.5
18 pain agnosia 11.3
19 5-nucleotidase syndrome 11.3
20 gastroesophageal reflux 11.3
21 schizophrenia 11.3
22 short bowel syndrome 11.3
23 dumping syndrome 11.3
24 neuroendocrine tumor 11.3
25 duodenogastric reflux 11.3
26 vipoma 11.3
27 arthrogryposis, distal, type 1a 11.2
28 diabetes mellitus, noninsulin-dependent 11.2
29 parkinson disease, late-onset 11.2
30 prader-willi syndrome 11.2
31 small cell cancer of the lung 11.2
32 tobacco addiction 11.2
33 rett syndrome 11.2
34 restless legs syndrome 11.2
35 zollinger-ellison syndrome 11.2
36 pancreatoblastoma 11.2
37 ileus 11.2
38 hematuria, benign familial 11.0
39 polycystic kidney disease 3 with or without polycystic liver disease 11.0
40 functional gastric disease 11.0
41 agnosia 11.0
42 fibrolamellar carcinoma 11.0
43 atypical follicular adenoma 11.0
44 postgastrectomy syndrome 11.0
45 carcinoid syndrome 11.0
46 congestive heart failure 10.7
47 lung cancer 10.7
48 heart disease 10.7
49 ige responsiveness, atopic 10.6
50 autosomal recessive disease 10.6

Graphical network of the top 20 diseases related to Netherton Syndrome:



Diseases related to Netherton Syndrome

Symptoms & Phenotypes for Netherton Syndrome

Human phenotypes related to Netherton Syndrome:

58 31 (show all 48)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 malabsorption 58 31 hallmark (90%) Very frequent (99-80%) HP:0002024
2 urticaria 58 31 hallmark (90%) Very frequent (99-80%) HP:0001025
3 irregular hyperpigmentation 58 31 hallmark (90%) Very frequent (99-80%) HP:0007400
4 sparse scalp hair 58 31 hallmark (90%) Very frequent (99-80%) HP:0002209
5 fine hair 58 31 hallmark (90%) Very frequent (99-80%) HP:0002213
6 asthma 58 31 hallmark (90%) Very frequent (99-80%) HP:0002099
7 eczema 58 31 hallmark (90%) Very frequent (99-80%) HP:0000964
8 acanthosis nigricans 58 31 hallmark (90%) Very frequent (99-80%) HP:0000956
9 trichorrhexis nodosa 58 31 hallmark (90%) Very frequent (99-80%) HP:0009886
10 congenital nonbullous ichthyosiform erythroderma 58 31 hallmark (90%) Very frequent (99-80%) HP:0007479
11 increased circulating ige level 31 hallmark (90%) HP:0003212
12 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
13 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
14 recurrent respiratory infections 58 31 frequent (33%) Frequent (79-30%) HP:0002205
15 emphysema 58 31 frequent (33%) Frequent (79-30%) HP:0002097
16 seizure 31 frequent (33%) HP:0001250
17 decreased circulating antibody level 31 frequent (33%) HP:0004313
18 short stature 58 31 occasional (7.5%) Occasional (29-5%) HP:0004322
19 dehydration 58 31 occasional (7.5%) Occasional (29-5%) HP:0001944
20 aminoaciduria 58 31 occasional (7.5%) Occasional (29-5%) HP:0003355
21 dry skin 58 31 occasional (7.5%) Occasional (29-5%) HP:0000958
22 skin rash 58 31 occasional (7.5%) Occasional (29-5%) HP:0000988
23 ectopic kidney 58 31 occasional (7.5%) Occasional (29-5%) HP:0000086
24 hydronephrosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000126
25 erythroderma 58 31 occasional (7.5%) Occasional (29-5%) HP:0001019
26 sparse eyelashes 58 31 occasional (7.5%) Occasional (29-5%) HP:0000653
27 sparse and thin eyebrow 31 occasional (7.5%) HP:0000535
28 intestinal atresia 31 very rare (1%) HP:0011100
29 recurrent infections 58 31 Occasional (29-5%) HP:0002719
30 seizures 58 Frequent (79-30%)
31 ichthyosis 58 Very frequent (99-80%)
32 failure to thrive 31 HP:0001508
33 decreased antibody level in blood 58 Frequent (79-30%)
34 abnormality of the hair 58 Very frequent (99-80%)
35 immunologic hypersensitivity 58 Very frequent (99-80%)
36 sparse eyebrow 58 Occasional (29-5%)
37 abnormality of the musculature 31 HP:0003011
38 angioedema 31 HP:0100665
39 increased circulating total ige level 58 Very frequent (99-80%)
40 brittle hair 31 HP:0002299
41 decreased circulating igg level 31 HP:0004315
42 hypereosinophilia 31 HP:0032061
43 parakeratosis 31 HP:0001036
44 villous atrophy 31 HP:0011473
45 allergic rhinitis 31 HP:0003193
46 hypernatremic dehydration 31 HP:0004906
47 brittle scalp hair 31 HP:0004779
48 food allergy 31 HP:0500093

Symptoms via clinical synopsis from OMIM:

56
Growth Other:
failure to thrive

Respiratory Airways:
asthma

Muscle Soft Tissue:
angioedema

Skin Nails Hair Skin Histology:
parakeratosis
psoriasiform epidermal hyperplasia

Neurologic Central Nervous System:
developmental delay

Skin Nails Hair Hair:
sparse eyebrows
sparse, brittle scalp hair
trichorrhexis invaginata ("bamboo hair")

Skin Nails Hair Skin:
urticaria
generalized erythroderma
ichthyosis linearis circumflexa
congenital lamellar ichthyosis

Immunology:
asthma
recurrent infections
angioedema
food allergy
hay fever
more
Hematology:
hypereosinophilia

Metabolic Features:
hypernatremic dehydration

Head And Neck Eyes:
sparse eyebrows

Abdomen Gastrointestinal:
enteropathy with villous atrophy
intestinal atresia (rare)

Clinical features from OMIM:

256500

UMLS symptoms related to Netherton Syndrome:


trichorrhexis invaginata

Drugs & Therapeutics for Netherton Syndrome

Drugs for Netherton Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 13)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Pimecrolimus Approved, Investigational Phase 1, Phase 2 137071-32-0 17753757 6447131
2
Adalimumab Approved Phase 2 331731-18-1 16219006
3 Analgesics, Non-Narcotic Phase 1, Phase 2
4 Immunologic Factors Phase 1, Phase 2
5 Analgesics Phase 1, Phase 2
6 Calcineurin Inhibitors Phase 1, Phase 2
7 Dermatologic Agents Phase 1, Phase 2
8 Immunosuppressive Agents Phase 1, Phase 2
9 Antirheumatic Agents Phase 1, Phase 2
10 Anti-Inflammatory Agents Phase 1, Phase 2
11 Anti-Inflammatory Agents, Non-Steroidal Phase 1, Phase 2
12 Immunoglobulins Phase 2
13 Antibodies Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Randomized Double-blinded Pilot Study of the Efficacy and Safety of Dupilumab Versus Placebo in Patients With Netherton Syndrome Not yet recruiting NCT04244006 Phase 2, Phase 3 Dupilumab Prefilled Syringe
2 Exploratory Safety and Systemic Absorption of Elidel (Pimecrolimus) 1% Cream for the Treatment of Netherton Syndrome Completed NCT00208026 Phase 1, Phase 2 Pimecrolimus 1% Cream
3 Phase II Clinical Trial Using Humira in Netherton Syndrome Completed NCT02113904 Phase 2 Adalimumab
4 A Multicenter Study With a Randomized, Double-Blind, Placebo-Controlled Period, Followed by an Open-Label Maintenance Dosing Period to Evaluate the Efficacy and Safety of Secukinumab in Patients With Ichthyoses Active, not recruiting NCT03041038 Phase 2 Secukinumab;Placebo
5 Phase I Study of Ex-vivo Lentiviral Gene Therapy for the Inherited Skin Disease Netherton Syndrome Unknown status NCT01545323 Phase 1
6 A First-In-human Study to Evaluate Safety and Tolerability of Topical BPR277 in Healthy Volunteers, and Proof of Concept (PoC) Studies to Evaluate the Safety, Tolerability, and Efficacy of Topical BPR277 in Patients With Atopic Dermatitis and Netherton Syndrome Completed NCT01428297 Phase 1 BPR277 ointment (controlled application);Placebo (Vehicle);BPR277 ointment;Placebo (Vehicle);BPR277;Placebo (Vehicle)
7 Syndrome de Netherton : Aspects Cliniques, Physiopathologiques et Identification de Cibles thérapeutiques Unknown status NCT02081313
8 Defining the Skin and Blood Biomarkers of Ichthyosis Recruiting NCT03417856
9 SynCardia 70cc Temporary Total Artificial Heart (TAH-t) for Destination Therapy (DT) Recruiting NCT02232659

Search NIH Clinical Center for Netherton Syndrome

Cochrane evidence based reviews: netherton syndrome

Genetic Tests for Netherton Syndrome

Genetic tests related to Netherton Syndrome:

# Genetic test Affiliating Genes
1 Netherton Syndrome 29 SPINK5

Anatomical Context for Netherton Syndrome

MalaCards organs/tissues related to Netherton Syndrome:

40
Skin, Heart, Testes, Kidney, Endothelial, Bone Marrow, Eye

Publications for Netherton Syndrome

Articles related to Netherton Syndrome:

(show top 50) (show all 634)
# Title Authors PMID Year
1
A case of Netherton syndrome with intestinal atresia, a novel SPINK5 mutation, and a fatal course. 61 56 6
28832989 2017
2
Is c.1431-12G>A A common European mutation of SPINK5? report of a patient with Netherton Syndrome. 61 6 56
28289593 2016
3
Comèl-Netherton syndrome defined as primary immunodeficiency. 56 61 6
19683336 2009
4
Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. 6 56 61
10835624 2000
5
LEKTI proteolytic processing in human primary keratinocytes, tissue distribution and defective expression in Netherton syndrome. 56 61 54
12915442 2003
6
Netherton syndrome: disease expression and spectrum of SPINK5 mutations in 21 families. 56 54 61
11841556 2002
7
A case of Netherton syndrome with mutation in SPINK5 and FLG. 61 56
28943498 2017
8
Netherton Syndrome: A Genotype-Phenotype Review. 56 61
27905021 2017
9
Transgenic kallikrein 5 mice reproduce major cutaneous and systemic hallmarks of Netherton syndrome. 56 61
24534191 2014
10
Matriptase initiates activation of epidermal pro-kallikrein and disease onset in a mouse model of Netherton syndrome. 61 56
20657595 2010
11
Lethal, neonatal ichthyosis with increased proteolytic processing of filaggrin in a mouse model of Netherton syndrome. 56 61
15590704 2005
12
Severe hypernatremic dehydration in an infant with Netherton syndrome. 61 56
11693786 2001
13
Localization of the Netherton syndrome gene to chromosome 5q32, by linkage analysis and homozygosity mapping. 56 61
10712206 2000
14
Altered lamellar body secretion and stratum corneum membrane structure in Netherton syndrome: differentiation from other infantile erythrodermas and pathogenic implications. 61 56
10411158 1999
15
Comèl-Netherton syndrome complicated by papillomatous skin lesions containing human papillomaviruses 51 and 52 and plane warts containing human papillomavirus 16. 61 56
10354085 1999
16
Netherton's syndrome: a syndrome of elevated IgE and characteristic skin and hair findings. 54 56
7822652 1995
17
LEKTI, a novel 15-domain type of human serine proteinase inhibitor. 56
10419450 1999
18
RNA surveillance. Unforeseen consequences for gene expression, inherited genetic disorders and cancer. 56
10098411 1999
19
Netherton's syndrome in a male. 56
5170973 1971
20
Neterton's syndrome and ichthyosis linearis circumflexa. 56
4242601 1969
21
Multiple defects of the hair shaft in Netherton's disease. Association with ichthyosis linearis circumflexa. 56
5359904 1969
22
Netherton's syndrome. 56
5652709 1968
23
Netherton's disease in two sisters. 56
6024735 1967
24
NETHERTON'S DISEASE; TRICHORRHEXIS INVAGINATA (BAMBOO HAIR), CONGENITAL ICHTHYOSIFORM ERYTHRODERMA AND THE ATOPIC DIATHESIS. A HISTOPATHOLOGIC STUDY. 56
14070837 1964
25
A unique case of trichorrhexis nodosa; bamboo hairs. 56
13582191 1958
26
Elastase 2 is expressed in human and mouse epidermis and impairs skin barrier function in Netherton syndrome through filaggrin and lipid misprocessing. 54 61
20179351 2010
27
A heterozygous null mutation combined with the G1258A polymorphism of SPINK5 causes impaired LEKTI function and abnormal expression of skin barrier proteins. 61 54
19438860 2009
28
A functional polymorphism in the SPINK5 gene is associated with asthma in a Chinese Han Population. 61 54
19534795 2009
29
Correlation between SPINK5 gene mutations and clinical manifestations in Netherton syndrome patients. 61 54
17989726 2008
30
Netherton syndrome: successful use of topical tacrolimus and pimecrolimus in four siblings. 54 61
17343588 2007
31
Transglutaminase inhibitors induce hyperproliferation and parakeratosis in tissue-engineered skin. 61 54
17223863 2007
32
Proteolytic processing of human growth hormone by multiple tissue kallikreins and regulation by the serine protease inhibitor Kazal-Type5 (SPINK5) protein. 61 54
17140555 2007
33
Netherton syndrome: report of identical twins presenting with severe atopic dermatitis. 61 54
16670861 2006
34
Serine protease activity and residual LEKTI expression determine phenotype in Netherton syndrome. 61 54
16601670 2006
35
Corneodesmosomal cadherins are preferential targets of stratum corneum trypsin- and chymotrypsin-like hyperactivity in Netherton syndrome. 61 54
16628198 2006
36
[Netherton syndrome]. 61 54
16956571 2006
37
Netherton syndrome: a case report and review of the literature. 54 61
16796630 2006
38
SPINK5, the defective gene in netherton syndrome, encodes multiple LEKTI isoforms derived from alternative pre-mRNA processing. 54 61
16374478 2006
39
hK5 and hK7, two serine proteinases abundant in human skin, are inhibited by LEKTI domain 6. 61 54
16307658 2005
40
Acute pancreatitis in a young girl with the Netherton syndrome. 61 54
16291148 2005
41
Netherton syndrome in two Japanese siblings with a novel mutation in the SPINK5 gene: immunohistochemical studies of LEKTI and other epidermal molecules. 54 61
16225619 2005
42
A Japanese infant with localized ichthyosis linearis circumflexa on the palms and soles harbouring a compound heterozygous mutation in the SPINK5 gene. 61 54
16120162 2005
43
Characterization and expression analysis of the Spink5 gene, the mouse ortholog of the defective gene in Netherton syndrome. 54 61
15780751 2005
44
LEKTI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum. 61 54
15675955 2005
45
Netherton syndrome with extensive skin peeling and failure to thrive due to a homozygous frameshift mutation in SPINK5. 61 54
15942217 2005
46
Epidermal differentiation: the role of proteases and their inhibitors. 54 61
15679120 2004
47
LEKTI demonstrable by immunohistochemistry of the skin: a potential diagnostic skin test for Netherton syndrome. 61 54
15606522 2004
48
Epidermal detachment, desmosomal dissociation, and destabilization of corneodesmosin in Spink5-/- mice. 61 54
15466487 2004
49
SPINK5 and Netherton syndrome: novel mutations, demonstration of missing LEKTI, and differential expression of transglutaminases. 54 61
15304086 2004
50
Association between polymorphisms in the SPINK5 gene and atopic dermatitis in the Japanese. 61 54
14551605 2003

Variations for Netherton Syndrome

ClinVar genetic disease variations for Netherton Syndrome:

6 (show top 50) (show all 220) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SPINK5 NM_006846.3(SPINK5):c.81+2T>ASNV Pathogenic 429608 rs1131691490 5:147444937-147444937 5:148065374-148065374
2 SPINK5 NM_006846.3(SPINK5):c.2468del (p.Lys823fs)deletion Pathogenic 523932 rs565782662 5:147499875-147499875 5:148120312-148120312
3 SPINK5 NM_006846.3(SPINK5):c.1437del (p.Glu480fs)deletion Pathogenic 529155 rs1554104853 5:147484520-147484520 5:148104957-148104957
4 SPINK5 NM_006846.3(SPINK5):c.690del (p.Lys230fs)deletion Pathogenic 570884 rs1561684604 5:147473936-147473936 5:148094373-148094373
5 SPINK5 NM_001127698.2(SPINK5):c.2557C>T (p.Arg853Ter)SNV Pathogenic 623372 rs753621591 5:147503414-147503414 5:148123851-148123851
6 SPINK5 NM_006846.3(SPINK5):c.354_357del (p.Cys119fs)deletion Pathogenic 625164 rs1561680487 5:147466036-147466039 5:148086473-148086476
7 SPINK5 NM_006846.3(SPINK5):c.1816_1820+21delinsCTindel Pathogenic 625166 rs1561695740 5:147491454-147491479 5:148111891-148111916
8 SPINK5 NM_006846.3(SPINK5):c.995del (p.Met332fs)deletion Pathogenic 625167 rs1561686960 5:147477542-147477542 5:148097979-148097979
9 SPINK5 NM_006846.3(SPINK5):c.355_371delinsGACAACATATGACAACAGATGAC (p.Cys119_Lys124delinsAspAsnIleTer)indel Pathogenic 661320 5:147466040-147466056 5:148086477-148086493
10 SPINK5 NM_006846.4(SPINK5):c.374del (p.Thr125fs)deletion Pathogenic 654217 5:147466059-147466059 5:148086496-148086496
11 SPINK5 NM_006846.4(SPINK5):c.850del (p.Glu284fs)deletion Pathogenic 639460 5:147475436-147475436 5:148095873-148095873
12 SPINK5 NM_006846.3(SPINK5):c.1089T>G (p.Tyr363Ter)SNV Pathogenic 646119 5:147478875-147478875 5:148099312-148099312
13 SPINK5 NM_006846.4(SPINK5):c.2579del (p.Lys860fs)deletion Pathogenic 664791 5:147503434-147503434 5:148123871-148123871
14 SPINK5 NM_006846.3(SPINK5):c.1915_1916del (p.Leu639fs)deletion Pathogenic 645505 5:147493950-147493951 5:148114387-148114388
15 SPINK5 NM_006846.3(SPINK5):c.1888-1G>ASNV Pathogenic 654917 5:147493924-147493924 5:148114361-148114361
16 SPINK5 NM_006846.4(SPINK5):c.1012C>T (p.Gln338Ter)SNV Pathogenic 835174 5:147478798-147478798 5:148099235-148099235
17 SPINK5 NM_006846.4(SPINK5):c.1825C>T (p.Gln609Ter)SNV Pathogenic 843075 5:147492435-147492435 5:148112872-148112872
18 SPINK5 NM_006846.3(SPINK5):c.2368C>T (p.Arg790Ter)SNV Pathogenic 5266 rs121908387 5:147499626-147499626 5:148120063-148120063
19 SPINK5 NM_006846.3(SPINK5):c.283-2A>TSNV Pathogenic 5267 rs587777749 5:147465966-147465966 5:148086403-148086403
20 SPINK5 NM_006846.3(SPINK5):c.2468dup (p.Lys824fs)duplication Pathogenic 5268 rs565782662 5:147499874-147499875 5:148120311-148120312
21 SPINK5 NM_006846.4(SPINK5):c.2671C>T (p.Arg891Ter)SNV Pathogenic 852460 5:147504332-147504332 5:148124769-148124769
22 SPINK5 NM_006846.3(SPINK5):c.1302+4A>TSNV Pathogenic 279898 rs201269335 5:147481003-147481003 5:148101440-148101440
23 SPINK5 NM_006846.3(SPINK5):c.2264dup (p.Asn755fs)duplication Pathogenic 279899 rs748978134 5:147498566-147498567 5:148119003-148119004
24 SPINK5 NM_006846.3(SPINK5):c.652C>T (p.Arg218Ter)SNV Pathogenic 351517 rs199757347 5:147470777-147470777 5:148091214-148091214
25 SPINK5 NM_001127698.2(SPINK5):c.1431-12G>ASNV Pathogenic/Likely pathogenic 372516 rs368134354 5:147484503-147484503 5:148104940-148104940
26 SPINK5 NM_001127698.2(SPINK5):c.891C>T (p.Cys297=)SNV Pathogenic/Likely pathogenic 374066 rs752941297 5:147477438-147477438 5:148097875-148097875
27 SPINK5 NM_006846.4(SPINK5):c.2423C>T (p.Thr808Ile)SNV Likely pathogenic 848986 5:147499681-147499681 5:148120118-148120118
28 SPINK5 NM_006846.4(SPINK5):c.81+5G>ASNV Likely pathogenic 835648 5:147444940-147444940 5:148065377-148065377
29 SPINK5 NM_006846.3(SPINK5):c.2441+1G>ASNV Likely pathogenic 574736 rs1561701382 5:147499700-147499700 5:148120137-148120137
30 SPINK5 NM_006846.3(SPINK5):c.817_818del (p.Asn273fs)deletion Likely pathogenic 505094 rs761490126 5:147475401-147475402 5:148095838-148095839
31 SPINK5 NM_006846.3(SPINK5):c.1964G>A (p.Gly655Asp)SNV Conflicting interpretations of pathogenicity 418504 rs142227576 5:147494001-147494001 5:148114438-148114438
32 SPINK5 NM_006846.3(SPINK5):c.2739+10deldeletion Conflicting interpretations of pathogenicity 503813 rs769519367 5:147504409-147504409 5:148124846-148124846
33 SPINK5 NM_006846.3(SPINK5):c.3018T>A (p.Cys1006Ter)SNV Conflicting interpretations of pathogenicity 459574 rs766978225 5:147510875-147510875 5:148131312-148131312
34 SPINK5 NM_001127698.2(SPINK5):c.2243A>G (p.Glu748Gly)SNV Conflicting interpretations of pathogenicity 449103 rs181639116 5:147498551-147498551 5:148118988-148118988
35 SPINK5 NM_006846.3(SPINK5):c.750C>T (p.Asp250=)SNV Conflicting interpretations of pathogenicity 529170 rs199793551 5:147474000-147474000 5:148094437-148094437
36 SPINK5 NM_006846.4(SPINK5):c.1451G>A (p.Arg484Lys)SNV Conflicting interpretations of pathogenicity 784576 5:147484535-147484535 5:148104972-148104972
37 SPINK5 NM_006846.4(SPINK5):c.1132A>C (p.Lys378Gln)SNV Conflicting interpretations of pathogenicity 708757 5:147480056-147480056 5:148100493-148100493
38 SPINK5 NM_006846.4(SPINK5):c.489T>A (p.Ala163=)SNV Conflicting interpretations of pathogenicity 725675 5:147469071-147469071 5:148089508-148089508
39 SPINK5 NM_006846.4(SPINK5):c.1732C>A (p.Arg578=)SNV Conflicting interpretations of pathogenicity 795219 5:147491370-147491370 5:148111807-148111807
40 SPINK5 NM_006846.3(SPINK5):c.1431-10T>GSNV Conflicting interpretations of pathogenicity 351523 rs759079847 5:147484505-147484505 5:148104942-148104942
41 SPINK5 NM_006846.3(SPINK5):c.1607+7G>TSNV Conflicting interpretations of pathogenicity 351526 rs541432320 5:147486734-147486734 5:148107171-148107171
42 SPINK5 NM_006846.3(SPINK5):c.803G>A (p.Arg268His)SNV Conflicting interpretations of pathogenicity 389608 rs375727921 5:147475389-147475389 5:148095826-148095826
43 SPINK5 NM_006846.3(SPINK5):c.2124T>C (p.Ala708=)SNV Conflicting interpretations of pathogenicity 389979 rs200884153 5:147498011-147498011 5:148118448-148118448
44 SPINK5 NM_006846.3(SPINK5):c.2736A>G (p.Ala912=)SNV Uncertain significance 351535 rs773053071 5:147504397-147504397 5:148124834-148124834
45 SPINK5 NM_006846.3(SPINK5):c.739C>T (p.Arg247Cys)SNV Uncertain significance 351518 rs371290967 5:147473989-147473989 5:148094426-148094426
46 SPINK5 NM_006846.3(SPINK5):c.*229A>CSNV Uncertain significance 351550 rs759149324 5:147516783-147516783 5:148137220-148137220
47 SPINK5 NM_006846.3(SPINK5):c.2290G>T (p.Gly764Trp)SNV Uncertain significance 351532 rs778017808 5:147498598-147498598 5:148119035-148119035
48 SPINK5 NM_006846.3(SPINK5):c.1605G>A (p.Val535=)SNV Uncertain significance 351524 rs201831966 5:147486725-147486725 5:148107162-148107162
49 SPINK5 NM_006846.3(SPINK5):c.*358A>GSNV Uncertain significance 351552 rs527953668 5:147516912-147516912 5:148137349-148137349
50 SPINK5 NM_006846.3(SPINK5):c.2360T>C (p.Ile787Thr)SNV Uncertain significance 351533 rs759856421 5:147499618-147499618 5:148120055-148120055

Expression for Netherton Syndrome

Search GEO for disease gene expression data for Netherton Syndrome.

Pathways for Netherton Syndrome

Pathways related to Netherton Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.02 TGM1 SPINK5 PI3 KLK5 KLK14 FLG
2
Show member pathways
12.46 KLK7 KLK6 KLK5 KLK4 KLK14 CTRL
3
Show member pathways
11.96 PI3 ELANE DCD CTSG
4
Show member pathways
11.73 TGM1 SPINK5 PI3 KLK5 KLK14 FLG
5 11.03 KLK7 KLK6 KLK5 KLK4 KLK14

GO Terms for Netherton Syndrome

Cellular components related to Netherton Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 10.03 SPINK5 PI3 KLK7 KLK6 KLK5 KLK4
2 extracellular space GO:0005615 10.02 PI3 KLK7 KLK6 KLK5 KLK14 GBA
3 extracellular exosome GO:0070062 10.01 TGM3 TGM1 SLC26A2 GBA ELANE DSC1
4 desmosome GO:0030057 9.5 DSG1 DSC1 CDSN
5 secretory granule GO:0030141 9.5 KLK7 KLK6 KLK5 KLK4 KLK14 ELANE
6 epidermal lamellar body GO:0097209 9.33 SPINK5 KLK7 KLK5
7 cornified envelope GO:0001533 9.1 TGM1 PI3 FLG DSG1 DSC1 CDSN

Biological processes related to Netherton Syndrome according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 defense response to bacterium GO:0042742 9.85 IGHE ELANE DCD CTSG
2 keratinization GO:0031424 9.81 TGM3 TGM1 DSG1 DSC1
3 epidermis development GO:0008544 9.74 KLK7 KLK5 CDSN
4 protein catabolic process GO:0030163 9.67 KLK4 ELANE CTRL
5 antimicrobial humoral response GO:0019730 9.67 PI3 ELANE DCD CTSG
6 keratinocyte differentiation GO:0030216 9.62 TGM3 TGM1 FLG CDSN
7 defense response to fungus GO:0050832 9.61 ELANE DCD CTSG
8 proteolysis GO:0006508 9.61 KLK7 KLK6 KLK5 KLK4 KLK14 ELANE
9 positive regulation of G protein-coupled receptor signaling pathway GO:0045745 9.58 KLK6 KLK5 KLK14
10 positive regulation of immune response GO:0050778 9.56 ELANE CTSG
11 peptide cross-linking GO:0018149 9.56 TGM3 TGM1 PI3 FLG
12 extracellular matrix disassembly GO:0022617 9.55 KLK7 KLK5 KLK4 ELANE CTSG
13 skin morphogenesis GO:0043589 9.54 GBA CDSN
14 amelogenesis GO:0097186 9.52 KLK5 KLK4
15 cell envelope organization GO:0043163 9.48 TGM3 TGM1
16 positive regulation of antibacterial peptide production GO:0002803 9.46 KLK7 KLK5
17 cornification GO:0070268 9.28 TGM1 SPINK5 PI3 KLK5 KLK14 FLG

Molecular functions related to Netherton Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hydrolase activity GO:0016787 9.96 KLK7 KLK6 KLK5 KLK4 KLK14 GBA
2 peptidase activity GO:0008233 9.81 KLK7 KLK6 KLK5 KLK4 KLK14 ELANE
3 serine-type endopeptidase activity GO:0004252 9.56 KLK7 KLK6 KLK5 KLK4 KLK14 ELANE
4 structural constituent of epidermis GO:0030280 9.37 PI3 FLG
5 protein-glutamine gamma-glutamyltransferase activity GO:0003810 9.32 TGM3 TGM1
6 serine-type peptidase activity GO:0008236 9.23 KLK7 KLK6 KLK5 KLK4 KLK14 ELANE

Sources for Netherton Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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