Neonatal inflammatory skin and bowel disease

Summary

Neonatal inflammatory skin and bowel disease (MONDO:0017411) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 1
• Phenotypes (HPO): 18

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

18 HPO clinical features (Orphanet curated; top 18 by frequency):

HPO ID	Term	Frequency
HP:0000498	Blepharitis	Frequent (30-79%)
HP:0001805	Onychogryposis	Frequent (30-79%)
HP:0003765	Psoriasiform dermatitis	Frequent (30-79%)
HP:0005406	Recurrent bacterial skin infections	Frequent (30-79%)
HP:0008396	Chronic monilial nail infection	Frequent (30-79%)
HP:0010783	Erythema	Frequent (30-79%)
HP:0011131	Perianal rash	Frequent (30-79%)
HP:0011228	Horizontal eyebrow	Frequent (30-79%)
HP:0011354	Generalized abnormality of skin	Frequent (30-79%)
HP:0012390	Anal fissure	Frequent (30-79%)
HP:0025085	Bloody diarrhea	Frequent (30-79%)
HP:0031123	Recurrent gastroenteritis	Frequent (30-79%)
HP:0040181	Chapped lip	Frequent (30-79%)
HP:0040189	Scaling skin	Frequent (30-79%)
HP:0100038	Slow-growing scalp hair	Frequent (30-79%)
HP:0200039	Pustule	Frequent (30-79%)
HP:0410017	Otitis externa	Frequent (30-79%)
HP:0001712	Left ventricular hypertrophy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	neonatal inflammatory skin and bowel disease
Mondo ID	MONDO:0017411
OMIM	614328
Orphanet	294023
UMLS	C4751120
MedGen	1648296
GARD	0017355
Is cancer (heuristic)	no

Also known as: inflammatory skin and bowel disease, neonatal

Data availability: 1 ClinVar variant · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inflammatory bowel disease › neonatal inflammatory skin and bowel disease

Related subtypes (39): Crohn disease, colitis, proctitis, ulcerative proctosigmoiditis, inflammatory bowel disease 11, cutaneous photosensitivity-lethal colitis syndrome, inflammatory bowel disease 1, inflammatory bowel disease 2, inflammatory bowel disease 3, inflammatory bowel disease 7, inflammatory bowel disease 5, inflammatory bowel disease 8, inflammatory bowel disease 6, inflammatory bowel disease 4, inflammatory bowel disease 9, inflammatory bowel disease 10, inflammatory bowel disease 12, inflammatory bowel disease 13, inflammatory bowel disease 14, inflammatory bowel disease 15, inflammatory bowel disease 16, inflammatory bowel disease 17, inflammatory bowel disease 18, inflammatory bowel disease 19, inflammatory bowel disease 20, inflammatory bowel disease 21, inflammatory bowel disease 22, inflammatory bowel disease 23, inflammatory bowel disease 24, inflammatory bowel disease 26, inflammatory bowel disease 27, undetermined colitis, cap polyposis, IL10-related early-onset inflammatory bowel disease, inflammatory bowel disease (infantile ulcerative colitis) 31, autosomal recessive, inflammatory bowel disease 30, TRIM22-related inflammatory bowel disease, ALPI-related inflammatory bowel disease, inflammatory bowel disease 29

Subtypes (2): inflammatory skin and bowel disease, neonatal, 1, inflammatory skin and bowel disease, neonatal, 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1908951	NM_003183.6(ADAM17):c.1951C>T (p.Arg651Ter)	ADAM17	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ADAM17	Definitive	Autosomal recessive	inflammatory skin and bowel disease, neonatal, 1	6
EGFR	Strong	Autosomal recessive	inflammatory skin and bowel disease, neonatal, 2	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ADAM17	Orphanet:294023	Neonatal erythroderma-autoinflammation-inflammatory bowel disease syndrome
EGFR	Orphanet:251576	Gliosarcoma
EGFR	Orphanet:251579	Giant cell glioblastoma

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ADAM17	HGNC:195	ENSG00000151694	P78536	Disintegrin and metalloproteinase domain-containing protein 17	gencc,clinvar
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ADAM17	Disintegrin and metalloproteinase domain-containing protein 17	Transmembrane metalloprotease which mediates the ectodomain shedding of a myriad of transmembrane proteins including adhesion proteins, growth factor precursors and cytokines important for inflammation and immunity.
EGFR	Epidermal growth factor receptor	Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Protease	1	18.3×	0.071
Kinase	1	13.9×	0.071

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ADAM17	Protease	yes	3.4.24.86	Peptidase_M12B, Disintegrin_dom, MetalloPept_cat_dom_sf
EGFR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	1
calcaneal tendon	1
oocyte	1
gingiva	1
gingival epithelium	1
nipple	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADAM17	294	ubiquitous	marker	oocyte, adrenal tissue, calcaneal tendon
EGFR	285	ubiquitous	marker	nipple, gingiva, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EGFR	18,421
ADAM17	3,140

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EGFR	P00533	388
ADAM17	P78536	33

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 73. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by EGFR	2	326.3×	5e-04	ADAM17, EGFR
Signaling by ERBB4	2	271.9×	5e-04	ADAM17, EGFR
PLCG1 events in ERBB2 signaling	1	1427.5×	0.009	EGFR
Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	1427.5×	0.009	ADAM17
Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	815.7×	0.009	ADAM17
PTK6 promotes HIF1A stabilization	1	815.7×	0.009	EGFR
Release of Hh-Np from the secreting cell	1	713.8×	0.009	ADAM17
Signaling by NOTCH1 HD Domain Mutants in Cancer	1	634.4×	0.009	ADAM17
Inhibition of Signaling by Overexpressed EGFR	1	634.4×	0.009	EGFR
EGFR interacts with phospholipase C-gamma	1	571.0×	0.009	EGFR
EGFR Transactivation by Gastrin	1	571.0×	0.009	EGFR
CD163 mediating an anti-inflammatory response	1	571.0×	0.009	ADAM17
Regulated proteolysis of p75NTR	1	519.1×	0.009	ADAM17
ERBB2 Activates PTK6 Signaling	1	407.9×	0.009	EGFR
GRB2 events in EGFR signaling	1	380.7×	0.009	EGFR
Constitutive Signaling by NOTCH1 HD Domain Mutants	1	380.7×	0.009	ADAM17
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	380.7×	0.009	EGFR
SHC1 events in EGFR signaling	1	356.9×	0.009	EGFR
Constitutive Signaling by EGFRvIII	1	356.9×	0.009	EGFR
ERBB2 Regulates Cell Motility	1	356.9×	0.009	EGFR
PI3K events in ERBB2 signaling	1	335.9×	0.009	EGFR
Signaling by ERBB2 ECD mutants	1	335.9×	0.009	EGFR
GAB1 signalosome	1	317.2×	0.009	EGFR
GRB2 events in ERBB2 signaling	1	317.2×	0.009	EGFR
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	285.5×	0.009	EGFR
Developmental Lineage of Mammary Gland Myoepithelial Cells	1	271.9×	0.009	EGFR
Signal transduction by L1	1	259.6×	0.009	EGFR
Respiratory syncytial virus (RSV) attachment and entry	1	248.3×	0.009	EGFR
SHC1 events in ERBB2 signaling	1	237.9×	0.009	EGFR
NOTCH3 Activation and Transmission of Signal to the Nucleus	1	237.9×	0.009	EGFR

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
ERBB2-EGFR signaling pathway	2	1685.2×	3e-05	ADAM17, EGFR
positive regulation of epidermal growth factor receptor signaling pathway	2	495.6×	2e-04	ADAM17, EGFR
positive regulation of G1/S transition of mitotic cell cycle	2	401.2×	2e-04	ADAM17, EGFR
epidermal growth factor receptor signaling pathway	2	247.8×	4e-04	ADAM17, EGFR
phosphatidylinositol 3-kinase/protein kinase B signal transduction	2	210.7×	4e-04	ADAM17, EGFR
positive regulation of cell growth	2	183.2×	4e-04	ADAM17, EGFR
regulation of mast cell apoptotic process	1	8426.0×	0.001	ADAM17
negative regulation of cardiocyte differentiation	1	8426.0×	0.001	EGFR
positive regulation of cell migration	2	61.7×	0.003	ADAM17, EGFR
signal release	1	2808.7×	0.003	ADAM17
cellular response to high density lipoprotein particle stimulus	1	2808.7×	0.003	ADAM17
positive regulation of protein kinase C signaling	1	2808.7×	0.003	EGFR
morphogenesis of an epithelial fold	1	2106.5×	0.003	EGFR
response to UV-A	1	2106.5×	0.003	EGFR
regulation of peptidyl-tyrosine phosphorylation	1	1685.2×	0.003	EGFR
cytokine precursor processing	1	1685.2×	0.003	ADAM17
production of molecular mediator involved in inflammatory response	1	1203.7×	0.004	ADAM17
salivary gland morphogenesis	1	1203.7×	0.004	EGFR
regulation of axon regeneration	1	1203.7×	0.004	ADAM17
positive regulation of cell population proliferation	2	33.6×	0.004	ADAM17, EGFR
protein insertion into membrane	1	1053.2×	0.004	EGFR
Notch receptor processing	1	936.2×	0.004	ADAM17
ubiquitin-dependent endocytosis	1	936.2×	0.004	EGFR
germinal center formation	1	842.6×	0.004	ADAM17
cerebral cortex cell migration	1	766.0×	0.005	EGFR
neutrophil mediated immunity	1	702.2×	0.005	ADAM17
positive regulation of leukocyte chemotaxis	1	648.1×	0.005	ADAM17
amyloid precursor protein catabolic process	1	601.9×	0.005	ADAM17
positive regulation of T cell chemotaxis	1	561.7×	0.005	ADAM17
wound healing, spreading of epidermal cells	1	526.6×	0.005	ADAM17

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ADAM17	PREDNISOLONE
EGFR	LEVODOPA

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EGFR	175	4
ADAM17	8	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PREDNISOLONE	4	ADAM17
LEVODOPA	4	EGFR
CLOTRIMAZOLE	4	EGFR
ERLOTINIB HYDROCHLORIDE	4	EGFR
CISPLATIN	4	EGFR
PONATINIB	4	EGFR
AFATINIB	4	EGFR
CHROMIC CHLORIDE	4	EGFR
BACITRACIN	4	EGFR
ZINC CHLORIDE	4	EGFR
LAPATINIB DITOSYLATE	4	EGFR
VEMURAFENIB	4	EGFR
FEDRATINIB	4	EGFR
AXITINIB	4	EGFR
SORAFENIB	4	EGFR
DASATINIB ANHYDROUS	4	EGFR
NICLOSAMIDE	4	EGFR
SELUMETINIB	4	EGFR
TERFENADINE	4	EGFR
ALECTINIB	4	EGFR
NERATINIB	4	EGFR
IBRUTINIB	4	EGFR
AFATINIB DIMALEATE	4	EGFR
CABOZANTINIB	4	EGFR
DACOMITINIB	4	EGFR
DACOMITINIB ANHYDROUS	4	EGFR
CERITINIB	4	EGFR
VANDETANIB	4	EGFR
TRIBROMSALAN	4	EGFR
BOSUTINIB	4	EGFR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
EGFR	6,531	Binding:6211, Functional:173, ADMET:138, Toxicity:9
ADAM17	288	Binding:257, Functional:25, ADMET:5, Toxicity:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ADAM17	3.4.24.86	ADAM 17 endopeptidase
EGFR	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ADAM17	288
EGFR	6,531

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
PREDNISOLONE	4	ADAM17
LEVODOPA	4	EGFR
CLOTRIMAZOLE	4	EGFR
ERLOTINIB HYDROCHLORIDE	4	EGFR
CISPLATIN	4	EGFR
PONATINIB	4	EGFR
AFATINIB	4	EGFR
CHROMIC CHLORIDE	4	EGFR
BACITRACIN	4	EGFR
ZINC CHLORIDE	4	EGFR
LAPATINIB DITOSYLATE	4	EGFR
VEMURAFENIB	4	EGFR
FEDRATINIB	4	EGFR
AXITINIB	4	EGFR
SORAFENIB	4	EGFR
DASATINIB ANHYDROUS	4	EGFR
NICLOSAMIDE	4	EGFR
SELUMETINIB	4	EGFR
TERFENADINE	4	EGFR
ALECTINIB	4	EGFR
NERATINIB	4	EGFR
IBRUTINIB	4	EGFR
AFATINIB DIMALEATE	4	EGFR
CABOZANTINIB	4	EGFR
DACOMITINIB	4	EGFR
DACOMITINIB ANHYDROUS	4	EGFR
CERITINIB	4	EGFR
VANDETANIB	4	EGFR
TRIBROMSALAN	4	EGFR
BOSUTINIB	4	EGFR

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	ADAM17, EGFR
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.