Inflammatory skin and bowel disease, neonatal, 2

Summary

Inflammatory skin and bowel disease, neonatal, 2 (MONDO:0014481) is a disease caused by EGFR (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: EGFR (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 63

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	inflammatory skin and bowel disease, neonatal, 2
Mondo ID	MONDO:0014481
OMIM	616069
DOID	DOID:0061191
UMLS	C4015130
MedGen	863567
GARD	0018430
Is cancer (heuristic)	no

Also known as: EGFR neonatal inflammatory skin and bowel disease · inflammatory skin and bowel disease, neonatal, 2 · inflammatory skin and bowel disease, neonatal, type 2 · neonatal inflammatory skin and bowel disease caused by mutation in EGFR · NISBD2

Data availability: 63 ClinVar variants · 5 GenCC gene-disease records.

Disease family

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 › inflammatory skin and bowel disease, neonatal, 2

Related subtypes (1): inflammatory skin and bowel disease, neonatal, 1

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

63 retrieved; paginated sample, class counts are floors:

31 uncertain significance, 21 conflicting classifications of pathogenicity, 6 benign, 2 pathogenic, 1 likely benign, 1 benign/likely benign, 1 drug response

ClinVar	Variant (HGVS)	Gene	Classification	Review
157499	NM_005228.5(EGFR):c.1283G>A (p.Gly428Asp)	EGFR	Pathogenic	criteria provided, single submitter
3338124	NM_005228.5(EGFR):c.1094T>A (p.Ile365Asn)	EGFR	Pathogenic	no assertion criteria provided
16613	NM_005228.5(EGFR):c.2369C>T (p.Thr790Met)	EGFR	drug response	reviewed by expert panel
1004409	NM_005228.5(EGFR):c.1739T>C (p.Ile580Thr)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1017706	NM_005228.5(EGFR):c.8C>T (p.Pro3Leu)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1026153	NM_005228.5(EGFR):c.2180A>G (p.Tyr727Cys)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1057685	NM_005228.5(EGFR):c.2386G>A (p.Gly796Ser)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1123013	NM_005228.5(EGFR):c.769G>A (p.Glu257Lys)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
134025	NM_005228.5(EGFR):c.2024G>A (p.Arg675Gln)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
134027	NM_005228.5(EGFR):c.2885G>A (p.Arg962His)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1684707	NM_005228.5(EGFR):c.292C>T (p.Arg98Ter)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
584703	NM_005228.5(EGFR):c.3629C>T (p.Ala1210Val)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
837195	NM_005228.5(EGFR):c.1936A>C (p.Ile646Leu)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
837739	NM_005228.5(EGFR):c.968T>C (p.Val323Ala)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
850344	NM_005228.5(EGFR):c.1900G>A (p.Glu634Lys)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
850694	NM_005228.5(EGFR):c.2518G>A (p.Ala840Thr)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
857836	NM_005228.5(EGFR):c.1557G>T (p.Glu519Asp)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
858191	NM_005228.5(EGFR):c.38C>T (p.Ala13Val)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
938400	NM_005228.5(EGFR):c.434A>G (p.His145Arg)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
954844	NM_005228.5(EGFR):c.3405C>A (p.Asn1135Lys)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
957697	NM_005228.5(EGFR):c.1437A>C (p.Lys479Asn)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
957865	NM_005228.5(EGFR):c.938C>T (p.Ala313Val)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
959977	NM_005228.5(EGFR):c.3572C>T (p.Thr1191Ile)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
960197	NM_005228.5(EGFR):c.1051A>G (p.Ile351Val)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1036068	NM_005228.5(EGFR):c.3034G>C (p.Asp1012His)	EGFR	Uncertain significance	criteria provided, multiple submitters, no conflicts
1045698	NM_005228.5(EGFR):c.3409G>A (p.Glu1137Lys)	EGFR	Uncertain significance	criteria provided, multiple submitters, no conflicts
1051224	NM_005228.5(EGFR):c.286G>A (p.Val96Met)	EGFR	Uncertain significance	criteria provided, multiple submitters, no conflicts
1053190	NM_005228.5(EGFR):c.534G>A (p.Met178Ile)	EGFR	Uncertain significance	criteria provided, multiple submitters, no conflicts
1056156	NM_005228.5(EGFR):c.3368C>T (p.Pro1123Leu)	EGFR	Uncertain significance	criteria provided, multiple submitters, no conflicts
1059673	NM_005228.5(EGFR):c.340G>A (p.Glu114Lys)	EGFR	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 2 · 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
EGFR	Strong	Autosomal recessive	inflammatory skin and bowel disease, neonatal, 2	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EGFR	Orphanet:251576	Gliosarcoma
EGFR	Orphanet:251579	Giant cell glioblastoma

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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: 1 · 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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
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.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gingiva	1
gingival epithelium	1
nipple	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
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

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EGFR	P00533	388

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 37. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
PLCG1 events in ERBB2 signaling	1	2855.0×	0.004	EGFR
PTK6 promotes HIF1A stabilization	1	1631.4×	0.004	EGFR
Inhibition of Signaling by Overexpressed EGFR	1	1268.9×	0.004	EGFR
EGFR interacts with phospholipase C-gamma	1	1142.0×	0.004	EGFR
EGFR Transactivation by Gastrin	1	1142.0×	0.004	EGFR
ERBB2 Activates PTK6 Signaling	1	815.7×	0.004	EGFR
GRB2 events in EGFR signaling	1	761.3×	0.004	EGFR
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	761.3×	0.004	EGFR
SHC1 events in EGFR signaling	1	713.8×	0.004	EGFR
Constitutive Signaling by EGFRvIII	1	713.8×	0.004	EGFR
ERBB2 Regulates Cell Motility	1	713.8×	0.004	EGFR
PI3K events in ERBB2 signaling	1	671.8×	0.004	EGFR
Signaling by ERBB2 ECD mutants	1	671.8×	0.004	EGFR
GAB1 signalosome	1	634.4×	0.004	EGFR
GRB2 events in ERBB2 signaling	1	634.4×	0.004	EGFR
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	571.0×	0.004	EGFR
Developmental Lineage of Mammary Gland Myoepithelial Cells	1	543.8×	0.004	EGFR
Signal transduction by L1	1	519.1×	0.004	EGFR
Respiratory syncytial virus (RSV) attachment and entry	1	496.5×	0.004	EGFR
SHC1 events in ERBB2 signaling	1	475.8×	0.004	EGFR
NOTCH3 Activation and Transmission of Signal to the Nucleus	1	475.8×	0.004	EGFR
Signaling by ERBB2 TMD/JMD mutants	1	475.8×	0.004	EGFR
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	1	439.2×	0.004	EGFR
Signaling by ERBB2 KD Mutants	1	423.0×	0.004	EGFR
Downregulation of ERBB2 signaling	1	380.7×	0.004	EGFR
Signaling by ERBB2	1	346.1×	0.004	EGFR
EGFR downregulation	1	346.1×	0.004	EGFR
Signaling by EGFR	1	326.3×	0.004	EGFR
Signaling by ERBB4	1	271.9×	0.005	EGFR
Extra-nuclear estrogen signaling	1	170.4×	0.007	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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of cardiocyte differentiation	1	16852.0×	0.003	EGFR
positive regulation of protein kinase C signaling	1	5617.3×	0.003	EGFR
morphogenesis of an epithelial fold	1	4213.0×	0.003	EGFR
response to UV-A	1	4213.0×	0.003	EGFR
regulation of peptidyl-tyrosine phosphorylation	1	3370.4×	0.003	EGFR
salivary gland morphogenesis	1	2407.4×	0.003	EGFR
protein insertion into membrane	1	2106.5×	0.003	EGFR
ubiquitin-dependent endocytosis	1	1872.4×	0.003	EGFR
ERBB2-EGFR signaling pathway	1	1685.2×	0.003	EGFR
cerebral cortex cell migration	1	1532.0×	0.003	EGFR
eyelid development in camera-type eye	1	1053.2×	0.004	EGFR
digestive tract morphogenesis	1	991.3×	0.004	EGFR
positive regulation of phosphorylation	1	842.6×	0.004	EGFR
xenobiotic transport	1	842.6×	0.004	EGFR
embryonic placenta development	1	766.0×	0.004	EGFR
positive regulation of peptidyl-serine phosphorylation	1	766.0×	0.004	EGFR
negative regulation of epidermal growth factor receptor signaling pathway	1	766.0×	0.004	EGFR
positive regulation of DNA replication	1	581.1×	0.005	EGFR
positive regulation of epidermal growth factor receptor signaling pathway	1	495.6×	0.006	EGFR
cellular response to estradiol stimulus	1	411.0×	0.006	EGFR
positive regulation of G1/S transition of mitotic cell cycle	1	401.2×	0.006	EGFR
hair follicle development	1	383.0×	0.006	EGFR
negative regulation of protein catabolic process	1	366.4×	0.006	EGFR
positive regulation of DNA repair	1	358.6×	0.006	EGFR
cellular response to epidermal growth factor stimulus	1	318.0×	0.006	EGFR
epithelial cell proliferation	1	312.1×	0.006	EGFR
cellular response to amino acid stimulus	1	306.4×	0.006	EGFR
positive regulation of fibroblast proliferation	1	295.6×	0.006	EGFR
positive regulation of miRNA transcription	1	290.6×	0.006	EGFR
positive regulation of protein phosphorylation	1	276.3×	0.006	EGFR

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
EGFR	LEVODOPA

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EGFR	175	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
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
BITHIONOL	4	EGFR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
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
EGFR	6,531

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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)
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
BITHIONOL	4	EGFR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	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.