Dermatitis, atopic, 2

Summary

Dermatitis, atopic, 2 (MONDO:0011596) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 61

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dermatitis, atopic, 2
Mondo ID	MONDO:0011596
MeSH	C565293
OMIM	605803
DOID	DOID:0110098
UMLS	C1853965
MedGen	340100
Is cancer (heuristic)	no

Also known as: ATOD2 · atopic dermatitis type 2 · atopic eczema caused by mutation in FLG · dermatitis, atopic, susceptibility to, 2 · dermatitis, Atopic, type 2 · FLG atopic eczema

Data availability: 61 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › dermatitis, atopic, susceptibility to › dermatitis, atopic, 2

Related subtypes (8): dermatitis, atopic, 3, dermatitis, atopic, 4, dermatitis, atopic, 5, dermatitis, atopic, 6, dermatitis, atopic, 7, dermatitis, atopic, 8, dermatitis, atopic, 9, dermatitis, atopic, 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

61 retrieved; paginated sample, class counts are floors:

23 pathogenic/likely pathogenic, 12 uncertain significance, 10 likely pathogenic, 8 pathogenic, 6 conflicting classifications of pathogenicity, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
16319	NM_002016.2(FLG):c.1501C>T (p.Arg501Ter)	CCDST	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2580821	NM_002016.2(FLG):c.7564C>T (p.Gln2522Ter)	CCDST	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265475	NM_002016.2(FLG):c.10225C>T (p.Arg3409Ter)	CCDST	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
279933	NM_002016.2(FLG):c.9947C>G (p.Ser3316Ter)	CCDST	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3376676	NM_002016.2(FLG):c.1217C>G (p.Ser406Ter)	CCDST	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3767602	NM_002016.2(FLG):c.9999G>A (p.Trp3333Ter)	CCDST	Pathogenic	criteria provided, multiple submitters, no conflicts
381660	NM_002016.2(FLG):c.7249C>T (p.Gln2417Ter)	CCDST	Pathogenic	criteria provided, multiple submitters, no conflicts
3906969	NM_002016.2(FLG):c.441del (p.Arg151fs)	CCDST	Pathogenic	criteria provided, single submitter
419550	NM_002016.2(FLG):c.557dup (p.Asn186fs)	CCDST	Pathogenic	criteria provided, multiple submitters, no conflicts
419605	NM_002016.2(FLG):c.6950_6957del (p.Ala2316_Ser2317insTer)	CCDST	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
420115	NM_002016.2(FLG):c.3321del (p.Gly1109fs)	CCDST	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
429704	NM_002016.2(FLG):c.10969C>T (p.Arg3657Ter)	CCDST	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
450522	NM_002016.2(FLG):c.2362C>T (p.Arg788Ter)	CCDST	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
488829	NM_002016.2(FLG):c.4420C>T (p.Arg1474Ter)	CCDST	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
504216	NM_002016.2(FLG):c.477dup (p.Glu160fs)	CCDST	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
50930	NM_002016.2(FLG):c.9740C>A (p.Ser3247Ter)	CCDST	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
50932	NM_002016.2(FLG):c.7339C>T (p.Arg2447Ter)	CCDST	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
522001	NM_002016.2(FLG):c.7031C>G (p.Ser2344Ter)	CCDST	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
522879	NM_002016.2(FLG):c.5170G>T (p.Gly1724Ter)	CCDST	Pathogenic	criteria provided, single submitter
523875	NM_002016.2(FLG):c.487G>T (p.Gly163Ter)	CCDST	Pathogenic	criteria provided, multiple submitters, no conflicts
620135	NM_002016.2(FLG):c.3418C>T (p.Arg1140Ter)	CCDST	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
817045	NM_002016.2(FLG):c.3222_3225del (p.Ser1074fs)	CCDST	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1032025	NM_002016.2(FLG):c.5368C>T (p.Gln1790Ter)	FLG	Pathogenic	criteria provided, multiple submitters, no conflicts
1322922	NM_002016.2(FLG):c.138+1G>C	FLG	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16321	NM_002016.2(FLG):c.7661C>G (p.Ser2554Ter)	FLG	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1723739	NM_002016.2(FLG):c.6834_6838del (p.Ser2279fs)	FLG	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280718	NM_002016.2(FLG):c.2218C>T (p.Arg740Ter)	FLG	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
429703	NM_002016.2(FLG):c.1248dup (p.Ser417fs)	FLG	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
545968	NM_002016.2(FLG):c.8117C>G (p.Ser2706Ter)	FLG	Pathogenic	criteria provided, multiple submitters, no conflicts
546021	NM_002016.2(FLG):c.7837A>T (p.Arg2613Ter)	FLG	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 18 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FGFR1	Orphanet:168953	Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement
FGFR1	Orphanet:2117	Hartsfield syndrome
FGFR1	Orphanet:220386	Semilobar holoprosencephaly
FGFR1	Orphanet:2396	Encephalocraniocutaneous lipomatosis
FGFR1	Orphanet:251576	Gliosarcoma
FGFR1	Orphanet:251579	Giant cell glioblastoma
FGFR1	Orphanet:251615	Pilomyxoid astrocytoma
FGFR1	Orphanet:2645	Osteoglosphonic dysplasia
FGFR1	Orphanet:280200	Microform holoprosencephaly
FGFR1	Orphanet:314950	Primary hypereosinophilic syndrome
FGFR1	Orphanet:3157	Septo-optic dysplasia spectrum
FGFR1	Orphanet:3366	Non-syndromic metopic craniosynostosis
FGFR1	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
FGFR1	Orphanet:478	Kallmann syndrome
FGFR1	Orphanet:93258	Pfeiffer syndrome type 1
FGFR1	Orphanet:93924	Lobar holoprosencephaly
FGFR1	Orphanet:99798	Oligodontia
FLG	Orphanet:461	Recessive X-linked ichthyosis

Cohort genes → proteins

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	clinvar
FLG	HGNC:3748	ENSG00000143631	P20930	Filaggrin	clinvar
CCDST	HGNC:55988	ENSG00000236427		cervical cancer associated DHX9 suppressive transcript	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FGFR1	Fibroblast growth factor receptor 1	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
FLG	Filaggrin	Aggregates keratin intermediate filaments and promotes disulfide-bond formation among the intermediate filaments during terminal differentiation of mammalian epidermis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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	9.2×	0.209
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
FLG	Other/Unknown	no		S100/CaBP7/8-like_CS, EF_hand_dom, Filaggrin
CCDST	Other/Unknown	no

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
calcaneal tendon	1
stromal cell of endometrium	1
skin of hip	1
upper arm skin	1
upper leg skin	1
lower esophagus mucosa	1
male germ line stem cell (sensu Vertebrata) in testis	1
quadriceps femoris	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
FLG	162	tissue_specific	yes	upper leg skin, upper arm skin, skin of hip
CCDST	111	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, lower esophagus mucosa, quadriceps femoris

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGFR1	5,693
FLG	2,165
CCDST	0

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR1	P11362	83
FLG	P20930	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. Enrichment computed across 3 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 FGFR1 amplification mutants	1	2855.0×	0.006	FGFR1
FGFR1c and Klotho ligand binding and activation	1	1427.5×	0.006	FGFR1
Signaling by plasma membrane FGFR1 fusions	1	1427.5×	0.006	FGFR1
Epithelial-Mesenchymal Transition (EMT) during gastrulation	1	713.8×	0.008	FGFR1
FGFR1b ligand binding and activation	1	634.4×	0.008	FGFR1
Signaling by activated point mutants of FGFR1	1	475.8×	0.008	FGFR1
FGFR1c ligand binding and activation	1	380.7×	0.008	FGFR1
Phospholipase C-mediated cascade: FGFR1	1	335.9×	0.008	FGFR1
Downstream signaling of activated FGFR1	1	271.9×	0.008	FGFR1
Signal transduction by L1	1	259.6×	0.008	FGFR1
PI-3K cascade:FGFR1	1	259.6×	0.008	FGFR1
SHC-mediated cascade:FGFR1	1	248.3×	0.008	FGFR1
FRS-mediated FGFR1 signaling	1	228.4×	0.008	FGFR1
Formation of paraxial mesoderm	1	203.9×	0.008	FGFR1
Negative regulation of FGFR1 signaling	1	184.2×	0.009	FGFR1
Signaling by FGFR1 in disease	1	146.4×	0.009	FGFR1
Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin	1	139.3×	0.009	FLG
PI3K Cascade	1	135.9×	0.009	FGFR1
NCAM signaling for neurite out-growth	1	135.9×	0.009	FGFR1
Constitutive Signaling by Aberrant PI3K in Cancer	1	63.4×	0.019	FGFR1
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	48.4×	0.023	FGFR1
Formation of the cornified envelope	1	43.9×	0.025	FLG
PIP3 activates AKT signaling	1	33.4×	0.031	FGFR1
RAF/MAP kinase cascade	1	30.5×	0.032	FGFR1

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
vitamin D3 metabolic process	1	4213.0×	0.004	FGFR1
positive regulation of mitotic cell cycle DNA replication	1	4213.0×	0.004	FGFR1
positive regulation of parathyroid hormone secretion	1	4213.0×	0.004	FGFR1
regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	4213.0×	0.004	FGFR1
regulation of phosphate transport	1	2808.7×	0.004	FGFR1
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	1	2808.7×	0.004	FGFR1
regulation of lateral mesodermal cell fate specification	1	2808.7×	0.004	FGFR1
ventricular zone neuroblast division	1	2106.5×	0.004	FGFR1
negative regulation of fibroblast growth factor production	1	2106.5×	0.004	FGFR1
positive regulation of phospholipase activity	1	1685.2×	0.004	FGFR1
regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling	1	1685.2×	0.004	FGFR1
diphosphate metabolic process	1	1685.2×	0.004	FGFR1
chordate embryonic development	1	1404.3×	0.004	FGFR1
positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway	1	1404.3×	0.004	FGFR1
cementum mineralization	1	1203.7×	0.004	FGFR1
auditory receptor cell development	1	936.2×	0.004	FGFR1
paraxial mesoderm development	1	842.6×	0.004	FGFR1
lung-associated mesenchyme development	1	842.6×	0.004	FGFR1
response to sodium phosphate	1	842.6×	0.004	FGFR1
outer ear morphogenesis	1	766.0×	0.005	FGFR1
branching involved in salivary gland morphogenesis	1	702.2×	0.005	FGFR1
organ induction	1	601.9×	0.005	FGFR1
mesenchymal cell proliferation	1	561.7×	0.005	FGFR1
cornification	1	526.6×	0.006	FLG
positive regulation of endothelial cell chemotaxis	1	495.6×	0.006	FGFR1
cell projection assembly	1	468.1×	0.006	FGFR1
regulation of postsynaptic density assembly	1	443.5×	0.006	FGFR1
positive regulation of vascular endothelial cell proliferation	1	421.3×	0.006	FGFR1
middle ear morphogenesis	1	351.1×	0.007	FGFR1
phosphatidylinositol-mediated signaling	1	351.1×	0.007	FGFR1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
FGFR1	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR1	93	4
FLG	0	0
CCDST	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	FGFR1
PEMIGATINIB	4	FGFR1
NINTEDANIB	4	FGFR1
FEDRATINIB	4	FGFR1
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1
AXITINIB	4	FGFR1
SORAFENIB	4	FGFR1
NICLOSAMIDE	4	FGFR1
INFIGRATINIB PHOSPHATE	4	FGFR1
INFIGRATINIB	4	FGFR1
REGORAFENIB	4	FGFR1
ENTRECTINIB	4	FGFR1
CABOZANTINIB	4	FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	FGFR1
NINTEDANIB ESYLATE	4	FGFR1
BRIGATINIB	4	FGFR1
ERDAFITINIB	4	FGFR1
UPADACITINIB	4	FGFR1
FUTIBATINIB	4	FGFR1
PAZOPANIB	4	FGFR1
SUNITINIB	4	FGFR1
DASATINIB	4	FGFR1
MIDOSTAURIN	4	FGFR1
LINIFANIB	3	FGFR1
SEMAXANIB	3	FGFR1
OLVEREMBATINIB	3	FGFR1
BRIVANIB ALANINATE	3	FGFR1
ORANTINIB	3	FGFR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FGFR1	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
FGFR1	1,465

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)
PONATINIB	4	FGFR1
PEMIGATINIB	4	FGFR1
NINTEDANIB	4	FGFR1
FEDRATINIB	4	FGFR1
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1
AXITINIB	4	FGFR1
SORAFENIB	4	FGFR1
NICLOSAMIDE	4	FGFR1
INFIGRATINIB PHOSPHATE	4	FGFR1
INFIGRATINIB	4	FGFR1
REGORAFENIB	4	FGFR1
ENTRECTINIB	4	FGFR1
CABOZANTINIB	4	FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	FGFR1
NINTEDANIB ESYLATE	4	FGFR1
BRIGATINIB	4	FGFR1
ERDAFITINIB	4	FGFR1
UPADACITINIB	4	FGFR1
FUTIBATINIB	4	FGFR1
PAZOPANIB	4	FGFR1
SUNITINIB	4	FGFR1
DASATINIB	4	FGFR1
MIDOSTAURIN	4	FGFR1
LINIFANIB	3	FGFR1
SEMAXANIB	3	FGFR1
OLVEREMBATINIB	3	FGFR1
BRIVANIB ALANINATE	3	FGFR1
ORANTINIB	3	FGFR1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	FGFR1
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	2	FLG, CCDST

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FLG	0	—
CCDST	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.