Exfoliative ichthyosis

Summary

Exfoliative ichthyosis (MONDO:0017339) is a disease with 3 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 3
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	exfoliative ichthyosis
Mondo ID	MONDO:0017339
Orphanet	289586
UMLS	C1838440
MedGen	325027
GARD	0017329
Is cancer (heuristic)	no

Also known as: autosomal recessive exfoliative ichthyosis · exfoliative ichthyosis · ichthyosis exfoliativa

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

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › epidermal disease › ichthyosis › inherited ichthyosis › autosomal recessive congenital ichthyosis › exfoliative ichthyosis

Related subtypes (12): autosomal recessive congenital ichthyosis 1, autosomal recessive congenital ichthyosis 4A, autosomal recessive congenital ichthyosis 11, autosomal recessive congenital ichthyosis 5, autosomal recessive congenital ichthyosis 8, ichthyosis, congenital, autosomal recessive 12, bathing suit ichthyosis, self-healing collodion baby, acral self-healing collodion baby, congenital non-bullous ichthyosiform erythroderma, ichthyosis, congenital, autosomal recessive 14, ichthyosis, congenital, autosomal recessive 13

Subtypes (3): superficial epidermolytic ichthyosis, peeling skin syndrome 4, peeling skin syndrome 5

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
9310	NM_000423.3(KRT2):c.1459G>A (p.Glu487Lys)	KRT2	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 5 · 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
CSTA	Supportive	Autosomal recessive	exfoliative ichthyosis	6
SERPINB8	Supportive	Autosomal recessive	exfoliative ichthyosis	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CSTA	Orphanet:263534	Acral peeling skin syndrome
CSTA	Orphanet:289586	Exfoliative ichthyosis
SERPINB8	Orphanet:263548	Peeling skin syndrome type A
SERPINB8	Orphanet:289586	Exfoliative ichthyosis
KRT2	Orphanet:455	Superficial epidermolytic ichthyosis

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CSTA	HGNC:2481	ENSG00000121552	P01040	Cystatin-A	gencc
SERPINB8	HGNC:8952	ENSG00000166401	P50452	Serpin B8	gencc
KRT2	HGNC:6439	ENSG00000172867	P35908	Keratin, type II cytoskeletal 2 epidermal	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CSTA	Cystatin-A	This is an intracellular thiol proteinase inhibitor.
SERPINB8	Serpin B8	Has an important role in epithelial desmosome-mediated cell-cell adhesion.
KRT2	Keratin, type II cytoskeletal 2 epidermal	Probably contributes to terminal cornification.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.0

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
Other/Unknown	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CSTA	Other/Unknown	no		Cystatin_dom, Prot_inh_stefin, Prot_inh_cystat_CS
SERPINB8	Other/Unknown	no		Serpin_fam, Serpin_CS, Serpin_dom
KRT2	Other/Unknown	no		Keratin_II, IF_conserved, Keratin_2_head

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gingiva	1
oral cavity	1
pharyngeal mucosa	1
monocyte	1
mononuclear cell	1
skin of leg	1
skin of hip	1
upper arm skin	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CSTA	248	ubiquitous	marker	pharyngeal mucosa, oral cavity, gingiva
SERPINB8	185	ubiquitous	marker	monocyte, skin of leg, mononuclear cell
KRT2	162	tissue_specific	yes	upper arm skin, upper leg skin, skin of hip

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CSTA	2,102
KRT2	1,783
SERPINB8	979

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CSTA	P01040	14

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SERPINB8	P50452	91.48
KRT2	P35908	67.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the cornified envelope	2	58.6×	0.002	CSTA, KRT2
Dissolution of Fibrin Clot	1	271.9×	0.009	SERPINB8
Keratinization	1	18.6×	0.088	KRT2
Hemostasis	1	12.0×	0.101	SERPINB8
Developmental Biology	1	4.8×	0.194	KRT2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
keratinocyte activation	1	2808.7×	0.005	KRT2
positive regulation of epidermis development	1	1123.5×	0.005	KRT2
keratinocyte migration	1	802.5×	0.005	KRT2
negative regulation of endopeptidase activity	1	561.7×	0.005	SERPINB8
keratinocyte development	1	510.7×	0.005	KRT2
peptide cross-linking	1	468.1×	0.005	CSTA
epithelial cell-cell adhesion	1	401.2×	0.005	SERPINB8
cornification	1	351.1×	0.005	KRT2
negative regulation of proteolysis	1	224.7×	0.007	CSTA
keratinocyte proliferation	1	193.7×	0.008	KRT2
keratinocyte differentiation	1	82.6×	0.015	CSTA
intermediate filament organization	1	80.2×	0.015	KRT2
keratinization	1	78.0×	0.015	KRT2
epidermis development	1	70.2×	0.015	KRT2
cell-cell adhesion	1	33.8×	0.029	CSTA

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · 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).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SERPINB8	1	2
CSTA	0	0
KRT2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	SERPINB8

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SERPINB8	6	Binding:6

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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)
MOLIBRESIB	2	SERPINB8

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	SERPINB8
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	CSTA, KRT2

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)
CSTA	0	—
KRT2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.