peeling skin syndrome type A

Summary

peeling skin syndrome type A (MONDO:0014555) is a disease with 2 cohort genes.

At a glance

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

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		40	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	peeling skin syndrome type A
Mondo ID	MONDO:0014555
OMIM	616265
Orphanet	263548
DOID	DOID:0070522
UMLS	C4015729
MedGen	864166
GARD	0017258
Is cancer (heuristic)	no

Also known as: generalised deciduous skin type A · generalised peeling skin syndrome type A · generalized deciduous skin type A · generalized peeling skin syndrome type A · non-inflammatory generalised peeling skin syndrome type A. · non-inflammatory generalized peeling skin syndrome type A. · non-inflammatory peeling skin syndrome type A · peeling skin syndrome 3 · peeling skin syndrome type 3 · PSS type A · PSS3

Data availability: 1 ClinVar variant · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › epidermal disease › ichthyosis › inherited ichthyosis › peeling skin syndrome › generalized peeling skin syndrome › peeling skin syndrome type A

Related subtypes (2): generalized peeling skin syndrome type C, peeling skin syndrome 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

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
183645	NM_001127895.2(CHST8):c.229C>T (p.Arg77Trp)	CHST8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
FLG2	Strong	Autosomal recessive	peeling skin syndrome 6	6
CHST8	Supportive	Autosomal recessive	peeling skin syndrome type A	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CHST8	Orphanet:263548	Peeling skin syndrome type A
FLG2	Orphanet:263548	Peeling skin syndrome type A

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
CHST8	HGNC:15993	ENSG00000124302	Q9H2A9	Carbohydrate sulfotransferase 8	gencc,clinvar
FLG2	HGNC:33276	ENSG00000143520	Q5D862	Filaggrin-2	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CHST8	Carbohydrate sulfotransferase 8	Catalyzes the transfer of sulfate to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans.
FLG2	Filaggrin-2	Essential for normal cell-cell adhesion in the cornified cell layers.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CHST8	Other/Unknown	no		Sulfotransferase, Carb_sulfotrans_8-10
FLG2	Other/Unknown	no		S100/CaBP7/8-like_CS, EF_hand_dom, Filaggrin

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adenohypophysis	1
male germ line stem cell (sensu Vertebrata) in testis	1
pituitary gland	1
penis	1
skin of hip	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CHST8	167	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, pituitary gland, adenohypophysis
FLG2	122	tissue_specific	yes	upper leg skin, skin of hip, penis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FLG2	2,574
CHST8	880

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CHST8	Q9H2A9	79.90
FLG2	Q5D862	33.09

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Reactions specific to the complex N-glycan synthesis pathway	1	571.0×	0.004	CHST8
Neutrophil degranulation	1	11.5×	0.085	FLG2

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
epidermis morphogenesis	1	1404.3×	0.004	FLG2
carbohydrate biosynthetic process	1	766.0×	0.004	CHST8
hormone biosynthetic process	1	702.2×	0.004	CHST8
sulfur compound metabolic process	1	561.7×	0.004	CHST8
proteoglycan biosynthetic process	1	421.3×	0.004	CHST8
establishment of skin barrier	1	227.7×	0.006	FLG2
central nervous system development	1	57.7×	0.020	CHST8
cell adhesion	1	18.7×	0.053	FLG2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHST8	0	0
FLG2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
FLG2	6	Binding:6

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

0 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.

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	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	CHST8, FLG2

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)
CHST8	0	—
FLG2	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.